Financial Data and Key Metrics Changes - The company reported approximately $570 million in cash, providing a runway into 2028 based on the current operating plan [7] - The overall response rate in the RESILIENT-one study was 35%, with a 40% response rate in patients who progressed after chemotherapy [17][18] - The median duration of response was just under nine months across all groups [18] Business Line Data and Key Metrics Changes - The company is advancing multiple clinical-stage programs, including CLN978 for autoimmune diseases and CLN619 for non-small cell lung cancer [6] - Zipilertinib, the oral EGFR tyrosine kinase inhibitor, has shown promising results in patients with EGFR exon 20 mutations, with breakthrough therapy designation by the FDA [11][12] Market Data and Key Metrics Changes - EGFR mutated non-small cell lung cancer accounts for 16% of all non-small cell lung cancer, with exon 20 mutations representing approximately 12%, translating to an annual incidence of about 3,000 to 5,000 patients in the U.S. [67] - The company noted that patients with exon 20 mutations tend to have a poorer prognosis, highlighting the unmet need for effective therapies [68] Company Strategy and Development Direction - The company plans to pursue regulatory interactions for a potential U.S. NDA filing in the second half of the year [22][23] - There is an expansive development program for zipilertinib across multiple patient segments, including relapsed refractory disease and frontline settings [69][70] - The company retains 50% of the rights for zipilertinib in the U.S. and has a co-development and co-commercialization arrangement with partners at Tahoe [77][78] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the clinical profile of zipilertinib, noting its favorable safety profile compared to existing therapies [75] - The company anticipates significant uptake of zipilertinib once it becomes available, particularly as an oral option for patients [60][62] Other Important Information - The RESILIENT-two study will provide data on patients with active brain metastases and those with uncommon EGFR mutations in the second half of the year [79] - The RESILIENT-three study is ongoing, comparing zipilertinib plus chemotherapy to standard care [72] Q&A Session Summary Question: What is the efficacy of zipilertinib in patients with brain metastases? - The drug has shown encouraging preliminary data in patients with brain metastases, with good disease control observed [84][86] Question: What is the breakdown of patients in real-world settings? - Most patients are heavily pretreated, often having received chemotherapy and amivantamab before seeking other options [88][90] Question: Is there any data on the role of MET amplification in exon 20? - The response to this question was not directly addressed in the provided content, indicating a need for further research [94]

Core Insights - Taiho Oncology, Inc. and Cullinan Therapeutics, Inc. announced positive results from the REZILIENT1 trial for zipalertinib in treating non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations [1][4] - The trial results will be presented at the 2025 ASCO Annual Meeting [1] Company Overview - Taiho Oncology specializes in developing and commercializing orally administered anti-cancer agents, focusing on solid tumors and hematological malignancies [9] - Cullinan Therapeutics is dedicated to creating new standards of care in cancer and autoimmune diseases, with a diversified portfolio of clinical-stage assets [11] Clinical Trial Details - REZILIENT1 is a Phase 1/2 global study evaluating the efficacy and safety of zipalertinib in patients with advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations [5] - The primary endpoints of the trial were overall response rate (ORR) and duration of response (DOR) [5] Efficacy Results - Zipalertinib demonstrated a confirmed ORR of 35.2% overall, with a median DOR of 8.8 months and progression-free survival of 9.4 months [8] - In patients who received prior platinum-based chemotherapy, the ORR was 40% with a median DOR of 8.8 months [8] - Subgroup analyses showed a confirmed ORR of 30% and median DOR of 14.7 months in patients who had prior amivantamab [8] Safety Profile - The safety profile of zipalertinib was manageable and consistent with previously reported data [8]

