Core Insights - Royalty Pharma has acquired a royalty interest in Nuvalent's neladalkib and zidesamtinib for up to $315 million [1][4] - Neladalkib and zidesamtinib are next-generation tyrosine kinase inhibitors (TKIs) targeting specific mutations in non-small cell lung cancer (NSCLC) [2] - Positive pivotal results for neladalkib have been reported, showing durable activity and a well-tolerated safety profile [3] Transaction Details - The acquisition includes a low-single digit royalty on worldwide net sales of both therapies, expected to last until approximately 2041 to 2042 [4] - The total investment for the royalty interest is capped at $315 million [4] Product Development Status - Neladalkib is in a Phase 3 study for TKI-naïve patients, while zidesamtinib is under FDA review with an action date of September 18, 2026 [3] - Analyst consensus projects sales of neladalkib to reach approximately $3.5 billion and zidesamtinib to reach approximately $1.9 billion by 2035 [3] Company Background - Royalty Pharma is the largest buyer of biopharmaceutical royalties and funds innovation across the biopharmaceutical industry [6] - The company has a diverse portfolio that includes royalties on over 35 commercial products and 20 development-stage candidates [6]

NEW YORK, Dec. 16, 2025 (GLOBE NEWSWIRE) -- Royalty Pharma plc (Nasdaq: RPRX) today announced that it has acquired a pre-existing royalty interest in Nuvalent’s neladalkib and zidesamtinib from an undisclosed third party for up to $315 million. Neladalkib and zidesamtinib are next-generation tyrosine kinase inhibitors (TKIs). Neladalkib is in development for patients with ALK mutation-positive non-small cell lung cancer (NSCLC) and zidesamtinib is in development for ROS1 mutation-positive NSCLC. Both therap ...

Core Insights - Nuvalent, Inc. has appointed Ron Squarer to its Board of Directors, enhancing its leadership in oncology therapeutics [1][2] - Squarer brings over 30 years of experience in oncology drug development and commercialization, having held significant roles in various pharmaceutical companies [2][3] - The company is preparing for the potential approval and launch of zidesamtinib for TKI pre-treated ROS1-positive non-small cell lung cancer in 2026 [2][3] Company Overview - Nuvalent, Inc. is a clinical-stage biopharmaceutical company focused on developing precisely targeted therapies for cancer, specifically targeting clinically proven kinase targets [4] - The company utilizes expertise in chemistry and structure-based drug design to create innovative small molecules aimed at overcoming resistance and minimizing adverse events [4] - Nuvalent is advancing a robust pipeline that includes investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, along with multiple discovery-stage research programs [4]

Summary of Nuvalent FY Conference Call - December 04, 2025 Company Overview - Nuvalent is a biotechnology company with a focus on kinase targets and structure-based drug design, established approximately seven years ago [4][5] - The company aims to address unmet medical needs in oncology by partnering with physicians to understand patient requirements and therapy limitations [4] Key Programs and Milestones - The OnTarget 2026 operating plan outlines ambitious milestones for 2025, including pivotal data sets for ROS1 and ALK programs, and NDA submission for TKI pretreated ROS1 [5] - The company anticipates its first potential drug approval in 2026 [5] ALK Non-Small Cell Lung Cancer Market - The current market for ALK non-small cell lung cancer is estimated at $2 billion to $2.5 billion [8] - Nuvalent aims to grow this market by providing durable responses across all treatment lines, not just capturing a portion of it [8] Clinical Data Highlights - NVL-655 has treated over 1,000 patients, making it one of the fastest enrolling oncology small molecule trials [10] - In the third-line patient population, NVL-655 shows an 18-month duration of response, double that of lorlatinib [11] - In the second-line setting, NVL-655 demonstrates a 46% response rate with 60% of patients still responding at the 18-month mark [12] Patient Advocacy and Enrollment - Nuvalent collaborates closely with patient support groups, which enhances enrollment rates and patient advocacy for new treatment options [16][17] - The company has successfully enrolled 540 patients in its ROS1 program, aided by these collaborations [17] Safety Profile - NVL-655 has a clean CNS safety profile, with transaminase elevations being the primary concern, which are manageable and transient [18] Regulatory Strategy - The NDA for the ROS1 program has been accepted with standard review timing, and the company is preparing for a pre-NDA meeting with the FDA [30][20] - Nuvalent plans to present full data at future medical meetings [20] Competitive Landscape - Crizotinib remains the standard of care for ROS1 patients, despite newer entrants facing challenges due to neurocognitive side effects [35][37] - Nuvalent's zidesamtinib is designed to avoid these issues, providing a differentiated profile that appeals to physicians and patients [36] Commercialization Strategy - Nuvalent is building its commercial presence with a dedicated team and plans to engage key prescribers and healthcare decision-makers [39] - The company is positioned to operate independently but remains open to strategic partnerships for global expansion [40][41] HER2 Program - The HER2 program, NVL-330, is designed to penetrate the brain effectively while addressing skin and GI toxicities associated with other HER2 therapies [43] Conclusion - Nuvalent is on track to bring two drugs to market within the next 12 months, with a strong focus on patient needs, innovative drug design, and strategic regulatory engagement [39][41]

