Immunotherapy is proving a massive draw for investors and big pharma companies alike. These privately-owned immuno-oncology startups have bagged hefty funding rounds in the last two years.
For decades, the mainstays of cancer treatment have been chemotherapy, radiotherapy, and surgery. In the last decade, however, a new option has emerged: cancer immunotherapy, which boosts the immune system’s fight against cancer cells.
One of the best-known forms of immunotherapy is immune checkpoint inhibitors, the first of which, Yervoy, was approved by the U.S. Food and Drug Administration (FDA) in 2011 for the treatment of melanoma. These antibody drugs are designed to block immune checkpoints, proteins on the surface of immune cells that bind to a target cell and send an “off” signal to the immune cell. Blocking these immune checkpoints prevents cancer cells from hijacking the proteins and evading immune attack.
Another form of immunotherapy that is attracting huge interest is CAR-T cell therapy. This involves extracting a patient’s T cells, genetically engineering them to hunt cancer cells more effectively, and reinfusing them into the patient. The first CAR-T therapy, named Kymriah, was approved by the U.S. FDA in 2017 for the treatment of a form of blood cancer.
Despite their potential to produce long lasting benefits, cancer immunotherapies have limitations. One is that not all patients respond to cancer immunotherapy; this is sometimes due to tumors creating a complex “microenvironment” that suppresses the immune system. And CAR-T therapy has several other drawbacks: it is expensive, limited to blood cancer, and can take a long time to produce from cancer patients’ own cells.
There are many biotech startups aiming to overcome these challenges in cancer immunotherapy, and many have attracted large venture capital funding rounds in the last few years. Check below for our list of six private immuno-oncology startups around the world that have raised the biggest funding rounds in the last two years.
1. Bicara Therapeutics
Founded: 2020 | Headquarters: Cambridge, Massachusetts, U.S.
Bicara Therapeutics was spun out from compatriot company Biocon, which was founded by the Indian billionaire Kiran Mazumdar-Shaw.The startup raised $108 million in a Series B financing round in March 2023, co-led by Red Tree Venture Capital and RA Capital Management. Bicara is using the funding to fuel the development of its lead program and the rest of its pipeline aimed at treating solid tumors.
Bicara’s lead candidate is a dual-action bifunctional antibody that blocks the protein epidermal growth factor receptor (EGFR), an established target linked to many types of tumors. The candidate also traps transforming growth factor beta (TGF-β), which boosts tumor growth in the presence of EGFR and is linked to immune suppression in the tumor microenvironment. Blocking the two together is intended to hit the tumor harder than blocking EGFR alone and can also lower the risk of side effects.
According to interim data from a Phase I/Ib trial released in June 2023, Bicara’s lead candidate in combination with the checkpoint inhibitor Keytruda achieved a 65% overall response rate (ORR) in late-stage human papillomavirus (HPV)-negative head and neck squamous cell carcinoma. The company heralded this result as better than Keytruda alone.
Bicara also has an immunotherapy candidate in preclinical development and other undisclosed projects at the discovery stage.
2. Domain Therapeutics
Founded: 2001 | Headquarters: Strasbourg, France, and Montreal, Canada
Domain Therapeutics makes this list due to an impressive $42 million Series A round that it raised in May 2022, co-led by Panacea Venture, CTI Life Sciences, and 3B Future
The company is developing cancer drugs that target a type of cell surface proteins called G protein-coupled receptors (GPCRs). According to the company, some GPCRs play a major role in helping tumors to suppress the immune system and resist immune checkpoint inhibitor treatments.
One of Domain’s lead programs is in Phase I development and is designed to block receptors of adenosine, a chemical signal that some tumors release into the microenvironment to help them to escape the immune response. By blocking these receptors, specifically A2aR and A2bR, Domain is crafting therapies that can be combined with existing immunotherapies to benefit cancer patients who do not respond to current approaches.
Domain has been developing its lead program in tandem with Merck KGaA since 2017 and is eligible for more than €240 million in milestones and undisclosed royalties.
Domain is using its Series A winnings to advance the clinical development of another Phase I-stage program, this time blocking a protein called prostaglandin receptor 4. Additionally, the company is advancing two GPCR programs toward clinical testing, and researching other discovery-stage programs targeting GPCRs and degeneration, with results similarly expected in late 2023.
3. Elpiscience Biopharmaceuticals
Founded: 2017 | Headquarters: Shanghai, China
Elpiscience Biopharmaceuticals focuses on developing the next generation of immune checkpoint inhibitors and other cancer immunotherapies and aims to take at least one program into clinical testing each year.
Elpiscience raised an impressive Series C round worth $105 million in May 2021, which was led by the Hong Kong-based private equity firm Greater Bay Area Homeland Development Fund. Elpiscience has been using the financing to expand its R&D around the world, including advancing programs into clinical trials in the U.S. and launching strategic partnerships.
