OncoC4 Doses First Patient in Phase 1 Trial of ONC-783, First-in-Class T-Cell Engager Targeting neoCD24
核心洞察
OncoC4 (搜索) announced first-patient dosing in the Phase 1 trial (NCT07408258) of ONC-783, the first-and-only clinical-stage T-cell engager targeting the cancer-specific glycoform of CD24 (搜索) (neoCD24 (搜索)).
ONC-783 uses a subcutaneous formulation designed to provide gradual systemic exposure, potentially mitigating cytokine release syndrome (CRS) risk compared with intravenous T-cell engagers.
The first patient was dosed at Columbia University Irving Medical Center, with treatment well tolerated and no severe adverse events, CRS, or ICANS observed to date.
OncoC4 (搜索) Inc., a late clinical-stage biopharmaceutical company based in Rockville, Maryland, announced dosing of the first patient in its Phase 1 clinical trial (NCT07408258) of ONC-783, an investigational T-cell engager developed on the company's proprietary neoCD24 (搜索) platform. The milestone follows clearance of the Investigational New Drug (IND) application and marks the first clinical evaluation of a T-cell engager targeting the cancer-specific glycoform of CD24 (搜索) (neoCD24).
"This milestone demonstrates OncoC4 (搜索)'s leading position in developing first-in-class cancer therapeutics," said Dr. Yang Liu, CEO and Chief Scientific Officer. "CD24 (搜索) is expressed in nearly 70% of human cancers, and abnormal glycosylation in malignant cells produces the neoCD24 (搜索) 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."
A First-in-Class Mechanism Targeting neoCD24
ONC-783 is the world's first and only clinical-stage T-cell engager targeting the cancer-specific glycoform of CD24 (搜索). The drug candidate is designed to address the limitations of existing immunotherapies by selectively targeting the tumor-specific epitope while redirecting T cells for potent anti-tumor activity. Preclinical studies have demonstrated broad anti-tumor activity for ONC-783 across multiple solid tumor and hematologic malignancies, including pancreatic cancer (搜索), lung cancer, breast cancer (搜索), colorectal cancer (搜索), ovarian cancer (搜索), glioblastoma, and mantle cell lymphoma, supporting the potential of ONC-783 as a treatment across multiple tumor types.
The neoCD24 (搜索) platform addresses a longstanding challenge in targeting CD24 (搜索). While CD24 is expressed in nearly 70% of human cancers, it is also expressed at significant levels in normal tissues, where it plays a key role in regular cell growth, tissue maintenance, and immune system function. OncoC4 (搜索) discovered that abnormal glycosylation in malignant cells produces the neoCD24 epitope, a tumor-specific antigen that is largely absent from normal tissues, enabling the development of cancer-specific therapeutics targeting CD24.
Subcutaneous Formulation Designed to Mitigate CRS Risk
A subcutaneous formulation was developed for ONC-783 to enable gradual systemic exposure and provide a potential safety advantage compared with intravenously administered T-cell engagers. This design is intended to potentially mitigate the risk of cytokine release syndrome (CRS), a known challenge associated with T-cell engager therapies.
Trial Design and Early Safety Observations
ONC-783 is being tested in ONC-783-001, a Phase 1 open-label, dose-escalation study in the United States to evaluate the safety, pharmacokinetics (PK), and efficacy of ONC-783 as a single agent in patients with advanced/metastatic solid tumors, focusing on colorectal cancer (搜索), ovarian cancer (搜索), pancreatic cancer (搜索), or breast cancer (搜索). OncoC4 (搜索) has engaged several clinical centers across the U.S. to recruit patients, including Columbia University Irving Medical Center and The University of Texas MD Anderson Cancer Center.
The first study patient was successfully dosed at Columbia University Irving Medical Center. The treatment was well tolerated, and no severe adverse events, cytokine release syndrome, or immune effector cell-associated neurotoxicity syndrome (ICANS) have been observed to date.
"We are extremely excited to partner with OncoC4 (搜索) to explore the potential of targeting neoCD24 (搜索) to bring clinical benefit for cancer patients with limited treatment options," added Dr. Aiwu Ruth He, Professor of Medicine and medical oncologist at Columbia University Irving Medical Center in New York City. "Advanced solid tumors (搜索) remain a significant challenge, and this innovative mechanism offers a promising new approach for patients who have progressed or intolerant to standard therapy."
Company Pipeline and Context
OncoC4 (搜索) is a privately held, late clinical-stage biopharmaceutical company engaged in the discovery and development of novel biologics for the treatment of cancer and immunological diseases. Its pipeline features assets with first-in-class and best-in-class potential, including AI-081, a fully owned bispecific antibody candidate targeting PD-1 (搜索) and VEGF (搜索); ONC-841, a first-in-class anti-SIGLEC-10 (搜索) antibody in a Phase 2 trial for oncology indications and a Phase 1 trial for neurodegenerative diseases; and gotistobart (BNT316/ONC-392), a tumor microenvironment-selective Treg depletion candidate targeting CTLA-4 (搜索) co-developed with BioNTech across multiple solid tumor indications, including an ongoing pivotal clinical trial in squamous non-small cell lung cancer.