neladalkib (GSK6739060) / Royalty, GSK - LARVOL DELTA

ALK Me Anything: A Rare Sarcoma's Grand Peritoneal Debut (ACG 2026) - "Pathology revealed ALK-positive EIMS, and the patient was initiated on alectinib. He enrolled in a clinical trial for neladalkib and currently remains on the drug with significant reduction of tumor burden on imaging...Figure: (B) Rearrangement of ALK-1 by Vysis LSI ALK dual color break apart. FISH probe was positive (arrow)."

Dyspepsia • Eosinophilia • Sarcoma • Solid Tumor • ALK

Targeting the Tumor, Tripping the Liver: A Rare Case of Neladalkib-Induced DILI (ACG 2026) - "Neladalkib was held and LFTs peaked (AST 6,594; ALT >5,000)...She received N-acetylcysteine (NAC) infusion and hemodiafiltration...The absence of viral markers and unremarkable liver imaging strongly point toward a drug-induced etiology; concurrent medications of colchicine and sertraline were likely non-contributors...Figure: Figure 1. DILI Resolution timeline by ALT, AST, Ammonia, and INRx10"

Clinical • Hepatology • Immunology • Infectious Disease • Liver Failure • Lung Cancer • Nephrology • Oncology • Septic Shock • Solid Tumor • ALK

Neladalkib (NVL-655), a highly selective anaplastic lymphoma kinase (ALK) inhibitor, compared to alectinib in first-line treatment of patients with ALK-positive advanced non-small cell lung cancer: The phase 3 ALKAZAR study. (ASCO 2025) - P3 | "Additional analyses will be conducted to investigate candidate biomarkers and molecular mechanisms of response and resistance to neladalkib and alectinib. The study is open to accrual."

Clinical • Metastases • P3 data • CNS Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

ALKOVE-1: Efficacy and safety of neladalkib in patients with advanced ALK+ NSCLC. (ASCO 2026) - P1/2 | "c Pts with 1 prior 2nd generation ALK TKI (alectinib, n=44; brigatinib, n=2) ± chemo: ORR 48% (22/46) and DOR ≥ 12 m of 74% (95% CI: 48, 88). In this ALK TKI pre-treated data set, neladalkib demonstrated clinically meaningful activity, including in pts with CNS disease, ALK G1202R single or compound mutations, and prior lorlatinib. Encouraging preliminary activity was also observed in TKI-naïve pts. Neladalkib's safety profile was consistent with its ALK-selective, TRK-sparing design."

Clinical • Metastases • CNS Disorders • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK

Phase I Study of Gilteritinib for ALK-Positive Non-Small Cell Lung Cancer: Preliminary Results of Efficacy and Toxicity (IASLC-WCLC 2026) - P1 | "One patient with confirmed PR received 7 prior lines of systemic therapy and tumor was found to harbor the ALK I1171N/L1198F mutations which are predicted to convey resistance to lorlatinib and NVL-655. Early safety and efficacy data support the continued enrollment of patients onto this study. Comprehensive molecular profiling is underway to identify biomarkers that define the subgroup that would benefit from gilteritinib."

Clinical • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Musculoskeletal Pain • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • AXL • CTCs • FLT3 • KIT

NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations. (PubMed, Cancer Discov) - "These preclinical findings are supported by three case studies from an ongoing first-in-human phase I/II trial of NVL-655 which demonstrate preliminary proof-of-concept clinical activity in heavily pretreated patients with ALK fusion-positive non-small cell lung cancer, including in patients with brain metastases and single or compound ALK resistance mutations. Significance: By combining broad activity against single and compound ALK resistance mutations, brain penetrance, and selectivity, NVL-655 addresses key limitations of currently approved ALK inhibitors and has the potential to represent a distinct advancement as a fourth-generation inhibitor for patients with ALK-driven cancers."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Phase I/II ALKOVE-1 study of NVL-655 in ALK-positive (ALK+) solid tumours (ESMO 2024) - P1/2 | "NVL-655 demonstrated encouraging efficacy & durability in heavily pretreated ALK+ NSCLC pts, including pts who exhausted available therapies (including lorlatinib), with ALK single and compound resistance mutations, and with CNS metastases. Safety was favorable, consistent with the ALK-selective, TRK-sparing design. Ph 2 enrollment is ongoing with registrational intent for previously treated pts."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

NVL-655, a Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor, in Patients with Advanced ALK-Positive Solid Tumors: The Phase 1/2 ALKOVE-1 Study (ELCC 2023) - P1/2 | "Longitudinal analysis of circulating tumor DNA will be performed, including ALK mutation profiling and other relevant biomarkers. The phase I portion of the study is ongoing."

