On July 13, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported it will present two posters for its parallel lead programs, NVL-655, an ALK-selective inhibitor and NVL-520, a ROS1-selective inhibitor, at the IASLC 2022 World Conference on Lung Cancer (WCLC) Annual Meeting taking place August 6-9, 2022 in Vienna, Austria (Press release, Nuvalent, JUL 13, 2022, View Source [SID1234616663]). Posters will be archived on the Nuvalent website at www.nuvalent.com.

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The first poster characterizes NVL-655 alongside other ALK inhibitors in a patient-derived model of lorlatinib-resistant ALK-positive non-small cell lung cancer (NSCLC) with the treatment-emergent G1202R/T1151M compound resistance mutation. NVL-655 has previously demonstrated differentiation through broad preclinical activity across diverse ALK oncoproteins, resistance mutations, and tumor types while maintaining strong selectivity for ALK over TRKB. Nuvalent recently announced the first patient has been dosed with NVL-655 in the ALKOVE-1 Phase 1/2 study for patients with advanced ALK-positive NSCLC and other solid tumors.

A "Trial in Progress" poster will also be presented with background and study design for the ongoing ARROS-1 Phase 1/2 study of NVL-520 for patients with advanced ROS1-positive NSCLC and other solid tumors. The multicenter, open-label, dose-escalation and expansion trial is currently evaluating NVL-520 as an oral monotherapy in the Phase 1 portion of the study. Nuvalent plans to share preliminary dose-escalation data from ARROS-1 in the second half of 2022.

Details for the E-poster presentations are as follows:

Title: Preclinical Activity of NVL-655 in a Patient-Derived NSCLC Model with Lorlatinib-Resistant ALK G1202R/T1151M Mutation
Authors: H. Mizuta1, L. Bigot1, A. Tangpeerachaikul2, H.E. Pelish2, L. Friboulet1
Abstract Number: EP08.02-020
Session Category: Metastatic Non-small Cell Lung Cancer
Session Title: Molecular Targeted Treatments
Session Date and Time: August 7, 2022, 9:45am – 6:00pm CEST

1Gustave-Roussy, Villejuif, France; 2Nuvalent, Inc., Cambridge, MA, USA

Title: NVL-520, a Highly Selective ROS1 Inhibitor, in Patients with Advanced ROS1-Positive Solid Tumors: The Phase 1/2 ARROS-1 Study
Authors: A. Drilon1, S-H.I. Ou2, S. Gadgeel3, M. Johnson4, A. Spira5, G. Lopes6, B. Besse7, E. Felip8, A.J. van der Wekken9, A. Calles10, M.J. de Miguel11, D.R. Camidge12, Y. Elamin13, S. Liu14, J. Bauman15, D. Haggstrom16, G. Riley17, H.E. Pelish17, V.W. Zhu17, J.J. Lin18
Abstract Number: EP08.02-041
Session Category: Metastatic Non-small Cell Lung Cancer
Session Title: Molecular Targeted Treatments
Session Date and Time: August 7, 2022, 9:45am – 6:00pm CEST

1Memorial Sloan Kettering Cancer Center, New York/NY/USA ,2University Of California Irvine Medical Center, Orange/CA/USA ,3Henry Ford Cancer Institute, Detroit/MI/USA ,4Sarah Cannon Research Institute, Nashville/TN/USA,5NEXT Oncology – Virginia Cancer Specialists, Fairfax/VA/USA ,6Sylvester Comprehensive Cancer Center at the University of Miami and the Miller School of Medicine, Miami/FL/USA ,7Institut Gustave Roussy, Villejuif Cedex/FR,8Hospital Vall d’Hebron, Barcelona/ES ,9University of Groningen, University Medical Centre Groningen,Groningen/NL ,10Hospital Universitario Gregorio Marañón, Madrid/ES,11 START Madrid-HM CIOCC, Madrid/ES,12University of Colorado Cancer Center, Anschutz Medical Campus, Aurora/CO/USA ,13MD Anderson Cancer Center, Houston/TX/USA ,14Georgetown University, Washington/DC/USA ,15Fox Chase Cancer Center, Philadelphia/PA/USA,16Levine Cancer Institute, Atrium Health, Charlotte/NC/USA ,17Nuvalent, Inc., Cambridge/MA/USA ,18Massachusetts General Hospital, Boston/MA/USA

About NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M ("GRLM"), G1202R / G1269A ("GRGA"), or G1202R/L1198F ("GRLF"). NVL-655 has been optimized for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 study (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.

About NVL-520

NVL-520 is a novel brain-penetrant ROS1-selective inhibitor designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with the prevalent G2032R resistance mutation and those with the S1986Y/F, L2026M, or D2033N resistance mutations. NVL-520 has been optimized for brain penetrance to potentially improve treatment options for patients with brain metastases. NVL-520 has been observed in preclinical studies to selectively inhibit wild-type ROS1 and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and drive more durable responses for patients. NVL-520 is currently being investigated in the ARROS-1 study (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors.