DR5 agonists are one of oncology’s longest-running disappointments.
The thesis is elegant. Death Receptor 5 sits on the surface of cancer cells, and if you activate it, the cell self-destructs via apoptosis. Pharma chased this hard in the 2000s and 2010s. Mapatumumab. Conatumumab. Tigatuzumab. Dulanermin.
All of them failed.
The antibodies couldn’t cluster DR5 receptors well enough to trigger real apoptosis, and the ones that hit harder caused liver damage because DR5 is expressed in healthy tissue too.
The field moved on. The target still works in biology. The problem was always selectivity.
Cambridge-based ImmuVia thinks they’ve cracked it with a two-step approach. Their lead asset, IMV-M, is a bispecific antibody built on their Cancerlysinâ„¢ platform. It targets DR5, same as the old drugs.
But IMV-M can’t activate DR5 on its own. First, it has to find and bind MUC16 on the tumor cell surface. Only after that initial handshake does it cluster DR5 and trigger cell death.
The tumor has to introduce itself before IMV-M pulls the trigger.
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That conditional mechanism is the whole thesis. Old DR5 drugs couldn’t tell a cancer cell from a hepatocyte. IMV-M is designed to confirm it’s sitting on a tumor before activating.
The first targets are ovarian cancer and pancreatic cancer. Both are known for high MUC16 expression, but ovarian is especially interesting. MUC16 is the protein behind CA-125, the biomarker clinicians have used to monitor ovarian cancer for decades.
ImmuVia is repurposing that same tumor biology as a targeting mechanism.
IMV-M is still preclinical.
No clinical data to evaluate yet.
The company recently partnered with Quantori to bring in AI-driven computational workflows for development, which signals urgency to get closer to an IND.
Worth tracking alongside: Inhibrx Biosciences is the other company still pursuing DR5. Their asset ozekibart is in late-stage colorectal cancer, with PFS data expected to mature soon. If that reads out well, the entire DR5 space gets a second look, and ImmuVia’s conditional approach becomes even more compelling.
DR5 works. The old drugs couldn’t aim.
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