Core Viewpoint - Nuvalent, Inc. has submitted a New Drug Application (NDA) for zidesamtinib, a ROS1-selective inhibitor, to the FDA for treating adult patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) who have previously received at least one ROS1 tyrosine kinase inhibitor (TKI) [1][2] Group 1: Zidesamtinib and Clinical Trials - Zidesamtinib is designed to overcome limitations of existing ROS1 inhibitors and is effective against tumors with treatment-emergent ROS1 mutations, such as G2032R [3][4] - The ARROS-1 Phase 1/2 clinical trial is investigating zidesamtinib in patients with advanced ROS1-positive NSCLC and other solid tumors, focusing on safety, tolerability, and preliminary anti-tumor activity [4] - The FDA has assigned a PDUFA target action date of September 18, 2026, for the NDA submission [1] Group 2: Company Overview - Nuvalent, Inc. is a clinical-stage biopharmaceutical company focused on developing targeted therapies for cancer, leveraging expertise in chemistry and structure-based drug design [5] - The company is advancing a pipeline that includes investigational candidates for ROS1-positive, ALK-positive, and HER2-altered NSCLC, along with multiple discovery-stage research programs [5]

Core Insights - Nuvalent, Inc. reported topline results from its ALKOVE-1 Phase 1/2 trial evaluating neladalkib in TKI-pretreated patients with advanced ALK-positive NSCLC, establishing a recommended Phase 2 dose of 150 mg once daily [1][2] Group 1: Trial Results - The primary analysis included 253 TKI-pretreated patients, with a median of three prior therapy lines; 51% had received chemotherapy [2] - A 31% response rate was observed, with 76% of responses ongoing after six months, decreasing to 64% after 12 months and 53% after 18 months [3] - The study has not yet reached the median duration of response after 11.3 months of follow-up [4] Group 2: TKI-Naïve Patients - Preliminary data from 44 TKI-naïve patients showed an objective response rate of 86% and a complete response rate of 9%, with two of the 38 responders having progressed [4] - Duration of response for TKI-naïve patients ranged from 1.7+ to 14.8+ months, with 91% having a DOR of at least 6 and 12 months [5] - In patients with measurable intracranial lesions, the intracranial objective response rate was 78%, and the intracranial complete response rate was 44% [5] Group 3: Future Plans and Market Reaction - The company plans to discuss the topline pivotal data with the U.S. FDA at a pre-New Drug Application meeting [6] - Following the announcement, NUVL stock increased by 16.04% to $111.98 [6]

