Iambic Therapeutics has initiated the dosing of the first subject in its Phase I/Ib clinical trial of IAM1363, a novel therapeutic agent targeting human epidermal growth factor receptor 2 (HER2)-driven cancers.
A selective and brain-penetrant small molecule inhibitor, IAM1363, has been designed to expand the therapeutic index and minimise toxicities by avoiding off-target inhibition of epidermal growth factor receptor (EGFR).
The multicentre, open-label, dose escalation and dose optimisation trial aims to assess the tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of IAM1363.
In the trial, the therapy will be evaluated both as a single agent and along with trastuzumab in patients with advanced cancers exhibiting HER2 alterations.
The study is structured into three distinct parts: Part 1 is monotherapy dose-escalation, Part 2 is dose optimisation, and Part 3 is Simon 2-stage evaluation.
IAM1363 has shown over a thousand-fold selectivity for HER2 over EGFR in preclinical studies. This selectivity is accompanied by a promising pharmacokinetic and safety profile, preferential tumour enrichment, and the ability to penetrate the central nervous system.
When tested in HER2 tumour models, including intracranial tumour models, the product exhibited favourable efficacy and tolerability versus other tyrosine kinase inhibitors and HER2-targeted antibody-drug conjugates.
IAM1363 was developed using AI-driven discovery platform of the company. This platform combines physics-informed machine learning with experimental automation to detect therapeutic candidates possessing varied drug profiles.
Iambic Therapeutics chief medical officer Neil Josephson said: “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.”
