BLU-701 / Blueprint Medicines, ZAI Lab - LARVOL DELTA

(HARMONY) Study of BLU-701 in EGFR-mutant NSCLC (clinicaltrials.gov) - P1/2 | N=20 | Terminated | Sponsor: Blueprint Medicines Corporation | N=160 ➔ 20 | Trial completion date: Dec 2024 ➔ Dec 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jun 2024 ➔ Dec 2022; Lack of efficacy

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thoracic Cancer

A phase 1/2 study of the highly selective EGFR inhibitor, BLU-701, in patients with EGFR-mutant non–small cell lung cancer (NSCLC). (ASCO 2022) - P1/2 | "Patients will be enrolled into 3 treatment cohorts: part 1A (n≈40–80; BLU-701), part 1B (n≈35; BLU-701 + osimertinib), and part 1C (n≈18; BLU-701 + carboplatin and pemetrexed). Patients may receive treatment until disease progression, unacceptable toxicity, or other discontinuation criteria are met. Enrollment in this study has started, and sites will be open across North America, Europe, and Asia."

Clinical • P1/2 data • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • HER-2 • KRAS • NTRK1 • NTRK2 • NTRK3 • ROS1

(HARMONY) Study of BLU-701 in EGFR-mutant NSCLC (clinicaltrials.gov) - P1/2 | N=160 | Active, not recruiting | Sponsor: Blueprint Medicines Corporation | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thoracic Cancer • EGFR

BLU-945 or BLU-701 as single agents versus their combination with osimertinib in EGFR L858R driven tumor models (AACR-NCI-EORTC 2022) - "The in vivo antitumor activities of BLU-945 and BLU-701 as single agents suggest both BLU-945 and BLU-701 have the potential to be used as 1L therapy in patients with EGFR L858R-driven NSCLC. The superior in vivo antitumor activity of BLU-945 or BLU-701 in combination with osimertinib in prolonging the DOR or increasing tumor growth inhibition in these models may have clinical application in improving outcomes of patients with EGFR L858R-driven NSCLC in 1L settings."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Phase 1/2 Study of BLU-701, a Highly Selective EGFR Inhibitor, in Patients With EGFR-Mutant Non-Small Cell Lung Cancer (IASLC-WCLC 2022) - P1/2 | "Patients will be enrolled into 3 treatment cohorts: part 1A (n≈40-80; BLU-701), part 1B (n≈35; BLU-701 + osimertinib), and part 1C (n≈18; BLU-701 + carboplatin and pemetrexed). Patients may receive treatment until disease progression, unacceptable toxicity, or other discontinuation criteria are met. Enrollment has started, and sites will be open across North America, Europe, and Asia."

Clinical • P1/2 data • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • HER-2 • KRAS • NTRK1 • NTRK2 • NTRK3 • ROS1

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

Antitumor activity of BLU-945 and BLU-701 as single agents and in combination in EGFR L858R-driven models of NSCLC (AACR 2022) - "The in vivo antitumor activities of BLU-945 and BLU-701 in preclinical tumor models suggest that both BLU-945 and BLU-701 have the potential to be used in patients with EGFR L858R-driven NSCLC, including those who are treatment naïve or previously treated with 3G TKI. Combining BLU-945 and BLU-701 may enable coverage of frequent on-target resistance mechanisms, including the EGFR C797S mutation, in addition to the common L858R activating mutation."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Zai Lab Announces Financial Results and Corporate Updates for Twelve Months Ended December 31, 2021 (GlobeNewswire) - "Odronextamab: Anticipated 2022 Partner and Zai Milestone: Complete enrollment in the potentially pivotal Phase 2 study in B-NHL; CLN-081: Enroll first patient in Greater China in the Phase 2a potentially pivotal study in NSCLC; Provide a regulatory update in the first quarter of 2022; BLU-701: Present initial Phase 1/2 HARMONY trial data for BLU-701 in EGFR-driven NSCLC in the second half of 2022."

Enrollment status • P1/2 data • Regulatory • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

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

BLU-701 tumour suppression and intracranial activity as a single agent and in combination with BLU-945 in models of non-small cell lung cancer (NSCLC) driven by EGFR mutations (BTOG 2022) - "Consistent with its brain penetration properties, BLU-701 exhibited dose-dependent brain tumour inhibition that surpassed gefitinib and erlotinib in an EGFR ex19del PC9-luc CDX model in which cells were implanted intracranially or inoculated in the carotid artery (followed by migration to the brain). The in vivo activity of BLU-701 supports its potential as a treatment for patients with EGFR-mutated NSCLC, including those with the C797S mutation resistant to covalent 3rd-generation TKIs, such as osimertinib. Its intracranial penetrance and brain tumour response suggest potential benefits in treating and/or preventing brain metastases. Broader EGFR mutational coverage could be achieved with BLU-701 and BLU-945 in combination, which could potentially prolong responses."

Combination therapy • Brain Cancer • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

(HARMONY) Study of BLU-701 in EGFR-mutant NSCLC (clinicaltrials.gov) - P1/2; N=160; Recruiting; Sponsor: Blueprint Medicines Corporation; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thoracic Cancer • EGFR

Phase 1/2 Study Targeting EGFR Resistance Mechanisms in NSCLC (clinicaltrials.gov) - P1/2; N=160; Not yet recruiting; Sponsor: Blueprint Medicines Corporation

Clinical • New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thoracic Cancer • EGFR

Zai Lab Announces Third Quarter 2021 Financial Results and Corporate Updates (GlobeNewswire) - "[For Tebotelimab] Provide an update regarding ongoing studies and plans for the next stage of development; Present preclinical data supporting combination of BLU-945 and BLU-701 in EGFR-driven NSCLC at a medical conference; Initiate Phase 1 trial of BLU-701 in EGFR-driven NSCLC in the fourth quarter of 2021; [for ZL-1201] Determine a recommended Phase 2 dose in the ongoing Phase 1 trial; [For Simurosertib] Initiate a Phase 2 biomarker-driven proof-of-concept study."

New P2 trial • Preclinical • Trial status • Lung Cancer • Non Small Cell Lung Cancer

Zai Lab and Blueprint Medicines Announce Strategic Collaboration and License Agreement for BLU-945 and BLU-701 in Greater China (GlobeNewswire) - “Zai Lab Limited…and Blueprint Medicines Corporation…announced an exclusive collaboration and license agreement for the development and commercialization of BLU-945 and BLU-701 for the treatment of patients with epidermal growth factor receptor (EGFR) -driven non-small cell lung cancer (NSCLC) in Greater China, including mainland China, Hong Kong, Macau and Taiwan….Blueprint Medicines will receive an upfront cash payment of $25 million and will be eligible to receive up to $590 million in potential development, regulatory and sales-based milestone payments, and tiered royalties on a product-by-product basis ranging from the low-teens to mid-teens on annual net sales of BLU-945 and BLU-701 in Greater China, subject to adjustment in specified circumstances. In addition, Zai Lab will be responsible for all the development costs for BLU-945 and BLU-701 occurring in Greater China and will receive the rights to develop and exclusively commercialize BLU-945 and BLU-701 in the region.”

Licensing / partnership • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Blueprint Medicines Reports Third Quarter 2021 Financial Results (PRNewswire) - "The company expects to achieve the following near-term milestones: (i) Initiate a Phase 1 trial of BLU-701 in patients with EGFR-driven NSCLC in the fourth quarter of 2021; (ii) Present preclinical data supporting combination of BLU-945 and BLU-701 in EGFR-driven NSCLC at a medical conference in early 2022; (iii) Initiate a Phase 1 trial of BLU-222, a CDK2 inhibitor targeting cyclin-E aberrant cancers, in the first quarter of 2022."

