While President Trump continues to promote antimalarial drugs such as hydroxychloroquine sulfate and azithromycin to treat COVID-19—“What do you have to lose?” he exclaimed during the April 4 Coronavirus Task Force Briefing—the global community of drug discovery researchers and biopharmas is developing a much broader menu of therapeutic options.

In all, the tally of vaccines and treatments in development against COVID-19 as of April 13 was at least 161 candidates—more than double the 60 candidates highlighted in GEN‘s previous A-List summarizing therapies in the works against SARS-CoV-2, Catching Up to Coronavirus: Top 60 Treatments in Development.

Our latest collection includes the combination trumpeted by Trump—hydroxychloroquine, marketed by Sanofi as Plaquenil®, and azithromycin, marketed by Pfizer as Zithromax® or “Z-Pak”—as well as chloroquine phosphate, made by Bayer and numerous Chinese manufacturers.

Trump declared in a March 21 tweet that the hydrochloroquine-azithromycin combination has “a real chance to be one of the biggest game changers in the history of medicine.”

Supporters of the combo cite positive results published by a Chinese research team, including a March 18 study in Nature-published Cell Discovery suggesting that “HCQ can efficiently inhibit SARS-CoV-2 infection in vitro” and has “good potential to combat the disease.” They acknowledged that the possibility awaits confirmation by clinical trials,” added the researchers, who in February reported positive in vitro results for chloroquine phosphate and Gilead Sciences’ remdesivir.

Indeed the combination has not been assessed in the scaled-up clinical trials that would indicate whether the drugs are safe and effective, as Eric Topol, MD, noted emphatically in an April 5 tweet

Interviewed on Fox News Channel, William A. Haseltine, PhD, the HIV/AIDS research pioneer and Chairman of ACCESS Health International, cautioned against embracing the hydroxychloroquine-azithromycin combo based on anecdotal evidence: “It’s sad to me that people are promoting that drug,” citing conflicting studies that have shown mild or no effect: “Whatever effect it has, it will be very mild.”

Haseltine also termed “nonsense” the Lazarus effect described of some patients using the combination therapy by Kurt Hegmann, MD, MPH, director of the Rocky Mountain Center for Occupational and Environmental Health at the University of Utah, who claimed to see “responses that are equivalent to Lazarus — literally the biblical Lazarus — people almost dead coming back.”

Until new treatments show sufficient safety and effectiveness to gain approval, Haseltine wrote April 6, healthcare providers should offer patients passive immune therapy in three stages: “The first stage is sera from convalescents. The second is purified antibody fractions that are safer and more potent, but also achievable—hopefully by summer. The third is monoclonal antibodies, which will take more time but is already on the fast track.”

A passive antibody therapy consisting of antibodies from the blood of recovered COVID-19 patients is being studied in a clinical trial by a consortium that includes Johns Hopkins Bloomberg School of Public Health, Mayo Clinic, Montefiore Medical Center/Albert Einstein College of Medicine, and Washington University in St. Louis. CSL Behring and Takeda Pharmaceutical lead another consortium working to develop another plasma-based treatment, an unbranded anti-SARS-CoV-2 polyclonal hyperimmune immunoglobulin therapy.

150 and Counting

To better navigate through the escalating number of potential therapeutic options for COVID-19, GEN has divided this updated list of candidates into four categories, based on their developmental and (where applicable) clinical progress to date:

● “Front runner– candidates include the top most-mentioned therapeutics in development, based on advanced stages of activity, favorable data or both.

● “Definitely maybe”- candidates are those in earlier phases with the most promising partners, or more advanced candidates well under way in development that have generated uneven data.

● “Gathering Speed – candidates apply interesting technology, attracting notable partners, or both, but without consistently solid data.

● “The Long Tail” – candidates appear to be longshots pending additional details from their developers and/or clinical progress.

GEN has also labeled the most common treatment types by color, including antibodies (blue), antivirals (orange), RNA-based treatments (purple), and vaccines (red).

Including vaccines and treatments, the number of COVID-19-related clinical trials tripled during March—from 53 as of March 1 to 152 as of March 29, according to research by Geoffrey C. Porges, MBBS, senior research analyst at SVB Leerink. The largest number of these clinical phase therapeutics (49) were antivirals, followed by 46 small molecule drugs, 26 biologics, 18 plasma/cell derived treatments, and only 4 vaccines.

Other interesting COVID-19 fighting approaches may yet emerge into additional candidates soon: A team at Johns Hopkins University School of Medicine has published a preprint showing promising results for prazosin as a treatment against cytokine storm, among the worst effects associated with the virus. In the U.K., Ossianix is screening its library of VNAR antibodies that bind to the human transferrin receptor and can target the lung in rodents and non-human primates for their effect against SARS-CoV-2.

Other institutions are studying whether familiar blockbuster drugs with success outside virology may also prove effective against COVID-19. Among such clinical trials in progress are studies assessing Novartis’ Gilenya® (fingolimod), one examining Celebrex® (celecoxib), and even a study evaluating sildenafil citrate, the phosphodiesterase-5 (PDE5) inhibitor better known as Viagra®.

Among the 18 candidates in our leading “Front Runner” category are several drugs that have garnered considerable media attention, including Gilead’s Remdesivir, Inovio’s INO-4800, Regeneron/Sanofi’s Kevzara® (sarilumab), Roche/Genentech’s Actemra (tocilizumab), and Distributed Bio’s bioengineered antibodies.

Key:
● ANTIVIRAL
● VAX
● ANTIBODY
● RNA

Front Runners – 18 candidates

 

BioNTech, Pfizer, and Fosun Pharma

Candidate: BNT162

Type: Potential first-in-class mRNA vaccine designed to induce immunity and prevent COVID-19 infection

Status: BioNTech and Pfizer said April 9 they intend to launch their first clinical trials for an mRNA COVID-19 vaccine as soon as the end of April, initially in the United States and Europe across multiple sites. The companies said they will advance multiple candidates.

Pfizer agreed to pay BioNTech $185 million upfront—including $72 million in cash and a $113 million equity investment—and up to $563 million in payments tied to achieving milestones. Pfizer will initially fund 100% of the development costs, and BioNTech will repay Pfizer its 50% share of these costs during commercialization of the vaccine.

The companies announced their up-to-$748 million COVID-19 vaccine development partnership in March, focusing on BNT162, the first treatment to emerge from BioNTech’s accelerated COVID-19-focused development program, “Project Lightspeed.”

The BioNTech-Pfizer partnership is worldwide except China, where BioNTech is partnering with Fosun Pharma to jointly develop BNT162. Fosun has agreed to make a $50 million equity investment, and pay BioNTech up to $85 million in additional upfront and milestone payments. The companies will share future gross profits from the sale of the vaccine in China.

 

CanSino Biologics

Candidate: Vaccine for prevention of COVID-19

Type: Recombinant Novel Coronavirus Disease Vaccine incorporating the Adenovirus Type 5 Vector (Ad5-nCoV)

Status: CanSino on April 9 said it and China’s Beijing Institute of Biotechnology, Academy of Military Medical Sciences, plan to initiate phase II clinical trial for Ad5-nCoV in China.

Last month, CanSino received approval from Chinese authorities to begin human trials of the vaccine, co-developed with China’s Beijing Institute of Biotechnology, Academy of Military Medical Sciences, and is looking for volunteers for the six-month Phase I study (ChiCTR2000030906). CanSino and the Academy are using Sartorius’ BIOSTAT® STR single-use bioreactor system for upstream preparation of the recombinant vaccine, Sartorius said March 25.

The vaccine candidate is the first novel coronavirus vaccine for COVID-19 to advance to Phase I in China. The company has cited results from animal studies showing that the vaccine candidate can induce strong immune response in animal models.

 

Chugai Pharmaceutical and Zhejiang Hisun Pharmaceutical

Candidate: Tocilizumab (Actemra® in the U.S.), alone and in combination with favipiravir (Avigan® in the U.S.)

Type: Humanized monoclonal antibody targeting interleukin-6

Status: Peking University First Hospital on March 16 registered an up-to-150 patient study assessing tocilizumab, marketed in China by Roche subsidiary Chugai Pharmaceutical, in combination with the Zhejiang Hisun Pharmaceutical-marketed drug favipiravir in adults with COVID-19 (ChiCTR2000030894). A 94-patient trial assessing Tocilizumab alone has been registered by The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) (ChiCTR2000029765).

 

CytoDyn

Candidate: Leronlimab (PRO 140)

Type: Humanized IgG4 monoclonal antibody. Leronlimab is CytoDyn’s lead candidate, and is a CCR5 antagonist for patients who experience respiratory illness as a result of COVID-19 with potential for multiple therapeutic indications.

Status: CytoDyn on April 13 appointed its Chairman, Scott A. Kelly, MD, to the additional position of Chief Medical Officer and Head of Busines Development, a move it said would accelerate evaluation of leronlimab for COVID-19 and other indications.

Four days earlier, CytoDyn highlighted positive results from seven patients with severe COVID-19 after seven days of treatment with leronlimab: All seven showed “dramatic” immune restoration, especially in the CD8 T-lymphocyte population, and a “further dramatic” reduction in the critical cytokine storm cytokines IL-6 and TNF-alpha. At a “leading medical center in Southern California,” CytoDyn said, one severe COVID-19 patient was removed from external ventilation three days after treatment with leronlimab, and two moderate COVID-19 patients were removed from external oxygen support one day following leronlimab treatment,and discharged from the hospital. Based on these results, another four patients with moderate COVID-19 have been administered leronlimab and results are pending, CytoDyn said.

A day earlier, CytoDyn said Novant Health had begun enrollment of patients for a Phase II randomized clinical trial, assessing leronlimab in patients with mild-to-moderate indications—the second trial site in the nation and first in the Southeastern U.S. to do so. The first two COVID-19 patients had been treated with leronlimab in that study, CytoDyn said. In the U.K., CytoDyn is collaborating with the U.K.’s Department of Health to provide emergency access to leronlimab for severe and critically ill COVID-19 patients, with a formal request to be submitted soon to the Medicines and Healthcare Products Regulatory Agency (MHRA).

Enrollment is also underway in a second leronlimab study in COVID-19, a 390-patient Phase IIb/III trial in severely and critically ill COVID-19 patients. Patients are set to be administered leronlimab for two weeks, with the primary endpoint being the mortality rate at 28 days and a secondary endpoint of mortality rate at 14 days. The company will perform an interim analysis on the data from 50 patients.

CytoDyn also said it has treated 15 severely ill COVID-19 patients with leronlimab at four hospitals, under an emergency IND granted by the FDA (ten patients were treated in New York).

CytoDyn said April 2 eight of the severely ill COVID-19 patients treated with leronlimab showed “significant improvement” in immunologic biomarkers: “We continue to see increases in the profoundly decreased CD8 T-lymphocyte percentages by Day 3, normalization of CD4/CD8 ratios, and resolving cytokine production including reduced IL-6 correlating with patient improvement,” stated Bruce Patterson, MD, CEO and founder of IncellDx, a diagnostic partner and advisor to CytoDyn.

CytoDyn has initiated enrollment in a planned 75-patient Phase II trial for leronlimab treatment of COVID-19 patients with mild-to-moderate indications—and under the same IND is also proceeding with its second COVID-19 clinical trial, a planned 342-patient Phase IIb/III study in critically ill COVID-19 patients, with the primary endpoint being the mortality rate at 14 days.

CytoDyn and Longen China Group has said they will begin exploring leronlimab as a potential treatment for coronavirus as well as cancer.

Leronlimab has completed nine clinical trials in over 800 people, according to CytoDyn, including meeting its primary endpoints in a pivotal Phase III trial in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients. CytoDyn plans to file a BLA with the FDA in HIV during Q1 2020. Leronlimab has the FDA’s Fast Track designation as a combination therapy with highly active antiretroviral therapy (HAART) for HIV-infected patients, and for metastatic triple-negative breast cancer—for which CytoDyn saiod April 3 it has requested to meet with the FDA to discuss new clinical data in support of a Breakthrough Therapy designation from the agency.

 

Distributed Bio

Candidates: Antibodies bioengineered to fight COVID-19

Type: Broadly neutralizing antibodies based on the company’s SuperHuman platform, which according to the company is the world’s most advanced computationally optimized human antibody library for antibody discovery.

Status: Distributed Bio’s CEO, president, and chairman Jacob Glanville, PhD, wrote April 2 that after nine weeks using its Tumbler technology, the company has generated thousands of extremely potent picomolar antibody binders that block known neutralizing ACE2 epitopes, blocking the SARS-CoV-2 from infecting human cells. “Hundreds of potent candidate therapeutic antibodies discovered that block the ACE2 receptor interaction with virus,” Distributed stated in a presentation.

A day earlier in a series of tweets, Glanville said the company’s approach was a “candidate cure” for COVID-19, and added: “We are trying to get this out by September but it will need funding and efficient GMP manufacturing.” That earned the company attention from news outlets as varied as Yahoo! FinanceFox News Channel, and Radio New Zealand.

In March, Glanville told a South Korean outlet that the company is working to extract five SARS-CoV-2 antibodies and mutate them into 1 billion different types to see whether any of the antibodies bind to the virus that causes COVID-19.

If a potential antibody is identified this month, it could be mass produced in August or September, said Glanville, who gained fame after being featured in the Netflix docu-series “Pandemic: How to Prevent an Outbreak” in January.

 

Fujifilm Holdings and Zhejiang Hisun Pharmaceutical

Candidate: Favipiravir (marketed by Fujifilm as Avigan® and by Hisun in China as Favilavir)

Type: Broad spectrum anti-viral agent that is designed to selectively and potently inhibit the RNA-dependent RNA polymerase (RdRp) of RNA viruses. Japan has approved Avigan for novel or re-emergent influenza and was previously used to treat Ebola patients in Guinea.

Status: Japan’s Prime Minister Shinzo Abe told reporters in March that his government will partner with other countries to launch trials of on COVID-19 patients and ramp up its production, with plans to pursue approval if it succeeds in clinical trials now underway at Fujita Health University Hospital in Aichi Prefecture and other institutions, according to NHK.

Zhang Xinmin, an official at China’s Science and Technology Ministry, told reporters March 17 that favipiravir produced positive results in clinical trials in Wuhan and Shenzhen involving 340 patients—including a shortening of the time after treatment that patients tested negative for COVID-19 from 11 days to four, and improved lung conditions in 91% of treated patients vs. 62% of untreated patients, as measured via x-rays. Fujifilm has responded with a statement stressing that Avigan remained under study and had not been approved.

Japan’s Health Minister Katsunobu Kato said his ministry would recommend Avigan, developed by Fujifilm-owned Toyama Chemical, for use as a coronavirus treatment after test dosages appeared effective in mild and asymptomatic cases at least two medical institutions. In China, the National Health Commission approved Hisun’s version of the drug as an investigational treatment for SARS-CoV-2.

 

Gilead Sciences

Candidate: Remdesivir (GS-5734)

Type: Nucleotide prodrug

Status: Gilead has dramatically increased the patient populations of three Phase III trials of remdesivir now recruiting participants—from 600 to 1,600 moderate COVID-19 patients in one study (NCT04292730), and from 400 to 2,400 severe disease patients in the other (NCT04292899). The other study is in approximately 800 COVID-19 patients with a broad mix of symptoms, according to Gilead Chairman and CEO Daniel O’Day (up from 440 participants as listed on ClinicalTrials.gov, NCT04280705); that study was  launched by the National Institute of Allergy and Infectious Diseases (NIAID;), and was highlighted March 22 on CBS’ “60 Minutes.”

The three are among seven trials assessing remdesivir’s safety and effectiveness, O’Day stated in an April 11 “open letter.”

On April 4, O’Day stated Gilead’s goal of producing more than 500,000 treatment courses by October, and more than 1 million treatment courses by the end of this year. O’Day said the company significantly increased its available supply of remdesivir to 1.5 million individual doses, including finished product ready for distribution as well as investigational medicine in the final stages of production.

“Depending on the optimal duration of treatment, which is something we are studying in clinical trials, this supply could equate to well over 140,000 treatment courses for patients,” O’Day wrote.

Gilead has launched two Phase III trials in the U.K. assessing remdesivir in patients with moderate to severe COVID-19 at an initial 15 sites, after receiving urgent public health research (UPHR) status from the Chief Medical Office.

On March 25, Gilead requested that the FDA rescind the orphan drug designation the company was granted for remdesivir in COVID, which confers seven years of marketing exclusivity, and said it will waive all benefits that accompany the designation. The company’s action followed criticism by Sen. Bernie Sanders, who accused Gilead of “profiteering” and benefiting from a “corporate giveaway” since the NIH is overseeing a clinical trial of the drug.

Three days earlier, Gilead said it was shifting how it allowed severely ill patients to access remdesivir, from individual compassionate use requests to expanded access programs, citing an “exponential increase” in demand. A 25-year-old New Jersey man was airlifted to the Hospital of the University of Pennsylvania to enter a clinical trial where the drug was being offered, his mother told The New York Times.

Rear Adm. Richard Childs, an assistant surgeon general and lung specialist at the NIH, told The Wall Street Journal in a report published March 13 that remdesivir showed a positive effect on 14 Americans who contracted SARS-CoV-2 aboard the Diamond Princess cruise ship, and received the drug during treatment at Japanese hospitals.

Remdesivir showed “no adverse events” when administered to the first American confirmed to be infected with SARS-CoV-2, members of the Washington State 2019-nCoV Case Investigation Team reported in a case study published in The New England Journal of Medicine.

Remdesivir is also under study in three U.S. trials: A study in 600 patients with moderate COVID-19 (NCT04292730), one in 400 severe disease patients (NCT04292899), and a 440-patient study launched by the National Institute of Allergy and Infectious Diseases (NIAID; NCT04280705). The NIAID study was highlighted March 22 on CBS’ “60 Minutes.”  The segment by correspondent Bill Whittaker included comments by a 67-year-old patient, Carl Goldman.

Other trials of remdesivir include a large study in France (2020-000936-23), and two Chinese studies, one of 308 mild/moderate patients (NCT04252664), the other of 453 severe patients (NCT04257656).

Remdesivir and chloroquine phosphate were “highly effective in the control of 2019-nCoV infection in vitro,” a team of Chinese researchers reported in a study published February 4 in Cell Research.

 

Incyte and Novartis

Candidate: Jakafi® / Jakavi® (ruxolitinib)

Type: Janus kinase (JAK1/JAK2) inhibitor first approved by the FDA in 2011, with indications in polycythemia vera, myelofibrosis, and acute graft-versus-host disease. Marketed as Jakafi in the U.S. by Incyte, and as Jakavi outside the U.S. by Novartis.

Status: Incyte and Novartis said April 2 they planned to launch a Phase III clinical trial (RUXCOVID) to assess the efficacy and safety of Jakafi/Jakavi plus standard-of-care (SoC), compared to SoC therapy alone, in patients with COVID-19 associated cytokine storm.

In the U.S., Incyte added, it intends to begin an open-label emergency Expanded Access Program (EAP) that will allow eligible patients with severe COVID-19 associated cytokine storm to receive Jakafi while it is being studied for that indication. The company added that it is increasing manufacturing efforts to respond to anticipated supply needs related to its COVID-19 studies.

Outside the U.S., Novartis has established an international compassionate use program for eligible patients, and said it is working to manage the anticipated increase in COVID-19 related requests for Jakavi without interrupting access for patients using the drug for its authorized indications. Novartis cited other efforts to fight COVID-19, including its $20 million global fund to support communities impacted by the disease, and its commitment of 130 million doses of hydroxychloroquine to support pandemic response.

 

Inovio Pharmaceuticals and Beijing Advaccine Biotechnology

Candidate: INO-4800

Type: DNA vaccine

Status: Inovio said April 6 the FDA accepted its IND application for INO-4800, paving the way for clinical testing of INO-4800 in healthy volunteers. A Phase I trial of INO-4800 will enroll up to 40 healthy adult volunteers in Philadelphia at the Perelman School of Medicine at the University of Pennsylvania, and Kansas City, MO, at the Center for Pharmaceutical Research), where screening of potential participants has already begun.

Last month, Inovio joined biologics CDMO Ology Bioservices on March 24 to announce that Ology was awarded an $11.9 million Department of Defense (DoD) contract to work with Inovio on DNA technology transfer to rapidly manufacture INO-4800 and deliver it to DoD for upcoming clinical trials.

On March 22, Inovio was among developers of COVID-19 drug and vaccine candidates highlighted March 22 on CBS’ “60 Minutes.”

Ten days earlier, Inovio said it received a $5 million grant from the Bill and Melinda Gates Foundation to accelerate testing and scale-up of CELLECTRA® 3PSP, a hand-held smart device for the intradermal delivery of INO-4800. Inovio is partnering with Beijing Advaccine Biotechnology on a Phase I trial in China in parallel with the company’s clinical development efforts in the U.S. to develop INO-4800 as a coronavirus treatment.

Inovio will develop INO-4800 through Phase I testing in the U.S., and has launched preclinical testing for clinical product manufacturing. INO-4800 development is also supported by a $9-million grant from the Coalition for Epidemic Preparedness Innovations (CEPI).

 

Janssen Pharmaceutical Cos. (J&J) and BARDA

Candidates: Lead vaccine candidate and two backups to prevent COVID-19

Type: Not specified, but based on vaccine constructs created and tested by J&J with Beth Israel Deaconess Medical Center (BIDMC), part of Harvard Medical School, using Janssen’s AdVac® technology.

Status: Johnson & Johnson expects to start Phase I human trials by September for its lead COVID-19 vaccine candidate, and has expanded its vaccine R&D and clinical testing partnership between J&J’s Janssen Pharmaceutical Cos. and the Biomedical Advanced Research and Development Authority (BARDA) that is valued at over $1 billion.

J&J said it aims to have clinical data available by year’s end on the safety and efficacy of its lead COVID-19 vaccine candidate, an accelerated development and testing timeframe it said would allow vaccine availability for emergency use in early 2021. The company anticipates it can have the first batches of a COVID-19 vaccine available for FDA emergency use authorization in early 2021.

J&J plans to begin production at its own risk “imminently,” and has committed to bringing an “affordable” vaccine to the public on a not-for-profit basis for emergency pandemic use.

 

Moderna

Candidate: mRNA-1273

Type: Novel lipid nanoparticle (LNP)-encapsulated mRNA vaccine encoding for a prefusion stabilized form of the Spike (S) protein.

Status: Moderna on March 29 said it was accelerating work on mRNA-1273 and was engaged in discussions for outside funding of such activities. CEO Stéphane Bancel detailed that acceleration a few days earlier during a Synbiobeta “town hall” presentation. He said a reason the SARS-CoV-2 vaccine development had been so fast was the work Moderna had done over the past two years in an existing collaboration with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) Dale and Betty Bumpers Vaccine Research Center (VRC) to develop a vaccine against MERS-CoV.

Moderna’s platform is based on injecting mRNA into cells to produce protein in human cells—an idea Bancel first viewed as crazy before realizing that making a human protein in a human cell is probably not going to be worse than making it in bacteria: “We don’t guess the biology—we use the biology of nature.”

Moderna was among developers of COVID-19 drug and vaccine candidates highlighted March 22 on CBS’ “60 Minutes.”

Also in March, Moderna disclosed in a regulatory filing that Bancel told Goldman Sachs representatives that while a commercially-available vaccine probably won’t be available for 12-18 months, a vaccine might be available in the fall of 2020 under emergency use authorization. He also said the Company was scaling up manufacturing capacity toward producing millions of doses per month, in the potential form of individual or multi-dose vials.

Moderna dosed the first patient in a Phase I open-label, dose-ranging trial of mRNA-1273 (NCT04283461) in males and non-pregnant females, 18 to 55 years old, occurring at Kaiser Permanente Washington Health Research Institute in Seattle. The 45-patient study will assess the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 3 dosages in healthy adults. The first batch of mRNA-1273 was shipped in February to the VRC, which partnered with Moderna in designing the vaccine.

