BLU-451 / Blueprint Medicines - LARVOL DELTA

BLU-451-1101: (Concerto) Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations (clinicaltrials.gov) - P1/2 | N=332 | Active, not recruiting | Sponsor: Blueprint Medicines Corporation | Recruiting ➔ Active, not recruiting

EGFR exon 20 • Enrollment closed • Metastases • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Blueprint Medicines Highlights 2024 Corporate Strategy and Business Priorities at 42nd Annual J.P. Morgan Healthcare Conference (PRNewswire) - "Discontinue further investment in the early clinical-stage therapies BLU-945 and BLU-451 for EGFR-mutant NSCLC and explore strategic options, including potential out-licensing, based on the evolving external landscape and emerging clinical data....Present data for BLU-222 in combination with ribociclib and fulvestrant in patients with HR+/HER2- breast cancer in the first half of 2024. Provide update on BLU-222 registration plan in HR+/HER2- breast cancer in the second half of 2024."

Discontinued • P1/2 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BLU-451 is a CNS-penetrant, wild-type-sparing EGFR inhibitor with broad coverage of uncommon EGFR mutations across structure-based subsets. (AACR-NCI-EORTC 2023) - No abstract available

Oncology

BLU-451-1101: (Concerto) Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations (clinicaltrials.gov) - P1/2 | N=332 | Recruiting | Sponsor: Blueprint Medicines Corporation | Trial completion date: Dec 2024 ➔ Jul 2026

EGFR exon 20 • Metastases • Trial completion date • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Emerging phase 1 data of BLU-451 in advanced NSCLC with EGFR exon 20 insertions. (ASCO 2023) - P1/2 | "Background: In patients (pts) with NSCLC harboring EGFR exon 20 insertions (ex20ins), treatment options are limited, with platinum-based chemotherapy with/without programmed death-ligand 1 inhibitors being the standard of care in first line, and recent accelerated approvals of mobocertinib and amivantamab in the USA for second-line treatment. As of the data cutoff, BLU-451 monotherapy was generally well tolerated, with early evidence of clinical activity in heavily pretreated pts with EGFR ex20ins–positive NSCLC. Early data at initial dose levels consisted of tumor reduction including responses, CNS activity, and ctDNA responses. The dose escalation is ongoing to determine the MTD and/or RP2D."

EGFR exon 20 • Metastases • P1 data • CNS Disorders • Cough • Fatigue • Gastrointestinal Disorder • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pruritus • Respiratory Diseases • Solid Tumor • EGFR • PD-L1

Blueprint Medicines Highlights Clinical Progress Across Precision Oncology Pipeline at 2023 ASCO Annual Meeting (PRNewswire) - P1/2 | N=332 | NCT05241873 | Sponsor: Blueprint Medicines Corporation | "Results from the ongoing dose escalation part of the CONCERTO trial of BLU-451 in heavily pretreated patients with NSCLC driven by EGFR exon 20 insertions (n=48) or atypical mutations (n=9) showed evidence of safety and clinical benefits, including central nervous system (CNS) activity....In patients with EGFR exon 20 insertion-positive NSCLC, BLU-451 demonstrated evidence of clinical activity including circulating tumor DNA (ctDNA) clearance, tumor reductions including confirmed partial responses, and CNS activity. Multiple patients showed CNS benefits including one who had a partial CNS response per RECIST version 1.1 criteria and one who had a CNS complete response with resolution of multiple non-target brain lesions, as highlighted by patient vignettes in the presentation. In patients with NSCLC driven by atypical EGFR mutations..."

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

BLU-451-1101: Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations (clinicaltrials.gov) - P1/2 | N=332 | Recruiting | Sponsor: Blueprint Medicines Corporation | N=150 ➔ 332

EGFR exon 20 • Enrollment change • Metastases • Brain Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR

"#PLCClive23 Dr. @ElaineShumMD explains what makes #EGFR exon 20 insertions unique and outlines the available targeted agents: amivantamab and mobocertinib. New agents show a lot of promise including CLN-081, sunvozertinib, and BLU-451." (@StephenVLiu)

EGFR exon 20 • EGFR

Ministry of Food and Drug Safety, approval of 7 clinical trials including Samil Pharmaceutical’s gastrointestinal motility regulator [Google translation] (Health Korea News) - "Medspace has been approved for the phase 1/2 clinical trial of the targeted anti-cancer drug 'BLU-451'. The efficacy and safety of 'BLU-451' will be evaluated in 15 advanced cancer patients with EGFR exon 20 insertion mutations. The test will be conducted at three institutions including Asan Medical Center in Seoul."

