Iambic Therapeutics Presents Promising Phase 1/1b Data on HER2 Inhibitor IAM1363 at 2025 ESMO Congress
lambic Therapeutics, a clinical-stage life science and technology company leveraging an AI-powered drug discovery and development platform, today announced encouraging early clinical data from its ongoing Phase 1/1b study of IAM1363. This novel HER2-targeting small molecule tyrosine kinase inhibitor (TKI) has demonstrated monotherapy activity in heavily pretreated patients with a range of HER2-altered cancers. The findings were presented at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin.
IAM1363 is a brain-penetrant, irreversible type II HER2 inhibitor designed for high selectivity and broad applicability across tumor types with HER2 amplification, overexpression, or mutation. The molecule is highly selective—showing over 5,000-fold selectivity for HER2 over EGFR—and has demonstrated pan-mutant activity, tumor enrichment, and favorable brain penetrance. These features make IAM1363 a differentiated candidate in a competitive therapeutic space where options are limited, especially for patients with central nervous system involvement or rare HER2 alterations.
Initial data from the trial suggest that IAM1363 is active in several difficult-to-treat cancers, including HER2-mutant non-small cell lung cancer (NSCLC), HER2-positive breast and gastric cancers, and indications for which no HER2-directed tyrosine kinase inhibitors or antibodies are approved—such as HER2-mutant renal cell carcinoma and HER2-amplified NSCLC and ovarian cancer.
Among patients with HER2-targetable alterations treated at doses of ≥960 mg once daily, best overall response (BOR) data were assessed using RECIST 1.1 and RANO-BM criteria. Partial responses were observed in 28% (N=18) of patients with measurable systemic disease. In patients with measurable brain metastases, 33% (N=3) achieved partial responses. These results underscore IAM1363’s potential for treating both systemic and intracranial disease in HER2-driven tumors.
“This is one of the first compelling demonstrations of clinical activity and safety from a next-generation drug candidate developed by a TechBio company,” said Tom Miller, PhD, Co-Founder and CEO of Iambic Therapeutics. “IAM1363’s performance reinforces its promise as a potential best-in-class HER2 inhibitor and validates the predictive power of our AI-driven platform. We’re proud of how rapidly we’ve moved from discovery to clinical impact—delivering a molecule into trials in just two years and presenting proof-of-concept data within a year of first-in-human dosing.”
The IAM1363 program is a direct outcome of Iambic’s proprietary AI platform, which integrates advanced machine learning models with structure-based drug design to accelerate discovery and development timelines. The platform’s success in optimizing IAM1363 demonstrates its potential to transform early-stage drug discovery, particularly for complex targets requiring selectivity, brain penetration, and activity across mutational landscapes.
“We are encouraged by IAM1363’s emerging safety and pharmacokinetic profile and, more importantly, by the tumor shrinkage observed in patients who had exhausted standard-of-care options,” said Neil Josephson, MD, Chief Medical Officer of Iambic. “These early results support further evaluation of IAM1363 as a monotherapy, and we’re actively planning combination studies as part of our next phase of development.”
The ongoing Phase 1/1b study (NCT06253871) is an open-label, multi-center trial designed to evaluate IAM1363’s safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy in patients with advanced or metastatic HER2-altered cancers. The dose escalation and dose optimization components are currently enrolling across multiple U.S. sites, and the study recently expanded into Europe. Iambic plans to further broaden enrollment to additional sites in the U.S., EU, UK, and Asia-Pacific (APAC) regions during the fourth quarter of 2025.
With a strong scientific rationale, rapid clinical progress, and early signs of durable response in hard-to-treat populations, IAM1363 is well positioned to become a foundational treatment for HER2-driven cancers. The results presented at ESMO 2025 also affirm the broader capabilities of Iambic’s AI platform to generate clinically meaningful compounds faster and with greater precision than traditional methods.
