Davoceticept

BioNTech’s messenger RNA technology led to a successful Covid-19 vaccine that provides it with plenty of cash for pipeline expansion. The company is deploying some of that capital in a new partnership that gives it a share of OncoC4’s lead drug candidate, an antibody addressing a target that is seeing renewed R&D interest. Deal terms announced Monday call for the two companies to share in the development of the OncoC4 drug, ONC-392. The plan is to develop the antibody as a monotherapy or in combination with other immunotherapies in various solid tumors; a Phase 3 test in non-small cell lung cancer (NSCLC) is on track to begin this year. BioNTech will pay OncoC4 $200 million up front and get global rights to its drug. Privately held OncoC4 could earn milestone payments, plus royalties if the research leads to a commercialized product. Details about those payments were not disclosed. The target of OncoC4’s drug is CTLA-4, a protein found on immune cells that keeps immune responses in check. In cases of cancer, this protein has the effect of keeping T cells from recognizing and killing cancer cells. A class of drugs called checkpoint inhibitors block such proteins, freeing up the immune cells to fight cancer. Bristol Myers Squibb checkpoint inhibitor Yervoy was the first CTLA-4-blocking drug approved by the FDA, winning its initial regulatory nod in 2011 for treating advanced melanoma. This BMS antibody has since gone on to land additional approvals in other types of cancer. OncoC4 describes its lead drug as a next-generation anti-CTLA-4 antibody. The company says this drug was designed to target the immunosuppressive regulatory T cells found in the tumor microenvironment while sparing such immune cells found in healthy tissues. This approach is intended to lead to fewer immune-related adverse effects. Yervoy and other checkpoint inhibitors come with warnings that these drugs can cause immune-mediated adverse reactions, some of which can be fatal. In a Phase 1/2 clinical trial in patients with advanced solid tumors, ONC-392 showed encouraging clinical activity, both as a single agent and in combination with Keytruda, a Merck checkpoint inhibitor that addresses a different target on immune cells called PD-1. Data have been presented at the past two annual meetings of the Society for Immunotherapy of Cancer (SITC). BioNTech and OncoC4 say the data from the monotherapy study in NSCLC that is resistant to PD-1 inhibitors support advancing ONC-392 to a pivotal test in that type of lung cancer. This study, with a targeted enrollment of 600 patients, will compare the OncoC4 drug to docetaxel, a type of chemotherapy that’s a standard treatment for advanced NSCLC. A separate Phase 2 test is evaluating ONC-392 in combination with Keytruda in ovarian cancer that is resistant to platinum-based chemotherapy. “Because of its specific mechanism of action, we believe ONC-392 has the potential to broaden the reach of CTLA-4-targeting immunotherapy,” Yang Liu, OncoC4’s co-Founder, CEO and chief scientific officer said in a prepared statement. “We very much look forward to working hand-in-hand with BioNTech in developing ONC-392 for cancer indications with unmet medical needs.” The agreement calls for BioNTech and OncoC4 to share equally in clinical development costs. For studies that will test combinations outside of PD-1 inhibition, including combinations with drug candidates from BioNTech’s pipeline, the German company will handle clinical trials. The deal gives BioNTech exclusive worldwide commercialization rights for any successfully developed products. OncoC4 may participate in their commercialization in certain markets, but those details will be negotiated in the future. Yervoy stood alone as the only FDA-approved CTLA-4 inhibitor until relatively recently. Last October, AstraZeneca won approval for its drug, Imjudo, as a treatment for the most common type of liver cancer. That decision followed clinical trial failures in lung cancer and bladder cancer. Weeks after that approval, AstraZeneca landed an additional approval in advanced NSCLC. Both regulatory decisions cover the use of the antibody in combination with another AstraZeneca checkpoint inhibitor, Imfinzi. Some CTLA-4 efforts are still in the clinic. Xilio Therapeutics’ CTLA-4-blocking antibody, XTX101, is in early clinical development for solid tumors. Two Agenus antibodies, botensilimab and balstilimab, are being tested as monotherapies and in various combinations. Mid-stage tests are evaluating the drugs in colorectal cancer, melanoma, pancreatic cancer, and cervical cancer. Not all CTLA-4-targeting efforts have panned out. Last October, the death of a second patient led Alpine Immune Sciences to stop the Phase 1 clinical test of davoceticept, a fusion protein designed to block both CTLA-4 and PD-L1. Photo by Flickr user Marco Verch via a Creative Commons license