Nuvalent：药物开发进展符合预期

Yi Zhao+1 917 344 8324yi.zhao@bernsteinsg.com Price Target NUVL 172.00 USD(189.00OLD) Nuvalent: On Target drug development We rate NUVL Outperform with a $172PT and think that the market is underestimating thepotential for both neladalkib (ALK+ NSCLC) and zidesamtinib (ROS1+ NSCLC). Nuvalent’stwo lead medicines offer a unique opportunity among biopharmaceutical stocks: potentialbest-in-class efficacy profile with high probability of success that is under-appreciated bythe market. Our projected risk-adjusted total portfolio peak revenue of $9.8B is currently56% higher than consensus estimates. Specifically, we think the growth trajectory andtotal addressable market for zidesamtinib (ROS1+ NSCLC) remains under-appreciated. Wecalculate that ~37% of newly diagnosed ROS1+ NSCLC patients are currently receivingtargeted treatment. This treatment rate is significantly lower than the mature EGFRm NSCLCmarket benchmark of 85% established by Tagrisso. Neladalkib and zidesamtinib offer aTagrisso-like market, making upside that has yet to be fully appreciated based on the currentstock price. We sharpen our answer post-ASCO by updating our PT to $172. Our updated modeling ismore conservative in beginning years post-launch in 1L ALK and ROS NSCLC. We factor inthe potential for some stickiness in the current 1L SOC treatments that we project NUVLto displace. We maintain the same peak share assumptions, however allow for maturityof NUVL’s 1L data to support increased rate of prescribing pattern changes for newlydiagnosed patients. This is also supported by our KOL feedback at ASCO breakfast (USPharma & Biotech: Insights from a physician on the ground at ASCO) Investment ImplicationsWe maintain NUVL Outperform with PT $172 (+88% upside) based on our DCFvaluation. DETAILS Key messages: 1. We project neladalkib to be the new standard of care for advanced/metastatic ALK+ NSCLC patients2. ALK TKI market is set for take-off because of new treatments: Neladalkib is leading the way3. Zidesamtinib looks like the best-in-class ROS1+: First key approval is on tap by the end of the year4. ROS1+ NSCLC market potential is underestimated: Zidesamtinib is a catalyst for growth Company summary.Nuvalent, Inc. is a clinical-stage biopharmaceutical company developing targeted small-moleculeinhibitors for cancers driven by specific kinase alterations. The company usesstructure-based drug designto address keylimitations of existing therapies, including resistance mutations, limited CNS penetration, and off-target toxicities. Pipeline overview and key upcoming catalystsNuvalent’s pipeline comprises three lead therapeutic candidates:zidesamtinib (NVL-520) for ROS1-driven cancers, neladalkib (NVL-655) for ALK-driven cancers, and NVL-330 for HER2-alterednon-small cell lung cancer (Exhibit 1). Zidesamtinib (NVL-520) is being evaluated in the ARROS-1 Phase 1/2 study (NCT05118789), which includes: 1. Registrational cohorts on TKI-pretreated pts that has data readout and filed New Drug Application (NDA) in 2025, with aPDUFA date 09/18/2026. 2. A registrational cohort on TKI-naïve pts that has enrolled 104 pts as of June 2025. Preliminary data on 35 pts waspresented which showed early signs of long durability, CNS response. The company planned to file a supplemental NewDrug Application (sNDA) for indication expansion. And we anticipate to see a data update before that. Neladalkib (NVL-655) is under registrational evaluation in the ALKOVE-1 Phase 1/2 study (NCT05384626) for: 1. Previously treated ALK-positive NSCLC. Nuvalent announced the submission of NDA to FDA for its approval in TKI pre-treated advanced ALK-positive NSCLC with a PDUFA date 11/27/2026. We think the data has demonstrated a promisingefficacy and safety profile that supports both its approval and market uptake (discussed in detail later). 2. Other ALK-positive solid tumors, with preliminary data on 34 pts across 14 different types demonstrated promising earlysignals of durable response (See data presentation at ESMO 2025). The company presented the updated pivotal data for ALKOVE-1 during ASCO 2026 (Abstract 8503 presentation) withadditional information from more patients that are lorlatinib-experienced, which from our view further support its long durabilityvs lorlatinib in TKI-pre-treated patients, see the data updates in Exhibit 3, Exhibit 5, Exhibit 6. Neladalkib is further being evaluated in the ALKAZAR Phase 3 trial (NCT06765109) as a frontline option for ALK-positive NSCLC(See study design at ASCO 2025, #136b). The study started enrollment from July 2025, with a primary completion estimated in Dec 2029. A total of ~450 TKI-naïve pts were planned to enroll and would be randomized at 1:1 beingtreated with neladalkib or Alectinib, with a primary endpoint of mPFS. Nuvalent is exploring the efficacy and safety of NVL-330, a HER2-targeted selective TKI in HERoex-1 Ph1/2 studyamong HER2-altered NSCLC.We expect the company to share some preliminary results in 2026. Ma