OncoC4 Doses First Patient in Phase 1 Trial of ONC-783, First Clinical-Stage T-Cell Engager Targeting Cancer-Specific CD24 Glycoform

OncoC4 announced dosing of the first patient in a phase 1 clinical trial (NCT07408258, ONC-783-001) of ONC-783, the company's investigational T-cell engager built on its proprietary neoCD24 platform, following clearance of the drug's Investigational New Drug application.¹ The first patient was dosed at Columbia University Irving Medical Center.¹ OncoC4 describes ONC-783 as the world's first and only clinical-stage T-cell engager targeting neoCD24, a cancer-specific glycoform of CD24.¹

How does ONC-783 work, and why does the CD24 glycoform matter?

CD24 is expressed in nearly 70% of human cancers, but it is also expressed at meaningful levels in normal tissue, where it supports cell growth, tissue maintenance, and immune function, a dual expression pattern that has historically made CD24 difficult to target safely.¹ OncoC4 has said abnormal glycosylation in malignant cells produces neoCD24, a distinct epitope that is largely absent from normal tissue, allowing ONC-783 to selectively engage tumor cells while minimizing the on-target, off-tumor toxicity that has limited other T-cell engagers.¹ This tumor-restricted-glycoform strategy mirrors an approach other companies have taken to make historically difficult targets more tractable, developing antibodies or engagers that selectively bind a cancer-specific version of a protein rather than the protein itself.³ ONC-783 is administered subcutaneously, a formulation OncoC4 said was developed specifically to provide gradual systemic exposure and a potential safety advantage over intravenously administered T-cell engagers.¹

What did early clinical and preclinical data show?

Preclinical studies demonstrated anti-tumor activity for ONC-783 across a broad range of solid tumor and hematologic malignancies, including pancreatic, lung, breast, colorectal, and ovarian cancer, glioblastoma, and mantle cell lymphoma.¹ In the first dosed patient, treatment was well tolerated, with no severe adverse events, cytokine release syndrome, or immune effector cell-associated neurotoxicity syndrome observed to date.¹ The phase 1 study is an open-label, dose-escalation trial evaluating safety, pharmacokinetics, and efficacy of ONC-783 as a single agent in patients with advanced or metastatic solid tumors, with a particular focus on colorectal, ovarian, pancreatic, and breast cancer, enrolling across multiple US sites including Columbia University Irving Medical Center and the University of Texas MD Anderson Cancer Center.¹

What did company and investigator leadership say?

Dr. Yang Liu, chief executive officer and chief scientific officer of OncoC4, said in a press release, "This milestone demonstrates OncoC4's leading position in developing first-in-class cancer therapeutics. 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."¹ Dr. Aiwu Ruth He, professor of medicine and medical oncologist at Columbia University Irving Medical Center, said, "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."¹

What else is in OncoC4's pipeline?

ONC-783 joins a broader OncoC4 pipeline of first-in-class and best-in-class oncology and immunology candidates, including AI-081, a bispecific antibody targeting PD-1 and VEGF, and ONC-841, a first-in-class anti-SIGLEC-10 antibody currently in a phase 2 oncology trial and a separate phase 1 trial for neurodegenerative disease.¹ OncoC4 also has a strategic collaboration with BioNTech to co-develop gotistobart (BNT316/ONC-392), a tumor microenvironment-selective Treg depletion candidate targeting CTLA-4, currently in a pivotal trial for squamous non-small cell lung cancer.¹

References

1. OncoC4 announces first patient dosing in Phase 1 clinical trial of ONC-783 for the treatment of advanced solid tumors. News release. OncoC4 Inc; August 17, 2026. Accessed August 17, 2026.
2. Panagiotou E, Syrigos NK, Charpidou A, Kotteas E, Vathiotis IA. CD24: a novel target for cancer immunotherapy. J Pers Med. 2022;12(8):1235. doi:10.3390/jpm12081235
3. Brassard J, Hughes MR, Dean P, et al. A tumor-restricted glycoform of podocalyxin is a highly selective marker of immunologically cold high-grade serous ovarian carcinoma. Front Oncol. 2023;13:1286754. doi:10.3389/fonc.2023.1286754