On March 27, 2024 Iambic Therapeutics, a biotechnology company developing novel therapeutics using its unique AI-driven discovery platform, reported that the first patient has been dosed in its Phase 1 clinical study evaluating IAM1363, a selective and brain-penetrant inhibitor of HER2 signaling for the treatment of HER2-driven cancers (Press release, Iambic Therapeutics, MAR 27, 2024, View Source [SID1234641521]).
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"Using Iambic’s AI platform, we have been able to rapidly discover and advance a candidate that is highly selective for inhibiting HER2 compared to effects on EGFR and other tyrosine kinase receptors that contribute to toxicity in patients. Along with its demonstrated CNS penetrance and potential to inhibit both wild-type HER2 and common HER2 mutants, we believe IAM1363 can be a highly differentiated, best-in-class small molecule for the treatment of HER2-altered cancers," said Iambic’s Chief Medical Officer, Neil Josephson, M.D.
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 as monotherapy and in combination with trastuzumab in patients with advanced HER2 cancers.
IAM1363 is a selective and brain-penetrant small molecule inhibitor of wild-type and oncogenic mutant HER2 proteins, designed to expand the therapeutic index compared to available HER2 inhibitors and to avoid toxicities from off-target inhibition of EGFR, a related receptor tyrosine kinase. 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 antibody-drug conjugates. IAM1363 was identified using Iambic’s AI-driven discovery platform, which unifies physics-informed machine learning and experimental automation to identify therapeutic candidates with differentiated drug profiles.
"For the patients I see in clinic there remains a significant need to improve therapies for HER2-driven cancers. Even with recent advances in the field we still lack treatments that can provide long-term disease control in multiple tumor types and for disease that has metastasized to the brain. IAM1363 is a promising agent because of its potency and selectivity for HER2, and its ability to readily cross the blood brain barrier. Because of its selective targeting, I see great potential for it to be developed across the entire spectrum of HER2 altered cancers, both as a single agent and in combination with other standard of care therapies," said Dr. Alexander Spira at Virginia Cancer Specialists in Fairfax, Virginia and principal investigator on the Phase 1 study of IAM1363.