Summary of Nuvalent's Conference Call Company and Industry Overview - **Company**: Nuvalent - **Industry**: Oncology, specifically focusing on ALK-positive non-small cell lung cancer (NSCLC) Key Points and Arguments 1. **Top-line Data Announcement**: Nuvalent announced pivotal data from the ALKOVE-1 trial of neladalkib for ALK-positive NSCLC patients, highlighting the need for new treatment options in this space [2][4][9] 2. **Current Treatment Landscape**: - Alectinib is the standard of care with a 79% objective response rate (ORR) and median progression-free survival (PFS) of 25.7 months [4] - Lorlatinib, a third-generation TKI, is the only approved therapy after second-generation TKIs but has limitations, including CNS adverse events in over 50% of patients [5][6] 3. **Identified Opportunities**: - Need for effective treatments for patients in the third line and beyond who have exhausted available therapies [7] - Potential to improve on the durability of response for TKI-pretreated patients who are lorlatinib naive [7] - Opportunity to provide a well-tolerated therapy for TKI-naive patients that addresses ALK resistance mutations and brain metastases [7][8] 4. **Neladalkib's Design Goals**: - First ALK-selective compound targeting ALK oncogenic drivers and resistance mutations while ensuring good CNS penetration and avoiding neurotoxicities [8][9] 5. **Clinical Trial Design**: - ALKOVE-1 is a multi-cohort trial evaluating neladalkib in heavily pretreated patients and TKI-naive patients [10][11] - Enrollment reached 781 patients by the data cutoff date of August 29, 2025 [12][14] 6. **Efficacy Results**: - In TKI-pretreated patients, ORR was 31% with a median duration of response (DOR) not reached [17] - In lorlatinib-experienced patients, ORR was 26% with a median DOR of 17.6 months [18] - In lorlatinib-naive patients, ORR was 46% with a median DOR not reached [20] - Notable responses in patients with ALK resistance mutations, including a 68% ORR in those with G1202R mutation [18] 7. **CNS Activity**: - Intracranial ORR of 32% in TKI-pretreated patients with measurable CNS lesions, indicating potential for neladalkib to address CNS disease [22][23] 8. **Safety Profile**: - Generally well tolerated with treatment-emergent adverse events (TEAEs) primarily being low-grade and reversible [24][25] - 15% of patients experienced TEAEs, with transaminase elevations being the most common [24] 9. **Market Opportunity**: - Current ALK market valued at approximately $2 billion, with potential for significant growth [39] - The company aims to establish neladalkib as a best-in-class drug for ALK-positive NSCLC [9][32] Additional Important Information - **Regulatory Plans**: Nuvalent plans to discuss data with the FDA for potential NDA submission for TKI-pretreated patients [32][43] - **Expanded Access Program**: Over 200 patients enrolled in the expanded access program, indicating strong interest and need for neladalkib [48] - **Future Directions**: Ongoing development for other ALK-positive solid tumors and HER2-altered NSCLC [33][34] This summary encapsulates the critical insights from Nuvalent's conference call, focusing on the company's advancements in treating ALK-positive non-small cell lung cancer and the potential market implications.