Clinical • IO biomarker • Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK

Neladalkib: “Meaningful clinical responses for TKI-pretreated (range 1-5 prior ALK-TKI) across both lorlatinib-naïve (ORR = 46%, median DOR not reached, DOR > 12 months for 80% and lorlatinib experienced patients (ORR = 26%; median DOR of 17.6 months)”; Non-small cell lung cancer (Nuvalent) - Thoracic Malignancies Summit 2026

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

GSK completes $10.6 billion acquisition of Nuvalent (Investing.com) - "The transaction has an aggregate equity value of approximately $10.6 billion (£8.0 billion). Net of cash acquired, GSK’s aggregate investment totals approximately $9.4 billion (£7.1 billion). GSK completed a tender offer to acquire all of Nuvalent’s outstanding shares...The acquisition adds three lung cancer assets to GSK’s oncology portfolio. Zidesamtinib (NVL-520) and neladalkib (NVL-655)....The acquisition also includes NVL-330, which is in phase I development for HER2-altered NSCLC."

M&A • Non Small Cell Lung Cancer

ALKAZAR: Neladalkib (NVL-655) for TKI-naive Patients With Advanced ALK-Positive NSCLC (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: Nuvalent Inc. | Initiation date: Mar 2025 ➔ Jul 2025

Trial initiation date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

GSK plc…announced that it has entered an agreement to acquire Nuvalent, Inc…a Boston-based clinical-stage biopharmaceutical company focused on creating precisely targeted oncology therapies, for $10.6 billion. (GSK Press Release) - "Both assets...are in review with target decision dates of 18 September 2026 for zidesamtinib and 27 November 2026 for neladalkib. Subject to FDA approval, they are expected to launch in 2026 and have multi-blockbuster potential. The third asset, NVL-330, is a potential best-in-class HER2 inhibitor currently in phase I trials for HER2-altered NSCLC...The acquisition provides GSK with immediate new sales growth opportunities, improving profit contributions from 2027, and a platform in lung cancer for rapid expansion with Ris-Rez, our B7-H3 targeted ADC in phase III clinical development...Under the terms of the merger agreement, GSK will commence a tender offer to acquire all of Nuvalent’s outstanding shares of Class A and Class B common stock at a purchase price of $124 per share in cash within 10 business days."

Launch US • Licensing / partnership • PDUFA • Non Small Cell Lung Cancer

The U.S. FDA has accepted for filing Nuvalent’s NDA for neladalkib, an investigational ALK-selective inhibitor, in tyrosine kinase inhibitor (TKI) pre-treated advanced ALK-positive non-small cell lung cancer (NSCLC). (Nuvalent Press Release) - "The application has been granted Priority Review and assigned a PDUFA target action date of November 27, 2026. The submission is based on data in TKI pre-treated patients with advanced ALK-positive NSCLC treated with neladalkib in the global, registration-directed ALKOVE-1 Phase 1/2 clinical trial."

FDA filing • PDUFA • Priority review • Non Small Cell Lung Cancer

Pivotal Data for Neladalkib in TKI Pre-treated Patients with Advanced ALK-positive NSCLC from ALKOVE-1 Clinical Trial (PRNewswire) - "The pivotal data to be presented, initially announced in November 2025, are from TKI pre-treated patients with advanced ALK-positive NSCLC treated with neladalkib in the global, registration-directed ALKOVE-1 Phase 1/2 clinical trial. In this population, neladalkib demonstrated encouraging overall activity, including intracranial responses, the ability to address key drivers of disease progression, and a generally well-tolerated safety profile consistent with its ALK-selective, TRK-sparing design."

P1/2 data • Non Small Cell Lung Cancer

The novel ALK K1150dup mutation mediates resistance to frontline lorlatinib and retains sensitivity to gilteritinib. (PubMed, NPJ Precis Oncol) - "Functional studies using EML4::ALK-dependent Ba/F3 cells demonstrated that ALK K1150dup confers resistance to lorlatinib and other ALK-TKIs including NVL-655 (neladalkib), with sustained ALK phosphorylation and downstream signaling. These findings reveal K1150dup as a previously unidentified mechanism of resistance to first-line lorlatinib, and highlight gilteritinib as a potential therapeutic option for patients harboring this mutation. Notably, they also challenge the prevailing assumption that first-line lorlatinib precludes the emergence of single on-target ALK resistance mutations."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4

Enrollment is ongoing in ALKAZAR, the company’s global Phase 3 randomized, controlled trial designed to evaluate neladalkib for the treatment of patients with TKI-naïve ALK-positive NSCLC. (PRNewswire) - "The company expects to continue to progress the ALKAZAR trial throughout 2026."

Trial status • Non Small Cell Lung Cancer

Neladalkib: “Topline efficacy results: TKI pre-treated, Lorlatinib-naïve”; Non-small cell lung cancer (Nuvation Bio) - Corporate Presentation: “Safety profile of neladalkib was generally well tolerated and consistent with its ALK-selective, TRK-sparing design"

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Nuvalent to Present Pivotal Data from ALKOVE-1 Trial of Neladalkib in TKI Pre-treated Advanced ALK-positive NSCLC at the 2026 American Society of Clinical Oncology Annual Meeting (PRNewswire) - "Nuvalent, Inc....announced that pivotal data for neladalkib, an investigational ALK-selective inhibitor, in TKI pre-treated patients with advanced ALK-positive non-small cell lung cancer (NSCLC) from the global ALKOVE-1 Phase 1/2 clinical trial, in addition to preliminary data for TKI-naïve patients, will be presented during an oral presentation at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting from May 29 – June 2, 2026, in Chicago...Additionally, preliminary data in patients with advanced ROS1-positive solid tumors outside of NSCLC from the global ARROS-1 Phase 1/2 clinical trial of zidesamtinib, an investigational ROS1-selective inhibitor, will be presented during a poster session."

