On March 28, 2024 Nested Therapeutics, a biotechnology company pioneering a next-generation precision medicine platform to address hard-to-treat cancers, reported that the U.S. Food and Drug Administration (FDA) cleared the investigational new drug (IND) application for NST-628 for the treatment of patients with advanced solid tumors harboring genetic alterations in the RAS-MAPK pathway (Press release, Nested Therapeutics, MAR 28, 2024, View Source [SID1234641595]). NST-628 is a mechanistically novel, fully brain penetrant non-degrading pan-RAF/MEK molecular glue that targets RAF and MEK nodes in the RAS-MAPK pathway.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The significant majority of KRAS-, NRAS-, and BRAF-mutant tumors are not addressable by currently approved therapies, creating a pressing need for new medicines that provide superior, durable efficacy and tolerability for people living with these hard-to-treat cancers," said Philip Komarnitsky, M.D., Ph.D., chief medical officer of Nested. "We believe that NST-628 has the potential to provide a differentiated clinical profile, including a superior therapeutic index and prevention of pathway reactivation, for patients with advanced solid tumors harboring RAS-MAPK pathway alterations. The IND clearance for NST-628 is an important step in the advancement of our first clinical-stage program, and with clinical trial sites already activated, we look forward to dosing the first patients in this trial in the first half of this year."
The Phase 1 open-label, single-arm, two-part study (NCT06326411) is intended to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of single agent NST-628 in adult patients with RAS-MAPK pathway mutated/dependent advanced solid tumors who have exhausted standard treatment options. The study includes two parts: dose escalation (Part A) followed by dose expansion (Part B). The primary objectives for Part A are delineating NST-628’s safety profile and establishing the recommended dose for Part B. For more information, visit clinicaltrials.gov.
About NST-628
NST-628 is a fully brain-penetrant, mechanistically novel non-degrading molecular glue that targets multiple nodes in the RAS/MAPK pathway. NST-628 was developed based on Nested’s proprietary structural insights of how signaling complexes form and function in cancer and addresses common pitfalls of other MAPK-targeted compounds, which remain unable to circumvent the risk of resistance via signaling pathway reactivation. Preclinical data evaluating all biomarkers relevant to RAS/MAPK-driven cell and patient-derived models collectively demonstrate superior anti-tumor activity, including in RAS and central nervous system-implanted tumor models, and tolerability of NST-628 compared to other MAPK-targeted compounds administered as either single agents or in combination. With a half-life and metabolic profile optimized to achieve a superior therapeutic index on a daily dosing schedule, as well as full intrinsic blood brain barrier penetrance, these data support NST-628’s potential as a best-in-class treatment for RAS and RAF-driven cancers.