Nimbus Therapeutics, LLC ("Nimbus Therapeutics" or "Nimbus"), a biotechnology company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, today announced the completion of dose escalation (Part A) in its Phase 1/2 clinical trial of NDI-219216, the company's investigational non-covalent Werner syndrome helicase (WRN) inhibitor for the treatment of microsatellite instability-high (MSI-H) tumors.

Data thus far from the dose escalation portion of the trial demonstrated that NDI-219216 has a favorable safety profile, with no dose-limiting toxicities or severe treatment-related adverse events observed through the maximum administered dose (MAD). No maximum tolerated dose (MTD) was reached. Pharmacokinetic and pharmacodynamic data indicated that NDI-219216 achieved robust WRN target engagement for more than 24 hours at multiple dose levels. The company completed dose escalation approximately nine months ahead of schedule, with enrollment continuing to accelerate across global clinical sites.

"Completing dose escalation represents an important milestone in the clinical development of NDI-219216," said Anita Scheuber, M.D., Ph.D., Senior Vice President, Therapeutic Area Head, Oncology at Nimbus. "We are encouraged by the favorable safety profile and robust target coverage that is translating into early clinical activity in patients. The accelerated timeline, driven by strong patient recruitment, underscores the significant unmet need in this patient population. These results reinforce our confidence in NDI-219216's differentiated profile and its potential to address patients with MSI-H tumors who have limited treatment options. We look forward to sharing clinical data at an upcoming scientific conference."

The Phase 1/2 clinical trial (NCT06898450) is an open-label study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of NDI-219216 in patients with advanced solid tumors. The study is being conducted in three parts: Part A (dose escalation), Part B (dose optimization), and Part C (dose expansion). With Part A now complete, the trial is advancing to Part B, which will determine the recommended dose(s) for further evaluation.

About NDI-219216

NDI-219216 is a highly potent and selective non-covalent investigational inhibitor of Werner syndrome helicase (WRN) activity being developed for the treatment of MSI-H tumors. WRN is a DNA helicase required for DNA replication and DNA repair and is a validated synthetic lethal target for tumors with microsatellite instability (MSI). MSI is a phenotypic consequence of deficient mismatch repair (dMMR) and occurs in various tumor types, including colorectal, gastric, and endometrial cancers. In preclinical studies, treatment with NDI-219216 exhibited robust antitumor activity across multiple cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) MSI-H tumor models, including models for colorectal, gastric, and endometrial cancers.

About Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage, structure-based drug discovery company developing novel small molecule medicines designed to act against well-validated but difficult-to-drug targets implicated in multiple human diseases. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus' pipeline includes a WRN inhibitor in Phase 1/2 clinical development (NCT06898450) and a diverse portfolio of preclinical programs across oncology, immunology, and metabolism, including a SIK inhibitor program and other undisclosed metabolic targets. The company is headquartered in Boston, Mass. To learn more about Nimbus, please visit www.nimbustx.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20251219363150/en/