 

Regeneron Pharmaceuticals and Sanofi

Candidate: Kevzara® (sarilumab)

Type: Interleukin-6 (IL-6) receptor antagonist approved by the FDA in 2017 to treat adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.

Status: Regeneron Pharmaceuticals and Sanofi said March 30 they dosed the first ex-U.S. patient in the second multi-center, double-blind, Phase II/III trial (NCT04315298) conducted as part of the Kevzara COVID-19 program assessing Kevzara® (sarilumab) in severe COVID-19 patients. The 300-patient second trial will assess the safety and efficacy of adding a single intravenous dose of Kevzara to usual supportive care, compared to supportive care plus placebo.

On March 16, the companies said they had launched the first Phase II/Phase III clinical trial of Kevzara in the U.S. in severe COVID-19 patients. Up to 400 adults hospitalized with serious complications from COVID-19 will be assessed in that study, set to begin in medical centers in New York.

The global clinical program has been launched in Italy, Spain, Germany, France, Canada, Russia and the U.S. Regeneron leads clinical studies in the U.S., while Sanofi does so overseas.

 

Roche (Genentech)

Candidate: Actemra® (tocilizumab)

Type: Interleukin-6 (IL-6) receptor antagonist approved by the FDA in 2010, with indications in rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and cytokine release syndrome.

Status: Genentech, a Member of the Roche Group, said March 23 it won formal FDA approval for a Phase III trial  in collaboration with the Biomedical Advanced Research and Development Authority (BARDA) to assess Actemra to treat adults with severe COVID-19. “Our goal is to start the study as early as possible in April,” and complete it this summer, Levi Garraway, Roche’s chief medical officer, told McClatchy DC.

The randomized, double-blind, placebo-controlled trial, named COVACTA (NCT04320615), will evaluate the safety and efficacy of intravenous Actemra plus standard of care in hospitalized adults with severe COVID-19 pneumonia, compared to placebo plus standard of care. The trial will seek to enroll approximately 330 patients worldwide, including the U.S. The trial’s primary and secondary endpoints include clinical status, mortality, mechanical ventilation and intensive care unit (ICU) variables. Patients will be followed for 60 days post-randomization, and an interim analysis will be conducted to look for early evidence of efficacy, Genentech said.

The company also said it will provide 10,000 vials of Actemra to the U.S. Strategic National Stockpile for potential future use at the direction of the U.S. Department of Health and Human Services (HHS).

A Chinese research team in March published a study showing positive results for Actemra: 19 of 20 severe COVID-19 patients were discharged from hospital an average 13.5 days after treatment.

China’s National Health Commission earlier this month included Actemra in its 7th updated diagnosis and treatment plan for COVID-19, to treat patients with high levels of IL-6 and serious lung damage. Actemra is also under study as a COVID-19 treatment in three active Chinese clinical trials, according to the Chinese Clinical Trials Registry: A 188-patient study (ChiCTR2000029765), a 150-patient trial assessing Actemra in combination with favipiravir (ChiCTR2000030894); a 120-patient trial in combination with continuous renal replacement therapy (CRRT) (NCT04306705); a 100-patient trial in combination with intravenous immunoglobulin and CRRT (ChiCTR2000030442 ); and a 60-patient trial with JinYu Bio-Technology Co., which markets the drug as CMAB806 (ChiCTR2000030196).

In Italy, Actemra is the subject of an up-to-330-patient trial Phase II trial (TOCIVID-19; NCT04317092) and an up-to-30-patient Phase II trial (NCT04315480) designed to study the drug as a single 8mg/Kg dose in patients affected by severe pneumonia correlated to SARS-CoV2.

 

Sanofi, Pfizer, and various manufacturers

Candidates: Combination of Plaquenil® (hydroxychloroquine sulfate) and Zithromax® or Z-Pak (azithromycin); monotherapies Chloroquine phosphate (formerly Aralen®); Chloroquine hydrochloride (formerly Aralen Hydrochloride®); Zithromax (azithromycin); Zmax (azithromycin extended release) ●●●

Type: Plaquenil and the chloroquine treatments are antimalarial drugs; plaquanil has also been approved by the FDA for lupus erythematosus and rheumatoid arthritis. Chloroquine, for extraintestinal amebiasis. Zithromax and Zmax are antibacterials indicated for adults with acute bacterial sinusitis, and community-acquired pneumonia. Zithromax is also indicated for acute bacterial exacerbations of chronic obstructive pulmonary disease.

Status: President Trump on April 4 said the U.S. government will place 29 million doses of hydroxychloroquine into the Strategic National Stockpile to allow for use by COVID-19 patients—the latest action by his administration to promote use of that drug, alone and in combination with Zithromax (“I just hope that hydroxychloroquine wins, coupled with, perhaps, the Z-Pak”)—despite concerns expressed by Anthony Fauci, MD, Director of the NIH’s National Institute of Allergy and Infectious Diseases, that more data was needed on the safety and efficacy of the drugs.

Trump’s remarks came five days after the FDA on March 28 issued an emergency use authorization  allowing healthcare providers to make available chloroquine phosphate or hydroxychloroquine sulfate to “patients for whom a clinical trial is not available, or participation is not feasible,” adding “FDA encourages the conduct and participation in randomized controlled clinical trials that may produce evidence concerning the effectiveness of these products in treating COVID-19.”

The University of Oxford plans to recruit 40,000 participants for a double-blind, randomized, trial assessing chloroquine phosphate or hydroxychloroquine sulfate compared with placebo (NCT04303507). The Population Research Institute is recuirting 1,500 participants for an open-label, parallel group, randomized controlled trial (NCT04324463).

Two other clinical trials are now recruiting healthcare workers as patients to assess hydroxychloroquine. One is an up-to-440-patient randomized study (NCT04331834) by the Barcelona Institute for Global Health; the other is an up-to-360 patient no-randomized study (NCT04333225) by Baylor Research Institute. Two other trials are being conducted in Australia, where the government of Prime Minister Scott Morrison on April 2 exempted hydroxychloroquine from the nation’s register of therapeutic goods, conditioned on the drug being imported, manufactured, or supplied via contract or arrangement with the health department.

Sanofi has offered French authorities “millions of doses” of Plaquenil, enough to treat up to 300,000 people. Sanofi obtained FDA approval for both Plaquenil (in 1955) and Aralen (in 1949), though the company has discontinued marketing brand-name Aralen. Pfizer gained FDA approval for Zithromax in 1991. All three drugs are marketed as generics by numerous companies worldwide. Among generic manufacturers, Mylan said in March it would restart production of hydroxychloroquine sulfate tablets at its West Virginia manufacturing facility while Teva Pharmaceutical Industries committed to donating more than 10 million doses by this month.

The combination of hydroxychloroquine and azithromycin has gained public attention for successful results in some studies. Notably, a study in press March 17 in the journal International Journal of Antimicrobial Agents was a 42-patient study in which 26 patients completed treatment with hydroxychloroquine, six with hydroxychloroquine and azithromycin, and 16 patients served as a control group receiving symptomatic treatment and antibiotics (six halted hydroxychloroquine treatment early).

According to the study, “100% of patients treated with hydroxychloroquine and azithromycin combination were virologicaly cured comparing with 57.1% in patients treated with hydroxychloroquine only, and 12.5% in the control group.” The study’s corresponding author, Professor Didier Raoult, MD, PhD, of l’Institut Hospitalo-Universitaire (IHU) Méditerranée Infection in Marseille—who discussed the results in a YouTube video posted March 17—has been appointed by the French government to research possible COVID-19 treatments.

A Chinese research team published positive results for hydroxychloroquine in COVID-19 patients, concluding March 18 in Cell Discovery that: “HCQ can efficiently inhibit SARS-CoV-2 infection in vitro. In combination with its anti-inflammatory function, we predict that the drug has a good potential to combat the disease. This possibility awaits confirmation by clinical trials.”

Another Chinese team concluded that chloroquine and Gilead Sciences’ Remdesivir were “highly effective in the control of 2019-nCoV infection in vitro,” according to a study published February 4 in the Nature-owned journal Cell Research that added: “They should be assessed in human patients suffering from the novel coronavirus disease.” Another Chinese team reported March 4 in Clinical Infectious Diseases that “Hydroxychloroquine was found to be more potent than chloroquine.”

However, neither the French nor Chinese studies were randomized clinical trials. The French investigators also acknowledged the “small sample size” in their conclusion—as cited by critics, along with the side effects of hydroxychloroquine. Critics also cite the death of a man after he and his wife ingested fish tank cleaner containing chloroquine phosphate; the death was disclosed March 23 by healthcare provider Banner Health, which added that his wife was in critical condition at a Banner hospital. Supporters of chloroquine phosphate have countered that the couple ingested a far higher dose than a doctor would have prescribed.

Other clinical trials of hydroxychloroquine for COVID-19 are underway in China vs. placebo (NCT04261517) and vs. AbbVie’s Kaletra (NCT04307693). While the ‘1517 study showed positive preliminary outcomes, its sample size was small (N=30, randomized 1:1 to treatment or placebo), and virological clearance rate was for placebo patients (93.3%) vs. hydroxychloroquine (86.7%). Radiological progression showed on 5 hydroxychloroquine patients (33.3) vs. 7 placebo patients (46.7%). A multi-nation trial comparing chloroquine with Kaletra in up to 3,040 patients (NCT04304053) was recruiting patients as of March 24.

 

University of Pittsburgh

Candidate: PittCoVacc, short for “Pittsburgh Coronavirus Vaccine”

Type: Microneedle array (MNA)-delivered recombinant protein subunit vaccine targeting SARS-CoV-2.

Status: Pitt researchers on April 1 published a study in the open access journal EBioMedicine detailing their development of PittCoVacc. Louis Falo, MD, PhD, and Andrea Gambotto, MD, were co-senior authors of the study, which reported that PittCoVac generated a surge of antibodies against SARS-CoV-2 within two weeks of MNA delivery when tested in mice.

The MNA is a fingertip-sized patch of 400 small needles made of sugar and protein pieces, designed to deliver the spike protein pieces into the skin, where the needles dissolve. The microneedle array can sit at room temperature until it is needed.

“MNA delivery of coronaviruses-S1 subunit vaccines is a promising immunization strategy against MERS-CoV and SARS-CoV-2 infection and can be adapted for other subunit vaccines against a broad range of infectious diseases,” the researchers concluded.

Pitt said its researchers are applying for an IND approval from the FDA, and aim to start a Phase I human clinical trial in the next few months.

 

Vir Biotechnology and Alnylam

Candidates: Small interfering RNA (siRNA) treatments for up to nine infectious disease targets—including three host factors required for SARS-CoV-2 infection.

Type: siRNA treatment(s) to be identified by Alnylam that target highly conserved regions of coronavirus RNAs. Alnylam has designed and synthesized over 350 siRNAs targeting all available SARS-CoV and SARS-CoV-2 genomes, which will be screened in in vitro potency assays, the companies said.

Status: Vir and Alnylam said April 2 they are again expanding their 2-1/2-year-old siRNA collaboration, agreeing to develop novel siRNAs for up to nine infectious disease targets. The companies agreed to advance up to three additional host factor-targeting candidates to treat SARS-CoV-2 and potentially other coronaviruses. The companies named two of the three targets, angiotensin converting enzyme-2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2), adding that the third may emerge from Vir’s functional genomics work.

Potential coronavirus RNAi candidates will be discovered by Alnylam, with Vir leading development and commercialization. Alnylam will have the option to either share equally in any profits and losses associated with the development and commercialization of each coronavirus program—or instead earn development and commercialization milestones and royalties on net sales of any products resulting from the collaboration.

Another target for which a siRNA is to be developed is hepatitis B virus, the focus of the Vir-2218 (ALN-HBV02) program now in Phase I/II studies. The companies announced initial positive Phase I/II data for Vir-2218 in November 2019.

The companies launched their partnership in October 2017, initially agreeing to develop up to five novel siRNAs to treat infectious diseases, starting with Vir-2218, plus RNAi products for up to four additional infectious disease targets of Vir’s choosing. The companies expanded into coronavirus siRNAs on March 4, with Alnylam having designed and synthesized over 350 siRNAs targeting highly conserved regions of the SARS-CoV-2 genome.

 

Vir Biotechnology, Biogen, and NIAID (with WuXi Biologics and Xencor)

Candidates: Two versions of a human monoclonal antibody.

Types: Monoclonal antibody versions engineered through Vir’s platform and designed to neutralize SARS-CoV-2 live virus by binding to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1 (SARS). That, according to VIr, indicates that the epitope is highly conserved, and thus makes it harder for escape mutants to develop.

Each version has a half-life extending alteration to potentially extend the time over which the antibody provides protection.

One version has been developed with a second “vaccinal” mutation designed to increase short-term potency; the other version doesn’t have that mutation. The mutation allows the antibody to function both as a therapeutic and a vaccine, Vir says. The lead candidates are among additional antibodies identified by Vir that bind to different sites, and therefore could be used in combination with the lead development candidates.

Status: Vir Biotechnology on March 25 said it intended to move “as soon as possible” both versions of its lead antibody candidate into human Phase I/II trials, after two separate labs confirmed that the antibody neutralized SARS-CoV-2. The trial is expected to start within 3–5 months.

“The candidate could have implications for not only the current pandemic, but may have utility in the future both as a vaccine, and a therapeutic should other coronaviruses emerge,” Cowen analyst Phil Nadeau wrote.

To save development time, Vir said, it transferred the lead development candidate at-risk to WuXi Biologics and Biogen, both of which joined Vir in announcing COVID-19-focused collaborations in recent weeks. Vir announced its partnership with Biogen in March, and with WuXi the previous month. The WuXi partnership is a development and manufacturing collaboration to advance and produce human monoclonal antibodies to treat COVID-19. Should the antibodies receive regulatory approvals, WuXi Biologics has rights to commercialize therapies in Greater China and Vir, in all other markets worldwide.

Vir’s novel antibodies will have extended half lives through Xencor’s Xtend™ Fc technology, to which Vir has licensed non-exclusive rights under a technology license agreement announced March 25 by Xencor.

The company added that it is continuing to search for additional antibodies from survivors of SARS-CoV-2, SARS-CoV-1, and other coronaviruses.

 

Vir Biotechnology and GlaxoSmithKline (GSK)

Candidates: Antibodies, vaccines, and functional genomics products

Type: Antiviral antibodies based on Vir’s proprietary monoclonal antibody platform technology; Vaccines based on GSK’s vaccine technologies; Functional genomics products based on genome-wide CRISPR screening of host targets

Status: GSK agreed to make a $250 million equity investment in Vir under an R&D collaboration designed to advance COVID-19 candidates into Phase II clinical trials later this year, the companies said April 6. The companies agreed to identify new anti-viral antibodies, and study existing ones, to prevent and treat COVID-19 and future coronaviruses.

GSK and Vir also agreed to research vaccines designed to prevent SARS-CoV-2 and other coronaviruses, as well as combine their expertise in CRISPR screening and artificial intelligence to identify products based on genome-wide CRISPR screening of host targets expressed in connection with exposure to SARS-CoV-2.

Definitely Maybe – 17 candidates

 

AbbVie

Candidate: Kaletra® (also marketed as Aluvia; lopinavir/ritonavir)

Type: HIV-1 protease inhibitor indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and children 14 days old and older.

Status: AbbVie on March 31 announced a $35 million donation to support COVID-19 relief efforts by healthcare systems and other groups.

A 44-patient trial (NCT04252885) delivered disappointing results, concluding that both Kaletra and Arbidol (umifenovir) “seems little benefit for improving the clinical outcome of mild/moderate COVID-19,” and that Kaletra might lead to more adverse events than Arbidol, researchers reported in a preprint posted March 23 on medRxiv—but cautioned that further verification was needed because of the small sample size.

Kaletra fared worse in a 199-patient Chinese study (ChiCTR2000029308) that was published March 18 in The New England Journal of Medicine: “In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care.”

In March, AbbVie waived patent rights to Kaletra after Israel issued a compulsory license for Kaletra as a treatment against SARS-CoV-2—while Mylan gave up its 180-day U.S. exclusivity for its generic version, allowing other drugmakers to make the antiviral should the HIV treatment prove effective against the SARS-CoV-2. AbbVie confirmed it was collaborating with health agencies and institutions globally to determine antiviral activity as well as efficacy and safety of Kaletra against COVID-19. The agencies include European health authorities, the FDA, the Centers for Disease Control and Prevention, the NIH, and the Biomedical Advanced Research and Development Authority (BARDA).

China’s National Health Commission in January authorized Kaletra to treat pneumonia caused by SARS-CoV-2. AbbVie donated RMB 10 million ($1.4 million) of Kaletra to Chinese authorities “as an experimental option to support this growing public health crisis.” And the Health Commission of Henan Province announced that three confirmed cases of patients diagnosed with new coronavirus infections recovered after taking Kaletra, a combination of ritonavir and lopinavir. Nucleic acid testing of more than 20 confirmed cases of patients infected with new coronavirus, admitted to hospitals in Zhejiang Province turned negative after taking Kaletra, according to Ascletis Pharma, which is evaluating a combination therapy of its own candidates ASC09 and ritonavir (See below).

 

Alexion Pharmaceuticals

Candidate: Soliris® (eculizumab)

Type: Complement inhibitor approved for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

Status: Alexion said March 24 it had discussed possible options to investigate Soliris in COVID-19 with global health authorities, in order to better understand the role of terminal complement inhibition in managing the severe pneumonia associated with the virus. Alexion added that it had provided Soliris as an experimental emergency treatment for a small number of patients with COVID-19 infection and severe pneumonia at the request of physicians, and in accordance with relevant national regulatory agencies.

 

Amgen and Adaptive Biotechnologies

Candidate: Antibodies targeting SARS-CoV-2 to potentially prevent or treat COVID-19

Type: Fully-human neutralizing antibodies to be discovered and developed

Status: Amgen and Adaptive Biotechnologies said April 2 they will partner to discover and develop antibodies through a collaboration intended to combine Adaptive Bio’s immune medicine platform for identifying virus-neutralizing antibodies with Amgen’s expertise in immunology, antibody engineering, and novel antibody therapy development.

Adaptive Bio will use its high throughput platform to rapidly screen the B cell receptors from individuals who have recovered from COVID-19, enabling identification of tens of thousands of naturally occurring antibodies. Amgen will select, develop and manufacture antibodies designed to bind and neutralize SARS-CoV-2. Amgen subsidiary deCODE Genetics in Iceland will provide genetic insights from patients who were previously infected with COVID-19.

The companies said they will begin work immediately upon signing a Memorandum of Understanding whose terms were not disclosed, and will finalize financial details and terms “in the coming weeks.”

 

APEIRON Biologics

Candidate: APN01

Type: Recombinant human angiotensin-converting enzyme 2 (rhACE2) developed to treat acute lung injury, acute respiratory distress syndrome, and pulmonary arterial hypertension.

APN01 is designed to imitate the human enzyme ACE2 so that the virus can no longer infect the cells, as SARS-CoV-2 binds to soluble ACE2/APN01 instead of ACE2 on the cell surface. APN01 is also designed to reduce harmful inflammatory reactions in the lungs and protects against acute lung injury/acute respiratory distress syndrome (ALI/ARDS).

Status: APEIRON said April 2 it received regulatory approvals in Austria, Germany, and Denmark to initiate a Phase II clinical trial of APN01 to treat COVID-19 (NCT04335136). The trial aims to compare APN01 to placebo in up to 200 severely infected COVID-19 patients at 10 sites. The first patients are expected to be dosed shortly, according to the company.

APN01 has been shown to be safe and well-tolerated in a total of 89 healthy volunteers and patients with pulmonary arterial hypertension (PAH) and ALI/ARDS in previously completed Phase I and Phase II clinical trials, APEIRON said.

In March, The First Affiliated Hospital of Guangzhou Medical University disclosed on ClincalTrials.gov that a planned open label, randomized, controlled, pilot clinical study of APN01 in patients with severe SARS-CoV-2 infection had been withdrawn without Chinese Center for Drug Evaluation (CDE) approval. No explanation has been given on the company’s website or on ClinicalTrials.gov. The trial was designed to obtain preliminary biologic, physiologic, and clinical data in patients with COVID-19 treated with rhACE2 or control patients, to help determine whether a subsequent Phase IIb trial is warranted.

Suzhou-based Angalpharma coordinated the Chinese clinical trial, with support from dMed Pharmaceutical, a CRO based in Shanghai.

 

Ascletis Pharma

Candidate: Ganovo® (danoprevir)

Type: Oral hepatitis C virus protease inhibitor

Status: Ascletis on March 24 trumpeted successful results from a Chinese clinical trial, the first such study of Ganovo in patients with COVID-19, assessing Ganovo compared with ritonavir (NCT04291729). The company stated that after 4- to 12-day treatment of Ganovo combined with ritonavir, all 11 patients with moderate COVID-19—two treatment-naïve, nine treatment-experienced—were discharged from the hospital. The first negative RT-PCR test occurred at a median of 2 days, with occurrences ranging from 1 to 8 days, and absorption in CT scans occurred at a median 3 days, ranging from 2 to 4 days. The trial was conducted at The Ninth Hospital of Nanchang. Ascletis announced the discharge of the study’s first three patients on February 26.

“Clinical findings suggest that danoprevir combined with ritonavir is a promising therapeutic option for COVID-19,” Ascletis stated.

In February, Ascletis said it was actively assisting “relevant medical institutions and medical researchers” in clinical trials assessing the combination of Ascletis’ ASC09 and ritonavir for COVID-19, following a request they made to the company. Ascletis applied in January to the National Medical Products Administration and its Drug Evaluation Center to include ritonavir and ASC09 fixed-dose combination into the national emergency channel.

ASC09 is in other Chinese clinical trials, including another study in combination with ritonavir (ChiCTR2000029603), and studies in combination with ritonavir compared with AbbVie’s Kaletra (lopinavir/ritonavir) (NCT04261907), and in combination with Tamiflu (oseltamivir) compared with ritonavir/Tamiflu and Tamiflu alone (NCT04261270). Tamiflu is distributed in the U.S. by Genentech, a member of the Roche Group, under license from Gilead Sciences.

 

Athersys

Candidate: MultiStem® for acute respiratory distress syndrome (ARDS)

Type: Adult-derived “off-the-shelf” therapy under development for several neurological and cardiovascular diseases, as well as inflammatory, immune and related disorders. Developed from Multipotent Adult Progenitor Cells (MAPC®) obtained from the bone marrow of healthy, consenting adult donors.

Status: Athersys Founder, Chairman, and CEO Gil Van Bokkelen, PhD, told Ed Henry on his Fox News Channel program “America’s Newsroom” April 1 that the company was in active talks with the FDA about the design and implementation of a Phase III study of MultiStem “that will involve several hundred patients, that will be focused specifically on COVID-19 patients that are experiencing [ARDS].”

In March, Van Bokkelen told GEN the company was planning to launch the Phase III trial “as soon as possible.” The company has won the Biomedical Advanced Research and Development Authority (BARDA)’s designation as a “Highly Relevant” program for COVID-19 based on earlier positive results for MultiStem in ARDS, plus the FDA’s Fast Track designation for the MultiStem clinical program in ARDS—the only Fast Track designation for an ARDS treatment.

 

Bayer and numerous Chinese manufacturers

Candidate: Chloroquine phosphate (marketed by Bayer as Resochin®)

Type: Phosphate salt of chloroquine, a quinoline compound with antimalarial and anti-inflammatory properties. Resochin was discovered by Bayer and introduced into clinical practice in 1947 to treat malaria.

