Iambic files IND for IAM217, a brain-penetrant KIF18A inhibitor designed with AI

What Iambic is asking the FDA to clear

According to Iambic, the IND covers a Phase 1/2 clinical trial of IAM217 for triple-negative breast cancer, ovarian cancer and other solid tumors with chromosomal instability (CIN). The company describes IAM217 as a brain-penetrant, differentiated inhibitor of KIF18A.

In a preclinical brain metastasis model, IAM217 produced approximately 90% regression of established intracranial tumors, the company says. In nonclinical studies it was also observed to have potent and selective target engagement and a favorable drug-drug interaction profile. Subject to FDA clearance of the IND, IAM217 will become Iambic's second program to enter clinical trials.

Why KIF18A is the target

KIF18A is a mitotic motor protein, a kinesin, that governs chromosome alignment during cell division. Iambic says cancer cells with CIN, which it calls a hallmark of many of the most aggressive and treatment-refractory cancers, depend on KIF18A to complete cell division, while normal cells tolerate its inhibition. That, the company argues, creates a potential therapeutic window distinct from broadly cytotoxic antimitotic agents.

The company also points to emerging clinical evidence that potentially validates KIF18A as an important target for high-grade serous ovarian cancer, and to preclinical evidence for other malignancies, including triple-negative breast cancer.

How the molecule was designed

Iambic says it designed IAM217 without access to a high-resolution co-crystal structure of KIF18A bound to an inhibitor. Instead, its NeuralPLexer model supplied structural insights. The company states that the allosteric binding mode gives mechanistic selectivity over other kinesin family members and avoids the cytotoxic liabilities associated with tubulin-targeting mitotic agents.

Enchant and earlier Iambic property-prediction AI tools were then used for large-scale multi-parameter optimization. Starting from an initial set of 100 nM-class hits found in 24 high-throughput experimentation plates, AI-guided design improved potency to multiple 10 nM-class compounds. At the same time, the team worked on oral bioavailability, reduced CYP-mediated drug-drug interaction liabilities and engineered CNS penetrance. At the lead identification stage, brain penetrance was achieved within approximately six months, according to Iambic.

Pete Olson, PhD, Chief Scientific Officer, said: "This investigational medicine could not have been nominated without our AI-driven platform, allowing us to optimize for key properties and quickly move through IND-enabling studies."

The wider pipeline and what comes next

Iambic is also advancing IAM1363, a highly selective and brain-penetrant HER2 inhibitor, in an ongoing Phase 1/1b trial. It expects to submit an IND for IAM-C1, a CDK2/4 dual inhibitor, later in the fourth quarter of 2026 and, subject to FDA clearance, to begin a Phase 1/2 trial.

CEO Tom Miller, PhD, said the company believes it is "seeing meaningful productivity from our molecular superintelligence platform." For now, IAM217 remains an investigational candidate: the IND has been submitted but not cleared, and the efficacy data come from preclinical models. Iambic says it plans a broad development path across solid tumors with chromosomal instability, with a biomarker-informed strategy and a focus on patients with brain metastases.