EpiBiologics, a leader in tissue-selective extracellular protein degradation,  announced that the first patient has been dosed with EPI-326 in its global Phase 1 clinical study. EPI-326 is the company’s tissue-selective bispecific antibody that degrades all oncogenic mutant and wild type forms of EGFR for EGFR-driven cancers. The first-in-human study is evaluating EPI-326 in patients with advanced non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) with the potential to expand into colorectal cancer (CRC).

“Patients face persistent challenges with current EGFR-targeted therapies, including resistance and poor tolerability,” said Eric Humke, M.D., Ph.D., Chief Medical Officer of EpiBiologics. “EPI-326 was designed to address those limitations through a mutation-agnostic, tissue-selective approach to localize EGFR degradation to tumors while sparing healthy tissue. We believe EPI-326 can drive strong durable efficacy as a monotherapy and in combinations, and ultimately enable treatment in earlier settings.”

The Phase 1 study (NCT07462377) is designed to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of EPI-326 as a monotherapy in patients with advanced NSCLC and HNSCC. The study is currently enrolling patients at sites in the U.S. and is planned to initiate sites in the Asia-Pacific region, including South Korea.

AACR Highlights

New data presented today at the AACR New Drugs on the Horizon session highlight EPI-326’s activity across multiple tumor models, potential in combination settings, and encouraging tolerability profile:

• Broad anti-tumor activity: EPI-326 showed robust preclinical in vivo efficacy in both classical and drug-resistant (C797S) EGFR-mutant NSCLC models, as well as in wildtype HNSCC and CRC tumor models. In an EGFR-mutant NSCLC preclinical model, EPI-326 monotherapy drove a high complete response rate and demonstrated stronger activity than EGFR inhibitors.
• Combination potential: Preclinical studies combining EPI-326 with frontline standard-of-care therapies, including tyrosine kinase inhibitors (TKIs) and KRAS inhibitors for NSCLC and CRC cancers respectively, led to deeper and more durable anti-tumor responses.
• Favorable tolerability profile: EPI-326 was well tolerated in multidose non-human primate toxicology studies to a maximal feasible dose of 204 mg/kg, with no evidence of stereotypical EGFR-related toxicities. This safety window supports the company’s monotherapy strategy and provides a strong basis for evaluating EPI-326 in combination with standard-of-care therapies.

“What stands out in these data is the combination of robust anti-tumor activity with an excellent tolerability profile,” said Shyra Gardai, Ph.D., Chief Scientific Officer of EpiBiologics. “This is the central promise of tissue-selective degradation. We are now pursuing similar therapeutic approaches across multiple targets in oncology and immunology.”

Additional AACR presentations highlight EpiBiologics’ pipeline progress. New data from the company’s cMET degrader-ADC support advancement of this dual mechanism EpiTAC, which combines targeted degradation with a cytotoxic payload and may safely address high unmet needs, including tumors with low cMET expression. Together with new data from the company’s cKIT program, these presentations underscore the potential to generate tissue-selective EpiTACs against receptor tyrosine kinases implicated across multiple tumor types.

“Advancing EPI-326 into the clinic, alongside key data presented at AACR, gives us an early view into the broader opportunity for EpiTACs,” said Ann Lee-Karlon, Ph.D., Chief Executive Officer of EpiBiologics. “This milestone builds on the momentum of our recent Series B financing, and we are delighted to welcome Roche Venture Fund as a new investor in our syndicate. Our goal is to build highly differentiated bispecific antibodies to selectively degrade membrane and soluble targets for oncology and immunology where new approaches are needed the most.”