Company expects to initiate dosing in the
Phase 1 study of NST-628 in patients with advanced solid tumors
harboring genetic alterations in the MAPK pathway in first half of
2024
CAMBRIDGE, Mass., March 28,
2024 /PRNewswire/ -- Nested Therapeutics, a
biotechnology company pioneering a next-generation precision
medicine platform to address hard-to-treat cancers, today announced
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. 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.
"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.
About Nested Therapeutics
Nested Therapeutics is a
biotechnology company focused on discovering and developing novel,
targeted, small molecule precision medicine therapies for patients
with cancer by using mutation clusters to identify druggable
pockets. With a platform that utilizes insights from genomics,
computational chemistry, proteomics and AI, Nested is working to
reach untapped mutations with the potential to improve outcomes for
millions of patients. To learn more, visit www.nestedtx.com and
follow Nested Therapeutics on Twitter (@Nestedtx) and LinkedIn.
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SOURCE Nested Therapeutics Inc.