Nuvalent Outlines FDA Timelines for ROS1, ALK Drugs as $1.4B Cash Fuels Global Launch Plans

Nuvalent executives provided updates on the company's lead oncology programs, including the FDA's acceptance of the NDA for zidesamtinib in ROS1-positive non-small cell lung cancer (NSCLC) and plans to submit an NDA for NVL-655 in ALK-positive NSCLC in the first half of 2026. The company also discussed its global commercialization strategy, pipeline plans, and strong financial position with over $1.4 billion in cash.

The FDA accepted Nuvalent's NDA for zidesamtinib in TKI-pretreated ROS1-positive NSCLC, with a PDUFA date of September 18, 2026. Commercial readiness efforts are underway to support a potential U.S. launch later this year. The company also plans to submit data to support a potential indication expansion in TKI-naïve ROS1 in the second half of the year.

For NVL-655 in ALK-positive NSCLC, Nuvalent completed a pre-NDA meeting with the FDA for TKI-pretreated patients and is on track to submit an NDA in the first half of the year. The company has breakthrough designation and is pursuing a previously treated label supported by single-arm data. The company is also progressing the phase 3 ALCAZAR study in TKI-naïve ALK patients.

The chief executive officer described Nuvalent as a company built around deep chemistry and structure-based drug design expertise, with an emphasis on clinically validated kinase targets. The company works closely with physicians to understand limitations of existing therapies—such as target coverage, central nervous system (CNS) activity, and tolerability—and then applies "innovative chemistry" to address those gaps.

On the path toward a broader, line-agnostic ROS1 label, management described how follow-up requirements influenced timing. Prior ROS1 precedents involved following patients for 12 months post-response, but Nuvalent aligned with the FDA on six months post-response for the previously treated setting, supporting the company's earlier submission. For the frontline (TKI-naïve) cohort, the company had enrolled 104 patients as of June of last year—more than required—and kept enrollment open due to enthusiasm, while prioritizing longer follow-up. The company reiterated plans to submit frontline data in the second half of this year for FDA consideration of a line-agnostic extension.

Management positions zidesamtinib as differentiated by activity against ROS1 fusions and resistance mutations, CNS penetration and selectivity for tolerability. The chief executive officer characterized zidesamtinib as the "first and only" drug with that combination of attributes and said trial enrollment was rapid due to enthusiasm for the differentiated profile. Clinical performance was described as durable responses across treatment lines, strong activity in patients with ROS1 mutations, and deep responses in CNS disease, including what was called high CNS complete response rates.

For NVL-655, the chief executive officer described a "straightforward" case in the third-line setting, where available options perform poorly, and then focused on the second-line setting where lorlatinib is standard of care. Lorlatinib has a 7–9 month duration of response in second line. In patients who have not yet received lorlatinib, the company is seeing "60+%" of patients still in response at 1.5 years, which was characterized as "alectinib-like durability" in second line. This pattern—durability improving rather than worsening in later lines—was said to speak to NVL-655's activity against ALK mutations, CNS activity, and tolerability, allowing patients to remain on therapy longer.

NVL-655 is reported to show durable responses with manageable transaminase elevations addressed via early monitoring and dose management. Transaminase elevations were described as common across kinase inhibitors and across approved ALK TKIs. These events are often transient, reversible, occur early, are typically low grade, and asymptomatic, and are generally managed with dose interruption or reduction.

The company ended the year with approximately $1.4 billion in cash, which management says provides operating runway into 2029 and supports plans to build out global commercial capabilities and "go it alone" ex-U.S.

Nuvalent continues advancing a phase 1b/2 study in HER2-altered NSCLC. Management reiterated guidance to disclose a new development candidate by year-end.