Company Overview - Cullinan Therapeutics, Inc. is a biopharmaceutical company focused on developing targeted therapies across various modalities for autoimmune diseases and cancer [3] - The company has built a diversified portfolio of clinical-stage assets aimed at inhibiting key disease drivers and harnessing the immune system [3] - Cullinan aims to create new standards of care by identifying optimal targets and developing transformative therapeutics [3] Upcoming Events - The management team will host a company event at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL [1] - An in-person event for analysts and institutional investors is scheduled for June 1, 2025, at 6:30 p.m. CT, following the oral presentation of results from the pivotal Phase 2b REZILIENT1 trial [4] - Participation in the Jefferies 2025 Global Healthcare Conference will include a panel discussion on June 4, 2025, and a company presentation on June 5, 2025 [4] Investor Relations - Webcasts of the ASCO event and Jefferies Conference presentations will be available on the company's investor relations website [2] - Investors and analysts can register for the in-person event by contacting the Head of Investor Relations [4]

Core Insights - Cullinan Therapeutics, Taiho Pharmaceutical, and Taiho Oncology announced positive results from the Phase 2b cohorts of the REZILIENT1 trial for zipalertinib in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations [1][2] Efficacy Results - A total of 244 patients were enrolled in the REZILIENT1 trial, with 176 patients included in the overall efficacy population, showing a confirmed overall objective response rate (ORR) of 35% and a median duration of response (mDOR) of 8.8 months [3][7] - In patients who had received prior platinum-based chemotherapy, the ORR was 40% with an mDOR of 8.8 months [7] - For patients with prior chemotherapy and amivantamab, the ORR was 30% with an mDOR of 14.7 months [7] - Patients with brain metastases had an ORR of 31% with an mDOR of 8.3 months [7] Safety and Tolerability Results - Zipalertinib demonstrated a manageable safety profile, with the most common treatment-related adverse events (TRAEs) being paronychia (38.5%), rash (30.3%), and dermatitis acneiform (24.6%) [4][5] - The majority of TRAEs were grade 1 or 2, with grade ≥3 TRAEs including anemia (7%) and pneumonitis (2.5%) [5][4] About Zipalertinib - Zipalertinib is an orally available small molecule targeting EGFR mutations, specifically designed to inhibit EGFR variants with exon 20 insertion mutations while sparing wild-type EGFR [7][8] - It has received Breakthrough Therapy Designation from the FDA and is currently investigational [8] About EGFR Exon 20 Insertion Mutations - EGFR exon 20 insertions account for up to 4% of all NSCLC cases, making them the third most common EGFR mutation subtype [9]

Core Insights - Cullinan Therapeutics has received approval from the European Medicines Agency (EMA) for CLN-978, with Phase 1 studies in rheumatoid arthritis and Sjögren's disease set to begin in Q2 2025 [1][6] - The company is advancing its clinical development of CLN-978 across multiple autoimmune diseases and expects to share initial clinical data in systemic lupus erythematosus (SLE) by the end of 2025 [2] - The pivotal Phase 2b study of zipalertinib has met its primary endpoint, with results to be presented at the 2025 ASCO Annual Meeting [3] Immunology - CLN-978 is being developed for systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's disease, with ongoing Phase 1 studies in the U.S., Europe, and Australia [6] - The company plans to initiate a Phase 1 study for active, difficult-to-treat rheumatoid arthritis in Germany and Italy in Q2 2025 [6] - A Phase 1 study for active, moderate to severe Sjögren's disease is also set to begin in the U.S. in Q2 2025 [6] Oncology - The pivotal Phase 2b portion of the REZILIENT1 study of zipalertinib has met the primary endpoint of overall response rate in patients with EGFR ex20ins NSCLC [3][6] - The company plans to submit a New Drug Application (NDA) for relapsed/refractory EGFR ex20ins NSCLC in the second half of 2025 [6] - Development of CLN-619 in gynecological cancers has been discontinued due to preliminary results not meeting internal advancement thresholds [6] Financial Performance - As of March 31, 2025, the company reported cash and investments totaling $567.4 million, providing a runway into 2028 [3][11] - Research and development expenses for Q1 2025 were $41.5 million, up from $30.6 million in Q1 2024 [11][14] - The net loss attributable to Cullinan for Q1 2025 was $48.5 million, compared to $37.1 million for the same period in 2024 [11][14]