IAM1363 is an oral, highly selective, pan-mutant, and brain-penetrant small molecule inhibitor that selectively targets HER2 and HER2 mutants, while sparing EGFR. Amplification and mutations of HER2 drive a wide range of human cancers. HER2 TKIs have had limited success due to a compensatory mechanism that increases the required therapeutic index beyond that of available pan-ERBB and HER2 inhibitors.

IAM1363 exhibits greater than 1,000-fold in vivo selectivity against wild-type EGFR, favorable PK and safety profiles, preferential tumor enrichment, and effective CNS penetrance. Together these make IAM1363 a breakthrough molecule for realizing the full therapeutic potential of inhibiting HER2 signaling, while avoiding EGFR-driven toxicity. In vivo, IAM1363 has demonstrated favorable efficacy and tolerability across a range of HER2 tumor models, including intracranial models, outperforming benchmark TKIs and antibody-drug conjugates (ADCs).

KIF18A is a kinesin that helps regulate microtubule dynamics in the cell cycle metaphase. In healthy dividing cells there is little reliance on KIF18A, whereas chromosomally unstable tumor cells are critically dependent on it. Inhibition of this motor protein has potential for strong anti-proliferative effect across a wide range of solid tumors, while sparing healthy dividing cells.

IAM217 is a highly differentiated KIF18A inhibitor for triple-negative breast cancer, ovarian cancer, and other solid tumor indications. We have designed this allosteric inhibitor with a differentiated profile for excellent ADME and PK properties, a clean DDI profile, and brain-penetrance.

IAM-C1 is a small-molecule inhibitor with a highly differentiated selectivity profile, designed to specifically target CDK2 and CDK4, two cell-cycle kinases that are frequently dysregulated in various cancers. IAM-C1 has been designed to expand the therapeutic potential compared to clinically approved CDK4/6 inhibitors in HR+/HER2 breast cancer, the most common subtype.

CDK4/6 inhibitors are standard of care for HR+/HER2-metastatic breast cancer patients in the front- and later-line settings. Despite the success of these agents, many patients demonstrate either intrinsic or acquired resistance to the approved CDK4/6 inhibitors, leading to mortality, resulting in significant unmet medical need.