New P1 trial • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Blueprint Medicines Reports Second Quarter 2021 Financial Results (PRNewswire) - “Recorded $8.5 million in net product revenue during the second quarter of 2021 for AYVAKIT/AYVAKYT; Recorded $2.9 million in net product revenue during the second quarter of 2021 for GAVRETO; The company expects to achieve the following near-term milestones: Present preclinical data supporting combination of BLU-945 and BLU-701 in treatment-naïve EGFR-driven NSCLC in the second half of 2021; Initiate a Phase 1 trial of BLU-701 in patients with treatment-resistant EGFR-driven NSCLC in the second half of 2021; Initiate a Phase 1 trial of BLU-222, a CDK2 inhibitor targeting cyclin-E aberrant cancers, in the first half of 2022; Disclose topline data for the registration-enabling Part 2 of the PIONEER trial of AYVAKIT in non-advanced systemic mastocytosis in mid-2022.”

New P1 trial • P2 data • Preclinical • Sales • Aggressive Systemic Mastocytosis • Non Small Cell Lung Cancer

[VIRTUAL] BLU-701 is a highly potent, brain-penetrant and WT-sparing next-generation EGFR TKI for the treatment of sensitizing (ex19del, L858R) and C797S resistance mutations in metastatic NSCLC (AACR 2021) - "Third-generation, irreversible TKIs, such as osimertinib and lazertinib, have become standard of care and are now widely used as first-line therapy in EGFR-driven metastatic NSCLC. Due to its potent pharmacological activity and selectivity for mutant EGFR, BLU-701 has the potential to demonstrate activity in first-line and resistance settings as a single agent and in combination therapy, addressing potential tumor heterogeneity. The pre-clinical data described here supports the clinical development of BLU-701 in EGFR-driven NSCLC."

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

Blueprint Medicines Reports First Quarter 2021 Financial Results (PRNewswire) - “Initiate a global Phase 1 trial of BLU-945 in patients with treatment-resistant EGFR-driven NSCLC in the second quarter of 2021. Complete enrollment of the registration-enabling Part 2 of the PIONEER trial of AYVAKIT in non-advanced SM in mid-2021. Initiate the Phase 2/3 HARBOR trial of BLU-263 in patients with non-advanced SM in mid-2021. Initiate a Phase 1 trial of BLU-701 in patients with treatment-resistant EGFR-driven NSCLC in the second half of 2021. Present preclinical data supporting combination of BLU-945 and BLU-701 in treatment-naïve EGFR-driven NSCLC in the second half of 2021.”

Enrollment status • New P1 trial • New P2/3 trial • Preclinical • Aggressive Systemic Mastocytosis • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Blueprint Medicines Presents Preclinical Data Highlighting Broad Precision Therapy Research Pipeline at AACR Annual Meeting 2021 (PRNewswire) - "Blueprint Medicines Corporation...announced data from multiple poster presentations highlighting the breadth of the company's precision therapy pipeline at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021...Additional presentations of clinical data for AYVAKIT™ (avapritinib) and BLU-263 will be reported on Sunday, April 11, 2021...The preclinical data presented for BLU-701 and BLU-945 support the continued development of both candidates in patients with EGFR-driven NSCLC...BLU-945 has been cleared by the U.S. Food and Drug Administration (FDA) and an international Phase 1 dose escalation trial is expected to begin this quarter. Future clinical development of BLU-945 in combination with other agents across multiple treatment settings is planned. BLU-701 is expected to enter clinical development later this year."

New P1 trial • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Blueprint Medicines to Showcase Scientific Leadership in Precision Oncology and Hematology at AACR Annual Meeting 2021 (PRNewswire) - “Blueprint Medicines Corporation…announced plans to present new data for multiple research- and clinical-stage programs across the company's precision oncology and hematology portfolio at the American Association for Cancer Research (AACR) Annual Meeting 2021. Collectively, the planned data presentations will highlight the potential of Blueprint Medicines' precision therapies to deliver transformative benefits to broad patient populations with systemic mastocytosis, non-small cell lung cancer and cyclin E-aberrant cancers.”

Preclinical • Aggressive Systemic Mastocytosis • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology