Domain Therapeutics, a biopharmaceutical company in France and Canada developing cancer immunotherapies targeting G protein-coupled receptors (GPCRs), has closed a €39M ($42M) Series A financing round to move its lead candidate to clinical trials.

The approval of the first immune checkpoint inhibitor treatments in 2014 proved a gamechanger for cancer immunotherapy as they prevented tumors from hijacking and escaping the immune system. The hunt is now on for new classes of checkpoint inhibitors and one emerging target is proteins on the cell surface called GPCRs, some of which help tumors to block the attacks of immune cells. 

Domain Therapeutics’ €39M funding round this week, co-led by Panacea Venture, CTI Life Sciences, and 3B Future Health Fund, is a step forward for the French-Canadian startup as it seeks to prevent tumors from evading the immune system. The firm’s strategy is to find drugs that can block GPCRs involved in the process such as EP4R and CCR8. 

The company will use the financing to launch the clinical development of its lead EP4R antagonist; advance two additional GPCR programs, including an anti-CCR8 antibody, through preclinical testing; and progress its discovery-stage pipeline of assets targeting GPCRs.

The round comes decades after Domain Therapeutics was founded in 2001. Over the years, Domain has worked in multiple collaborations to co-develop GPCR blockers with big pharma companies including Pfizer, Boehringer Ingelheim, and Merck KGaA.

After having delivered a first GPCR drug candidate for immuno-oncology together with Merck KGaA, Domain is now committed to advance its own treatments reviving the immune system to defeat cancer,” said Pascal Neuville, CEO of Domain Therapeutics, in a public statement

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Immune checkpoints are proteins on the surface of immune T cells that normally prevent an immune response from being so strong it destroys healthy cells in the body. Cancer cells can exploit these proteins by sending an ‘off’ signal to the T cells, which can prevent the immune system from destroying the cancer. Immune checkpoint inhibitors prevent the ‘off’ signal from being sent, allowing T cells to kill cancer cells.

According to a spokesperson from Domain, the company’s small molecule cancer immunotherapies are designed to be delivered orally to make it easier to give to patients. “Nevertheless, for our antibody-based programs, such drugs have to be administered in intravenous route as any other therapeutic antibodies,” the spokesperson added.

GPCRs are often difficult drug targets to study because they are large, complex, and unstable proteins to set up and test in the lab. Domain uses arrays of biosensors called bioluminescent resonance energy transfer sensors to measure the behavior of GPCRs more stably and with more detail than traditional methods. Additionally, the firm is researching biomarkers, genetic mutations, and other clinical data that could identify patients most likely to benefit from its immunotherapies.

Domain and Merck’s first GPCR blocker entered clinical testing earlier this year, and the firm’s first wholly-owned candidate is expected to enter phase I by the end of 2022. Domain’s other wholly-owned programs could follow in the next two to three years. 

“It’s an important milestone for us since Domain is turning into a clinical-stage company. We anticipate first commercialization after five years depending on regulatory fast track process,” said Domain’s spokesperson. 

Domain is one of a large group of firms developing better ways to test drugs on GPCRs in the lab. The UK firm OMass Therapeutics raised a €90M Series B round last month to finance drug discovery technology based on native mass spectrometry that can take the fight to so-called ‘undruggable’ proteins, including some GPCRs. Another example is Confo Therapeutics in Belgium, which is working with Regeneron to develop drugs against GPCR targets.

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Cover image via Shutterstock

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