New P1/2 trial • Oncology

Blueprint Medicines Outlines 2027 Blueprint to Achieve Precision Medicine at Scale and Reports Third Quarter 2022 Financial Results at Investor Day 2022 (PRNewswire) - "Key Upcoming Milestones...Submit an IND to the FDA for BLU-525 for the treatment of EGFR-mutant NSCLC in the first quarter of 2023; Present initial data from the Phase 1/2 CONCERTO study of BLU-451 in patients with EGFR-mutant NSCLC in the first half of 2023; Present initial data from the Phase 1/2 VELA trial of BLU-222 in CDK2-vulnerable cancers in the first half of 2023."

IND • P1/2 data • Breast Cancer • Endometrial Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Estrogen Receptor Positive Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • HER2 Negative Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • CDK2 • KIT

Phase 1/2 Study of BLU-451, a Small Molecule Inhibitor of EGFR, in EGFR Exon 20 Insertion-Mutant Incurable Advanced Cancers (IASLC-WCLC 2022) - P1/2 | "While two EGFR ex20ins-targeting drugs were recently approved by the US Food and Drug Administration (amivantamab and mobocertinib), neither have established CNS activity. Phase 2 will enroll patients in 3 cohorts (n=18 each): patients treated with prior platinum-based chemotherapy and an EGFR ex20ins-targeted agent; patients treated with prior platinum but no EGFR ex20ins-targeted agent; and patients with active asymptomatic brain metastases treated with prior platinum with or without an EGFR ex20ins-targeted agent. The study is planned to enroll at approximately 40 centers in North America, the Asia-Pacific region, and/or Europe."

EGFR exon 20 • P1/2 data • Brain Cancer • CNS Tumor • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

Phase 1/2 study of BLU-451, a central nervous system (CNS) penetrant, small molecule inhibitor of EGFR, in incurable advanced cancers with EGFR exon 20 insertion (ex20ins) mutations. (ASCO 2022) - P1/2 | "While two EGFR ex20ins-targeting drugs were recently approved by the FDA (amivantamab and mobocertinib), neither have established CNS activity. Phase 2 will enroll patients in 3 cohorts (n = 18 each): patients with prior platinum-based chemotherapy and an EGFR ex20ins-targeted agent; patients with prior platinum but no EGFR ex20ins-targeted agent; and patients with active asymptomatic brain metastases with prior platinum with or without an EGFR ex20ins-targeted agent. The study is planned for approximately 40 centers in North America, the Asia-Pacific region, and/or Europe."

EGFR exon 20 • P1/2 data • Brain Cancer • CNS Tumor • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

Blueprint Medicines Reports Second Quarter 2022 Results (Blueprint Medicines Press Release) - "Key Upcoming Milestones...Present updated BLU-945 monotherapy data and initial dose escalation data for BLU-945 in combination with osimertinib from the Phase 1/2 SYMPHONY trial in EGFR-mutant NSCLC in the second half of 2022; Present initial clinical data from the Phase 1/2 HARMONY trial of BLU-701 in EGFR-mutant NSCLC in the second half of 2022; Present initial clinical data from the Phase 1/2 CONCERTO trial of BLU-451 in EGFR-mutant NSCLC in the first half of 2023; Present initial clinical data from the Phase 1/2 VELA trial of BLU-222 in CDK2-vulnerable cancers in the first half of 2023."

P1/2 data • Endometrial Cancer • Esophageal Adenocarcinoma • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • CDK2 • EGFR

LNG-451, a potent inhibitor of EGFR exon 20 insertion mutations with high CNS exposure (AACR 2022) - "While several small molecules have been approved (mobocertinib) or are in clinical development (e.g. CLN-081, BDTX-189) none have demonstrated meaningful CNS activity and they can be associated with treatment-limiting adverse events, including wild-type (WT) EGFR-mediated toxicities. An ex vivo imaging analysis of the brain and spinal cords from all animals at the end of the study showed a dose-dependent decrease in the bioluminescent signal in both brain and spinal cords from mice treated with LNG-451 relative to the vehicle control animals. Taken together, LNG-451 is a CNS-penetrant, wild-type EGFR-sparing, EGFR Ex20ins inhibitor that is expected to provide strong anti‑tumor efficacy for patients with advanced/metastatic solid cancers harboring oncogenic EGFR exon 20 insertions with reduced WT EGFR driven toxicities."