P1/2 data • Non Small Cell Lung Cancer • Solid Tumor

Nuvalent Announces Submission of New Drug Application to FDA for Neladalkib in TKI Pre-treated Advanced ALK-positive NSCLC (PRNewswire) - "The application is based on data in TKI pre-treated patients with advanced ALK-positive NSCLC treated with neladalkib in the global, registration-directed ALKOVE-1 Phase 1/2 clinical trial."

FDA filing • Non Small Cell Lung Cancer

Mutagenesis screens support potential best-in-class profile for neladalkib (NVL-655), a brain-penetrant and TRK-sparing ALK inhibitor (AACR 2025) - "Cells were treated with ENU for 1 day followed by alectinib (2G), lorlatinib (3G), or NVL-655 for 28 days. This preclinical study indicates the potential for NVL-655 to prevent acquisition of on-target resistance and thereby provide deeper and more durable target inhibition. The broad preclinical activity against ALK and diverse ALK mutations, together with its brain penetrance and TRK-sparing design, suggests NVL-655 as a potential best-in-class ALK therapy."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EML4

A patient with advanced ALK-positive NSCLC at diagnosis with a follow up of >7 years and multiple lines of systemic therapy and local ablative therapy (DKK 2026) - "He was initially treated with bevacizumab, carboplatin and pemetrexed outside our institution. Due to multiple side effects the therapy was switched to pembrolizumab after the 1st cycle...The patient started alectinib in 11/2018 with rapid clinical improvement and a partial response after 6 weeks...Side effects were hypercholesterinemia (>600 gm/dl) and hypertriglyceridemia (>400 mg/dl) requiring therapy with rosuvastatin and ezetrol...NGS again showed no new on/off-target resistance pattern and he continued lorlatinib...The patient was included in the Early Access Program of NVL-655 currently available at 6 European sites. He started therapy in 06/2025 in Paris and responded in PET-CT after six weeks. He had no side effects CTC >1° and is continuing the therapy."

Clinical • IO biomarker • Metastases • Dyslipidemia • Hypertriglyceridemia • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EML4 • NKX2-1 • PD-L1 • TP53

As part of this plan, Nuvalent anticipates the following 2026 milestones (PRNewswire) - "Commercial launch in the U.S. of zidesamtinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who received at least 1 prior ROS1 tyrosine kinase inhibitor (TKI), pending U.S. Food and Drug Administration (FDA) review; Submit data to FDA for potential indication expansion of zidesamtinib in TKI-naïve patients with advanced ROS1-positive NSCLC in the second half of 2026; Submit a New Drug Application (NDA) for neladalkib in TKI pre-treated patients with advanced ALK-positive NSCLC in the first half of 2026; Progress the ongoing ALKAZAR Phase 3 randomized, controlled trial of neladalkib for TKI-naïve patients with ALK-positive NSCLC; Progress the ongoing HEROEX-1 Phase 1a/1b trial of NVL-330 for patients with advanced HER2-altered NSCLC; and; Disclose a new development candidate by year-end 2026."

FDA filing • Launch US • Pipeline update • Trial status • Non Small Cell Lung Cancer

Royalty Pharma Acquires Royalty Interest in Nuvalent’s Neladalkib and Zidesamtinib for Up to $315 Million (The Manila Times) - "The expected royalty duration for both therapies extends through approximately 2041 to 2042....Existing analyst consensus projects neladalkib sales to be approximately $3.5 billion and zidesamtinib sales to be approximately $1.9 billion by 2035."

Commercial • Sales projection • Non Small Cell Lung Cancer

Nuvalent Announces Positive Topline Pivotal Data from ALKOVE-1 Clinical Trial of Neladalkib for TKI Pre-treated Patients with Advanced ALK-positive NSCLC (PRNewswire) - "In 253 ALK TKI pre-treated patients, ORR by BICR was 31% (95% CI: 26, 37), with initial estimated durability of response of 64% and 53% at the 12-month and 18-month landmarks, respectively. In the subset of 63 TKI pre-treated patients who were lorlatinib-naïve, ORR by BICR was 46% (95% CI: 33, 59), with initial estimated durability of response of 80% and 60% at the 12- and 18-month landmarks, respectively....Company plans to discuss pivotal data for the TKI pre-treated ALK-positive NSCLC population with the FDA at a pre-NDA meeting; detailed study results are planned for presentation at a future medical meeting."

P1/2 data • Non Small Cell Lung Cancer

Nuvalent…announced that the company will host a webcast and conference call on Monday, November 17, 2025 at 8:00 a.m. ET, to discuss topline pivotal data for neladalkib, an investigational ALK-selective inhibitor, in TKI pre-treated patients with advanced ALK-positive non-small cell lung cancer from the global ALKOVE-1 Phase 1/2 clinical trial (PRNewswire)

P1/2 data • Non Small Cell Lung Cancer