GSK6855547 / GSK - LARVOL DELTA

NVL-330, a selective HER2 tyrosine kinase inhibitor, in patients with advanced or metastatic HER2-altered non-small cell lung cancer: The phase 1 HEROEX-1 study. (ASCO 2025) - P1 | "The antibody drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) has received FDA accelerated approval for HER2-mutant NSCLC, but no tyrosine kinase inhibitors (TKIs) are currently approved for this indication...Analyses will be performed to evaluate tumor and blood-based biomarkers of response and other relevant biomarkers. The study is open to accrual."

Clinical • IO biomarker • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

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

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

Enrollment is ongoing in the HEROEX-1 Phase 1a/1b clinical trial evaluating the overall safety and tolerability of NVL-330 for pre-treated patients with HER2-altered NSCLC. (PRNewswire) - "The company expects to continue to progress the HEROEX-1 trial throughout 2026."

Trial status • Non Small Cell Lung Cancer

Preclinical characterization of NVL-330, a selective and brain penetrant HER2 tyrosine kinase inhibitor with broad activity on HER2 oncogenic alterations (AACR 2024) - "NVL-330 was broadly and selectively active against HER2 oncogenic alterations in vitro and in vivo, and demonstrated brain penetrance in rodents exceeding that of HER2 investigational TKI zongertinib and T-DXd. This preclinical profile supports the potential for NVL-330 to address a medical need for patients with HER2-driven cancers, including those with brain metastases."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

A Study of NVL-330 in Patients With Advanced or Metastatic HER2-altered NSCLC (HEROEX-1) (clinicaltrials.gov) - P1 | N=200 | Recruiting | Sponsor: Nuvalent Inc. | N=150 ➔ 200 | Trial completion date: Mar 2026 ➔ Feb 2027 | Trial primary completion date: Mar 2026 ➔ Jan 2027

Enrollment change • First-in-human • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

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

Preclinical intracranial activity of NVL-330, a selective HER2 tyrosine kinase inhibitor (AACR-NCI-EORTC 2025) - "In this preclinical study, NVL-330 was broadly and selectively active against HER2 oncogenic alterations and demonstrated favorable brain penetrance and/or intracranial activity compared to T-DXd, zongertinib, and sevabertinib. This differentiated preclinical profile supports the potential for NVL-330 to address a medical need for patients with HER2-driven cancers, including those with brain metastases."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ABCB1 • EGFR • HER-2

Nuvalent presented new preclinical data for its novel HER2-selective inhibitor, NVL-330, at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics... (PRNewswire) - "Compared to several currently available and investigational HER2 TKIs in the same preclinical assays, NVL-330 demonstrated a favorable efflux ratio and brain partitioning, metrics that are potentially positive predictors of brain exposure in humans. In preclinical models of intracranial activity, NVL-330 induced deep intracranial regression in mice. In the same models, the approved therapies T-DXd and zongertinib did not induce intracranial regression at their clinically relevant doses. Additionally, NVL-330 induced intracranial tumor regression in mice that had progressed in the CNS on zongertinib....The company expects to continue to progress the HEROEX-1 trial throughout 2025."

Preclinical • Trial status • Non Small Cell Lung Cancer • HER-2

Nuvalent to Present New Preclinical Data for HER2-Selective Inhibitor, NVL-330, at AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (PRNewswire)

Preclinical • Solid Tumor

Nuvalent to Present Trial in Progress Posters for the ALKAZAR Trial of Neladalkib and HEROEX-1 Trial of NVL-330 at the 2025 American Society of Clinical Oncology Annual Meeting (PRNewswire) - "The first 'Trial in Progress' poster will include background and study design for ALKAZAR (NCT06765109), a global, randomized, controlled Phase 3 trial designed to evaluate neladalkib versus the current standard of care for the treatment of patients with TKI-naïve ALK-positive non-small cell lung cancer (NSCLC)....The company plans to initiate the ALKAZAR trial in the first half of 2025. The second poster will include background and study design for the ongoing HEROEX-1 Phase 1a/1b clinical trial (NCT06521554) evaluating the overall safety and tolerability of NVL-330 for pre-treated patients with HER2-altered NSCLC."

