Nuvalent (NASDAQ:NUVL) executives said the company is preparing for two potential U.S. commercial launches later this year while advancing broader development plans across ALK, ROS1 and HER2-altered non-small cell lung cancer.
Speaking at TD Cowen’s Oncology Innovation Summit, Chief Executive Officer Jim Porter said Nuvalent’s strategy is built around chemistry and structure-based drug design aimed at improving on validated kinase inhibitor biology. Porter said the company focuses on understanding limitations of earlier-generation therapies and using “innovative chemistry” to address physician-identified patient needs.
Neladalkib NDA Advances With Priority Review
Porter said the ALKOVE-1 study supporting neladalkib showed two major themes: enrollment and durability. He said the study had enrolled 781 patients as of the company’s November update, compared with an original trial design of 250 patients, which he attributed to physician and patient interest in the drug’s differentiated profile.
Porter said neladalkib was designed to address the original ALK fusion, cover single and compound ALK resistance mutations, provide central nervous system penetration and avoid dose-limiting off-target effects. In patients who had progressed after lorlatinib, Porter said ALKOVE-1 showed a median duration of response of 17.6 months, which he described as more than double the durability of lorlatinib in that setting.
Porter said the company is seeking to use the ALKOVE-1 data to support a previously treated ALK indication, including patients treated after alectinib and lorlatinib, as well as patients who have not yet received lorlatinib. He said the ultimate label will be determined through discussions with the FDA.
Balcom said Nuvalent has not provided detailed guidance on additional data points expected at ASCO, but said the company plans to take an approach similar to its prior presentation of ROS1 pivotal data, using the same data cut while adding more detail from the earlier topline announcement.
Safety, Labeling and Commercial Considerations
Asked about potential monitoring requirements, Porter said he does not expect neladalkib’s label to differ substantially from other ALK inhibitors. He said transaminase elevations, a liver enzyme laboratory abnormality seen with other ALK drugs and kinase inhibitors, have also been observed with neladalkib. Porter said these events typically occur early, are generally asymptomatic, usually do not recur and can be managed by dose holds or dose reductions.
Balcom said it is too early to comment on neladalkib pricing. She said Nuvalent will consider learnings from other launches in the space, neladalkib’s profile and patient access when making pricing decisions.
Porter said the current previously treated ALK market may not reflect the potential market if a drug can keep patients on therapy longer. He cited alectinib’s historical impact on the ALK market as an example of how more durable treatment can expand a prevalent patient population.
ALKAZAR Phase 3 Trial Continues
Nuvalent is also evaluating neladalkib in the first-line ALK setting through the ALKAZAR phase 3 trial, which compares neladalkib with alectinib. Porter said the trial is designed to enroll 450 patients randomized one-to-one, with progression-free survival as the endpoint.
Porter said Nuvalent plans about 190 trial sites and currently has roughly 140 to 150 sites activated, based on ClinicalTrials.gov. He said enrollment is proceeding according to plan, though the company has not provided a specific enrollment completion timeline.
Porter said the timing of the trial readout will depend on enrollment, event rates and the statistical plan. Based on current modeling, he said Nuvalent estimates primary completion around the end of 2029, while cautioning that the timing could be faster or slower.
ROS1 Program Nears Potential Launch
For zidesamtinib, Porter said Nuvalent’s initial ROS1 submission covers previously treated patients, with a PDUFA date of Sept. 18. He said the company had separate registration-directed cohorts for previously treated and TKI-naive ROS1-positive lung cancer patients.
Porter said Nuvalent had enrolled more than 100 patients in the TKI-naive ROS1 cohort as of last June but needed additional follow-up before submitting those data. He said the company expects to be in a position this year to submit the TKI-naive data and will disclose the regulatory pathway once it has done so.
Porter said Nuvalent’s goal is to get drugs approved for patients as quickly as possible and that the company is commercially prepared to launch zidesamtinib if approved. He described the company’s broader opportunity as four launches over time: previously treated ROS1, TKI-naive ROS1, previously treated ALK and TKI-naive ALK.
HER2 Program Focuses on CNS Penetration
Porter also discussed Nuvalent’s HER2 program, including NVL-330. He said the unmet need in HER2-altered lung cancer is limited CNS penetration with existing therapy. Porter said Nuvalent designed NVL-330 to be broadly active against HER2 mutations, penetrate the CNS and be selective for HER2 versus wild-type EGFR, which he described as a dose-limiting toxicity concern.
Balcom said Nuvalent also remains on track to disclose a new development candidate by year-end.
About Nuvalent (NASDAQ:NUVL)
Nuvalent, Inc (NASDAQ:NUVL) is a clinical-stage precision oncology company focused on the discovery, development and commercialization of targeted therapies for patients with genetically defined cancers. Founded in 2019 and headquartered in San Diego, California, Nuvalent applies structure-guided drug design to develop small molecule inhibitors that address key oncogenic drivers. The company’s research platform integrates insights from cancer biology, medicinal chemistry and translational science to create therapies with differentiated selectivity and potency against validated targets.
Nuvalent’s lead pipeline candidates include NVL-520, a highly selective RET inhibitor designed to minimize off-target effects, and NVL-655, a potent covalent inhibitor targeting KRAS G12D mutations.
