OncoC4, the Rockville, Maryland-based late clinical-stage biopharmaceutical company, has dosed the first patient in a Phase 1 trial of ONC-783, a T-cell engager the company describes as the first and only clinical-stage therapy targeting neoCD24, a cancer-specific version of a protein found across a large share of human tumors. The open-label, dose-escalation study, registered as NCT07408258, is enrolling patients with advanced or metastatic colorectal, ovarian, pancreatic, and breast cancers at two sites: Columbia University Irving Medical Center and the University of Texas MD Anderson Cancer Center.
Why Targeting CD24 Has Been Tricky Until Now
CD24 shows up in nearly 70% of human cancers, which makes it an attractive drug target on paper, but it’s also present on healthy tissue, which has historically limited how selectively a CD24-targeted drug can attack tumors without damaging normal cells elsewhere in the body. OncoC4 says it identified a workaround: malignant cells carry an abnormally glycosylated version of the protein, which the company calls neoCD24, that’s largely absent from normal tissue. CEO and Chief Scientific Officer Dr. Yang Liu framed the science behind ONC-783 around that distinction: “CD24 is expressed in nearly 70% of human cancers, and abnormal glycosylation in malignant cells produces the neoCD24 epitope that is largely absent from the normal tissues. By exploiting this cancer-specific epitope, ONC-783 is designed to maximize selectivity for tumor cells while minimizing the risk of on-target/off-tumor toxicity that has limited other T-cell engagers.” Early results reported in the release show no severe adverse events, cytokine release syndrome, or neurotoxicity so far, though that’s based on the trial’s earliest stage and a very small number of patients.
What the Trial Investigator Is Watching For
Dr. Aiwu Ruth He, Professor of Medicine and a medical oncologist at Columbia University Irving Medical Center, is an investigator on the study and described the appeal of the mechanism for a patient population that’s often run out of standard options: “We are extremely excited to partner with OncoC4 to explore the potential of targeting neoCD24 to bring clinical benefit for cancer patients with limited treatment options. Advanced solid tumors remain a significant challenge, and this innovative mechanism offers a promising new approach for patients who have progressed or intolerant to standard therapy.” The drug is formulated for subcutaneous administration, which, if it holds up through later trials, would be simpler for patients than the intravenous infusions many T-cell engagers require.
A Rockville Company Building Out a Broader Pipeline
ONC-783 isn’t OncoC4’s only asset moving through development. The company’s furthest-along program, gotistobart (also known as BNT316/ONC-392), is a next-generation anti-CTLA-4 antibody partnered with BioNTech under a March 2023 collaboration that brought OncoC4 $200 million upfront plus potential milestones and royalties. OncoC4 also expanded its pipeline and manufacturing footprint in 2024 by merging with AcroImmune, a related company under common leadership, adding assets including a PD-1/VEGF bispecific antibody and in-house clinical manufacturing capacity. That combination kept its headquarters in Rockville, keeping OncoC4’s growing oncology pipeline anchored in the BioHealth Capital Region even as the company’s clinical trial sites and partnerships extend well beyond it.