Clinical protocol • Trial status • Non Small Cell Lung Cancer

Nuvalent Details Strategy to Seek First Potential Approval in 2026 and Outlines Key Anticipated 2025 Milestones (PRNewswire) - "As part of this plan, Nuvalent anticipates the following 2025 milestones: Report pivotal data for tyrosine kinase inhibitor (TKI) pre-treated patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) from its ARROS-1 Phase 1/2 trial of zidesamtinib in the first half of 2025; Submit a New Drug Application (NDA) for zidesamtinib with initial target indication of TKI pre-treated patients with advanced ROS1-positive NSCLC by mid-year 2025; Report pivotal data for TKI pre-treated patients with advanced ALK-positive NSCLC from its ALKOVE-1 Phase 1/2 trial of neladalkib (NVL-655) by year-end 2025; Initiate the ALKAZAR Phase 3 randomized, controlled trial of neladalkib for TKI-naïve patients with ALK-positive NSCLC in the first half of 2025; and Progress the HEROEX-1 Phase 1a/1b trial of NVL-330 for patients with advanced HER2-altered NSCLC."

FDA filing • P1/2 data • Trial status • Non Small Cell Lung Cancer

Nuvalent Highlights Corporate and Pipeline Achievements, Reiterates Key Anticipated Milestones, and Reports Third Quarter 2024 Financial Results (PRNewswire) - "Enrollment is ongoing in the HEROEX-1 Phase 1a/1b clinical trial evaluating NVL-330 for pre-treated patients with HER2-altered NSCLC. The trial will evaluate the overall safety and tolerability of NVL-330. Additional objectives include determination of the recommended Phase 2 dose (RP2D), characterization of the pharmacokinetic profile, and preliminary evaluation of anti-tumor activity."

Enrollment status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Nuvalent Highlights Pipeline Progress, Reiterates Key Anticipated Milestones, and Reports Second Quarter 2024 Financial Results (PRNewswire) - "Enrollment is ongoing in the HEROEX-1 Phase 1a/1b clinical trial evaluating NVL-330 for pre-treated patients with HER2-altered NSCLC (NCT06521554)...2024: Execute on Global Registrational Strategies: Progress the Phase 2 portion of its ARROS-1 trial of zidesamtinib in patients with advanced ROS1-positive NSCLC with registrational intent; Initiate the Phase 2 portion of its ALKOVE-1 trial of NVL-655 in patients with advanced ALK-positive NSCLC with registrational intent; Launch the front-line development strategy for its ALK program; Initiate the Phase 1 trial for its HER2 program. Present interim data from its ongoing ARROS-1 and ALKOVE-1 clinical trials at medical meetings; and, 2025: First Pivotal Data: 2026: First Approved Product."

Clinical data • Enrollment status • New P1 trial • P1/2 data • Trial status • Non Small Cell Lung Cancer • HER-2

Nuvalent Announces First Patient Dosed in HEROEX-1 Phase 1a/1b Clinical Trial of NVL-330, its Novel HER2-selective Inhibitor (PRNewswire) - "Nuvalent, Inc...announced the initiation of HEROEX-1, its Phase 1a/1b clinical trial evaluating its novel HER2-selective inhibitor, NVL-330, for pre-treated patients with HER2-altered non-small cell lung cancer (NSCLC)....HEROEX-1 is a Phase 1a/1b, multicenter, open-label, dose-escalation and expansion trial evaluating NVL-330 in pre-treated patients with advanced HER2-altered NSCLC, including those with HER2 exon 20 mutations."

Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of NVL-330 in Patients With Advanced or Metastatic HER2-altered NSCLC (HEROEX-1) (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Nuvalent Inc.

Metastases • New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

📣 Our 3rd program, NVL-330, is now in clinical development! Learn more about HEROEX-1, our Phase 1a/1b clinical trial of NVL-330 for pre-treated patients with HER2-altered #NSCLC, now open and enrolling. https://investors.nuvalent.com/2024-07-22-Nuvalent-Announces-First-Patient-Dosed-in-HEROEX-1-Phase-1a-1b-Clinical-Trial-of-NVL-330,-its-Novel-HER2-selective-Inhibitor #HER2 #oncology #biotech

👋 Connect with us at #AACR24, where we are presenting new data further characterizing the differentiated preclinical profiles of NVL-330 and zidesamtinib. View our posters: https://nuvalent.com/publications/?pag=1&filter=all Read more: ...

Nuvalent Presents New Preclinical Data Supporting Profiles of HER2-Selective Inhibitor, NVL-330, and ROS1-Selective Inhibitor, Zidesamtinib, at AACR Annual Meeting 2024 (PRNewswire) - "Nuvalent...announced the presentation of new preclinical data for its novel HER2-selective inhibitor, NVL-330....at the American Association for Cancer Research (AACR) Annual Meeting....In a preclinical comparison with the selective tyrosine kinase inhibitor, zongertinib, NVL-330 demonstrated: Similar potency and selectivity over wild-type EGFR; and, Higher CNS penetrance. In a preclinical comparison with antibody drug conjugate, T-DXd (Enhertu), NVL-330 demonstrated: Deeper response and higher CNS penetrance in an intracranial tumor model; and, Activity in cells with acquired resistance to T-DXd....In 2024, the company expects to initiate a Phase 1 trial for its HER2 program."

New P1 trial • Preclinical • Oncology

📊 Join us at the American Association for Cancer Research's Annual Meeting for new preclinical data on our HER2-selective inhibitor, NVL-330, and ROS1-selective inhibitor, zidesamtinib (NVL-520)! Learn more: https://bit.ly/4a1oVdQ #AACR24

Nuvalent Highlights Pipeline Progress, Reiterates Key Anticipated Milestones and Reports Fourth Quarter and Full Year 2023 Financial Results (PRNewswire) - "2024: Execute on Global Registrational Strategies: Progress the Phase 2 portion of its ARROS-1 trial of NVL-520 in patients with advanced ROS1-positive NSCLC with registrational intent; Initiate the Phase 2 portion of its ALKOVE-1 trial of NVL-655 in patients with advanced ALK-positive NSCLC with registrational intent; Launch the front-line development strategy for its ALK program; Present interim data from its ongoing ARROS-1 and ALKOVE-1 clinical trials at medical meetings; and, Initiate the Phase 1 trial for its HER2 program. 2025: First Pivotal Data; 2026: First Approved Product."

Clinical data • New P1 trial • P1/2 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Nuvalent to Present New Preclinical Data on HER2-Selective Inhibitor, NVL-330, and ROS1-Selective Inhibitor, zidesamtinib, at AACR Annual Meeting 2024 (PRNewswire) - "Nuvalent...announced upcoming preclinical data poster presentations further characterizing the preclinical profiles of its novel HER2-selective inhibitor, NVL-330, and novel ROS1-selective inhibitor, zidesamtinib (NVL-520), at the American Association for Cancer Research (AACR) Annual Meeting 2024..."

Preclinical • Solid Tumor

Nuvalent Announces $300M Public Stock Offering (Precision Medicine Online) - "Nuvalent on Monday announced an underwritten public offering of 56,698,780 shares of common stock at $57.99 per share, which it expects will bring in $281.6 million in proceeds...Nuvalent will also grant the underwriters a 30-day option to purchase an additional 15 percent, or $45 million, of shares at the public offering price. This will increase the total number of shares publicly offered to 57,474,776 and the total proceeds the company expects to raise to $323.9 million if the underwriters exercise their option in full....According to a filing with the US Securities and Exchange Commission, the firm will use the funds to advance its pipeline candidates, including the ROS1 inhibitor NVL-520, ALK inhibitor NVL-655, and HER2 inhibitor NVL-330. The firm will also use the proceeds for working capital and other general corporate purposes and may use the funds to in-license, acquire, or invest in product candidates or technologies to further grow its pipeline."

Financing • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

NVL-330 is a selective, brain-penetrant inhibitor of oncogenic HER2 exon 20 insertion mutations in preclinical models (AACR-NCI-EORTC 2022) - "NVL-330 is a wild-type EGFR-sparing, brain-penetrant small-molecule inhibitor of HER2 exon20ins in preclinical models, demonstrating the potential to address a medical need for HER2 exon 20 insertion mutant NSCLC patients."

HER2 exon 20 • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ABCB1 • EGFR • HER-2

Nuvalent Announces New Preclinical Data for Selective Kinase Inhibitors NVL-330 and NVL-655 (PRNewswire) - "Preliminary data from the Phase 1 portion of the ARROS-1 study of Nuvalent's parallel lead program, NVL-520, will also be presented at the 'New Drugs on the Horizon' oral plenary session on October 28, 2022....Preclinical data demonstrated that NVL-330 potently inhibited HER2ex20 in cell-based assays and was highly selective for HER2ex20 over the structurally related wild-type EGFR. This selectivity is a critical aspect of NVL-330's design given that inhibition of wild-type EGFR is associated with dose-limiting side effects including skin rash and gastrointestinal toxicity....In addition, the demonstrated preclinical brain penetrance and intracranial activity of NVL-330 suggests the potential for treating or preventing brain metastases. Brain metastases are present at diagnosis in an estimated 19% of HER2 mutant-positive NSCLC patients, and more patients will develop them during treatment."

P1 data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor