Nuvalent (NUVL) TD Cowen 45th Annual Healthcare Conference summary

Key program updates and catalysts

• Pivotal data for ROS1 and ALK programs expected in 2024, with first NDA submission targeted by mid-year and potential product approval by next year.

• ALK program includes second and third line cohorts, with breakthrough therapy designation and a focus on broader previously treated patient populations.

• HER2 program advancing through phase 1, aiming for improved brain penetrance and durability over current therapies.

• ALKAZAR frontline trial is open for enrollment, comparing NVL-655 to alectinib in TKI-naïve patients, with a primary endpoint of progression-free survival.

• Global regulatory engagement ongoing, leveraging breakthrough designations for both lead programs.

Clinical trial design and strategy

• ALKOVE-1 phase 2 enrolled 460 patients in 10 months, covering multiple cohorts including TKI-naïve and solid tumors.

• Data cut for regulatory submission will focus on response durability and patient follow-up, with ongoing FDA dialogue.

• ALKAZAR trial designed based on prior studies, with estimated completion in October 2029, but actual timing depends on event rates and enrollment.

• Interim analyses may be considered to expedite approval, with continued follow-up for overall survival data.

• Disclosure of top-line data will be via press release, with full data at future medical meetings.

Market opportunity and competitive landscape

• ALK market estimated at $2.5 billion, with alectinib as frontline standard and lorlatinib limited by response rates and duration.

• NVL-655 aims to expand the ALK market by offering deeper, more durable responses and broader mutation coverage.

• ROS1 market currently $400 million, with zidesamtinib positioned to address unmet needs in mutation coverage and CNS activity.

• Enrollment momentum in ARROS-1 (430 patients) indicates strong physician interest and potential to grow the ROS1 market.

• HER2 program targets exon 20 insertions with improved brain penetrance, differentiating from competitors like zongertinib.