Status: German federal health minister Jens Spahn on April 3 told the newspaper Bild that he hoped Resochin will prove effective against COVID-19, while cautioning that further studies were needed. Chloroquine has “shown fairly good efficacy” according to Sun Yanrong, deputy head of the China National Center for Biotechnology Development under the Ministry of Science and Technology (MOST), the state-owned Xinhua news agency reported on February 17, following clinical trials in over 10 hospitals in Beijing, as well as in south China’s Guangdong Province and central China’s Hunan Province.

In March, researchers at the University of Queensland in Australia said they hoped to launch large-scale trials of chloroquine, as well as AbbVie’s Kaletra® (See above), after both drugs successfully treated patients with COVID-19. Chinese news outlet Shine reported that Bayer had donated about €1.5 million (about $1.7 million) in medicines and additional financial aid to the Chinese Red Cross to support prevention, diagnosis, treatment, and containment of COVID-19 in China. Bayer’s Kunming, China factory mobilized 50,000 disposable surgical masks and 10,000 R95 medical masks to donate to the Kunming Red Cross Society, in response to a call from the Yunnan Provincial Department of Commerce.

Chloroquine and remdesivir were “highly effective in the control of 2019-nCoV infection in vitro,” a team of Chinese researchers reported in a study published February 4 in Cell Research. After China’s National Health Commission included chloroquine phosphate in its latest treatment guidelines for COVID-19 pneumonia, eight Chinese companies sped up manufacturing and supply of the drug, Shanghai Daily reported February 20.

 

Celularity and Sorrento Therapeutics

Candidate: CYNK-001

Type: Allogeneic, off-the-shelf Natural Killer (NK) cell therapy developed from placental hematopoietic stem cells; also being developed in multiple myeloma, acute myeloid leukemia, glioblastoma multiforme and various blood and solid tumors.

Status: Celularity on April 2 won FDA clearance for its IND of CYNK-001 in adults with COVID-19, allowing the company to begin a Phase I/II trial of up to 86 patients. The IND followed high-profile efforts to promote CYNK-001, including a March 13 op-ed commentary by CEO Robert J. Hariri, MD, PhD, in The Wall Street Journal, and public support by President Donald Trump’s personal lawyer Rudy Giuliani, who invited Hariri onto his “Common Sense podcast: “Trials need to be EXPEDITED,” he tweeted on March 27.

In a February presentation, Celularity stated that its anti-COVID-19 construct had been generated within weeks, and that its DAR-T and DAR-NK cells “will soon be produced for anti-COVID-19 activity testing.” The companies in January launched a clinical and manufacturing collaboration designed to expand the therapeutic use of Celularity’s CYNK-001 to COVID-19. Sorrento and Celularity agreed to assess CYNK-001 as a potential novel therapy for coronaviruses, specifically SARS-CoV-2.

Sorrento—which owns 25% of Celularity—agreed to use current existing capacity in its cGMP cell therapy manufacturing facilities in San Diego to supplement Celularity’s new cGMP facility in Florham Park, NJ. Sorrento said it is already in contact with “leading” scientists and local Chinese experts to discuss clinical validation and logistics requirements for fast-tracking CYNK-001 in China.

 

Cobra Biologics and Karolinska Institutet

Candidate: DNA vaccine against COVID-19

Type: Vaccine designed to deliver DNA to patient muscle to generate a viral antigen on which the immune system will react. The project will use Cobra’s 50L DNA suite in Sweden to support vaccine development by producing plasmid DNA in accordance with GMP.

Status: Cobra and Karolinska Institutet said March 30 they were awarded €3 million ($3.3 million) in emergency funding through the EU’s Horizon 2020 funding program for R&D and Phase I clinical trial testing of a DNA vaccine against COVID-19, as part of the OPENCORONA consortium. In addition to Karolinska Institutet, partners in the consortium also include Karolinska University Hospital, the Public Health Agency of Sweden (FoHM), IGEA, Adlego, and Giessen University.

 

CureVac

Candidate: Vaccine

Type: mRNA-based coronavirus treatment based on company’s vaccine platform

Status: CureVac on March 17 told reporters in a telephone briefing that it was committed to launching animal trials of its mRNA-based COVID-19 vaccine in April, and clinical trials in humans by early summer. The update came a day after the European Commission offered up to €80 million ($88 million) toward scaling up development and productions of the vaccine. The Coalition for Epidemic Preparedness Innovations (CEPI) awarded the company up to $8.3 million in January for accelerated vaccine development, manufacturing and clinical tests.

During the briefing and in a statement two days earlier, CureVac denied a report in the German newspaper Welt am Sonntag that the administration of President Donald Trump sought to lure German-based CureVac to the U.S. with funding to produce its vaccine exclusively for the U.S. market after then-CEO Dan Menichella visited the White House March 2 with other biopharma executives, while Germany’s government pressed for the company to stay in Tübingen and produce its vaccine for Germany and Europe.

U.S. ambassador to Germany, Richard Grenell denied the German news report via Twitter, but an unnamed German Health Ministry spokeswoman confirmed Germany’s interest in CureVac developing vaccines domestically in a statement to Reuters. Menichella resigned on March 11, and was succeeded by former CEO and founder Ingmar Hoerr, who just five days later took a temporary leave of absence for medical reasons “not caused by coronavirus,” the company said.

 

Eli Lilly and AbCellera

Candidates: Antibodies to treat and prevent COVID-19

Type: Anti-SAR-CoV-2 Antibodies based on AbCellera’s rapid pandemic response platform

Status: Eli Lilly and AbCellera said March 13 that they will partner to co-develop the most promising of 500+ unique fully human antibody sequences identified in a blood sample from one of the first U.S. patients to recover from COVID-19.

AbCellera will tap into the expertise of the Dale and Betty Bumpers Vaccine Research Center of the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), which will identify the antibodies that bind the pandemic strain of SARS-CoV-2 the best. AbCellera and Lilly committed to equally share initial development costs towards a treatment, after which Lilly has agreed to oversee all further development, manufacturing and distribution. If successful, Lilly will work with global regulators to bring a treatment to patients.

Globally, Lilly has joined a cross-industry collaboration and the Bill & Melinda Gates Foundation to accelerate the development, manufacturing and delivery of vaccines, diagnostics and treatments for COVID-19. The consortium of 17 life sciences companies, announced by the Foundation March 25, plans to will work with regulators and the World Health Organization to ensure promising studies are quickly scaled to help people worldwide.

 

I-Mab

Candidate: TJM2 (TJ003234)

Type: Neutralizing antibody against human granulocyte-macrophage colony stimulating factor (GM-CSF)

Status: I-Mab said April 3 that the FDA cleared its IND to initiate clinical study of TJM2 as a treatment for cytokine release syndrome associated with severe illness caused by COVID-19. I-Mab also obtained central institutional review board (IRB) approval from the Western Institutional Review Board on the same day. The planned trial is a multi-center, randomized, double-blind, placebo-controlled, three-arm study designed to assess the safety, tolerability and efficacy of TJM2 in reducing the severity of complications as well as levels of multiple cytokines in patients with severe COVID-19.

I-Mab added that it submitted an IND application to South Korea’s Ministry of Food and Drug Safety for a similar study in severe COVID-19 patients in South Korea.

 

Karyopharm Therapeutics

Candidate: XPOVIO® (selinexor)

Type: First-in-class, oral selective inhibitor of nuclear export (SINE), designed to block the cellular protein XPO1. Selinexor was granted FDA accelerated approval in July 2019 in combination with dexamethasone as a treatment for some adults with relapsed refractory multiple myeloma.

Status: Karyopharm said April 7 it will initiate a global randomized clinical trial evaluating low dose oral selinexor in hospitalized patients with severe COVID-19. The company noted that SINE compounds have been shown to disrupt the replication of multiple viruses in vitro and in vivo, and to mediate anti-inflammatory and anti-viral effects, including respiratory infections, in several animal models. Karyopharm cited a preprint study published March 20 in bioRxiv identifying SINE compounds as having the potential to interfere with key host protein interactions with SARS-CoV-2.

The company said it is still on track to submit a supplemental NDA to the FDA in combination with once-weekly Velcade® (bortezomib) and low-dose dexamethasone as a new second line treatment for patients with relapsed or refractory multiple myeloma, based on the BOSTON Phase III trial (NCT03110562).

 

Mesoblast

Candidate: RYONCIL™ (Remestemcel-L)

Type: Allogeneic mesenchymal stem cell (MSC) product candidate, now under FDA priority review for treating pediatric steroid-refractory acute graft versus host disease (aGVHD), with a Prescription Drug User Fee Act (PDUFA) action date of September 30, 2020.

Status: Mesoblast said April 6 it received FDA clearance for its IND application to treat patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 with intravenous infusions of remestemcel-L, nearly a month after disclosing March 10 it was in active discussions with government and regulatory authorities, medical institutions and biopharma companies about assessing remestemcel-L in that indication.

The company has cited a clinical study published in February which reported that allogeneic MSCs cured or significantly improved functional outcomes in all seven treated patients with severe COVID-19 pneumonia. Mesoblast also cited post-hoc analyses of a study in 60 chronic obstructive pulmonary disease (COPD) patients submitted for presentation at a future conference, showing significantly reduced inflammatory biomarkers, and significantly improved pulmonary function in patients with elevated inflammatory biomarkers. The same inflammatory biomarkers are also elevated in COVID-19.

“Consequently, remestemcel-L could be an effective treatment to reduce the high mortality in patients with COVID-19 who are older, have elevated inflammation biomarkers, and develop moderate to severe ARDS,” Mesoblast CEO Silviu Itescu told GEN. “Clinical trials using remestemcel-L in ARDS associated with COVID-19 disease are expected to be initiated shortly.”

 

Pfizer

Candidates: Antiviral compounds

Types: Unspecified

Status: Pfizer on March 13 restated earlier plans to develop its own antivirals against COVID-19 as well as collaborate with BioNTech on an mRNA vaccine to prevent the disease. The pharma giant also articulated five principles it said would govern its drug and vaccine development activity: Sharing tools and insights; creating “a SWAT team” of experts focused solely on fighting the pandemic; applying its drug development expertise; offering any excess manufacturing capacity to support other drug and vaccine developers; and building a “cross-industry rapid response team of scientists, clinicians and technicians” to improve response to future epidemics.

Earlier in March, Pfizer said it completed a preliminary assessment of antiviral compounds that were previously in development and that inhibited the replication of coronaviruses similar to the one causing COVID-19 in cultured cells. Pfizer said it was engaging with a third party to screen these compounds under an accelerated timeline and expected to have results back by the end of March.

“Toxicology studies would then need to be completed prior to any clinical development, but if successful, Pfizer hopes to be in the clinic by no later than the end of 2020,” the company added.

 

Regeneron Pharmaceuticals

Candidate: Antibody cocktail therapy

Type: Combination of neutralizing monoclonal antibodies leveraging Regeneron’s monoclonal antibody discovery platform called VelocImmune®, part of the company’s VelociSuite™ technologies.

Status: Regeneron on March 17 announced making progress in developing an antibody cocktail therapy against COVID-19, saying that it isolated hundreds of virus-neutralizing, fully human antibodies from its VelocImmune mice, genetically-modified to have a human immune system—as well as antibodies from humans who have recovered from COVID-19. From these antibody candidates, Regeneron said, it will select the top two antibodies for a ‘cocktail’ treatment “based on potency and binding ability to the SARS-CoV-2 spike protein, as well as other desirable qualities.” Regeneron said it is working to produce hundreds of thousands of prophylactic doses per month by the end of summer, and smaller quantities for initial clinical testing at the start of the summer.

Regeneron has also said it is developing the combination of REGN3048 and REGN3051 as a COVID-19 treatment. The combination completed a 48-patient Phase I trial in MERS-CoV last year (NCT03301090). In February, The Biomedical Advanced Research and Development Authority (BARDA) said it was expanding upon an earlier partnership agreement with Regeneron to develop “multiple monoclonal antibodies that, individually or in combination, could be used to treat new treatments.”

On April 1, New York Gov. Andrew M. Cuomo announced that Regeneron created 500,000 test kits for state use at no charge. The first batch of test kits was delivered to the state on March 30, and the state will receive an ongoing delivery of 25,000 kits per day, Cuomo said.

 

The University of Hong Kong (HKU)

Candidate: Vaccine against COVID-19

Type: Vaccine candidate based on the established flu-based DelNS1 live attenuated influenza virus (LAIV) platform, with the deletion of the key virulent element and immune antagonist, NS1, from the viral genome, adapted to express the surface protein of SARS-CoV-2. The vaccine uses flu vector to express a specific antigen to induce immunity targeting the critical element of the Receptor Binding Domain (RBD) of SARS-CoVs.

Status: On March 16, HKU’s State Key Laboratory for Emerging Infectious Diseases said it received an initial $620,000 from the Coalition for Epidemic Preparedness Innovations (CEPI) toward vaccine development. HKU researchers previously completed a proof-of-concept study testing their flu-based RBD vaccine system using a MERS-CoV animal infection model, and reported that vaccination with DelNS1-MERS-RBD LAIV provided full protection from pathogenic MERS-CoV. The team is currently conducting similar proof-of-concept studies in multiple animal models.

According to HKU, the vaccine candidate is one of five vaccine technologies by China’s Ministry of Science and Technology for further evaluation. HKU is partnering with Xiamen University to test the production of DelNS1-SARS-CoV2-RBD LAIV from eggs. The University is also collaborating with industrial partners in China—including Changchun-Baike, Hualan-Bio, Beijing Wantai, Sinovac, and CNBG China—to evaluate production of the vaccine candidate from MDCK cells.

Keeping an Eye On… – 70 candidates

 

AI Therapeutics

Candidate: LAM-002 (apilimod)

Type: Selective first-in-class, oral PIKfyve kinase inhibitor being developed in B-cell non-Hodgkin lymphoma and amyotrophic lateral sclerosis/frontotemporal dementia

Status: AI Therapeutics co-founder Jonathan Rothberg, PhD, told GEN the company is preparing INDs for submission to the FDA, with the goal of launching clinical trials of LAM-002 in COVID-19 in the second quarter. He citing new data that he said showed the drug was effective in cell assays in inhibiting the entry of SARS-CoV-2 through its first-in-class molecular mechanism. SAM-002 can also be combined with other antiviral drugs, which typically target other molecular mechanisms, like viral replication. AI is looking to combine SAM-002 with Gilead Sciences’ Remdesivir, said Rothberg, recipient of the 2013 National Medal of Technology and Innovation in Engineering for pioneering inventions and commercialization of next generation DNA sequencing technologies.

AI is collaborating with Yale University Medical School (clinical studies), and Zhejiang University (nonclinical). AI Therapeutics and collaborators have shown that in cell cultures, LAM-002 was effective alone and lowered the level of SARS-CoV-2 virus even more when combined with Gilead Sciences’ Remdesivir. “We have 50,000 pills ready to go, we have a drug that has been shown to be safe in 800 patients, and we just made a commitment for 110,000 more pills and material for 5 Million more,” Rothberg added.

 

AIM ImmunoTech

Candidate: Ampligen® (rintatolimod)

Type: Immune modulator indicated for severe chronic fatigue syndrome

Status: AIM ImmunoTech said April 6 it entered into a Material Transfer and Research Agreement (MTA) with Shenzhen Smoore Technology to research in China the efficacy of Smoore’s vaping device using Ampligen, to enable inhalation of the drug deep into the lungs at the first signs of COVID-19.

In March, the company said it was in talks with regulators in the Netherlands, where Ampligen was recently used to treat pancreatic cancer patients, to explore expedited preclinical and clinical trials of Ampligen. Protocols for those trials are in final stages of development. AIM ImmunoTech also said it was actively seeking investigators and sites for clinical trials—and disclosed talks with a potential partner in Argentina, GP-Pharm, to advance Ampligen in COVID-19. The drug is approved in Argentina to treat myalgic encephalomyelitis/chronic fatigue syndrome.

AIM ImmunoTech has stated in a prospectus that it partnered with ChinaGoAbroad, a matchmaking and advisory service for cross-border deals involving China, to facilitate the entry of Ampligen into China for use as a prophylactic/early-onset therapeutic against COVID-19. AIM ImmunoTech also said Japan’s National Institute of Infectious Diseases (NIID) will study Ampligen as a potential treatment for COVID-1, through a study to be conducted at NIID and the University of Tokyo.

The company filed three provisional patent applications with the U.S. Patent and Trademark Office in January.

 

 AlloVir and Baylor College of Medicine

Candidates: T-cell immunotherapies

Type: Allogeneic, off-the-shelf, virus specific T-cell therapy designed to restore natural T-cell immunity to fight off viral infections and diseases in immunocompromised patients, including recipients of stem cell and solid organ transplants

Status: Allovir said March 23 it is expanding its R&D collaboration with Baylor College of Medicine to include the discovery and development of allogeneic, off-the-shelf, virus specific T-cell therapies to combat SARS-CoV-2. The company aims to develop a therapy for multiple coronaviruses—including SARS-CoV and MERS-CoV—that can be used as a standalone treatment or incorporated into its multi-respiratory virus therapy candidate, ALVR106. The allogenic, off-the-shelf multi-specific T cell (VST) is being developed as a treatment for respiratory syncytial virus (RSV), influenza, parainfluenza virus (PIV), and human metapneumovirus (HMPV).

 

Altimmune and University of Alabama at Birmingham (UAB)

Candidate: AdCOVID

Type: Single-dose, intranasal vaccine designed to provide systemic immunity. Altimmune based the vaccine on proprietary platform technology that was applied in developing NasoVAX™, the company’s influenza vaccine candidate that showed positive Phase IIa results.

Status: Altimmune said March 30 it will partner with UAB to develop AdCOVID. The company said it is preparing for immunogenicity studies and manufacture of Phase I clinical trial material. Initially, Altimmune will work with UAB investigators on preclinical animal studies and characterization of the vaccine immunogenicity with the goal of enabling a Phase I trial in the third quarter.

On February 28, Altimmune said it completed the design and synthesis of the vaccine, and was “actively engaged in discussions with a number of potential partners.” Six UAB labs will work with Altimmune on the urgent collaboration, the University said.

 

Ansun Biopharma

Candidate: DAS181

Type: Recombinant sialidase with broad antiviral properties for the treatment of severe COVID-19

Status: Ansun on April 2 reported positive preliminary data from an investigator-initiated trial of DAS181 (NCT04324489), conducted in collaboration with the Renmin Hospital of Wuhan University. The study evaluated a 10-day treatment regimen of nebulized DAS181 administered to four patients with severe bilateral viral pneumonia and hypoxemia.

In the study’s first 14 days, the first two patients no longer required supplemental oxygen, and showed stabilized vital signs, increased oxygen saturation, and resolution of infiltrates on chest CT scans, according to Zuojiong Gong, MD, PhD, and Ke Hu, MD, the study’s principal investigators at Renmin Hospital. They added: “The third patient, who had been a persistent SARS-CoV-2 carrier for more than 33 days, was completely virus-free before the end of the 10-day DAS181 regimen and met all discharge criteria, and the fourth is currently undergoing treatment and showing positive trends.”

 

Baylor College of Medicine

Candidate: Vaccines against COVID-19

Types: Recombinant protein-based vaccine consisting of the receptor binding domain (RBD) of the spike protein of the coronavirus, designed to bind to receptors found deep in the host lung tissue.

Status: Peter J. Hoetz, MD, PhD, professor and dean of the National School of Tropical Medicine at Baylor College of Medicine (BCM), told China’s state news agency Xinhua on March 17 that his group at BCM’s Texas Children’s Hospital Center for Vaccine Development was working to develop a vaccine in collaboration with U.S. institutions that included the University of Texas Medical Branch, and the New York Blood Center, as well as the Virology Center at Fudan University in Shanghai.

The RBD for SARS has already been manufactured for clinical use, BCM said, and additional preclinical tests are being conducted to advance it into clinical trials to determine if it is safe, sufficiently protective, or cross-reactive against COVID-19. The Baylor College of Medicine teams are also developing the RBD from COVID-19.

 

 Brii Biosciences, Tsinghua University, and Third People’s Hospital of Shenzhen

Candidates: “Multiple” monoclonal antibodies to prevent and treat COVID-19

Type: Fully human neutralizing monoclonal antibodies from patients in China who have recovered from COVID-19

Status: Brii Bio joined Tsinghua University and Third People’s Hospital of Shenzhen on March 31 to announce a partnership and license agreement to discover, develop, manufacture and commercialize fully human neutralizing monoclonal antibodies against COVID-19. The collaboration aims to achieve an accelerated six-month timeline from the selection of a lead development candidate to first-in-human clinical trials, with potential for additional timeline acceleration, the partners said.

The partners also cited research by Linqi Zhang at Tsinghua University and Professor Zheng Zhang at Third People’s Hospital of Shenzhen, in a preprint published March 26 in bioRxiv. The researchers characterized antibody responses in eight COVID-19 patients and isolated 206 monoclonal antibodies specific to the SARS-CoV-2 receptor-binding domain. Of the antibodies with potential therapeutic potential against SARS-CoV-2, the most potent were P2C-1F11 and P2B-2F6.

 

British American Tobacco (Kentucky BioProcessing)

Candidate: Vaccine

Type: Vaccine based on BAT’s proprietary, fast-growing tobacco plant technology

Status: British American Tobacco’s Kentucky biotech subsidiary, Kentucky BioProcessing (KBP), said April 1 it has developed a potential COVID-19 vaccine that is in preclinical testing. Subject to finding partners and gaining government support, KBP said, it could manufacture between 1 and 3 million doses of the vaccine per week, starting in June. Work on the COVID-19 vaccine project will be carried out on a not-for-profit basis, according to KBP, which is a commercial entity.

KBP said it recently cloned a portion of COVID-19’s genetic sequence which led to the development of a potential antigen. The antigen was inserted into tobacco plants for reproduction and, once the plants were harvested, the antigen was then purified, and is now undergoing preclinical testing.

 

CalciMedica

Candidate: CM4620-IE

Type: Potent and selective small molecule CRAC channel inhibitor designed to prevent CRAC channel overactivation,

Status: CalciMedica on April 9 said it received a “Study May Proceed” letter from the FDA allowing it to study CM4620-IE in patients with severe COVID-19 pneumonia who are at risk for progression to acute respiratory distress syndrome (ARDS).

The company said it plans to enroll 60 patients with severe COVID-19 pneumonia in an open-label Phase II clinical study comparing 40 patients dosed with CM4620-IE plus standard of care to 20 patients assigned to standard of care alone. The first patients are being enrolled at Regions Hospital in St. Paul, MN, with additional patients are expected to be enrolled within the next week at Henry Ford Hospital in Detroit. Additional study sites are being evaluated.

 

Capricor Therapeutics

Candidate: CAP-1002

Type: Cardiac cell therapy consisting of allogeneic cardiosphere-derived cells. The cells are designed to function by releasing exosomes that are taken up largely by macrophages and T-cells and begin a cycle of repair.

Status: Capricor on April 3 said it has begun providing CAP-1002 to patients with advanced COVID-19 under the compassionate use pathway.  Two patients were treated last week at “a leading healthcare center” in Los Angeles, with additional patients planned in coming weeks. Capricor cited previously published preclinical data showing that CAP-1002 mitigated the release of anti-inflammatory cytokines as well as macrophage activation in a number of models of inflammation including sepsis and autoimmune diseases.

Capricor added that it has submitted an expanded-access IND application to the FDA, seeking to investigate using CAP-1002 in certain COVID-19 patients. The application is under review.

