On March 25, 2025 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported upcoming poster presentations further characterizing the preclinical profiles of its novel ALK-selective inhibitor, neladalkib, and novel ROS1-selective inhibitor, zidesamtinib, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 from April 25-30, 2025, in Chicago (Press release, Nuvalent, MAR 25, 2025, View Source [SID1234651432]).
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Details of the poster presentations are as follows:
Title: Mutagenesis screens support potential best-in-class profile for neladalkib (NVL-655), a brain-penetrant and TRK-sparing ALK inhibitor
Authors: Anupong Tangpeerachaikul*1, Henry E. Pelish1
Abstract Number: 1729
Session Category: Experimental and Molecular Therapeutics
Session Title: Kinase and Phosphatase Inhibitors 1
Session Date and Time: April 28, 2025, from 9:00 a.m.– 12:00 p.m. CT
Location: Poster Section 21
Poster Board Number: 4
Title: Crystal structure of drug-resistant ROS1 G2032R in complex with zidesamtinib, a clinical-stage ROS1 inhibitor with best-in-class potential
Authors: Joseph M. Magrino*1, Anupong Tangpeerachaikul1, Scot Mente1, Henry E. Pelish1
Abstract Number: 5616
Session Category: Experimental and Molecular Therapeutics
Session Title: Kinase and Phosphatase Inhibitors 3
Session Date and Time: April 29, 2025, from 2:00 p.m.– 5:00 p.m. CT
Location: Poster Section 20
Poster Board Number: 26
*Presenter, corresponding author; 1Nuvalent, Inc., Cambridge, MA, USA
About Zidesamtinib
Zidesamtinib is a novel brain-penetrant ROS1-selective inhibitor created with the aim to overcome limitations observed with currently available ROS1 inhibitors. Zidesamtinib is designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with treatment-emergent ROS1 mutations such as G2032R. In addition, zidesamtinib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and to drive deep, durable responses for patients across all lines of therapy. Zidesamtinib has received breakthrough therapy designation for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ROS1 tyrosine kinase inhibitors and orphan drug designation for ROS1-positive NSCLC.
About Neladalkib
Neladalkib is a novel brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. Neladalkib is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R. In addition, neladalkib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. Neladalkib has received breakthrough therapy designation for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ALK tyrosine kinase inhibitors and orphan drug designation for ALK-positive NSCLC.