On June 4, 2025 Iambic Therapeutics, a clinical-stage life science and technology company developing novel medicines using its AI-driven discovery and development platform, reported that it has completed dose escalation in IAM1363-01, its Phase 1/1b clinical trial evaluating IAM1363, a selective and brain-penetrant small molecule inhibitor of wild-type and oncogenic mutant HER2 (Press release, Iambic Therapeutics, JUN 4, 2025, View Source [SID1234653730]).
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With completion of dose escalation, Iambic is advancing two well-tolerated doses into the dose optimization phase of the study. Patients enrolling into dose optimization include those with HER2-altered cancers and brain metastases, any advanced cancer harboring a HER2 TKD (tyrosine kinase domain) mutation, and advanced HER2-amplified non-small cell lung cancer.
"We are very encouraged by the progress of the study and the pace at which we arrived at what we believe are potentially efficacious dose levels," said Neil Josephson, M.D, Iambic’s Chief Medical Officer. "IAM1363 provides us considerable flexibility to evaluate the treatment as a monotherapy and in combination with other targeted therapies as we look to address a broad range of HER2-altered cancers."
The Phase 1/1b trial, NCT06253871, is an open-label, multi-center, dose escalation and dose optimization study, designed to evaluate tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of IAM1363 in patients with advanced HER2 cancers. The study, which has multiple sites in the US, will expand to the EU, UK and APAC.
"Patients entering this study, particularly those with brain metastases, have few available treatment options," said Andrae Vandross, M.D., who leads the Phase 1 clinical trial group at NEXT Oncology in Austin, TX, a IAM1363 study site. "Our focus is on identifying important potential advances for these individuals and to look at novel approaches that may provide a therapeutic benefit."
In preclinical studies, IAM1363 has demonstrated over 1000-fold selectivity for HER2 compared to EGFR, a promising pharmacokinetic and safety profile, preferential tumor enrichment, and penetrance of the central nervous system. In HER2 tumor models, including intracranial tumor models, IAM1363 has demonstrated favorable efficacy and tolerability compared to benchmark tyrosine kinase inhibitors and HER2-targeted antibodies, and antibody-drug conjugates.
Iambic intends to present data from the study at the European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) in October 2025.
About Iambic’s AI-Driven Discovery Platform
The Iambic AI-driven platform was created to address the most challenging design problems in drug discovery, leveraging technology innovations such as Enchant (multimodal transformer model that predicts clinical and preclinical endpoints) and NeuralPLexer (best-in-class predictor of protein and protein-ligand structures). The integration of physics principles into the platform’s AI architectures improves data efficiency and allows molecular models to venture widely across the space of possible chemical structures. The platform enables identification of novel chemical modalities for engaging difficult-to-address biological targets, discovery of defined product profiles that optimize therapeutic window, and multiparameter optimization for highly differentiated development candidates. Through close integration of AI-generated molecular designs with automated chemical synthesis and experimental execution, Iambic completes design-make-test cycles on a weekly cadence.