EpiBiologics has posted a Phase 1 clinical trial (NCT07462377) for EPI-326, a tissue-selective bispecific antibody targeting EGFR in patients with locally advanced or metastatic EGFR-mutant non-small cell lung cancer and head and neck squamous cell carcinoma. The company, based in San Mateo, California and backed by a $107 million Series B round co-led by GV and Johnson & Johnson Innovation, built EPI-326 on its proprietary EpiTAC platform, which originated from the laboratory of UCSF chemist Jim Wells. Rather than blocking EGFR kinase activity or ligand binding, EPI-326 is designed to co-opt a tumor-enriched cell-surface receptor to force internalization and lysosomal degradation of EGFR protein, a mechanism the company describes as extracellular targeted protein degradation. If validated clinically, this would make EPI-326 the first agent to enter human testing with a mutation-agnostic, tissue-selective EGFR degradation mechanism, a distinct modality from the tyrosine kinase inhibitors and conventional monoclonal antibodies that currently dominate the EGFR treatment landscape.
The open-label, multicenter, sequential dose-escalation study plans to enroll approximately 110 adults aged 18 and older with an ECOG performance status of 0 to 2. Patients must have pathologically confirmed NSCLC harboring any documented EGFR mutation, insertion, or deletion as determined by validated molecular testing such as next-generation sequencing, or pathologically confirmed HNSCC. Disease must be locally advanced or metastatic. Exclusion criteria include symptomatic brain metastases, uncontrolled illness, and secondary malignancy diagnosed within three years unless curatively treated. EPI-326 is administered as a single agent via intravenous infusion; the trial listing does not specify dose levels or dosing frequency for the escalation cohorts. Primary endpoints are incidence of adverse events, serious adverse events, and dose-limiting toxicities, along with determination of the maximum tolerated dose and maximum administered dose. Secondary endpoints include pharmacokinetic parameters (AUC, Cmax, Cmin, clearance, volume of distribution), objective response rate, and duration of response. The trial has a planned start date of Q2 2026, with primary completion estimated for Q3 2029. Sites include MD Anderson Cancer Center in Houston, Sarah Cannon Research Institute in Nashville, START centers in San Antonio and Los Angeles, and Astera Cancer Care in New Jersey. The study was registered under an FDA IND pathway. As of March 2026, the trial status is listed as not yet recruiting.
EPI-326's mechanism diverges from existing EGFR-directed therapies in two respects. First, by inducing degradation of the EGFR protein rather than inhibiting its enzymatic function, the molecule eliminates both kinase-dependent and kinase-independent survival signaling, a limitation of small-molecule TKIs such as osimertinib, erlotinib, and afatinib. Second, the bispecific format engages a second receptor that is enriched in tumor tissue, which in principle confines EGFR degradation to malignant cells and spares normal epithelia in skin and gut, the tissues responsible for the rash and diarrhea that constrain dosing of every approved EGFR-targeting agent. Preclinical validation of this selectivity has not been disclosed in peer-reviewed publications. The EpiTAC platform from which EPI-326 emerged traces to academic work on engineered bispecific constructs that co-opt surface receptors for targeted degradation. No licensing or acquisition agreements related to EPI-326 have been publicly disclosed; the molecule appears to be a product of internal development at EpiBiologics.