Nuvalent (NUVL) Jefferies 2024 Global Healthcare Conference summary

Industry landscape and clinical needs

• ALK and ROS1 non-small cell lung cancer therapies face limitations in resistance mutations and CNS penetrance.

• Lorlatinib is highly active but limited by CNS toxicities due to off-target TRK inhibition.

• Alectinib remains the standard of care in the frontline, with lorlatinib used by some experienced physicians.

• In ROS1, crizotinib is standard but lacks brain penetrance and struggles with resistance mutations.

• Physicians seek drugs that address resistance, CNS penetrance, and avoid dose-limiting off-target effects.

Program updates and development strategy

• Phase II studies for ALK and ROS1 are ongoing globally, with strong enrollment and data updates expected in the second half of the year.

• Data updates will focus on follow-up and durability from phase I, with phase II data disclosure driven by enrollment and pivotal timelines.

• Frontline ALK strategy involves a global phase III trial comparing to alectinib, following established regulatory precedents.

• Regulatory alignment and dose selection for phase III have been achieved, with protocol discussions ongoing.

• HER2 program (NVL-330) targets exon 20 insertions with a wide therapeutic index and strong brain penetration; clinical study initiation is planned this year.

Commercialization and financial outlook

• Sufficient capital runway into 2027, with pivotal data and at least one approval anticipated in that timeframe.

• No partner needed to run phase III, but partnership may be sought for global commercialization, especially outside the US.

• Additional capital will be required for full funding of the phase III study; business development efforts are ongoing.