Of five clinical-stage programs in Elpiscience’s pipeline, the most advanced is a bispecific antibody—an antibody that can block two different targets at the same time. In the case of Elpiscience’s candidate, one arm blocks a protein called Delta-like ligand 4/Notch (DLL4), and another blocks a protein called vascular endothelial growth factor A (VEGF-A). These targets are vital for tumors to create blood vessels to sustain themselves, and VEGF is also instrumental in creating an immunosuppressive tumor microenvironment.
Elpiscience licensed the greater China development rights for its lead candidate from Compass Therapeutics in 2021, and the drug is being tested in combination with chemotherapy in Phase I and Phase II trials.
Other programs in Elpiscience’s pipeline include drugs that block immunosuppression in the tumor microenvironment and boost exhausted T cells to keep fighting cancer cells.
4. Grey Wolf Therapeutics
Founded: 2017 | Headquarters: Abingdon, U.K.
Grey Wolf Therapeutics aims to address a key way that some tumors resist current immunotherapies: they can hide cell surface markers of cancer known as neoantigens so that T cells cannot detect them, even when boosted by immunotherapy.
The company is developing small molecules that block two proteins known as endoplasmic reticulum aminopeptidases (ERAP1 and ERAP2). These proteins influence what antigens cells make visible to the immune system. By blocking these targets, Grey Wolf aims to change which antigens tumor cells present to immune cells, making them more visible for attack.
Grey Wolf’s lead candidate drug blocks ERAP1 and entered a Phase I trial in Australia in March 2023. The company has another ERAP1 program in preclinical development in addition to an ERAP2 program and more at the discovery stage.
To finance the clinical and preclinical development of its pipeline, Grey Wolf raised $49 million in an oversubscribed Series B round in January 2023. The round was led by Pfizer’s venture capital arm and Earlybird Venture Capital.
5. OriCell Therapeutics
Founded: 2015 | Headquarters: Shanghai, China
OriCell Therapeutics is striving to become a world leader in the development of novel cancer immunotherapies. In August 2022, the biotech company bagged more than $120 million in Series B cash in a round led by Qiming Venture Partners and Quan Capital. In February 2023, OriCell topped up with a $45 million Series B1 round led by RTW Investments and Qatar Investment Authority.
OriCell is using the funding to build up manufacturing muscle for clinical and commercial production and propel its pipeline, particularly in the U.S.
OriCell’s pipeline consists of a mixture of antibody drugs and cell therapies, six of which are at the clinical stage. The company’s most advanced CAR-T therapies are designed to treat solid tumors and blood cancer via emerging targets such as GPC-3 and GPRC5D. The cell therapies are also designed to contain more T memory cells than current therapies. These memory T cells are also designed to expand and attack cancer cells more efficiently than current therapies, potentially overcoming immunotherapy resistance in the tumor microenvironment.
OriCell expects to go public in an initial public offering in around 2025 and to launch its first cell therapy into the market by around 2026.
6. Umoja Biopharma
Founded: 2019 | Headquarters: Seattle, Washington, U.S.
Umoja Biopharma launched with a hefty $53 million Series A round in November 2020 led by MPM Capital and Qiming Venture Partners USA. The biotech startup followed up in June 2021 with a spectacular Series B round worth $210 million, led by SoftBank Vision Fund 2 and Cormorant Asset Management.
To tackle difficulties in manufacturing CAR-T therapies for cancer patients, Umoja is developing a pipeline of off-the-shelf cell therapies such as CAR-T therapies, in addition to CAR-T therapies that can be genetically engineered in vivo rather than in the lab.
One of Umoja’s most advanced clinical programs involves delivering viral vectors into patients that stimulate them to generate their own CAR-T cells. These cells are genetically engineered to be activated and to expand in response to treatment with the approved drug rapamycin, which simultaneously slows tumor growth and stops the patient’s immune system from attacking the viral vectors and genetically engineered cells. The program is currently at a preclinical stage, and Umoja expects to develop it in tandem with a partner.
Umoja is also recruiting cancer patients into a Phase I trial of its so-called “TumorTag” technology. This consists of small molecules that bind to cancer cells and stromal cells that are recruited by cancer cells in the tumor microenvironment to help suppress the immune system. This bound drug flags the cells for attack by CAR-T cells more precisely and effectively than current approaches.
Jonathan Smith is a freelance science journalist based in the U.K. and Spain. He previously worked in Berlin as reporter and news editor at Labiotech, a website covering the biotech industry. Prior to this, he completed a PhD in behavioral neurobiology at the University of Leicester and freelanced for the U.K. organizations Research Media and Society of Experimental Biology. He has also written for medwireNews, Biopharma Reporter, and Outsourcing Pharma.
This article was originally published in the August 2023 issue of Inside Precision Medicine. For more content like this and details on how to get a free subscription, go to www.insideprecisionmedicine.com.
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