Pipeline

Created for the Challenge

Nuvalent’s novel drug candidates solve for the dual challenges of kinase resistance and selectivity, with the goal of enabling durable responses for patients with cancer.

Nuvalent Pipeline

Indication
Drug Candidate
Resistance or Activating Mutation (s)
Discovery
IND Enabling
Phase 1
Pivotal Study
ROS1 NSCLC
NUV-520
G2032R
D2033N
L2026M
S1986F
ALK NSCLC
NUV-655
G1202R
G1202R/
L1196M
G1202R/
G1269A
Undisclosed
Undisclosed
Undisclosed
Programs

ROS1 fusions are an oncogenic driver alteration found in ~1-3% of patients with non-small cell lung cancer (NSCLC). The clinical utility of approved therapies for ROS1-driven NSCLC is limited by emergent resistance mutations as well as central nervous system (CNS) disease.

NUV-520

NUV-520 is a novel ROS1-selective inhibitor created for patients with advanced NSCLC tumors driven by a ROS1 fusion. NUV-520 is designed to remain active in tumors that have developed treatment resistance, including tumors with the prevalent G2032R solvent front mutation, in addition to other key mutations D2033N, L2026M, and S1986F mutations.

NUV-520 has been optimized for CNS penetrance to improve treatment options for patients with CNS metastasis. ROS1 selectivity is emphasized vs. the structurally-related tropomyosin receptor kinase (TRK) family in order to minimize CNS adverse events observed with dual TRK/ROS1 inhibitors and drive more durable responses in patients with ROS1-mutant variants. NUV-520 is planned to enter the clinic in 2021.

 

View our publications
“Dark blue 3D structure of ROS1 receptor tyrosine kinase with textured fuchsia inhibitor molecule enclosed in binding pocket

ALK fusions are an oncogenic driver alteration found in ~5% of patients with non-small cell lung cancer (NSCLC). The clinical utility of approved therapies for ALK-driven NSCLC is limited by emergent resistance mutations as well as central nervous system (CNS) disease.

NUV-655

NUV-655 is a novel ALK-selective inhibitor created for patients with advanced NSCLC tumors driven by an ALK fusion. NUV-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 or G1202R / G1269A.
 
NUV-655 has been optimized for CNS penetrance to improve treatment options for patients with CNS metastases. ALK-selectivity is emphasized to minimize CNS adverse events related to off-target inhibition of the structurally-related tropomyosin receptor kinase (TRK) family.

 

View our publications
“Teal 3D structure of ALK tyrosine kinase receptor with textured fuchsia inhibitor molecule (NUV-655) enclosed in binding site

At Nuvalent we are combining our close partnerships with physician-scientists, rigorous target selection, and disciplined program advancement to explore a robust pipeline of discovery programs with a focus on addressing the limitations of existing therapies for clinically proven kinase targets in oncology.
 
Our team combines clinical insights with deep expertise in structure-based drug design and oncology drug development to create new programs where we are able to rapidly advance molecules that are designed to precisely target driver kinases and spare off-targets. This molecular optimization and precise targeting, sometimes by avoiding highly similar off-targets, affords therapies designed to improve the lives of patients with cancer.