EGFR exon 20 • Lung Cancer • Oncology • Solid Tumor • EGFR

LNG-451 is a potent, CNS-penetrant, wild-type EGFR sparing inhibitor of EGFR exon 20 insertion mutations (AACR 2022) - "While several small molecules have been approved (mobocertinib) or are in clinical development (e.g. CLN-081, BDTX-189) none have demonstrated meaningful CNS activity and they can be associated with treatment-limiting adverse events, including wild-type (WT) EGFR-mediated toxicities. LNG-451 potently suppressed EGFR phosphorylation in tumor tissue (e.g. 99%, 3 h post 50 mg/kg dose) but had minimal-to modest suppression of phospho-EGFR in large intestine tissue (e.g. 4.2%, 3h post 50 mg/kg dose) and skin tissue (e.g 1.9%, 3h post 50 mg/kg dose). Taken together, LNG-451 is a wild-type EGFR-sparing, CNS-penetrant EGFR Ex20ins inhibitor that is expected to provide strong anti‑tumor efficacy for patients with advanced/metastatic solid cancers harboring oncogenic EGFR exon 20 insertions with reduced WT EGFR-driven toxicities."

EGFR exon 20 • Lung Cancer • Oncology • Solid Tumor • EGFR

Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: Blueprint Medicines Corporation | Not yet recruiting ➔ Recruiting | N=96 ➔ 150

EGFR exon 20 • Enrollment change • Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • PD-L1

Blueprint Medicines to Showcase Broad Precision Therapy Pipeline at AACR Annual Meeting 2022 (PRNewswire) - "Blueprint Medicines Corporation...announced plans to present new clinical and preclinical data for multiple programs across its precision therapy portfolio at the American Association for Cancer Research (AACR) Annual Meeting 2022 in New Orleans, April 8 to 13....With multiple drug candidates entering clinical trials, our AACR presentations feature initial results from the Phase 1/2 SYMPHONY study of BLU-945 in EGFR-driven non-small cell lung cancer, as well as data reinforcing our programs' differentiated preclinical profiles and significant potential to advance patient care."

Late-breaking abstract • P1/2 data • Preclinical • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thoracic Cancer

Blueprint Medicines Reports Fourth Quarter and Full Year 2021 Results (PRNewswire) - "The company plans to achieve the following milestones by mid-2022: (i) Initiate a Phase 1/2 trial of BLU-222 in cyclin E-CDK2 aberrant cancers in the first quarter of 2022; (ii) Initiate a Phase 1/2 trial of BLU-451 in EGFR exon 20 insertion-positive NSCLC in the first quarter of 2022; (iii) Present initial clinical data from the Phase 1/2 SYMPHONY trial of BLU-945 in the second quarter of 2022; (iv) Present preclinical data supporting the development of BLU-451 in EGFR exon 20 insertion-positive NSCLC in the second quarter of 2022; (v) Present preclinical data supporting the development of BLU-222 in cyclin E-CDK2 aberrant cancers in the second quarter of 2022."

EGFR exon 20 • New P1/2 trial • P1/2 data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations (clinicaltrials.gov) - P1/2 | N=96 | Not yet recruiting | Sponsor: Blueprint Medicines Corporation

EGFR exon 20 • New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • PD-L1

Blueprint Medicines Completes Acquisition of Lengo Therapeutics (PRNewswire) - "Blueprint Medicines Corporation...announced that the company has successfully completed its previously announced acquisition of Lengo Therapeutics and lead compound LNG-451, a potential best-in-class oral precision therapy in development for the treatment of non-small cell lung cancer (NSCLC) in patients with EGFR exon 20 insertion mutations...'we plan to advance LNG-451 into the clinic in the first quarter of 2022'...under the terms of the agreement, Blueprint Medicines acquired Lengo Therapeutics for $250 million in cash plus up to $215 million in additional potential payments based on the achievement of certain regulatory approval and sales-based milestones."

EGFR exon 20 • M&A • New trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Blueprint Medicines to Expand Precision Therapy Leadership in Lung Cancer with Acquisition of Lengo Therapeutics (PRNewswire) - "Blueprint Medicines Corporation...announced that the company has entered into a definitive agreement under which it will acquire Lengo Therapeutics, a privately held precision oncology company, for $250 million in cash plus up to $215 million in additional potential payments based on the achievement of certain regulatory approval and sales-based milestones. The acquisition includes Lengo Therapeutics' lead compound LNG-451, a potential best-in-class oral precision therapy in development for the treatment of non-small cell lung cancer (NSCLC) in patients with EGFR exon 20 insertion mutations...Based on these and other preclinical data, Lengo Therapeutics anticipates it will submit an investigational new drug (IND) application for LNG-451 to the U.S. Food and Drug Administration (FDA) in December 2021...Blueprint Medicines anticipates the acquisition will close in the fourth quarter of 2021..."

EGFR exon 20 • IND • M&A • Lung Cancer • Non Small Cell Lung Cancer • Oncology