 

CEL-SCI

Candidate: Ligand Antigen Epitope Presentation System (LEAPS) peptides

Type: Immunotherapy based on CEL-SCI’s patented LEAPS peptide platform technology, directed towards antigens within the NP protein of COVID-19 that elicit cytolytic T cell responses. Such responses attack the virus infected cellular “factories” within the infected host in order to eliminate the source of virus and help subdue the infection, CEL-SCI reasons. LEAPS peptides use conserved regions of coronavirus proteins to stimulate protective cell mediated T cell responses and reduce viral load.

Status: CEL-SCI on March 23 said it signed a collaboration agreement with the University of Georgia’s Center for Vaccines and Immunology to develop a LEAPS COVID-19 immunotherapy designed to treat patients at highest risk of dying from COVID-19. The collaboration will commence with pre-clinical studies based on the experiments previously conducted with LEAPS immunotherapy in collaboration with the National Institutes for Allergies and Infectious Diseases (NIAID) against another respiratory virus, H1N1, involved in the 2009 H1N1 flu pandemic.

The proposed LEAPS peptides for the COVID-19 study are directed towards antigens within the NP protein of SARS-Cov-2 virus that elicit cytolytic T cell responses. Unlike the viral glycoprotein “spike” antigens which are important for antibody-based vaccines, these NP-antigens are less variable between viral strains and less likely to change in response to antibodies elicited by prior infection or other vaccines, according to CEL-SCI. Cytolytic T cell responses attack the virus infected cellular “factories” within the infected host in order to eliminate the source of virus and help subdue the infection.

Also in March, CEL-SCI said it will develop an immunotherapy to treat COVID-19 and other diseases for which disease associated antigenic peptide(s) sequences have already been identified—including several other infectious diseases, some types of cancer, allergic asthma and allergy, select CNS diseases such as Alzheimer’s, and autoimmune diseases such as rheumatoid arthritis.

According to CEL-SCI, LEAPS has shown in several animal models the ability to design antigen-specific immunotherapeutic peptides that preferentially direct the immune response to a cellular, humoral (antibody) or mixed response and are also capable of enhancing important T-regulatory (Treg) responses. CEL-SCI has been awarded a $1.5 million grant by the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases toward IND-enabling studies of a LEAPS-based treatment in arthritis.

 

Celltrion Healthcare

Candidate: Antiviral treatment targeting COVID-19

Type: Monoclonal antibody to be selected

Status: Celltrion Group said April 3 it had begun the second phase of development for an antiviral treatment, in which it will partner with the Korea Centers for Disease Control and Prevention (KCDC) to screen antibodies to find the ones most effective in neutralizing SARS-CoV-2. The company last month secured 300 different types of antibodies that bind to the antigen last month during the first phase, creating a library of antibodies using the blood of recovered patients in South Korea.

Celltrion said it anticipates the candidate screening for the therapeutic monoclonal antibody will be complete by mid-April, sooner than originally expected. Upon candidate selection, “We will roll out mass production of the therapeutic antibody treatment, with a view to starting human trials this July,” Ki-Sung Kwon, Head of Celltrion’s R&D Unit, said in a statement.

In addition, Celltrion aims to launch a rapid self-testing diagnostic kit that could provide results within 15-20 minutes. The South Korean biologics developer has been selected as a preferred developer for a monoclonal antibody project to treat and prevent COVID-19 by KCDC. Celltrion also plans to develop a ‘super antibody’ candidate that can attach and neutralize multiple coronavirus related strains, including those causing COVID-19 and SARS.

 

Clover Biopharmaceuticals and Dynavax Technologies

Candidate: Vaccine to prevent COVID-19

Type: Combination of Clover’s protein-based coronavirus vaccine candidate (COVID-19 S-Trimer), plus Dynavax’s proprietary toll-like receptor 9 (TLR9) agonist adjuvant CpG 1018

Status: Dynavax and Clover on March 24 said they launched a research collaboration to develop a vaccine candidate to prevent COVID-19. Clover agreed to advance the evaluation of COVID-19 S-Trimer in preclinical studies. The companies said Clover could rapidly scale-up and produce large-quantities of a new coronavirus vaccine since it has one of the largest in-house, commercial-scale cGMP biomanufacturing capabilities in China.

Clover said it applied its patented Trimer-Tag© technology to design the viral spike (S)-protein construct and complete its gene synthesis once the genomic DNA sequence of SARS-CoV-2 became public in late January.

 

Cocrystal and Kansas State University Research Foundation

Candidates: Broad-spectrum antiviral compounds

Type: Protease inhibitors

Status: Cocrystal on March 6 said it was “aggressively” pursuing the development of novel antiviral compounds to treat Coronavirus infections using its established proprietary drug discovery platform. The company is leveraging patent rights and antiviral compounds it has licensed from Kansas State University Research Foundation (“KSURF”) to treat Coronavirus as well as Norovirus, an agreement announced in February. Cocrystal said its primary goal was to advance its program into preclinical development, and pursue collaborations as the program progressed through clinical phases.

 

CSL Behring and SAB Biotherapeutics

Candidate: SAB-185

Type: High-potency immunotherapy delivering human polyclonal antibodies targeted to SARS-CoV-2, generated from SAB’s proprietary DiversitAb™ platform

Status: CSL Behring and SAB Biotherapeutics said April 8 they will partner to develop SAB-185, which they said is expected to be ready for clinical evaluation as early as summer 2020.

CSL Behring has provided seed funding to offset some of SAB’s initial development costs, while SAB earlier this year secured approximately $7.2 million in funding from the Biomedical Advanced Research and Development Authority (BARDA) through an interagency agreement with the Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEO – CBRND). That funding will support SAB efforts to complete manufacturing and preclinical studies. CSL Behring has agreed to commit clinical, regulatory, manufacturing and supply chain expertise and resources to deliver the therapeutic to the market as soon as possible, on terms to be agreed with SAB.

Earlier this year, the companies agreed to apply DiversitAB technology as a new source for human immunoglobulin G (IgG), and the potential for new therapies to treat challenging autoimmune, infectious and idiopathic diseases.

 

Cynata Therapeutics

Candidate: Cell therapy targeting COVID-19

Type: Mesenchymal stem cell (MSC) based treatments

Status: Cynata and CEO Ross Macdonald have discussed the company’s therapeutic approach in a March 11 statement and recent interviews. That approach uses MSC to treat complications of COVID-19 such as sepsis, pneumonia and acute respiratory distress syndrome (ARDS). The company said it has achieved positive preclinical data for MSC therapies in sepsis and lung disease, and is collaborating with the Critical Care Research Group at Prince Charles Hospital in Brisbane, Australia, to investigate in an animal model the utility of Cymerus MSCs as a treatment for ARDS.

Cynata says the potential of MSCs in treating the consequences of COVID-19 is underpinned by a study published March 13 in Aging and Disease, concluding that the intravenous transplantation of MSCs was “safe and effective for treatment” in seven enrolled patients with COVID-19 pneumonia in Beijing. Pulmonary function and symptoms of all seven patients significantly improved in two days after MSC transplantation, while two patients with common pneumonia and one severe pneumonia patient recovered and were discharged 10 days after treatment.

 

Emergent BioSolutions

Candidates: COVID-HIG and COVID-EIG

Types: Human polyclonal hyperimmune with antibodies to SARS-CoV-2 (COVID-HIG) for severe hospitalized patients and protection for at-risk individuals; Equine-derived polyclonal hyperimmune with antibodies to SARS-CoV-2 (COVID-EIG) for severe hospitalized patients

Status: Emergent Biosolutions said March 11 it began development of COVID-HIG and COVID-EIG using its hyperimmune platforms. Hyperimmunes are polyclonal antibody therapeutics derived from plasma that leverage the immune response in humans or animals and can provide immediate protection from infection. Emergent said it has initiated plasma collection efforts for both human and equine platforms, with a goal of manufacturing clinical material within the next four to five months in anticipation of beginning a clinical study as early as the third quarter.

Ennaid Therapeutics

Candidate: ENU200

Type: Repurposed, patent-pending, oral antiviral drug previously approved by FDA

Status: Ennaid said April 2 it is advancing development of ENU200 to treat the up to 80% of asymptomatic, mild to moderate cases of COVID-19 viral infections. Ennaid said in-silico modeling conducted by the company has shown that ENU200 delivers specific antiviral activity against two SARS-CoV-2 proteins, S glycoprotein and Mpro. Ennaid reasons that the simultaneous blockage may result in enhanced antiviral activity that could successfully and broadly treat COVID-19 and other coronaviruses.

Ennaid said it is in talks with the FDA and other regulatory agencies worldwide on its planned Phase III in-home, self-dosing clinical trial, which would assess ENU200 in patients with asymptomatic, mild to moderate coronavirus infections. The trials would be monitored through the iClickCare® secure clinical reporting software service.

 

eTheRNA, EpiVax, Nexelis, REPROCELL, and CEV

Candidate: mRNA vaccine against SARS-CoV-2

Type: Intranasal vaccine integrating eTheRNA’s Trimix technology, an mRNA-based vaccine adjuvant that stimulates dendritic cells into activating a strong CD4 and CD8 T cell response; a combination of T cell epitopes from the virus on a single mRNA construct, using an in-silico epitope prediction and design approach from EpiVax to identify the target; and an intranasal vaccine delivery platform using a nasal atomizer and a proprietary formulation that delivers the mRNA to the nasal mucosa and optimizes expression.

eTheRNA said a formulation candidate is being repurposed for clinical use in collaboration with REPROCELL.

Status: eTheRNA said March 24 that it has started preclinical development of an mRNA vaccine against SARS-CoV-2 that is intended primarily for high-risk populations such as healthcare workers and families of confirmed cases. It is also designed to be protective against future variations of the virus by targeting conserved epitopes from the whole CoV-2 genome.

eTheRNA said it has formed a consortium with EpiVax, Nexelis, REPROCELL and CEV to develop the vaccine and help accelerate progress towards clinical trials; patient enrolment is expected in early 2021. Chinese partners may join the consortium “in due course,” the company added.

The consortium’s approach selects conserved epitopes from the whole viral genome to create a vaccine that mounts a strong T cell-based response against these epitopes, which the partners reason offers a better chance to overcome viral variability.

 

ExpreS2ion Biotechnologies, AdaptVac, and partners

Candidate: Vaccine against COVID-19

Type: Vaccine applying ExpreS2ion’s Drosophila S2 insect cell expression system, and AdaptVac’s capsid virus-like particle (cVLP) technology.

Status: ExpreS2ion said March 6 it is part of a consortium of vaccine developers and institutions that have been awarded an E2.7 million ($2.9 million) grant through the European Union’s Horizon 2020 funding program to support development of a COVID-19 vaccine candidate, including conducting a Phase I/IIa clinical trial. Joining ExpreS2ion as members of the consortium are AdaptVac, Leiden University Medical Center, Institute for Tropical Medicine (ITM) at University of Tübingen, University of Copenhagen, and Wageningen University.

The consortium aims to launch clinical investigations within 12 months, according to ExpreS2ion. The Danish developer of vaccines and diagnostics first announced its plan to develop a COVID-19 vaccine in February, saying it use Drosophila S2 to produce 2019-nCoV viral antigens in the company’s clinically validated cell lines, as well as in its HighMan-S2™ immunogenicity-enhancing cell line. The company said its goal was to produce the vaccine antigens and test these in mice to demonstrate immunogenicity, and through collaborations demonstrate efficacy in in vitro or animal models as they become available.

 

Fudan University, Shanghai JiaoTong University, and RNACure Biopharma

Candidate: Vaccine against COVID-19

Type: mRNA vaccine employing two strategies: researchers have placed the most emphasis on formulating mRNAs that can instruct the host to produce virus-like particles (VLPs) with morphological and structural features similar to those of native COVID-19 viruses and activate immune responses. The other approach uses mRNA to express the receptor-binding domain of the spike protein of COVID-19 to induce neutralizing-antibodies in the human body.

Status: Fudan University on March 7 announced the partnership, led by Fudan’s Prof. Lin Jinzhong, PhD. Researchers have formulated an mRNA cocktail containing three genes of COVID-19, which produce VLPs when used to co-transfect human cells— “the first time the world has witnessed modified mRNAs that can synthesize VLPs,” according to Fudan.

 

Generex Biotechnology (NuGenerex Immuno-Oncology) and EpiVax

Candidate: Ii-Key peptide vaccine

Type: Vaccine based on Generex’s Ii-Key immune system modulation technology platform

Status: Generex on March 19 said it has been in talks with the Biomedical Advanced Research and Development Authority (BARDA) and the U.S. Departments of Veterans Affairs and Health and Human Services, as well as with authorities in Canada, Greece, Iceland, Indonesia, Italy, Philippines, Romania, Saudi Arabia, and the U.K. for licensing Ii-Key-SARS-2 peptide vaccines as well as new, patented immunotherapy technology allowing those countries co-ownership of the Intellectual Property in their territories.

A week earlier, Generex said it would spin out its NuGenerex Immuno-Oncology (NGIO) subsidiary into a separate public company focused on advancing Ii-Key peptide vaccines into development to treat and prevent COVID-19 and other infectious diseases, as well as cancer, with partners in the U.S. and China. Generex filed a Form 10 Registration Statement for NGIO, to be effective in 60 days.

Earlier, Generex said it will use EpiVax’s computational tools to predict epitopes that can be used to generate peptide vaccines against SARS-CoV-2 using li-Key technology. The companies reached agreement after EpiVax identified a number of hotspots in the amino acid sequences of SARS-CoV-2 proteins.

Using epitopes predicted by EpiVax, Generex agreed to manufacture a series of synthetic amino acid peptides that mimic the epitopes of the virus and send them to Chinse researchers for testing in blood samples from patients who have recovered from COVID-19. The research team plans to select the best Ii-Key hybrid peptides to create a commercially viable vaccine that can proceed to human testing, Generex said.

According to the company, NGIO’s Ii-Key antigenic peptides have been shown to supercharge the immune system up to 100 times more than peptides alone.

Generex said in February it received a contract from the China Technology Exchange, Beijing Zhonghua Investment Fund Management Co. Ltd., Biology Institute of Shandong Academy of Sciences, and Sinotek-Advocates International Industry Development (Shenzhen) Co. Ltd. to develop a Ii-key vaccine. Generex said it would receive $1 million upfront to initiate project work in the U.S., a $5 million licensing fee for the Ii-Key technology, payment by the Chinese consortium for all costs and expenses related to the development of a COVID-19 vaccine, and a 20% royalty on each dose of vaccine produced.

 

GeoVax Labs and BravoVax

Candidates: Vaccine for prevention/control of COVID-19

Type: Vaccine based on GeoVax’s GV-MVA-VLPTM vaccine platform

Status: GeoVax said March 18 that the companies completed three vaccine candidates after making rapid progress with design, construction and in vitro characterizations. The companies will narrow down the candidates to the one that shows the best safety, immunogenicity and protective efficacy in upcoming animal studies. GeoVax and BravoVax aim to advance a vaccine candidate to human clinical trials before year’s end, GeoVax President and CEO David Dodd stated.

GeoVax said it was in talks with, and submitted applications to, the Biomedical Advanced Research and Development Authority (BARDA) and other U.S. and international funding agencies. The company noted that BARDA has $3.5 billion available toward supporting the manufacturing, production and purchase of vaccines, therapeutics, and diagnostics under the $2 trillion Coronavirus Aid, Relief, and Economic Security Act (CARES ACT), signed into law by President Donald Trump on March 27.

GeoVax disclosed its intent to collaborate with BravoVax, a vaccine developer in Wuhan, China, to develop a COVID-19 vaccine in January.

 

German Primate Center-Leibniz Institute for Primate Research, University of Aarhus, and partner institutions

Candidate: Camostat mesylate

Type: Inhibitor of the serine protease TMPRSS2. The drug is approved in Japan and South Korea for use in pancreatic inflammation.

Status: University of Aarhus on March 25 disclosed via ClinicalTrials.gov plans for the Phase I/II CamoCO-19 trial (NCT04321096). The estimated 180-patient, placebo-controlled randomized clinical trial is designed to assess camostat mesilate as a potential treatment for COVID-19. The study’s estimated primary completion date is December 31, 2020.

The trial was launched less than a month after a research team led by investigators at the German Primate Center reported in the journal Cell that they tested SARS-CoV-2 isolated from a patient, and found that camostat mesilate blocked entry of the virus into lung cells. “Our results suggest that camostat mesilate might also protect against COVID-19,” stated lead author Markus Hoffmann, PhD, of the Primate Center.

 

GlaxoSmithKline (GSK), CEPI, and University of Queensland

Candidate: Vaccine to prevent SARS-CoV-2

Type: Vaccine based on UQ “molecular clamp” technology, using GSK’s vaccine adjuvant platform

Status: GSK and the Coalition for Epidemic Preparedness Innovations (CEPI) said February 3 they would partner to develop a vaccine for SARS-CoV-2. CEPI agreed to coordinate engagements between GSK and CEPI-funded entities interested in combining their vaccine platforms with GSK’s adjuvant technology against SARS-CoV-2—starting with the University of Queensland, which is partnering with CEPI to develop its “molecular clamp” vaccine platform, in which a recombinant subunit vaccine of SARS-CoV-2 S protein is locked in prefusion conformation by polypeptide moiety.

Last month, GSK identified University of Queensland as one of five partner companies and research groups worldwide with which GSK is collaborating on COVID-19 vaccines using GSK’s vaccine adjuvant technology. GSK said it expected data to be reported from the collaborations over the next three months.

 

Greffex

Candidate: Vaccine to protect against COVID-19

Type: Fully-deleted, helper virus-independent adenovirus-based vector vaccine based on the company’s GreVac™ Plug-And-Play Technology

Status: Greffex on March 11 said it was prepared to advance its vaccine candidate into animal testing, with a commitment to distributing its vaccine for free to other countries upon approval. Two days earlier, Greffex CEO John Price told Fox News Channel’s “America’s Newsroom” broadcast that his company aimed to get its vaccine approved and available to patients by year’s end.

Last year, Greffex was awarded an $18.9 million contract from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), toward developing its GreVac™ Plug-And-Play Technology to expedite the production of vaccine candidates for biodefense and emerging infectious diseases.

Greffex says it has developed the world’s first universal vaccine platform that delivers unprecedented time-to-market, cost efficiency, efficacy, and safety by using proprietary clean viral vectors. The company has a pipeline of 12 vaccines that includes candidates for influenza, MERS-CoV, anthrax, Ebola, tetravalent Dengue, and Zika.

 

Grifols, BARDA, and FDA

Candidate: Anti-SARS-CoV-2 hyperimmune globulin therapy

Type: Plasma from convalescent COVID-19 patients, processed into a hyperimmune globulin

Status: Grifols on March 25 said it entered into a formal collaboration with the Biomedical Advanced Research Development Authority (BARDA), the FDA and other federal public health agencies to support preclinical and clinical studies to determine if anti-SARS-CoV-2 hyperimmune globulin therapy can successfully be used to treat COVID-19 disease.

Grifols said it will volunteer its expertise and resources by using its network of FDA-approved plasma donor centers; testing and qualifying donors in conjunction with other health agencies; processing plasma into hyperimmune globulin at a Clayton, NC, facility; and support studies to determine whether the treatment can be a viable treatment for COVID-19 and future emerging infectious diseases.

 

Hoth Therapeutics and Voltron Therapeutics (HaloVax)

Candidate: Vaccines to prevent, intercept or treat COVID-19

Type: Vaccines to be based upon VaxCelerate, a self-assembling vaccine platform exclusively licensed by Voltron from the Vaccine and Immunotherapy Center at Massachusetts General Hospital (MGH).

Status: Hoth and Voltron subsidiary HaloVax said April 2 they entered into a Sponsored Research Agreement with the Vaccine and Immunotherapy Center (VIC) of Massachusetts General Hospital to co-develop a new vaccine designed to protect patients at risk of COVID-19 infection, applying the Self-Assembling Vaccine (SAV) platform developed by the VIC and licensed exclusively to Voltron. The vaccine is expected to enter animal testing within the next 30 days, the companies said.

On March 27, Hoth and HaloVax said they agreed to jointly develop a salf-assembling vaccine to develop a vaccine designed to protect patients at risk COVID-19. The companies said the technology initially showed proof of concept in Lassa Fever, with support from the U.S. Department of Defense (DoD).

Four days earlier, Hoth and Voltron said they formed HaloVax, a joint venture, to begin preclinical studies for COVID-19 vaccine candidates with support from MGH. VaxCelerate—which consists of a fixed immune adjuvant and a variable immune target and offers several potential advantages over other compounds in combination therapy. In infectious applications, it allows rapid development against viruses and other pathogens. The vaccine focuses on both DNA and internal/external mutated proteins providing the immune system with more potential targets to attack.

 

iBio, TAMUS, and Beijing CC-Pharming

Candidate: IBIO-200, vaccine for preventing SARS-CoV-2 infection

Type: Plant-derived vaccine SARS-CoV-2 Virus-Like Particle (VLP)-based constructs manufactured using iBio’s FastPharming System™, designed to produce the nanoparticles in, and purify them from, plants.

Status: iBio said April 9 the Infectious Disease Research Institute (IDRI) will support preclinical development and provide clinical trial oversight for iBio’s IBIO-200 vaccine development program for COVID-19. iBio and IDRI also agreed to establish a separate, additional agreement within the next 60 days if the company opts to include one of IDRI’s novel adjuvants in the program.

In March, iBio said it advanced iBIO-200 to immunization studies at Texas A&M University System (TAMUS) laboratories, under a Master Joint Development Agreement established between iBio and TAMUS in 2016. The partners seek to optimize a combination of VLP and adjuvant to advance to human clinical trials. iBio has developed two types of VLPs, glycosylated and non-glycosylated, as options for development.

iBio said it created its proprietary VLP candidates in just a few weeks using FastPharming, then deployed the VLP platform to deliver VLPs for further development just weeks after designing the biologics. On March 18, iBio announced creation of the constructs and the filing seven days earlier of four provisional U.S. patent applications supporting the platform and other technologies for treating or preventing SARS-CoV-2 infections.

In February, iBio and Beijing CC-Pharming disclosed plans to develop and test a COVID-19 vaccine, combining the vaccine R&D experience—including work on the MERS-coronavirus—by CC-Pharming Chairman and CSO Kevin Wang, PhD, and iBio VP Upstream Bioprocessing Sylvain Marcel, PhD, in rapid design of manufacturing processes for biopharmaceutical production in plant-based expression systems. If successful, the research will deliver product candidates for production at iBio’s FastPharming Manufacturing Facility, built in 2010 with funding from the Defense Advanced Research Projects Agency (DARPA). The facility is equipped with automated hydroponics and vertical farming systems designed to produce biologics, using a relative of the tobacco plant.

 

ImmunoPrecise Antibodies (IPA) and EVQLV

Candidates: Coronavirus-neutralizing antibodies

Type: PolyTope mAb Therapy™, a defined antibody combination designed to target multiple epitopes and mechanisms of viral evasion, and enabled by IPA’s discovery platforms (including B Cell Select™ and DeepDisplay™) and ImmunoPrecise subsidiary Talem Therapeutics’ access to the transgenic animal platform OmniAb® for direct generation of human antibodies.

Status: IPA said March 30 that its collaboration partner EVQLV submitted its first panel of candidate therapeutic antibody sequences, comprised of DNA sequences encoding for potentially therapeutic antibodies against SARS-CoV-2. The sequences were generated in less than one week using computational antibody design, which combines mathematics, statistics, and computer science to identify high-affinity antibodies.

IPA said it will review the antibody candidates, then select approximately 1,200 ideal candidates characterized and screened by EVQLV’s artificial intelligence, and validate the antibody candidates in vitro at IPA’s lab facilities. The companies said they will continue to work on additional panels of computationally generated sequence candidates against SARS-CoV-2.

Earlier last month, IPA announced its PolyTope mAb Therapy approach to developing a COVID-19 treatment. The company also spoke of potentially developing a vaccine for COVID-19, but has not announced any such effort since then.

On February 20, IPA said it designated Ilse Roodink, PhD, chairwoman of Talem’s scientific committee, as its Coronavirus Global Project Leader.

 

Imperial College London

Candidate: Vaccine to protect against COVID-19

Type: Self-amplifying RNA vaccine, designed to inject new genetic code into a muscle, and instructing that muscle it to make a protein found on the surface of coronavirus, triggering a protective immune response.

Status: Imperial said March 20 that Prof. Robin Shattock, PhD, and colleagues developed a vaccine candidate within 14 days of getting the sequence from China. The researchers have been testing the vaccine on animals since February 10, and plan to move to clinical trials in the summer, Imperial said. “If all goes well it could be available sometime next year,” Shattock told the U.K.’s Channel 4 News.

 

InflaRx and Beijing Defengrei Biotechnology (BDB)

Candidate: IFX-1

Type: Potentially first-in-class monoclonal anti-human complement factor C5a antibody in development for COVID-19 as well as inflammatory indications that include hidradenitis suppurativa, ANCA-associated vasculitis and Pyoderma Gangraenosum.

Status: InflaRx on March 31 said it had enrolled the first patient into a randomized clinical trial in the Netherlands that is investigating the safety and efficacy of IFX-1 in patients with severe COVID-19-induced pneumonia. The patient is being treated at Amsterdam University Medical Centers, with additional centers in Germany and potentially other European countries planned.

InflaRx said it had received from its Chinese licensee BDB initial positive human data from the first two patients treated in a Chinese clinical trial with BDB-001, an anti-C5a antibody produced in China by BDB from the IFX-1 cell line. That data is part of a larger study on the role of complement activation in COVID-19, made public through a preprint and not yet independently verified by InflaRx.

 

Innovation Pharmaceuticals

Candidate: Brilacidin

Types: Vaccine and antiviral small molecule drug formulations against COVID-19 containing Defensin mimetic. The drug is in Phase II development in oral muscositis in head and neck cancer

Status: Innovation on April 1 announced a study published in the International Journal of Infectious Diseases that supported small molecule Brilacidin’s direct inhibition of SARS-CoV-2, based on testing on Vero cells at an undisclosed U.S. Regional Biocontainment Laboratory (RBL). At 16 hours post-infection, researchers observed a dose-dependent reduction in the SARS-CoV-2 infectious viral titers from Brilacidin treated cells as compared to the vehicle-alone control (Dimethyl sulfoxide or DMSO).

According to Innovation, the antiviral activity showed Brilacidin’s 3-in-1 therapeutic potential—antiviral, anti-inflammatory, antimicrobial—against COVID-19 and associated complications. In other indications, the company said, Brilacidin has shown the ability to inhibit interleukin-6 (IL-6) and other pro-inflammatory cytokines and chemokines identified as key drivers in worsening prognoses of COVID-19 patients.

Innovation said in March it was studying Brilacidin as a vaccine independent of the small molecule drug studies involving the RBL.In February, Innovation stated that it submitted a Material Transfer Agreement with a “leading U.S.-based virology laboratory” to study Brilacidin for SARS-CoV-2. If lab tests prove successful, Innovation said, it will expedite research and clinical development of Brilacidin “via pharmaceutical partnerships, academic collaborations and government grants.” Innovation has also submitted a preliminary summary of Brilacidin’s potential for treating coronavirus to the Biomedical Advanced Research and Development Authority (BARDA).

 

Institut Pasteur, Themis, and University of Pittsburgh

Candidate: Vaccine to treat COVID-19

Type: Measles vector vaccine engineered to express SARS-CoV-2 proteins on its surface 

Status: The Institut Pasteur leads a consortium that includes Themis and the University of Pittsburgh’s Center for Vaccine Research (CVR). The consortium has been awarded an initial $4.9 million by CEPI, the Coalition for Epidemic Preparedness Innovations. As a first step, CEPI funding will support the preclinical testing, initial manufacture of vaccine materials, and preparatory work for Phase I studies, CEPI said on March 19.

Pitt said CVR researchers expect to have a vaccine candidate ready for animal testing in Paris and Pittsburgh in April, to be complemented by development of an aerosol model of COVID-19 at CVR. By the end of the year, Pitt added, a total of 60 to 80 human volunteers in two sites in Europe will have been dosed with the vaccine. At the same time, Themis plans to generate a stockpile of the vaccine candidate in anticipation of a Phase II trial set to start early next year.

 

Izana Bioscience

Candidate: Namilumab (IZN-101)

Type: Fully human monoclonal antibody therapy targeting granulocyte-macrophage colony stimulating factor (GM-CSF), in development for rheumatoid arthritis and ankylosing spondylitis

Status: Izana said April 6 it initiated a two-center compassionate use study of namilumab to treat patients with rapidly worsening COVID-19 before ICU admission and prior to ventilation. The study is being conducted in cooperation with the Humanitas research group, led by Prof. Carlo Selmi, MD, PhD, head of the Rheumatology and Clinical Immunology Unit at Humanitas Research Hospital and Associate Professor of Internal Medicine at Humanitas University.

Separately, Ergomed said it is providing support for namilumab’s clinical development program. The study will take place in Bergamo and Milan, Italy.

According to Izana, namilumab is a Phase III-ready treatment being studied under emergency access. Discussions focused on COVID-19 are in progress with global regulatory authorities, including in the U.K.

 

Janssen Pharmaceutical Cos. (J&J) and BARDA

Candidate: Antiviral treatment for COVID-19

Type: To be determined

Status: J&J said March 30 that the company and the Biomedical Advanced Research and Development Authority (BARDA) will both provide unspecified additional funding intended to enable expansion of ongoing work to identify potential antiviral treatments against COVID-19.

Janssen plans to accelerate its ongoing work in screening compound libraries, including compounds from other pharmaceutical companies, with the goal of identifying potential treatments against the novel coronavirus. These antiviral screening efforts are being conducted in partnership with the Rega Institute for Medical Research (KU Leuven/University of Leuven), in Belgium.

Janssen and BARDA said in February that they have been working closely with global partners to screen Janssen’s library of antiviral molecules to accelerate the discovery of potential COVID-19 treatments.

 

Johns Hopkins

Candidates: Antibodies targeting SARS-CoV-2

Types: Antibodies from the blood plasma or serum of people who have recovered from COVID-19 infection.

Status: Johns Hopkins researchers Arturo Casadevall, MD, PhD, and Liise-anne Pirofski, MD, published a paper March 13 in The Journal of Clinical Investigation detailing their treatment approach to COVID-19: “Human convalescent serum is an option for prevention and treatment of COVID-19 disease that could be rapidly available when there are sufficient numbers of people who have recovered and can donate immunoglobulin-containing serum.” The Johns Hopkins Research Team has put initial funding toward Casadevall’s project, to purchase equipment and set up an operation in Baltimore. Casadevall and his team are working now with state and federal officials to try to secure more resources, according to Johns Hopkins.

 

Kleo Pharmaceuticals and Green Cross LabCell (GCLC)–65

Candidate: COVID-19-targeting allogeneic Natural Killer (NK) cell combination therapy

Type: Combination of Kleo’s first non-oncology application of its Antibody Recruiting Molecule (ARM™) and GCLC’s NK cells

Status: Kleo on March 31 said it had entered a research collaboration with GCLC to rapidly develop a COVID-19-targeting allogeneic NK cell combination therapy, combining Kleo’s next-gen fully synthetic bispecific compounds designed to emulate or enhance the activity of biologics with GCLC’s allogeneic, or “off-the-shelf” NK cell therapies.

Earlier this year, Kleo received approval from the FDA to proceed with an ARM/NK clinical trial assessing the combination cell therapy in newly diagnosed, multiple myeloma patients. The ARM in that trial targets the cell surface protein CD38 and uses autologous cytokine induced memory like (CIML) NK cells to kill tumor cells.

In the context of COVID-19, the partners said, ARM acts as a neutralizing antibody to block direct binding on the virus to human cells, then enlists immune effector cells to eliminate viral particles and/or infected cells. The ARM can produce a long-term vaccination effect by activating and expanding immune memory cells.

 

La Jolla Pharmaceutical

Candidate: GIAPREZA™ (angiotensin II)

Type: Vasoconstrictor approved by the FDA in 2017 and indicated to increase blood pressure in adults with septic or other distributive shock. The drug was approved by the European Commission in August 2019 for refractory hypotension in adults with septic or other distributive shock, but is not yet commercially available in Europe.

GIAPREZA is designed to mimic the body’s endogenous angiotensin II peptide, which is central to the renin-angiotensin-aldosterone system, which in turn regulates blood pressure.

Status: La Jolla has disclosed five instances where it agreed to providing GIAPREZA for emergency use in patients with septic shock due to COVID-19: University Hospital Münster in Germany (April 7), Royal Surrey County Hospital in Guildford, Surrey, UK (April 6), University Hospital Frankfurt in Germany (announced April 3), Guy’s and St Thomas’ NHS Foundation Trust in London (April 2), and Italy (March 13).

 

Ligandal

Candidate: Vaccine

Type: Vaccine providing a fully synthetic scaffold for mimicking T-cell receptor and antibody binding epitopes, which can be rapidly custom-tailored to new mutant forms of a virus

Status: Ligandal presented its approach for rapid vaccine prototyping on its website, stating that its synthetic scaffold can additionally serve as a targeting ligand mimicking viral entry to target diseased cells and tissues with therapeutic agents. These “mini viral scaffolds can be synthesized in hours, and rapidly scaled to 100kg+ scale to meet global needs, Ligandal stated.

“Our next steps will relate to synthesis and characterization of these scaffolds, as well as additional techniques for mapping known and predicted immune-epitopes onto variable domains of the scaffolds,” the company added.

Unlike recombinant and other approaches, Ligandal said, its vaccine approach needs to use fewer than 70 amino acids out of an approximately 1,200 amino acid spike protein in order to generate a predicted trifunctional scaffold for ACE2 binding and TCR/antibody recognition.

 

Medicago

Candidates: Vaccine and antibody candidates

Types: Virus-Like Particle (VLP) vaccine and antibodies against SARS-CoV-2 developed through the company’s plant-based technology platform in collaboration with Laval University’s Infectious Disease Research Centre headed by Gary Kobinger, PhD, whose lab developed a successful Ebola vaccine. That research is being funded in part by the Canadian Institutes for Health Research.

Status: The Government of Canada announced March 23 that Medicago was among companies set to receive an unspecified amount of funding from the $192 million available for new, large-scale projects under the new Strategic Innovation Fund COVID-19 funding stream—part of the government’s $1 billion COVID-19 Response Fund. Two days earlier, the Government of Quebec awarded C$7 million (about $5 million) toward the company’s vaccine development effort.

Medicago said March 12 it successfully produced a coronavirus VLP 20 days after obtaining the SARS-CoV-2 gene—the first step in developing a vaccine for COVID-19. The vaccine will undergo preclinical testing for safety and efficacy, followed by human trials anticipated to start by summer (July/August) 2020.

 

MediciNova

Candidate: MN-166 (ibudilast)

Type: First-in-class, orally bioavailable, small molecule macrophage migration inhibitory factor (MIF) inhibitor and phosphodiesterase (PDE) -4 and -10 inhibitor

Status: MediciNova said April 8 it will initiate a clinical trial of MN-166 for acute respiratory distress syndrome (ARDS) caused by COVID-19. The study will be conducted by Yale’s Advanced Therapies Group. The lead principal investigator for the trial is Geoffrey Chupp, MD, professor of medicine (Pulmonology), director of the Yale Center for Asthma and Airway Disease and director of the Pulmonary Function Laboratory at Yale-New Haven Hospital.

Earlier human studies have shown significant reductions of serum MIF level after treatment with MN-166. It also attenuates activated glial cells, which play a major role in certain neurological conditions, MediciNova said. The company reasons that MN-166 could reduce the mortality of COVID-19 by limiting the hyperinflammation and ARDS associated with severe cases.

 

Merck KGaA

Candidate: Rebif® (interferon beta-1a)

Type: Interferon beta approved by the FDA for the treatment of relapsing forms of multiple sclerosis.

Status: Merck KGaA said March 19 it donated Rebif to the French Institut National de la Santé et de la Recherche Médicale (INSERM) following a request for use in a clinical trial. The trial (DisCoVeRy; 2020-000936-23 and NCT04315948)—sponsored by INSERM and launched March 11—is comparing Rebif to AbbVie’s Kaletra, Gilead Sciences’ Remdesivir, and Sanofi’s Plaquenil (hydroxychloroquine) in 3,100 patients.

 

Monash Biomedicine Discovery Institute (BDI) and Peter Doherty Institute of Infection and Immunity

Candidate: Ivermectin (marketed by Merck & Co. under the names Stromectol® and Mectizan®, but also available as a generic drug)

Type: Anti-parasitic drug approved by the FDA for Strongyloidiasis of the intestinal tract, and onchocerciasis (river blindness). Since 1987, Merck has committed to donating Mectizan—as much as needed, for as long as needed—with the goal of eliminating river blindness through the public-private partnership Mectizan Donation Program. The program was extended in 1998 to include lymphatic filariasis (LF).

Status: BDI and the Doherty Institute on April 3 published a preprint study in Antiviral Research  showing that Ivermectin essentially stopped the SARS-CoV-2 virus growing in cell culture within 48 hours, and reduced viral RNA significantly at 24 hours. The in vitro study will be followed up with human clinical trials, the institutions said.

 

NanoVirocides

Candidate: Antiviral therapy based on company’s novel nanomedicines platform.

Type: Broad-spectrum virus-binding ligand: “It is like a ‘Venus-Fly-Trap’ for the virus,” says Anil R. Diwan, PhD, president and executive chairman.

Status: NanoVirocides on March 16 said it completed the synthesis of “a number of” nanoviricide drug candidates for cell culture testing a few weeks after identification of virus-binding ligands, a result of the company tapping into its inventory of novel custom chemicals, including a polymer backbone that was previously manufactured in multi-kilogram quantities.

NanoVirocides confirmed in January that it was developing a COVID-19 treatment, stating that it “already found some lead candidate ligands in its chemical library” that can bind to the SARS-CoV spike protein just as it binds to cognate receptor angiotensin converting enzyme type 2 (ACE2).

The company’s technology relies on copying the human cell-surface receptor to which the virus binds, and making ligands that chemically attach to a nanomicelle, to create a nanoviricide®. When a virus comes in contact with the nanoviricide, the nanomicelle polymer is designed to fuse with the virus lipid envelope. The company said it has started preparing for testing of potential candidates in cell cultures against “low-threat” coronaviruses, including ones that use the ACE2 receptor, in its own BSL-2 virology laboratory at its Shelton, CT, campus.

NanoViricides added that it is working on developing collaborations to advance its COVID-19 program should an effective drug candidate be identified. If initial work suggests a potential for developing a successful antiviral,  NanoVirocides said in a Form 10-Q quarterly report filed February 24, it will pursue a license allowing use for coronaviruses from the license-holder of its technology TheraCour, whose 90% owner is NanoViroCides president and chairman Anil Diwan, PhD.

NanoVirocides also said it acquired and expanded two low-threat circulating coronaviruses in its BSL-certified virology lab, and has already expanded them to enable testing of drug candidates. One coronavirus, NL63, uses the same ACE2 receptor on human cells as SARS-CoV-2, although it does not cause a similarly severe disease in humans. If the test candidates show effectiveness in the cell culture studies against coronaviruses, the company reasons, that would provide a strong rationale for expecting they would be effective against SARS-CoV-2.

NanoVirocides added that it also successfully developed antiviral drug testing assays based on cell culture infection of low-threat coronaviruses in the BSL2 lab—a feat accomplished in a few weeks due to the expertise of senior virologist Brian Friedrich, PhD.

 

Neurimmune and Ethris

Candidate: Immunotherapy designed to produce inhaled mRNA-based antibodies directly in the lungs of COVID-19 patients

Type: mRNA-encoded, neutralizing anti-SARS-CoV-2 antibodies administered by inhalation

Status: The companies on March 31 announced their COVID-19 collaboration, designed to combine Neurimmune’s expertise in developing human antibodies via its RTM™ Technology platform, based on high-throughput immunoglobulin sequence analyses from COVID-19 patients who have recovered from the disease with Ethris’ pulmonary SNIM®RNA therapeutics platform.

The first product candidate is expected to begin clinical testing in the fourth quarter, pending regulatory approval, Neurimmune and Ethris said. The companies have agreed to jointly conduct R&D activities while sharing costs and revenues resulting from the collaboration—and intend to begin manufacturing of the drug product for clinical trials this summer.

 

Novavax and Emergent Biosolutions

Candidate: NVX-CoV2373 

Type: Stable, prefusion protein made using Novavax’ proprietary nanoparticle technology, and incorporating its proprietary saponin-based Matrix-M™ adjuvant.

Status: Novavax on April 8 said it identified a COVID-19 vaccine candidate, and will initiate a first-in-human clinical trial in mid-May. The Phase I trial is a placebo-controlled observer blinded study of ~130 healthy adults and includes assessment of dosage amount and number of vaccinations. The trial is expected to begin in mid-May with preliminary immunogenicity and safety results in July.

The company said NVX-CoV2373 was shown to be highly immunogenic in animal models measuring spike protein-specific antibodies, antibodies that block the binding of the spike protein to the receptor, and wild-type virus neutralizing antibodies. High levels of spike protein-specific antibodies with ACE-2 human receptor binding domain blocking activity and SARS-CoV-2 wild-type virus neutralizing antibodies were also seen after a single immunization.

In March, Emergent disclosed it retained an option to allocate manufacturing capacity for an expanded COVID-19 program under an agreement with Novavax to provide “molecule-to-market” contract development and manufacturing (CDMO) services to produce Novavax’s NanoFlu™, its recombinant quadrivalent seasonal influenza vaccine candidate.

Earlier in March, Emergent announced similar services to support clinical development of Novavax’s COVID-19 vaccine candidate, saying March 10 it agreed to produce the vaccine candidate and had initiated work, anticipating the vaccine candidate will be used in a Phase I study within the next four months. In February, Novavax said it had produced and was assessing multiple nanoparticle vaccine candidates in animal models prior to identifying an optimal candidate for human testing.

 

Novoteris and Mallinckrodt

Candidate: Thiolanox®, a high-dose inhaled nitric oxide therapy for the treatment of patients infected with SARS-CoV-2

Type: Pharmaceutical nitric oxide gaseous formulation supplied via Mallinckrodt’s high-pressure cylinders at 5,000 ppm (0.5% v/v) nitric oxide gas for inhalation canisters.

Status: Novoteris and Mallinckrodt said April 1 that the Therapeutic Products Directorate of Health Canada cleared the companies’ joint pilot clinical trial to investigate Thiolanox in patients infected with SARS-CoV-2 at Vancouver Coastal Health Authority facilities.  The study is designed to assess the safety and effectiveness of Thiolanox in treating COVID-19 and its associated lung complications. The companies said they expected to begin recruiting patients “in the coming days.”

 

OncoSec

Candidate: CORVax12

Type: Prophylactic vaccine against COVID-19, consisting of OncoSec’s TAVO™ (interleukin-12 or “IL-12” plasmid), in combination with a DNA-encodable version of the SARS-CoV-2 spike or “S” glycoprotein

Status: OncoSec said April 6 that Providence Cancer Institute, part of Providence St. Joseph Health, submitted to the FDA an IND application and have designed a protocol for a Phase I clinical trial evaluating CORVax12 in healthy adult volunteers, using OncoSec’s next-generation, investigational APOLLO generator technology for the first time clinically.

CORVax12 combines OncoSec’s IL-12 plasmid TAVO with an immunogenic component of the SARS-CoV-2 virus recently developed by researchers at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and licensed non-exclusively to OncoSec.

 

Persephone Biosciences

Candidate: Immune-boosting microbiome therapeutic to help prevent and fight SARS-CoV-2

Type: Treatment designed to be taken at the onset of symptoms or with a vaccine or antiviral drug to mount an effective immune response with long-lasting immunity and boost the immune system of those exposed to the virus. The treatment is being developed as a general enhancer of the immune system “may be effective against mutations, seasonal flu and future pandemics,” Persephone says.

Status: Persephone on April 2 announced the development of the immune-boosting microbiome therapeutic, and a stool-based diagnostic, and is seeking partners for preclinical development or clinical trials. The company’s proprietary Decode.Design.Cure® technology platform is designed to collect and analyze gut microbiome samples from thousands of patients through its nationwide Poop For The Cure® campaign, using artificial intelligence and next-generation genome sequencing technologies.

 

PharmaMar

Candidate: Aplidin® (plitidepsin)

Type: Anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. It specifically binds to the eEF1A2 and targets the non-canonical role of this protein, resulting in tumor cell death via apoptosis (programmed death).

Status: PharmaMar on April 2 said it it submitted its protocol for the Phase II APLICOV clinical trial of Aplidin to the Spanish Medicines and Healthcare Products Agency (AEMPS). The planned 160-patient trial would be a multicenter, randomized study in which two different doses of plitidepsin will be evaluated in hospitalized patients with COVID-19 pneumonia, to assess whether plitidepsin, administered intravenously for 5 days, reduces the proportion of patients who progress to Acute Respiratory Distress Syndrome (ARDS).

In March, PharmaMar announced the results of in vitro studies of plitidepsin in human coronavirus HCoV-229E, with a mechanism of multiplication and propagation that is very similar to that of SARS-CoV-2. The studies were carried out at the National Biotechnology Centre of the Spanish National Research Council (CSIC; Centro Nacional de Biotecnología). The studies confirmed that the therapeutic target of Aplidin, EF1A, is key to the multiplication and spread of the virus.

 

Pluristem Therapeutics

Candidate: PLX Cells for COVID-19

Type: “Off the shelf,” placenta-based allogeneic mesenchymal-like cells with immunomodulatory properties that induce the immune system’s natural regulatory T cells and M2 macrophages. Pluristem reasons PLX cells may prevent or reverse dangerous overactivation of the immune system by reducing the incidence and\or severity of COVID-19 pneumonia and pneumonitis.

Status: Pluristem on April 7 announced positive preliminary data from its compassionate use program treating seven patients suffering from acute respiratory failure and inflammatory complications associated with COVID-19 with PLX cells at three medical centers in Israel. Four of six patients who completed a one-week follow up showed improvement in respiratory parameters, of which three are in advanced stages of weaning from ventilators. One such patient showed no change, and one showed deterioration.

The company plans to apply to initiate a multinational regulated clinical trial program for the potential use of PLX cells in the treatment of patients suffering from complications associated with COVID-19.

In March, Pluristem said it had dosed three patients in two different Israeli hospitals under a compassionate use program for the treatment of COVID-19, as approved by the Israeli Ministry of Health. The company expects to enroll additional patients in Israel in coming days. Pluristem is studying the therapeutic effects of PLX cells through a collaboration with the BIH Center for Regenerative Therapy (BCRT) and the Berlin Center for Advanced Therapies (BeCAT) at Charite’ University of Medicine Berlin.

The company added that it is in talks with U.S. and European regulators to define its clinical strategy for COVID-19.

 

RedHill Biopharma

Candidates: Opaganib (Yeliva®, ABC294640) and RHB-107, in combination and individually

Types: Opaganib is a first-in-class, orally-administered, sphingosine kinase-2 (SK2) selective inhibitor with anticancer and anti-inflammatory activities, targeting multiple oncology, inflammatory and gastrointestinal indications. RHB-107 is a first-in-class, orally-administered inhibitor of S1 family of trypsin-like serine proteases with potential for use in multiple oncology, gastrointestinal and inflammatory indications.

Status: RedHill said April 13 the first two patients were treated with opaganib at “a leading hospital in Israel” under the company’s compassionate use program according to Israeli Ministry of Health guidelines, in addition to standard-of-care, which included hydroxychloroquine (HCQ) as background therapy. Preliminary findings from both patients, who suffered from moderate to severe acute respiratory symptoms related to SARS-CoV-2 infection, showed clinical improvement within days following the start of treatment with opaganib, RedHill said.

To date, both patients showed decreased supplemental oxygen requirements and decreased C-reactive protein (CRP) levels, and an increase in lymphocyte levels. One of the patients was released from the ICU within days of treatment initiation with opaganib.

RedHill said April 6 the first patient with a confirmed COVID-19 diagnosis had been dosed with opaganib at “a leading hospital in Israel.” Opaganib was administered under a compassionate use program in accordance with the Israeli Ministry of Health guidelines, with additional patients expected to be treated in the coming days.

Approximately 160 patients at three Italian hospitals will be treated with opaganib under an expanded access program (EAP) allowing immediate compassionate use of the drug, RedHill also said April 6.

RedHill said March 11 it was exploring opaganib and RHB-107 individually and in combination with hydroxychloroquine and other compounds as a COVID-19 treatment, based on preclinical data and literature indicating potential anti-viral activity. Opaganib was originally developed by Apogee Biotechnology, which received U.S. federal and state grants and contracts toward development. RedHill has licensed rights to RHB-107 from Heidelberg Pharma (formerly Wilex) worldwide except China, Taiwan, Macao, and Hong Kong.

 

Ridgeback Biotherapeutics and Drug Innovations at Emory (DRIVE)

Candidate: EIDD-2801

Type: Oral broad-spectrum NHC-prodrug (Beta-D-N4 hydroxycytidine-5’-isopropyl ester), a highly potent ribonucleoside analog designed to inhibit replication of multiple RNA viruses including SARS-CoV2.

Status: Ridgeback and DRIVE, a not-for-profit biotechnology company wholly owned by Emory University, said April 7 the FDA approved DRIVE’s IND application to begin human clinical trials of EIDD-2801

Ridgeback and DRIVE announced their collaboration to rapidly advance EIDD-2801 into human trials in March. Ridgeback agreed to advance EIDD-2801 through clinical development and ensure that it is available during the current pandemic.

Under the collaboration, Ridgeback has exclusively licensed EIDD-2801, which has shown broad spectrum activity against influenza, SARS, MERS, chikungunya, and equine encephalitis. On March 20, Ralph Baric, PhD, at The University of North Carolina at Chapel Hill, and colleagues from there, Emery, Vanderbilt University Medical Center, and the U.S. Centers for Disease Control and Prevention posted a preprint of a study reporting that both prophylactic and therapeutic administration of EIDD-2801 in mice infected with SARS-CoV or MERS-CoV improved pulmonary function, and reduced virus titer and body weight loss.

“The potency of NHC/EIDD-2801 against multiple coronaviruses, its therapeutic efficacy, and oral bioavailability in vivo, all highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses,” Baric and colleagues concluded.

In addition to COVID-19, EIDD-2801 is being developed to treat seasonal and pandemic influenza under a contract awarded to Emory Institute for Drug Development by the National Institute of Allergy and Infectious Diseases (NIAID) and for Venezuelan and Eastern equine encephalitis virus (VEEV and EEEV) by the Defense Threat Reduction Agency (DTRA).

 

Roivant Sciences

Candidate: Gimsilumab

Type: Fully human monoclonal antibody targeting granulocyte-macrophage colony stimulating factor (GM-CSF).

Status: On March 27, Roivant’s contract research organization Altasciences said it completed a Phase I trial (NCT04205851) of gimsilumab in patients with or at risk of developing acute respiratory distress syndrome (ARDS). Nine days earlier on March 18, Roivant said it had engaged with regulators in the U.S., Europe, and Asia to rapidly advance clinical development of gimsilumab to treat ARDS associated with SARS-CoV-2. Roivant cited research from Chinese patients showing that GM-CSF is a pro-inflammatory cytokine found to be up-regulated in the serum of COVID-19 patients.

According to Roivant, GM-CSF boosts the expression of pro-inflammatory cytokines such as TNF, IL-6, and IL-23, in addition to promoting the differentiation of Th1/17 cells and the polarization of macrophages to a M1-like phenotype. Gimsilumab has been tested in several non-clinical studies and two clinical studies, including the four-week, 36-patient Phase I study, which evaluated a subcutaneous formulation in healthy volunteers.

Roivant said it will prioritize trials of gimsilumab in patients with COVID-19 instead of a Phase II trial in a separate disease area which had been previously planned.

 

Sorrento Therapeutics

Candidate: STI-4398 (COVIDTRAP™), a vaccine to protect against SARS-CoV-2 infection

Type: ACE2 (angiotensin-converting enzyme 2)-Fc fusion protein (COVIDTRAP) designed to bind to the S1 domain of the spike protein of SARS-CoV-2. COVIDTRAP is a soluble recombinant fusion protein trap designed to block the SARS-CoV-2 virus from binding and infecting respiratory epithelial cells, which is expected to effectively interrupt the viral life cycle

Status: Sorrento said March 20 it produced a preclinical batch of the STI-4398 (COVIDTRAP) protein, and anticipates completing enabling studies for an expedited IND filing “in the next few months.”

In vitro cell studies for SARS-CoV-2 virus infection and neutralization are expected to be conducted in the next few weeks in collaboration with “world-leading” coronavirus experts, Sorrento said. Sorrento scientists are in parallel working speedily to generate a stable CHO (Chinese Hamster Ovary) manufacturing cell line that would enable high-yield cGMP production of the COVIDTRAP fusion protein.

Late last month, Sorrento said it entered into a research testing agreement with The University of Texas Medical Branch at Galveston for preclinical testing of Sorrento’s COVID-19 therapeutic product candidates.

 

Sorrento Therapeutics

Candidate: STI-6991 to prevent SARS-CoV-2 infection

Type: I-CellTM COVID-19 “decoy” cellular vaccine made of replication-deficient human erythroleukemia K562 immune-training cells expressing membrane-bound S1 protein of the SARS-CoV-2 virus.

Status: Sorrento said March 25 it was developing STI-6991, and was in active discussions with the FDA’s Center for Biologics Evaluation and Research under IND#019724 concerning IND-enabling studies, CMC (chemistry, manufacturing and controls), clinical protocol and end-points for potential accelerated approval. Sorrento said intends to submit a full package for an IND filing that would enable human clinical trials to start “as soon as possible.”

Sorrento expects to use a replicating cell line (human erythroleukemia, K562) to incorporate SARS-CoV-2’s spike protein or its S1 domain onto the cellular membrane so that the viral antigen is presented on a decoy cell surface to elicit both T cell and B cell immunities.

Late last month, Sorrento said it entered into a research testing agreement with The University of Texas Medical Branch at Galveston for preclinical testing of Sorrento’s COVID-19 therapeutic product candidates.

 

Takeda Pharmaceutical

Candidate: TAK-888

Type: Anti-SARS-CoV-2 polyclonal hyperimmune globulin (H-IG) a plasma derived-therapy designed to treat high-risk individuals with COVID-19.

Status: Takeda said March 4 it began development of TAK-888, part of the H-IG class of treatments that have previously shown effectiveness in treating severe acute viral respiratory infections. Such therapies are designed to concentrate pathogen-specific antibodies from plasma collected from recovered patients or vaccinated donors in the future.

Takeda said it had begun talks with health and regulatory agencies and healthcare partners in the U.S., Asia, and Europe to quickly advance its research into TAK-888. Those talks will include how to access plasma from people who have successfully recovered from COVID-19, or who have been vaccinated once a vaccine is developed, since these donors would have developed antibodies to the virus that could potentially prevent illness in COVID-19 patients, or at least mitigate its severity.

Takeda said it will initially produce the therapy in a segregated area within its manufacturing facility in Georgia, since the plasma needed for TAK-888 is unlikely to come from current plasma donors.

 

Ufovax (Scripps Research)

Candidate: Vaccine targeting SARS-CoV-2

Type: Nanoparticle vaccine based on one component self-assembling protein nanoparticle (1c-SApNP) platform technology invented by Jiang Zhu, PhD.  The vaccine consists of self-assembling virus-like particles made from identical proteins that are synthesized through the insertion of a single plasmid encoding the relevant gene into a CHO or C1 (DYAI) host cell, followed by one-step expression and two subsequent purifications.

The vaccine prototype features SARS-CoV-2 protein spikes protruding from a protein nanoparticle scaffold.

Status: Ufovax, a Scripps Research spinout company, said March 23 it successfully extended its vaccine platform technology to a vaccine against SARS-CoV-2. The platform previously delivered promising vaccine candidates to address global health challenges such as HIV, hepatitis C vaccine, Ebola, and respiratory syncytial virus (RSV).

“We hope to soon begin initial tests to see whether our vaccine can induce an immune response against SARS-CoV-2 in animal models and eventually in clinical trials,” Zhu stated.

 

University Hospitals (UH), ARMS Pharmaceutical, and Case Western Reserve University

Candidate: ARMS-1

Type: Oral spray antiviral applied before or during exposure to airborne pathogens.

Status: UH said April 2 it will lead the ARMS-I COVID Study, a clinical trial of ARMS Pharmaceutical’s ARMS-1. The trial will study ARMS-1 in UH caregivers, to assess whether the drug helps prevent airborne transmission of coronavirus and reduces the symptoms of healthcare providers who have tested positive for SARS-CoV-2. The randomized placebo-controlled crossover study is expected to begin within two weeks, according to Daniel I. Simon, MD, Chief Clinical & Scientific Officer and President, UH Cleveland Medical Center.

ARMS Pharmaceutical has articulated ARMS-1’s potential mechanism of action: A microbe-impermeable barrier is applied at the oropharynx, a gateway to the pathogenesis of viral upper respiratory infections, potentially blocking the ability for pathogens to reach mucosal tissue and begin the infection cycle. The barrier is infused with an antiviral which is believed to be resistant to antigenic drift and viral mutation which has the potential to kill pathogens that come into contact with the barrier, thus intensifying the effect of the barrier action

The Cleveland Foundation has authorized $1 million in emergency funding to support a significant portion of the clinical trial, using previously-restricted health-related research grant dollars.

 

University of Oxford and partners

Candidate: ChAdOx1 nCoV-19

Type: Vaccine based on an adenovirus vaccine vector and the COVID-19 spike protein. After vaccination, the surface spike protein of the coronavirus is produced, which primes the immune system to attack the coronavirus if it later infects the body.

Status: University of Oxford’s Oxford Vaccine Group said March 27 it has started screening healthy volunteers (aged 18-55) for the upcoming COV001 trial (NCT04324606) assessing ChAdOx1 nCoV-19. The trial, a collaboration between the Group and the University’s Jenner Institute, is set to recruit up to 510 volunteers who will receive either the ChAdOx1 nCoV-19 vaccine or a control injection.

Oxford’s team is led by Professors Sarah Gilbert, PhD; Andrew Pollard, MBBS, PhD; Teresa Lambe, PhD; Sandy Douglas, DPhil; and Adrian Hill, DPhil, started work designing a vaccine on January 10. On March 23, Gilbert was awarded £2.2 million ($2.7 million) by the U.K. government toward the research, one of six COVID-19 research projects to receive a combined £20 million ($24.5 million).

Cobra Biologics said March 31 it was part of an Oxford-led consortium to rapidly develop, scale-up and produce ChAdOx1. Joining Cobra and the Jenner Institute are cGMP contract manufacturing organizations ADVENT and Halix, Pall Life Sciences, University of Oxford Clinical Biomanufacturing Facility, and the Vaccines Manufacturing and Innovation Centre.

Cobra said it is actively planning for a fast set-up phase to facilitate efficient production of a GMP working cell bank, then 200L GMP viral vaccine. Consortium partners expect to develop and manufacture the vaccine candidate in multiple batches, to support a 1 million dose scale batch size, by summer 2020.

 

University of Queensland (UQ), CEPI, CSL Behring and Dynavax

Candidate: Vaccine

Type: “Molecular clamp” vaccine; UQ has isclosed work toward a version using CSL subsidiary Seqirus’ proprietary adjuvant technology, MF59®, as well as a version using Dynavax’s toll-like receptor 9 (TLR9) agonist adjuvant, CpG 1018™

Status: UQ on March 22 announced pledges of A$10 million ($6 million) from the government of Queensland, and A$3 million ($1.8 million) from Australia’s national government, toward accelerating development of its preclinical “molecular clamp” vaccine against COVID-19 by six months.

The University said in February it achieved proof of concept showing the feasibility of using molecular clamp technology to engineer a vaccine candidate that could be more readily recognized by the immune system, triggering a protective immune response. Keith Chappell, PhD, told The Australian his team experimented with 250 different formulations before settling on a candidate vaccine virus. UQ plans to produce greater quantities of the vaccine to enable additional testing, then advance to investigational clinical testing after the middle of the year.

Dynavax in March disclosed plans to partner with UQ on a COVID-19 prevention vaccine applying CpG 1018, building on a partnership launched by UQ and the Coalition for Epidemic Preparedness Innovations (CEPI) in January 2019 to develop a “molecular clamp” vaccine platform against multiple viral pathogens. Earlier this year, CEPI requested UQ use its rapid response technology, which allows for rapid generation of new vaccines from a virus’s genetic sequence information, to develop a vaccine against COVID-19.

On March 26, Dynavax added that it would make CpG 1018 available to other vaccine developers through CEPI, with both partners agreeing to identify vaccine programs that could benefit from the adjuvant, then coordinate engagements with those programs. CpG 1018 is the adjuvant used in HEPLISAV-B® [Hepatitis B Vaccine (Recombinant), Adjuvanted], an adult hepatitis B vaccine marketed by Dynavax following FDA approval in 2017.

CSL said in February it will provide technical expertise and a donation of MF59 to the University of Queensland’s preclinical development program. The University will use the adjuvant to test the viral protein it is developing with its molecular clamp technology, CSL said. The company also committed a donation of RMB 1 million ($143,000) to the China Red Cross toward efforts to combat the epidemic.

 

University of Saskatchewan (USask), Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac)

Candidate: Vaccine to protect against SARS-CoV-2

Type: Not specified

Status: USask on March 13 said VIDO-InterVac researchers had successfully grown SARS-Cov-2 in a cell culture, and were testing the vaccine candidate in animals. VIDO-InterVac said it was collaborating with several labs in and outside Canada, including the National Microbiology Laboratory in Winnipeg.

Volker Gerdts, DVM, director and CEO of VIDO-InterVac, said in a statement that resarchers hoped to have an indication by early April whether the vaccine generated at VIDO-InterVac can successfully protecting against SARS-coV-2. He anticipated another six months of testing, development and manufacturing would be needed before the vaccine would be ready for clinical testing.

VIDO-InterVac said it is working to build a pilot-scale manufacturing facility within its Level 3 containment facility. VIDO-InterVac received funding to start Phase 1 of the facility, but will need another C$10 million ($7 million) to fully establish the manufacturing facility to industry standards, Gerdts said.

 

University of Wisconsin-Madison, FluGen, and Bharat Biotech

Candidate: CoroFlu

Type: Intranasal vaccine for COVID-19 based on FluGen vaccine candidate M2SR, with production scale-up by Bharat

Status: UWMadison, FLuGen and Bharat said April 2 they had begun development and testing of CoroFlu, based on FluGen’s M2SR, a self-limiting version of the influenza virus that induces an immune response against the flu. M2SR was based on an invention by UW­Madison virologists and FluGen co-founders Yoshihiro Kawaoka, PhD, and Gabriele Neumann, PhD, with Kawaoka’s lab planning to insert gene sequences from SARS-CoV-2 into M2SR so that the new vaccine will also induce immunity against the coronavirus.

The partners said they expect to refine the CoroFlu vaccine concept and carry out tests in animal models at UW–Madison over the next three to six months. Bharat Biotech of Hyderabad, India, will then begin production scale-up for safety and efficacy testing in humans. CoroFlu could be in human clinical trials by the fall of 2020, the partners added.

 

Vanderbilt University Medical Center (VUMC)

Candidates: Antibody-based treatments to protect people exposed to COVID-19.

Types: To be identified. Researchers plan to rapidly isolate B cells producing antibodies targeting specific viral proteins. The monoclonal antibodies will be studied to find those capable of neutralizing SARS-CoV-2.

Status: VUMC said March 23 its Vanderbilt Vaccine Center (VVC) is building a comprehensive “toolkit” designed to identify and analyze antibodies isolated from the blood of survivors for their ability to neutralize SARS-CoV-2. With corporate, academic, and government partners, VVC is analyzing the antibodies based on their ability to inhibit the virus, with plans to develop and manufacture the most promising lead antibodies and advance them into clinical study. “Our goal is to prepare antibodies for human clinical trials by this summer,” VVC director James Crowe, MD, stated.

VUMC said it working with numerous providers of tools, technology, and services, including Berkeley Lights (“Beacon” cell selection platform), STEMCELL Technologies (custom cell-type specific isolation reagents), Twist Biosciences (rapid silicon-based DNA synthesis of antibody gene sequences), and 10x Genomics (Chromium Single Cell Immune Profiling Solution).

 

Vaxart and Emergent BioSolutions

Candidates: Five vaccines based on proprietary VAAST™ Platform

Type: Oral recombinant vaccines administered by room temperature-stable tablet

Status: Vaxart on March 31 disclosed that it had produced five COVID-19 vaccine candidates for testing in its preclinical models. Each vaccine construct is based on a different coronavirus antigen combination, Vaxart said, adding that it expects to advance the best performing vaccine to manufacturing for clinical trials.

Earlier in March, Vaxart agreed to use the “molecule-to-market” contract development and manufacturing (CDMO) services of Emergent BioSolutions in preparation for cGMP production of a vaccine. Those development services have since started, with Emergent expected to produce bulk cGMP vaccine for use in a Phase I study that Vaxart said it expects to initiate early in the second half of 2020. Vaxart also said it was prioritizing development of the COVID-19 vaccine by putting several vaccine programs on hold, including its therapeutic HPV vaccine program and a norovirus vaccine program for which the company completed a successful Phase I study, and was actively seeking a development partner.

Emergent has said it will provide development services out of its Gaithersburg, MD location and manufacture drug substance at its Bayview facility in Baltimore, designated a Center for Innovation in Advanced Development and Manufacturing (CIADM) by the U.S. Department of Health and Human Services.

Vaxart disclosed plans in January to generate vaccine candidates based on the published genome of SARS-CoV-2, and evaluate them in preclinical models based on their ability to generate both mucosal and systemic immune responses. The company cited a study published in The Lancet Infectious Diseases, showing that the Vaxart oral H1 influenza tablet vaccine primarily protected against infection based on mucosal immunity, compared with the injectable flu vaccine that protected primarily through systemic immunity.

 

VBI Vaccines and National Research Council of Canada (NRC)

Candidate: Pan-coronavirus vaccine targeting COVID-19, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS).

Type: Multivalent vaccine candidate based on VBI’s virus-like particle (eVLP) platform technology, and designed to co-express SARS-CoV-2, SARS-CoV, and MERS-CoV spike proteins on the same particle

Status: Cambridge, MA-based VBI Vaccines on March 31 announced its vaccine development collaboration with NRC, Canada’s largest federal research and development organization. The collaboration will combine VBI’s viral vaccine expertise, eVLP technology platform, and coronavirus antigens with the NRC’s COVID-19 antigens and assay development capabilities.

The NRC and VBI agreed to evaluate and select the optimal vaccine candidate. Following IND-enabling preclinical studies conducted at both the NRC’s core facilities and VBI’s research facility in Ottawa, ON, VBI said it believes clinical study materials could be available in the fourth quarter.

“We believe the trivalent construct could allow for the production of broadly reactive antibodies, which offer potential for protection from mutated strains of COVID-19 that may emerge over time,” stated Francisco Diaz-Mitoma, MD, PhD, VBI’s chief medical officer.

 

VERO Biotech

Candidate: GENOSYL® (nitric oxide) gas with GENOSYL DS delivery system

Type: Inhaled nitric oxide plus tankless delivery system

Status: VERO Biotech said March 24 that the first patient with COVID-19 infection complicating pulmonary hypertension has been treated with GENOSYL via the GENOSYL DS at home, under an emergency IND approved by the FDA. The patient was also treated with oxygen via nasal canula, and monitored remotely by clinicians. Two days later, VERO said the FDA granted the company “expanded access emergency use” allowing GENOSYL DS, to immediately be used for the treatment of cardiopulmonary symptoms associated with COVID-19.

 

Walter Reed Army Institute of Research and U.S. Army Medical Research Institute of Infectious Diseases

Candidates: Five vaccines to protect from COVID-19

Types: Not specified

Status: Secretary of the Army Ryan D. McCarthy said March 19 that the U.S. Army Medical Research and Development Command and U.S. Army Medical Research Institute of Infectious Diseases were working to develop five separate COVID-19 vaccines. McCarthy said the Army had received an additional $900 million toward efforts to prevent, detect, and treat the disease.

Among the vaccine candidates is one that was already in preclinical development in animal models, Col. Wendy Sammons-Jackson, director of the Military Infectious Diseases Research Program under USAMRDC, told Stars and Stripes.

 

Xijing Hospital and Massachusetts General Hospital

Candidate: Inhaled nitric oxide (iNO) for treatment of mild/moderate COVID-19

Type: Inhaled nitric oxide as a supportive measure for COVID-19 patients with associated pulmonary complications based on formulations shown to have successfully treated patients with SARS-CoV, due to its genomic similarity to SARS-CoV-2

Status: Xijing and MGH have launched two Phase II trials assessing inhaled nitric oxide in patients with mild/moderate COVID-19 (NCT04290871, withdrawn March 24; and NCT04305457, recruiting patients). A day later, the nitric oxide delivery device developer Nu-Med Plus said it was closely monitoring the trials, and had talks with the FDA about bringing its products to market more quickly. Nu-Med has also had talks with the U.S. Department of Veterans Affairs about research opportunities related to iNO technology and COVID-19.

Too Soon to Tell – 56 candidates

 

AJ Vaccines

Candidate: Vaccine to prevent COVID-19

Type: Not specified

Status: AJ Vaccines said March 6 it would develop a COVID-19 vaccine designed to use “the best possibly designed” antigens to mimic closely the authentic native structures of the virus. “The use of such technology is expected to induce the relevant immune responses and therefore protect against disease with a lower risk for side effects,” COO Jerome Cabannes stated.

 

Applied DNA Sciences and Takis Biotech

Candidate: Linear DNA vaccine

Type: To be based on PCR-produced linear DNA designed to induce antibodies that can neutralize SARS-CoV-2. Four preclinical vaccines have been designed based on the structure of the “Spike” protein, which enables uptake of the coronavirus by binding to specific receptors on the host cells.

Status: Applied DNA said March 24 that it filed a provisional patent application with the U.S. Patent and Trademark Office (USPTO) for its diagnostic assay under development for SARS-CoV-2—five days after announcing it had completed the design of the assay. The assay uses PCR-based detection of viral sequences that code for the Spike protein that is also the target of Applied DNA’s vaccine candidate partnered with Takis Biotech.

Rome-based Takis has won approval from the Italy’s Ministry of Health to begin a preclinical trial of Applied DNA’s COVID-19 vaccine candidate, with the first results expected to be available in April.

Applied DNA began large-scale production of the four vaccine candidates in March via the company’s proprietary PCR-based DNA (“LinearDNA”) manufacturing systems. “Within weeks of arrival we expect to immediately scale up PCR-based production of each vaccine candidate and ship them back to Takis who will determine each vaccine’s relative abilities to provoke an immune response in vaccinated mice” stated James A. Hayward, President and CEO of Applied DNA.

Applied’s majority-owned subsidiary LineaRx and Takis said in February they had formed a joint venture to develop the preclinical vaccine using PCR-based DNA manufacturing technology. The companies said advantages of their technology include the speed of production, the absence of antibiotics and their resistance genes, the purity of the DNA, the simplicity of design, the powerful immunogenicity proved in a prior linear DNA vaccine, the absence of any bacterial contaminants and the effectiveness of the vaccine gene without insertion into the patient’s genome.

 

Arcturus Therapeutics and Duke-NUS

Candidate: LUNAR-COV19

Type: Very low dose, potential single-shot, self-replicating mRNA vaccine devoid of viral material or co-adjuvants. The vaccine is based on its STARR™ (Self-Transcribing And Replicating RNA), which combines self-replicating RNA with LUNAR® (Lipid-enabled and Unlocked Nucleomonomer Agent modified RNA) lipid-mediated delivery system into a single solution to produce proteins inside the human body.

Status: Arcturus on April 9 announced plans to initiate a human clinical trial this summer for LUNAR-COV19. Under the guidance of the Singapore Health Sciences Authority (HSA), the trial plans to enroll up to 76 healthy volunteer adults including elderly individuals, with follow-up over several months to evaluate extent and duration of immune response. The initial GMP batch is to be delivered in June.

In March, Arcturus said its vaccine will incorporate the genetic correlation system developed by Duke-NUS Medical School in Singapore, designed to augment testing of vaccines by tracking genetic changes and their correlations. These gene expression changes can be measured within the first five days following vaccination and the data may also guide dose selection, Arcturus said.

Arcturus and Duke-NUS disclosed their partnership to produce a COVID-19 vaccine on March 4.

 

AstraZeneca

Candidate: Monoclonal antibodies to prevent COVID-19 disease. 

Type: Coronavirus-neutralizing antibodies developed through the company’s program to use the Defense Advances Research Project Agency’s Pandemic Prevention Platform (P3).

Status: AstraZeneca said April 8 it is exploring three potential sources for antibodies against SARS CoV-2: Patients who have recovered from COVID-19, immunized humanized mice, and lab techniques such as phage display: “AstraZeneca is aiming for clinical evaluation in the next 3 to 5 months.”

AstraZeneca also disclosed collaborations with external partners: The Chinese Academy of Sciences, and Vanderbilt University Medical Center have provided genetic sequences for antibodies they have discovered against SARS2-CoV-2 for further in silico and in vitro assessment, while the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and the University of Maryland School of Medicine are conducting preclinical safety and efficacy assessments of antibody candidates discovered through internal research.

The company said March 24 it will donate 9 million face masks for healthcare workers worldwide, with Italy receiving the first shipments.

 

Bellerophon Therapeutics

Candidate: INOpulse®

Type: Portable inhaled nitric oxide system (iNO) for the treatment of COVID-19. INOpulse has generated positive top-line Phase II results in pulmonary hypertension associated with pulmonary fibrosis (PH-PF), with a pivotal Phase III trial planned.

Status: Bellerophon on April 8 said it submitted an IND to the FDA for clinical trials of INOpulse, with plans for an up-to-500 patient randomized, open-label study (PULSE-CVD19-001) for which the company has applied for funding to the NIH and the Biomedical Advanced Research and Development Authority (BARDA). Three COVID-19 patients have completed treatment with INOpulse under an emergency expanded access program while several other patients are now on the therapy.

On March 31, the company said it treated its first COVID-19-diagnosed patient diagnosed with INOpulse at the University of Miami School of Medicine, after the FDA granted the company emergency expanded access allowing immediate use of the inhaled nitric oxide system to treat COVID19 patients under the care and supervision of their physician.

Bellerophon noted that SARS-CoV-2 is approximately 82% identical to severe acute respiratory syndrome related coronavirus (SARS-CoV), the virus behind the 2003-04 global SARS outbreak. The company cited past studies showing that nitric oxide could benefit SARS-CoV patients by preventing viral replication, improving arterial oxygenation, reducing the need for ventilation support, and preventing the proliferation of lung infiltrates.

 

Beroni Group

Candidate: Nanobody-based treatment

Type: Modified nanobody

Status: Beroni Group on April 3 said that its SARS-CoV-2 IgG/IgM Antibody Detection Kit received CE certification in Europe. The test, based on colloidal gold, is a rapid single-use immunochromatographic test intended for the qualitative detection of IgG and IgM protein from the SARS-CoV-2 virus in capillary “fingerstick” whole blood, plasma, and serum samples. The kit is designed to yield results in 10 minutes, and according to the company has a 97% accuracy rate.

Beroni said March 9 it was partnering with Tianjin University in China on cytological experiments set to begin for a nanobody-based COVID-19 treatment—to be followed by animal experiments, then clinical trials which are expected to occur in April. Beroni said it was in talks with “an international CRO/CDMO company with operations in the USA, Europe, and China” to use their research and manufacturing facilities to accelerate clinical trials for both the medical treatment and diagnostic kit.

 

BeyondSpring

Candidate: BPI-002

Type: Novel oral small molecule T-cell co-stimulator

Status: BeyondSpring said March 11 it submitted a provisional U.S. patent application designed to protect BPI-002 for methods of treating viral infections, including COVID-19, when administered alone or in combination with a vaccine.

According to the company, BPI-002 can potentially activate the adaptive immune system (including CD4+ helper T cells and CD8+ cytotoxic T cells) to directly attack and kill virally infected cells, including RNA virus, such as those causing COVID-19. If combined with a vaccine including COVID-19 vaccine, BeyondSpring reasons, BPI-002 could function as an adjuvant to provide improved long-term humoral (B-cell dependent) protection against future viral infection.

 

BioAegis Therapeutics

Candidate: rhu-pGSN

Type: Recombinant human plasma gelsolin therapy based on intellectual property licensed from Harvard Medical School

Status: BioAegis on April 2 said it is submitting requests to the FDA and other regulators seeking to accelerate clinical trials of its lead product rhu-pGSN in severe infection, specifically severe community-acquired pneumonia (sCAP), including COVID-19, and has engaged “leading” infectious disease experts to advise the proof of concept clinical trial strategy. The company reasons that administering rhu-pGSN as an adjunct to standard-of-care measures could prevent or limit organ injury and death in patients with severe coronavirus infections.

BioAegis said plasma gelsolin has been tested in over 20 animal studies, as well as a recent phase Ib/IIa study in hospitalized community-acquired pneumonia patients with no adverse safety signals.

 

Biocad

Candidates: Vaccine to emerge from three options in development

Type: mRNA vaccine based on previous pipelines for creation of mRNA-oncovaccines, an area where the company has specialized.

Status: Biocad said March 19 it was working to develop a COVID-19 vaccine, with the first animal studies scheduled for the end of April. Biocad disclosed that researchers from the Dongfang Hospital at Shanghai Tongji University and Chinese biotechnology company Stemirna have been working on the vaccine since the end of January, synthesizing matrix ribonucleic acid (mRNA) with several sequences of different antigens. The company said its vaccine can be manufactured in “less than five to six months” since it uses mRNA as opposed to recombinant proteins.

 

BioCryst Pharmaceuticals

Candidate: Galidesivir (BCX4430)

Type: Nucleoside RNA polymerase inhibitor designed to disrupt the viral replication process

Status: BioCryst said April 9 it has begun enrolling patients into a randomized, double-blind, placebo-controlled clinical trial to assess the safety, clinical impact and antiviral effects of galidesivir in patients with COVID-19. The trial, which will study 24 hospitalized adults diagnosed with moderate to severe COVID-19, is being funded by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID).

On March 5, the company said it was in active dialogue with U.S. public health authorities about whether galidesivir could be useful among potential approaches to treat and prevent COVID-19. Galidesivir has shown broad-spectrum activity in vitro against more than 20 RNA viruses in nine different families, including coronaviruses and viral disease families that include filoviruses, togaviruses, bunyaviruses, arenaviruses, paramyxoviruses, and flaviviruses.

“The virus causing COVID-19 is a coronavirus, but we do not yet know if galidesivir has activity against this specific virus,” BioCryst CEO, President, and Director Jon P. Stonehouse told analysts on the company’s quarterly conference call.

Since 2013, BioCryst has partnered with NIAID and BARDA to develop galidesivir under contracts totaling $82 million: “We have been working with them to figure out how we might help in this global health emergency,” Stonehouse said, adding that talks have focused on testing galidesivir on SARS-CoV-2, learning how to participate in clinical trials, and increasing drug supply.

Galidesivir is also being assessed for yellow fever in a Phase II trial (NCT03891420) under contracts with the National Institute of Allergy and Infectious Diseases (NIAID) and U.S. Department of Health and Human Services (HHS). Last year, galidesivir completed a 32-patient Phase I study in Marburg Virus Disease (NCT03800173).

 

BioXyTran

Candidate: BXT-10

Type: Polysaccharide galectin inhibitor designed to restore the adaptive immune system to normal function by binding to and neutralizing Galectin-3 and Galectin-1. Binding activity is localized to the galactose containing side branches, preventing the virus from entering the host cell, and thus modulating any existing cytokine storm. The company cites preclinical evidence that a galectin inhibitor can bind to the protein spikes of the coronavirus.

Status: Bioxytran on March 31 disclosed BXT-10’s expected mechanism of action against COVID-19 in a presentation that cited several studies published over the past five years indicating that Galectin-1 is implicated in viral pathogenesis. Studies in mice showed that mice share the same N-terminal domain as humans—and that both SARS and COVID-19 share the similar N-terminal domain. Bioxytran reasons that a galectin-1 inhibitor could bind to coronavirus spikes and reduce viral load.

“The journal articles provide a strong foundation that galectin-1 is implicated in COVID-19,” CEO David Platt stated.

A day earlier, BioXyTran said it intended to internally develop a novel carbohydrate Galectin inhibitor—and terminated an agreement announced March 24 to license a galectin inhibitor from its CEO and Chairman David Platt, PhD, saying the novel candidate “can be more responsive to the immediate needs posed by COVID-19.” Bioxytrain added that it planned to obtain additional funding for the internal development effort, and file for expedited trials under new FDA guidelines.

 

Chongqing Sidemu Biotechnology Technology

Candidate: Natural killer (NK) cell therapy

Type: Universal off-the-shelf NKG2D-ACE2 CAR-NK cells

Status: Chongqing Sidemu Biotechnology Technology and sponsor Chongqing Public Health Medical Center disclosed March 27 they are recruiting patients for an up to 90-patient Phase I/II clinical trial (NCT04324996) assessing the company’s universal off-the-shelf NKG2D-ACE2 CAR-NK cells secreting IL15 superagonist and granulocyte-macrophage colony-stimulating factor (GM-CSF)-neutralizing single-chain variable fragment (scFv).

 

Codagenix and Serum Institute of India

Candidate: Vaccine against CoVID-19

Type: Live-attenuated vaccine

Status: Codagenix said February 13 it will collaborate with the Serum Institute of India to rapidly co-develop a COVID-19 vaccine, adding that it has already designed “multiple” novel coronavirus vaccine candidate genomes using its proprietary deoptimization technology, which can digitally generate a full-length, deoptimized genome based on the outbreak sequence 3–5 days after acquiring the sequence.

Vaccine viruses will be grown and tested in vivo by contracted laboratories suitable for containment, before testing in clinical trials. The Serum Institute of India, a vaccine manufacturer and distributor with a global presence, will scale-up the manufacture of the vaccine to ensure its availability. Codagenix and Serum Institute said they are pursuing an accelerated development pathway and were eager to manufacture and test their vaccine candidates “as quickly as possible.”

 

Cytovia Therapeutics and Macromoltek

Candidate: Natural Killer (NK) immunotherapy targeting SARS-CoV-2

Type: NK cells leveraging Cytovia’s proprietary bi-functional technology, developed by co-founder Jean Kadouche, PhD. and novel antibodies neutralizing or blocking SARS CoV2, designed by Macromoltek, a computational antibody discovery company. The selected bi-functional antibodies

Status: Cytovia and Macromoltek said April 7 it will expand its NK immunotherapy programs beyond cancer and infectious diseases to include COVID-19, with plans to select an NKI immunotherapy candidate to begin clinical trials by year’s end, and make it available to patients in 2021. The companies will use a bi-functional approach they said holds potential to minimize virus escape from the immune response, thereby inhibiting the intensification of the inflammation leading to Acute Respiratory Syndrome (ARS). The activation of NK cells through the NKp46 receptor aims to destroy the virus-infected cells while the other arm can either block the entry of the virus into epithelial cells or neutralize circulating viruses.

NK activating antibodies were licensed last month from Yissum, the technology-transfer company of the Hebrew University of Jerusalem.

 

Emmaus Life Sciences

Candidate: Endari® (L-glutamine oral powder)

Type: Amino acid indicated to reduce the acute complications of sickle cell disease (SCD) in adult and pediatric patients 5 years of age and older.

Status: Emmaus said March 24 it is exploring whether Endari may be potentially beneficial to patients with COVID-19 as part of their oral rehydration therapy (ORT). According to the company, a study regarding ORT has suggested that an oral hydration solution containing glutamine and glucose might be superior to conventional glucose ORT in viral enteritis, but added that further research was warranted to confirm that hypothesis.

 

Enanta Pharmaceuticals

Candidate: To be determined

Type: Existing antiviral and respiratory candidates, plus drugs to be discovered

Status: Enanta on March 13 said it had begun a program to discover direct-acting antiviral drug candidates to treat COVID-19, using a two-pronged approach: Testing compounds from its antiviral compound library for potential activity against the virus, and discovering new candidates by using its expertise in direct-acting antiviral mechanisms. Four days later, Baird Equity Research cited that strategy, and the company’s antiviral experience, in upgrading Enanta to “Outperform”: “In our view, Enanta’s core competencies are a perfect fit for tackling the COVID-19 pandemic, head on.”

Enanta also said it will launch a Phase II dose ranging study in pediatric respiratory syncytial virus (RSV) patients and a Phase II study in adult transplant patients with RSV, in addition to its ongoing Phase IIb RSVP study in adult outpatients with community-acquired RSV, noting that patients at higher risk for RSV such as older adults and people with weakened immune systems show a similar patient profile as patients with COVID-19.

 

EUSA Pharma/The Papa Giovanni XXIII Hospital

Candidate: Sylvant (siltuximab)

Type: Monoclonal antibody targeting Interleukin-6 (IL-6), approved in the U.S., Europe, and other countries for the treatment of patients with multicentric Castleman disease (MCD).

Status: EUSA Pharma on April 1 announced initial preliminary results from the Papa Giovanni XXIII Hospital-sponsored SISCO (Siltuximab ISerious COVID-19) Study (NCT04322188). Interim data from the first 21 patients treated with Sylvant and followed for up to seven days showed that seven patients experienced a clinical improvement with a reduced need for oxygen support, while another nine patients saw their condition stabilize, indicated by no clinically relevant changes. C-Reactive Protein levels, a marker of systemic inflammation, declined from baseline through to Day 5 following treatment in all 16 patients who showed sufficient recorded values.

The next phase of data will compare outcomes in matched case-control patients not treated with Sylvant, and is expected in coming weeks. Twenty-one patients were enrolled in the study, which evaluated Sylvant in COVID-19 patients who had developed serious respiratory complications.

 

Flow Pharma

Candidate: FlowVax™ COVID-19

Type: Rapid synthetic peptide vaccine designed to protect against SARS-CoV-2 infection by targeting antigens at the center of the virus, which are least likely to mutate. FlowVax COVID-19 is an adjuvanted, room temperature stable, biodegradable microsphere peptide vaccine targeting nucleocapsid, loaded with a suite of 16 peptides with > 95% predicted world-wide population coverage. The vaccine can be given by injection or nasal spray.

Status: Flow Pharma said April 8 researchers at The University of Texas Medical Branch at Galveston (UTMB) at Galveston will begin testing FlowVax COVID-19 by challenging nonhuman primates with SARS-CoV-2 after the animals are vaccinated this month with FlowVax COVID-19.

The company has posted a presentation on its website noting that its COVID-19 vaccine uses the same platform as its FlowVax Ebola targeting nucleocapsid that had been shown effective in a mouse model at UTMB.

“Nucleocapsid proteins within COVID-19 contain multiple class I epitopes with predicted HLA [human leukocyte antigen] restrictions consistent with broad population coverage. A similar approach to a CTL [cytotoxic T-lymphocytes] vaccine design may be possible for that virus,” Flo Pharma Founder, CEO, and Director Reid Rubsamen MD, and colleagues concluded in a preprint paper posted March 9 on bioRxiv.

Flow Pharma’s vaccines use patented Size Exclusion Antigen Presentation Control (SEAPAC™) technology based on making vaccine microspheres the same size as human white blood cells.

 

GigaGen

Candidate: rCIG (recombinant anti-coronavirus 19 hyperimmune gammaglobulin)

Type: Recombinant polyclonal antibody therapy for the treatment of COVID-19.

Status: GigaGen on March 30 disclosed its effort to deveop rCIG, an intravenous therapy designed to reproduce whole antibody repertoires of recovered COVID-19 patients, including high concentrations of antibodies that target and prevent further replication of the COVID-19 virus. GigaGen uses its single-cell technology to capture and recreate complete libraries of antibodies from COVID-19 convalescent patients that can directly translate into antibody therapies—a method the company says is much more scalable than plasma from recovered COVID-19 patient donors since one person’s B cell repertoire can be used to generate a drug that treats millions of patients.

Other advantages cited by GigaGen include a decreased risk of contamination, greater batch to batch consistency, and “hundreds-fold” higher potency than plasma-derived equivalents, which may yield better clinical outcomes.

GigaGen is recruiting patients who have recovered from COVID-19 to donate blood for the development of rCIG. The company has signed a collaboration agreement with plasma collector/manufacturer Access Biologicals to expedite patient identification and assist with sample collection. GigaGen added that it will continue talks with the FDA toward expediting development.

 

GlaxoSmithKline (GSK) and Clover Biopharmaceuticals

Candidate: COVID-19 S-Trimer

Type: Protein-based coronavirus vaccine

Status: GSK agreed to provide Clover with its pandemic adjuvant system for further evaluation of S-Trimer in preclinical studies, the companies said in February, under a research collaboration whose value was not disclosed. GSK reasons that Clover could rapidly scale-up and produce large-quantities of a new coronavirus vaccine since it has one of the largest in-house, commercial-scale cGMP biomanufacturing capabilities in China.

On March 25, GSK said that Clover was one of five partner companies and research groups worldwide with which GSK is collaborating on COVID-19 vaccines using GSK’s vaccine adjuvant technology. GSK said it expected data to be reported from the collaborations over the next three months.

GSK also said it was donating $10 million to The COVID-19 Solidarity Response Fund, created by the UN Foundation and WHO, to support WHO and partners to prevent, detect, and manage the pandemic.

“GSK is the world leader in vaccines, and partnering with them significantly boosts our hopes of both the timely development of a vaccine, and the capability to produce it in large enough quantities necessary to curb the coronavirus outbreak,” said Michael Breen, director, Infectious Diseases, Pharma at GlobalData.

 

Heat Biologics and University of Miami

Candidate: Vaccine to protect against SARS-CoV-2 and other coronaviruses

Type: Vaccine based on Heat’s gp96 platform, designed to generate open docking sites for insertion of multiple SARS-CoV-2 antigens.

Status: Heat said March 23 that it will collaborate with University of Miami Miller School of Medicine to develop a proprietary UM COVID-19 point-of-care diagnostic test—more than two weeks after the partners agreed to develop a vaccine targeting SARS-CoV-2.

“The vaccine is designed to induce a multi-epitope specific memory CD8 T-cell response that protects against multiple, distinct coronavirus strains, and against potential future mutations of SARS-CoV-2 and other coronaviruses,” Heat said. The approach is designed to activate a potent immune response, without the potential for genomic integration of foreign DNA or viral vector instability possible with attenuated viral vaccines.

 

Helix Nanotechnologies

Candidate: Vaccine

Type: Peresonalized vaccines using technology originally developed against cancer

Status: Helix will use the personalized vaccine technology it created over two years against cancer to fight COVID-19, co-founder and CEO Hannu Rajaniemi told The Wall Street Journal in a report updated March 15. Also last month, the company received an investment of undisclosed size from Sam Altman, advisor to Y Combinator and president of the Silicon Valley accelerator from 2014–2019.

 

Immune System Regulation (ISR) Holding and TCER

Candidate: Immunolid ISR50

Type: Vaccine based on TCER AB’s platform technology for the production of proteins and ISR’s drug pipeline with immunostimulating immunolides.

Status: ISR said March 19 that it is partnering with TCER to develop a COVID-19 vaccine. Data from animal studies are expected to be ready during the second quarter of 2020, with the goal of starting testing in humans during the last quarter of this year. TCER conducts its research in close collaboration with Hans Grönlund, PhD’s research group Therapeutic Immune Design at the Center for Molecular Medicine at Karolinska Institutet.

ISR said in February it was exploring the potential of developing its Immunolid ISR50 vaccine as a treatment for COVID-19. Immunolid50 is in the final phase of toxicological studies, carried out in collaboration with Innostars in Shanghai, in anticipation of a future IND application allowing for human clinical trials.

 

Imophoron

Candidates: Multiple COVID-19 vaccines

Type: Vaccines based on company’s ADDomer® platform, a synthetic, self-assembling, nature-inspired virus-like particle (VLP)

Status: Imophoron statesd on its website that preclinical trials of its vaccine candidates will begin “within weeks.” The U.K. startup, based at the Unit DX Incubator in Bristol, said it is looking for partners to further the development of the COVID-19 candidates and the ADDomer rapid-response platform for vaccines to combat present and future infectious diseases. Imophoron cites as advantages of its approach the avoidance of induction of disease-enhancing antibody responses, ready manufacture and thermostability, avoiding the need for cold chain storage.

 

Impact BioMedical

Candidates: Linebacker and Equivir

Type: Unspecified compounds with the potential to bind Angiotensin converting enzyme 2 (ACE2) and block SARS-CoV-2 entry into cells

Status: Impact’s parent company Singapore eDevelopment said March 17 that Impact and scientific research partner GRDG Sciences conducted molecular docking studies using advanced computational models showing that its Linebacker and Equivir compounds successfully inhibited infection by SARS-CoV-2. The compounds will undergo testing after they were shown to block 3 integral viral mechanisms for SARS-CoV-2 replication and infection: the viral spike interaction point, helicase, and protease.

 

Israel Institute for Biological Research (IIBR)

Candidate: Vaccine to prevent COVID-19

Type: Not specified

Status: IIBR’s vaccine prototype has begun to be tested on rodents at its biochemical defense lab, Reuters reported March 31, after Israeli Prime Minister Benjamin Netanyahu issued a statement saying he was informed of “significant progress” in designing the prototype by IIBR’s director Shmuel Shapira, MD.

At a March 24 virtual conference hosted by Jerusalem Venture Partners, IIBR chief innovation officer Eran Zahavy, PhD, said the institute had shifted its entire focus to COVID-19, with three groups trying to develop a vaccine against the novel coronavirus, and other groups researching potential treatments.

Netanyahu directed IIBR, an Israeli government defense research institute, to develop a COVID-19 candidate in February. Netanyahu and the chief of Israel’s military, Lieutenant-General Aviv Kohavi, went into self-isolation at the end of March following exposure to coronavirus carriers. Both men have tested negative for the virus.

 

Jagiellonian University (Malopolska Centre of Biotechnology) and Nanjing University

Candidate: HTCC (N-(2-hydroxypropyl)-3-trimethylammonium 47 chitosan chloride)

Type: Antiviral compound designed to potentially inhibit 48 currently circulating coronaviruses

Status: Professor Krzysztof Pyrć, PhD, and colleagues at the Virogenetics Laboratory of Virology at Jagiellonian University’s Malopolska Centre of Biotechnology joined researchers from Nanjing University in publishing a March 31 preprint study in bioRxiv describing the antiviral activity of HTCC, which the researchers concluded may be used as a potential inhibitor of 48 highly pathogenic coronaviruses based on its inhibition of viral replication in Vero cells: “We believe that HTCC is a promising drug candidate that should be further studied, as it provides a ready-to-use solution for SARS-CoV-2 and future emerging coronaviruses.

 

Janssen Pharmaceutical Cos. (Johnson & Johnson)

Candidates: Prezista® (darunavir); Prezcobix™ (darunavir and cobicistat)

Types: HIV-1 protease inhibitor (darunavir); CYP3A inhibitor (cobicistat). Prezista and Prezcobix are approved treatments for HIV-1 infection.

Status: Johnson & Johnson confirmed March 16 that it was screening its marketed HIV treatment Prezista and other antiviral compounds to determine potential in vitro effect against SARS-CoV-2—and decried “anecdotal, unsubstantiated reports” that Prezista has antiviral effect against COVID-19. J&J emphasized that the drug “should not be administered without a boosting agent (ritonavir or cobicistat).”

The company cited preliminary, unpublished results from a previously reported in-vitro experiment in asserting: “it is not likely [Prezista] will have significant activity against SARS-CoV-2 when administered at the approved safe and efficacious dose for the treatment of HIV-1 infection.” The company also cited results from a single center, open label, randomized, and controlled trial conducted at Shanghai Public Health Clinical Center of Prezista and cobicistat in treating laboratory-confirmed 30 COVID-19 patients, which it said showed that the combination was not effective.

Janssen said in January it donated 300 boxes of Prezcobix to the Shanghai Public Health Clinical Center and Zhongnan Hospital of Wuhan University for use in research to support efforts in finding a solution against SARS-CoV-2. Another 50 boxes were provided to the Chinese Center for Disease Control and Prevention for laboratory-based investigations. Prezcobix is under study alone in one Chinese trial (NCT04252274), while another Chinese study is assessing Prezcobix compared with Kaletra (lopinavir/ritonavir) combined with thymosin a1 (ChiCTR2000029541). A Spanish trial is evaluating Prezcobix and chloroquine (NCT04304053), while a trial in Bangkok is assessing Prezcobix among numerous HIV protease inhibitors (THDMS-COVID19; NCT04303299).

 

Junshi Biosciences and Institute of Microbiology of the Chinese Academy of Sciences (IMCAS)

Candidate: Neutralizing antibodies

Type: Multiple strains of neutralizing antibodies (Nab) capable of keeping an infectious agent, usually a virus, from infecting a cell by neutralizing or inhibiting its biological effect. It could potentially facilitate virus clearance, altering the course of infection, Junshi reasons.

Status: Junshi Biosciences said March 20 that it signed a collaboration agreement with IMCAS to jointly develop neutralizing antibodies against COVID-19. The partners said they obtained multiple strains of neutralizing antibodies capable of effectively blocking viral invasion in laboratory assays and have conducted animal experiments. Preliminary in vitro and in vivo studies have verified the blocking activity of the NAb strains, Junshi said.

The company added that it was verifying the preclinical toxicology and in vivo activity of the antibodies in order to file IND applications with regulatory agencies in and outside China.

 

Kamada

Candidate: Anti-Corona Immunoglobulin (IgG)

Type: Polyclonal immunoglobulin based on company’s proprietary plasma-derived IgG platform technology as a potential treatment for severely ill coronavirus patients. The treatment is expected to be produced from plasma derived from donors recovered from the virus, which is anticipated to include antibodies to COVID-19.

Status: Kamada on March 11 announced plans to initiate development of an Anti-Corona IgG, emphasizing that its development and manufacturing plans were “highly” dependent on the availability of hyper-immune plasma and on the treatment’s to-be-determined regulatory path. “We are working with the Israeli regulatory authorities and local medical institutions to advance our program,” Kamada CEO Amir London stated.

 

Mallinckrodt

Candidate: INOmax® (nitric oxide)

Type: Inhaled nitric oxide (iNO) indicated in the U.S. for term and near-term neonates with hypoxic respiratory failure associated with pulmonary hypertension.

Status: Mallinckrodt said April 1 it was working with the FDA to make INOmax available to U.S. patients with pulmonary complications of COVID-19 “as quickly as possible through the appropriate regulatory mechanism.”

On March 12, Mallinckrodt said it was assessing “limited published evidence” of a potential role for its marketed INOmax as a supportive measure in treating patients with SARS-CoV-2 and associated pulmonary complications. The company cited a 2005 in vitro study showing iNO’s inhibitory effect on the replication cycle of severe acute respiratory syndrome-related coronavirus (SARS-CoV), and a 2004 study showing improved blood oxygenation, reduced supplemental oxygen, and reduced ventilator support in six SARS-CoV patients treated with iNO.

Mallinckrodt said it had submitted information to the NIH about evaluating iNO in acute respiratory distress syndrome (ARDS), informed the Biomedical Advanced Research and Development Authority (BARDA) of its ongoing study, and begun early talks with the FDA on submitting a pre-IND package in support of the potential use of iNO in coronavirus-associated ARDS.

 

Migal Galilee Research Institute

Candidate: Vaccine against COVID-19

Type: Oral vaccine for adults and children based on existing vaccine against avian coronavirus Infectious Bronchitis Virus (IBV)

Status: Chen Katz, PhD, research team leader with the Institute, told The Times of Israel on March 10 that the vaccine is on track to start months of clinical testing in “a few weeks.” Migal generated headlines February 27 by announcing “a scientific breakthrough” and expressing as its goal: “achieve safety approval in 90 days.” The Institute later clarified the breakthrough as its adapting for COVID-19 a convertible vaccine it spent four years researching with support from Israel’s Ministry of Science and Technology and Ministry of Agriculture.

 

Moleculin Biotech

Candidate: WP1122

Type: Prodrug of 2-DG (2-deoxy-D-glucose)

Status: Moleculin said March 17 it has partnered with the University of Texas Medical Branch at Galveston (UTMB) to conduct research on its lead candidate WP1122 and the rest of Moleculin’s patented portfolio of molecular inhibitors, for antiviral properties against COVID-19 and other viruses. The company cited a 2014 study showing 2-DG to be effective in treating porcine epidemic diarrhea virus (PEDV) infection. Three days later, Moleculin filed a new patent application covering the use of WP1122 and its analogs as therapies to limit the ability of coronavirus and other viruses to replicate.

Moleculin agreed to supply WP1122 and related inhibitors, as well as technical support, while UTMB agreed to begin testing the candidates against various viral disease models, including COVID-19, in connection with the UTMB Center for Biodefense and Emerging Infectious Diseases.

 

Mount Sinai Health System and Harbour BioMed (HBM)

Candidates: Monoclonal antibodies against the coronavirus SARS CoV 2

Type: Fully human monoclonal antibodies using HBM’s H2L2 Harbour Mice® platform.

Status: Mount Sinai and Harbour BioMed said March 6 they entered into a multi-year, multifaceted collaboration to generate monoclonal antibodies against SARS CoV 2 as well as develop novel, fully human antibodies to prevent and treat diseases in areas that include oncology and immunology.

 

Novan

Candidate: Topical oral or nasal treatment for COVID-19

Type: Nitric oxide treatment designed to target the reduction of viral shedding and transmission.

Status: Novan on March 23 said it will explore the use of its NITRICIL™ technology toward a COVID-19 treatment. NITRICIL is designed to facilitate use of nitric oxide by controlling its level of storage, rate of release, and molecule size for targeted delivery. Through NITRICIL, nitric oxide is stored on large polymers that allow the gas to be applied as timed-release chemical entities.

 

OyaGen

Candidate: OYA1

Type: Broad-spectrum antiviral showing activity in lab-based assays against SARS-CoV-2 and MERS-CoV, as well as dual target-specific antiviral activity against filoviruses such as Ebola. OYA1 won IND approval in the 1960s as a candidate to treat cancer, but showed a lack of efficacy.

Status: OyaGen on March 11 announced it will further study OYA1 for COVID-19 following unpublished positive results from collaborative research with the National Institute of Allergy and Infectious Diseases’ (NIAID) Integrated Research Facility at Fort Detrick, MD. The research, OyaGen said, suggested strong dose-dependent antiviral activity of its lead compound OYA1 against live SARS-CoV-2, based on in cell culture infectivity studies, the company said, adding that it will conduct further studies.

“The company anticipates that inhibition of SARS-CoV-2 using OYA1 will serve as a stop-gap treatment until appropriate vaccines are developed,” OyaGen added.

 

Pharmstandard

Candidate: Arbidol (umifenovir)

Type: Membrane fusion inhibitor developed as a treatment for influenza

Status: Pharmstandard is assessing Arbidol in clinical trials as monotherapy and in combinations that include AbbVie’s Kaletra (See above), Ascletis Pharma’s ASC09 (See above), lopinavir, ritonavir, carrimycin, and Bromhexine Hydrochloride (enrolling by invitation). A 240-patient study compared Arbidol to favipiravir, and concluded that “favipiravir can be considered as a preferred treatment approach to ordinary COVID-19 pneumonia,” according to a preprint posted March 27 on medRxiv: “Favipiravir has higher 7 day’s clinical recovery rate (71.43%) than arbidol (55.86%), and the time of cough relief and fever reduction of fabiravir was significantly shorter than that of arbidol.”

A 44-patient trial (NCT04252885) also generated disappointing results, researchers reported in a preprint posted March 23 on medRxiv. They found that both Arbidol and Kaletra “seems little benefit for improving the clinical outcome of mild/moderate COVID-19,” that Kaletra might lead to more adverse events—and that further verification was needed because of the small sample size.

Those trials were two of six that included Arbidol to be listed on ClinicalTrials.gov. China’s Ruijin Hospital is conducting the monotherapy trial (NCT04260594), while Jiangsu Famous Medical Technology Co. is including Arbidol among Western medicine options in a trial comparing it to traditional Chinese medicine in treating COVID-19 (NCT04306497) and various Chinese hospitals are investigating the other combination therapies (NCT04273763, NCT04261907, NCT04286503)

 

PrimeCell

Candidate: Remescor®

Type: Advanced Therapy Medicinal Product (ATMP) for human use, based on umenchenal cord-derived mesenchymal stromal cells (hUCT MSCs – Human Umbilical Cord Tissue Mesenchymal Stromal Cells)

Status: PrimeCell said March 27 that it finished research and submitted pharmaceutical documentation to the Czech national regulator of the pharma market, the State institute for drug control or SUKL, seeking to authorize compassionate use of Remescor.

Remescor was developed as part of a joint project by PrimeCell in the labs of the National Center of Tissues and Cells (NATIC) with St. George’s University Hospital, and St. Anne’s University Hospital Brno, International Clinical Research Center (FNUSA-ICRC)

 

Q Biomed and Mannin Research

Candidate: MAN-01

Type: Potential first-in-class drug for Intraocular Eye Pressure in Primary Open Angle Glaucoma, is also being developed as an adjunct treatment for vascular leakage and endothelial dysfunction seen in COVID-19 and other infectious diseases, based on the lead platform of research partner Mannin Research, which is designed to target the activation of the Angiopoietin-Tie2 signaling pathway.

Status: In its Form 10-K annual report filed February 28, Q Biomed said MAN-01’s mechanism of action may ameliorate vessel damage in diseases that include “infectious diseases, such as influenza and the current coronavirus outbreak.” Q Biomed and Mannin Research announced their collaboration on February 4.

In September 2019, the German state of Saxony awarded Mannin approximately a US $7.7 million grant to advance its novel therapeutics, including drugs and biologics that reduce endothelial dysfunction and loss of endothelial barrier integrity. Mannin recently submitted a funding application to the NIH’s Small Business Technology Transfer Grant to investigate specific applications of Mannin’s therapeutic platform.

 

Shanghai Hengrui Pharmaceutical

Candidate: Combination of anti-PD-1 antibody and thymosin

Type: Humanized monoclonal antibody targeting PD-1; 5-Da polypeptide hormone secreted by the thymus gland (thymosin)

Status: Chinese clinical trials assessing the combination treatment have been registered by Wuhan Jinyintan Hospital (Wuhan Infectious Diseases Hospital), which identified the anti-PD-1 antibody it is assessing as camrelizumab (120 patients; ChiCTR2000029806); West China Hospital, Sichuan University (ChiCTR2000030028); and Southeast University (120 patients; NCT04268537).

 

Sinovac Biotech

Candidate: Vaccine targeting SARS-CoV-2

Type: Formaldehyde inactivated vaccine with alum adjuvant

Status: Sinovac’s website discloses that the company is developing a vaccine against SARS-CoV-2, but offers little additional information beyond that offered by the World Health Organization. The vaccine type is similar to a Phase I vaccine candidate developed by Sinovac against SARS in the early 2000s, VP Meng Weining told Science.

 

Soligenix and University of Hawaiʻi (UH) at Mānoa

Candidate: Vaccine to prevent COVID-19

Type: Vaccine based on heat stable subunit filovirus platform, with enhanced stability at elevated temperatures.

Status: Soligenix said March 23 its ongoing collaboration with UH Mānoa was expanding to include vaccines against COVID-19. The partners will use a vaccine platform that includes a viral surface glycoprotein designed to mediate entry and fusion of the virus with host cells and is manufactured with a proprietary insect cell expression system coupled with protein-specific affinity purification. The protein antigen is one of three essential components of the platform; the other two are an adjuvant shown to enhance both cell mediated and humoral immunity, and a formulation which enables thermostabilization of the resulting mixture, avoiding the need for cold chain storage and shipping.

Soligenix’s Public Health Solutions business segment is partnering with Axel Lehrer, PhD, of the Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine (JABSOM).

 

Sorrento Therapeutics and Mabpharm

Candidate: STI-4920 (CMAB020) to treat COVID-19

Type: ACE-MABTM bi-specific fusion protein designed to bind to the spike protein of coronaviruses—including SARS-CoV-2 and SARS-CoV—which is expected to block SARS-CoV-2 from binding and infecting respiratory epithelial cells or ACE2-expressing cells to interrupt the viral life cycle.

Status: Sorrento said March 24 it will partner with Mabpharm to develop STI-4920, through a collaboration whose value was not disclosed. ACE-MABs have two functional arms: A fully human antibody that targets the spike protein of SARS-CoV-2 with high affinity, and a truncated ACE2 protein that binds to a different epitope of the spike protein. The fusion protein could also block the receptor binding domain with CD147 to mitigate lung inflammation and cytokine storm, according to Sorrento.

Sorrento has agreed to develop and commercialize ACE-MAB in North America and Europe, while Mabpharm retains rights in the rest of the world, including China and Japan. Sorrento has entered into a research testing agreement with The University of Texas Medical Branch at Galveston for preclinical testing of the company’s COVID-19 therapeutic product candidates.

 

Sorrento Therapeutics and SmartPharm Therapeutics

Candidate: Vaccine to protect against SARS-CoV-2 infection

Type: Next-generation, gene-encoded antibody vaccine

Status: Sorrento and SmartPharm said March 23 they will partner to develop a vaccine against COVID-19 by using monoclonal antibodies against SARS-CoV-2 discovered and/or generated by Sorrento that will be encoded into a gene for delivery using SmartPharm’s non-viral nanoparticle platform.

Plans for the collaboration may include candidate development as well as filing of an IND application in the next few months, the companies added. Sorrento has entered into a research testing agreement with The University of Texas Medical Branch at Galveston for preclinical testing of the company’s COVID-19 therapeutic product candidates.

 

Stermirna Therapeutics and Shanghai East Hospital of Tongji University

Candidate: Vaccine targeting COVID-19

Type: mRNA vaccine targeting SARS-CoV-2

Status: Chinese news website Yicai.com reported February 10 that the mRNA vaccine being developed by Stermirna Therapeutics and Shanghai East Hospital of Tongji University had begun testing on animals, following approval on an urgent basis in January. Li Hangwen, CEO of Stermirna Therapeutics, told Xinhua in January that no more than 40 days will be needed to manufacture a vaccine sample.

 

Symvivo

Candidate: bacTRL-Spike

Type: Bifidobacteria monovalent SARS-CoV-2 DNA oral vaccine for prevention of COVID-19

Status: Symvivo disclosed April 6 on ClinicalTrials.gov that it was recruiting up to 84 participants for an observer-blinded Phase I trial (NCT04334980) evaluating the safety, tolerability, and immunogenicity of bacTRL-Spike in healthy adults.

The vaccine is produced using Symvivo’s platform, in which orally administered, genetically modified probiotic bacteria colonize the gut, bind directly to intestinal epithelial cells and constitutively replicate, secrete and deliver plasmid DNA molecules encoding antigenic transgenes and neutralizing nanobodies.

 

Tiziana Life Sciences

Candidate: TZLS-501

Type: Fully-human anti-interleukin-6 receptor (anti-IL6R) monoclonal antibody (mAb) for treatment of patients infected with SARS-CoV-2, delivered directly into the lungs using a handheld inhaler or nebulizer.

Status: Tiziana said Aprl 9 it has submitted a provisional patent application for the delivery technology. The application covers treatment with the monoclonal antibody, as well as prophylactic intervention with a vaccine candidate, designed from Spike (S) protein of COVID-19. Tiziana acquired TZLS-501, formerly called NI-1201, from Novimmune in 2017 for undisclosed upfront, milestone, and future royalty payments: “We view NI-1201 as a potential game-changer for addressing the high unmet need of autoimmune and inflammatory diseases,” Tiziana Executive Chairman Gabriele Cerrone stated at the time.

 

Tianjin Sinobloway Biology

Candidate: IFN-alpha2b

Type: A form of interferon alpha that has been used to treat some patients with AIDS-related Kaposi sarcoma, hairy cell leukemia, and melanoma that has been removed by surgery, and some infections caused by viruses, such as hepatitis C virus.

Status: A team of Chinese, Cnadian, and Australian researchers on April 10 published a preprint study in medRxiv showing that among 77 COVID-19 patients admitted to Union Hospital, Tongii Medical College in Wuhan, China, treatment with IFN-alpha2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP. “These findings suggest that IFN-α2b should be further investigated as a therapy in COVID-19 cases,” the researchers concluded.

 

Tonix Pharmaceuticals Holding and Southern Research Institute

Candidate: TNX-1800 (live recombinant horsepox virus [rHPXV/SARS-CoV2-S3] vaccine from cell culture)

Type: Live modified horsepox virus vaccine for percutaneous administration to protect against COVID-19

Status: Tonix said March 24 that it will partner with Southern Research to develop and test TNX-1800, which is designed to express the Spike protein from the SARS-CoV-2 virus. Tonix plans to test whether vaccination of animals with TNX-1800 will elicit an immune response to the SARS-CoV-2 Spike protein and if so, whether such an immune response will protect animals against COVID-19-like disease. The company expects preliminary animal data in the third quarter of 2020, “but the COVID-19 pandemic may lead to a delay in this timeline,” Tonix acknowledged.

 

Tulane University

Candidates: Treatments, vaccines, and nanotechnology-based diagnostics

Types: To be determined

Status: The Tulane National Primate Research Center (TNPRC) said March 25 it was working on COVID-19 drugs, vaccines, and nanotechnology-based diagnostics, after becoming one of the first research facilities in the country to obtain approval from the U.S. Centers for Disease Control and Prevention (CDC) to receive live samples of COVID-19. TNPRC researchers are creating a nonhuman primate model to study COVID-19’s clinical progression, how it is transmitted through the air and how it specifically affects aging populations.

TNPRC Director Jay Rappaport, PhD, will lead researchers—who include Tony Hu, PhD, Weatherhead Presidential Chair in Biotechnology Innovation is working to develop a rapid test for COVID-19 using highly sensitive blood or saliva tests. Tulane announced the launch of its COVID-19 research program in February.

 

Union Therapeutics

Candidate: Niclosamide

Type: Novel “optimized salt” formulation of antihelminthic drug approved as a treatment for parasitic infections

Status: Union Therapeutics said April 12 it launched a program in partnership with Institut Pasteur Korea to test niclosamide, asserting that the drug showed potency more than 25 times higher than chloroquine and more than 40 times higher than Gilead Sciences’ remdesivir. A development program for niclosamide in COVID-19 being prepared for submission to Danish medical authorities, Union said. The drug is now the subject of a Phase IIb study in atopic dermatitis patients.

 

Vanda Pharma and University of Illinois at Chicago (UIC)

Candidate: Small molecules with the potential to treat COVID-19

Type: Small molecules that may prevent cathepsin-L cleavage of SARS-CoV-2 (COVID-19) glycoproteins that are required for viral processing in the host cell.

Status: Vanda on April 8 said it has launched a research partnership with UIC focused on the investigation of small molecules with the potential to treat COVID-19. In addition to studying cathepsin-L enzyme inhibition, Vanda said, the partners will also explore drugs that may block SARS-CoV-2 virus entry at the angiotensin converting enzyme 2 receptor, and the transmembrane protease serine 2 precursor.

The partners plan to launch in New York a clinical trial called ODYSSEY, a study of tradipitant in hospitalized patients with severe COVID-19 pneumonia that was announced on April 2.

 

Vaxil

Candidate: Vaccine to protect against COVID-19

Type: Vaccine based on signal peptide technology identified by Vaxil’s proprietary VaxHit™ bioinformatics platform, as well as in vivo experiments testing a tuberculosis signal peptide vaccine.

Status: Vaxil on March 10 said it submitted a new patent application for its anti-infective vaccines platform following the discovery of its COVID-19 vaccine candidate discovery. The application (U.S 62/987,310) covers claims for a coronavirus vaccine that is intended to provide broad patent protection for novel vaccines, pharmaceutical compositions and methods of treating and preventing an infectious disease as well as methods for producing a peptide vaccine against coronaviruses, Vaxil said.

Vaxil disclosed its COVID-19 vaccine candidate in February, saying that it planned to initiate non-GMP manufacturing followed by testing as the company explores partnerships and other possibilities.

 

Windtree Therapeutics

Candidate: KL4

Type: Proprietary synthetic, peptide-containing surfactant similar to human surfactant, approved by the FDA in a previous liquid dose formulation for respiratory distress syndrome in premature infants.

Status: Windtree said March 24 it will pursue the clinical study of its KL4 surfactant to potentially mitigate the pulmonary effects of severe COVID-19 infection. The company said it is actively pursuing several non-dilutive opportunities to fund this project, including government agencies and private foundations.

 

WPD Pharmaceuticals and CNS Pharma

Candidate: WP1122

Type: Prodrug of 2-deoxy-D-glucose (2-DG) whereby chemical elements are added to 2-DG to improve its delivery in vivo, then removed by normal metabolic processes.

Status: WPD on April 9 said independent research on WP1122 found 2-DG to reduce replication of SARS-CoV-2 by 100% in in vitro testing. WPD and CNS intend to move into clinical trials of WP1122 and other preclinical drugs on SARS-CoV-2 and other viruses. WPD has licensed a portfolio of drug candidates from Moleculin Biotech.

 

Zydus Cadila

Candidates: Vaccines targeting SARS-CoV-2

Types: Two approaches in development. In one approach, plasmid DNA is introduced into the host cells for translation into the viral protein, designed to elicit a strong immune response mediated by the cellular and humoral arms of the human immune system.

The other approach is a live attenuated recombinant measles virus vectored vaccine: The recombinant measles virus (rMV) produced by reverse genetics is expressed codon-optimized proteins of COVID-19 and induces long-term specific neutralizing antibodies, designed to provide protection from the infection.

Status: Zydus Cadila said February 15 it launched an accelerated research program. The company’s Vaccine Technology Centre in India is working on the plasmid DNA vaccine, while the company’s research arm in Europe, Etna Biotech is working on measles reverse genetics technology that had been successfully used in developing a SARS vaccine.

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