Company Overview - Nuvalent has a growing team of over 200 full-time employees (FTEs) and expects its cash runway to extend into 2028 [5] - The company has parallel lead programs for ROS1+ and ALK+ NSCLC in global clinical development, with potential for first FDA approval in 2026 [6] - Nuvalent leverages deep expertise in chemistry and structure-based drug design to maximize patient impact [7] Pipeline Programs - Zidesamtinib (NVL-520) is in an ongoing registration-directed Phase 2 trial for TKI-naïve and TKI pre-treated patients with ROS1+ NSCLC [16] - Neladalkib (NVL-655) is in an ongoing registration-directed Phase 2 trial for TKI pre-treated patients and an ongoing registration-directed Phase 3 trial for TKI-naïve patients with ALK+ NSCLC [16] - NVL-330 for HER2-altered NSCLC is in an ongoing Phase 1a/1b trial [16] Zidesamtinib (NVL-520) for ROS1+ NSCLC - In TKI pre-treated ROS1+ NSCLC, the ORR was 44% (51/117) across any prior ROS1 TKI and 51% (28/55) in patients with 1 prior ROS1 TKI [81] - Among TKI pre-treated patients with the ROS1 G2032R mutation, the ORR was 54% (14/26) [91] - In TKI-naïve ROS1+ NSCLC patients, the ORR was 89% (31/35) and the IC-ORR was 83% (5/6) [112] - 432 patients with ROS1-positive NSCLC were treated at the recommended Phase 2 dose (RP2D) as of March 21, 2025 [74] Neladalkib (NVL-655) for ALK+ NSCLC - In a heavily pre-treated ALK+ NSCLC population, the ORR was 38% (39/103) across all doses and 38% (15/39) at the RP2D [170] - Among patients with any ALK resistance mutation, the ORR at RP2D was 55% (12/22) [179] - For patients with compound ALK resistance mutations after prior lorlatinib, the ORR at RP2D was 64% (7/11) [179] - In ALK+ solid tumors beyond NSCLC, the overall ORR was 44% (15/34) [208] Market Opportunity - The combined worldwide sales for ALK and ROS1 TKIs in 2024 were approximately $3.1 billion [33] - Alectinib (1L Standard of Care, ALK+ NSCLC) sales were approximately $1.8 billion [34] - Crizotinib (1L Standard of Care, ROS1+ NSCLC) sales were $374 million in 2023 [34, 35] - Other ROS1 and ALK TKIs (Generally used 2L+) sales were approximately $1.2 billion [34]

Core Insights - Nuvalent, Inc. has completed its rolling NDA submission for zidesamtinib targeting TKI pre-treated advanced ROS1-positive NSCLC, marking a significant milestone in its pipeline [2][6] - The company is on track to report topline pivotal data for neladalkib in TKI pre-treated advanced ALK-positive NSCLC by the end of 2025 [2][6] - Nuvalent maintains a strong financial position with cash runway anticipated into 2028, supporting its transition to a fully integrated commercial-stage biopharmaceutical company [2][5] Pipeline Achievements - The NDA submission for zidesamtinib was supported by data presented at the IASLC 2025 World Conference on Lung Cancer [6] - Preliminary clinical data for neladalkib shows potential in treating advanced ALK-positive solid tumors beyond NSCLC, with ongoing evaluation in the ALKOVE-1 trial [6][7] - The ALKAZAR trial is evaluating neladalkib for TKI-naïve patients with advanced ALK-positive NSCLC, with enrollment ongoing [6][7] Financial Results - As of September 30, 2025, Nuvalent reported cash, cash equivalents, and marketable securities totaling $943.1 million [5][9] - Research and development expenses for Q3 2025 were $83.8 million, while general and administrative expenses were $28.9 million [5][9] - The net loss for Q3 2025 was $122.4 million, compared to a net loss of $84.3 million in Q3 2024 [5][9] Upcoming Events - Management will participate in a fireside chat at the Jefferies 2025 Global Healthcare Conference in London on November 19, 2025 [4]

Core Insights - Nuvalent, Inc. announced pivotal data for zidesamtinib, a novel ROS1-selective inhibitor, targeting advanced ROS1-positive non-small cell lung cancer (NSCLC) patients, which will be presented at the IASLC 2025 World Conference on Lung Cancer [1][2] - The company has initiated a rolling NDA submission for zidesamtinib, with the FDA agreeing to accept the NDA for the Real-Time Oncology Review pilot program, aiming for completion in Q3 2025 [2][3] Company Overview - Nuvalent, Inc. is a clinical-stage biopharmaceutical company focused on developing targeted therapies for cancer, specifically for clinically proven kinase targets [5][6] - The company leverages expertise in chemistry and structure-based drug design to create innovative small molecules that address treatment resistance and minimize adverse events [6] Product Details - Zidesamtinib is designed to be a brain-penetrant ROS1-selective inhibitor, effective against tumors that have developed resistance to existing ROS1 inhibitors, including those with treatment-emergent mutations [3][4] - The ARROS-1 Phase 1/2 clinical trial is investigating zidesamtinib in patients with advanced ROS1-positive NSCLC, with the Phase 1 portion focusing on safety and tolerability [4]