Core Insights - Cullinan Therapeutics is advancing its CLN-978 program across three active Phase 1 studies targeting systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's disease, while also in-licensing the BCMA-directed bispecific T cell engager velinotamig from Genrix Bio [1][2][4] - The company reported a net loss of $70.1 million for Q2 2025, compared to a net loss of $42.0 million for the same period in 2024, indicating increased operational expenses [9][13] - Cullinan has a strong cash position of $510.9 million as of June 30, 2025, providing a runway into 2028 for ongoing and future projects [9][10] Immunology Updates - The global Phase 1 study for CLN-978 in moderate to severe SLE is currently enrolling in the U.S., Europe, and Australia, with initial safety and B cell depletion data expected in Q4 2025 [4] - The Phase 1 study for active, difficult-to-treat RA is enrolling in Europe, with initial data anticipated in the first half of 2026 [4] - The Phase 1 study for moderate to severe Sjögren's disease is also enrolling in the U.S. and Europe following regulatory approval [4] Oncology Developments - Results from the pivotal Phase 2b portion of the REZILIENT1 study of zipalertinib were shared at the 2025 ASCO Annual Meeting, with further data expected at upcoming medical conferences [3][8] - Taiho Oncology plans to submit a New Drug Application (NDA) for zipalertinib in relapsed EGFR ex20ins NSCLC by the end of 2025, with enrollment for the pivotal REZILIENT3 study expected to complete in the first half of 2026 [3][8] - Clinical data for CLN-049, targeting relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), is set to be shared in Q4 2025 [8] Corporate Governance - The company appointed Dr. Mittie Doyle and Dr. Andrew Allen to its Board of Directors, effective August 7, 2025, bringing significant expertise in immunology and oncology [6] - Drs. Anne-Marie Martin and David Ryan will resign from the Board effective the same date [6] Financial Overview - Research and development expenses for Q2 2025 were $61.0 million, up from $36.3 million in Q2 2024, reflecting increased investment in clinical programs [9][13] - General and administrative expenses rose to $14.8 million in Q2 2025 from $13.8 million in the same period last year [13] - The total operating expenses for Q2 2025 were $75.8 million, compared to $50.0 million in Q2 2024 [13]

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]

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]