Announced CT-0525 as lead product candidate for anti-HER2 program; initial data expected by year-end 2024 Presented preclinical proof of concept data in liver fibrosis at ASGCT; expects to nominate a development candidate in the first quarter of 2025 Presented Regimen Level 1 data from Phase 1 sub-study utilizing CT-0508 in combination with pembrolizumab at AACR; expects to report Regimen Level 2 data in second quarter of 2024 Cash and cash equivalents of $56.5 million expected to fund the Company into the third quarter of 2025 PHILADELPHIA, May 9, 2024 /PRNewswire/ -- Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical-stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, today reported financial results for the quarter ended March 31, 2024, and highlighted recent business updates. "We enter the second quarter with a renewed focus on our programs that we believe exhibit the greatest potential and meaningful near-term milestones," said Steven Kelly, President and Chief Executive Officer of Carisma. "We are pleased by the continued clinical validation of our anti-HER2 CAR-M program as evidenced by the initial data from CT-0508 and are excited to shift our attention to the development of CT-0525, which we believe has the potential to significantly increase anti-tumor activity. The preclinical proof of concept data in liver fibrosis fuels our momentum to explore the potential of engineered macrophages beyond oncology. Carisma remains committed to advancing next-generation cell therapies that hold the potential to enhance treatment options for patients grappling with cancer and other serious disorders." First Quarter 2024 Highlights and Upcoming Milestones Ex Vivo Oncology CT-0525 (Anti-HER2 chimeric antigen receptor monocyte (CAR-Monocyte)) In late March 2024, Carisma made the decision to prioritize CT-0525 due to the potential for a CAR-Monocyte to have an approximately 2,000-fold increase in total exposure compared to a CAR-Macrophage. As a result, the Company believes that CT-0525 will be able to build on clinical anti-tumor activity observed in CT-0508, the Company's anti-HER2 CAR-Macrophage. CT-0525 is now Carisma's lead product candidate. Carisma expects to treat the first patient in the CT-0525 Phase 1 clinical study in the second quarter of 2024 and to report initial data from the study by year-end 2024. CT-0508 (Anti-HER2 CAR-Macrophage) Due to the prioritization of CT-0525, Carisma has ceased recruitment of new patients into Study 101 and its sub-studies. However, the Company will continue all study operations for enrolled subjects. On April 10, 2024, during its presentation at the American Association for Cancer Research (AACR) 2024 Annual Meeting, Carisma reported Regimen Level 1 data (n=3 patients) from the open label Phase 1 (Study 101) sub-study utilizing CT-0508 in combination with pembrolizumab, a programmed cell death protein 1 (PD-1) checkpoint inhibitor. Based on preliminary results from these three patients, the combination therapy has been generally well-tolerated after infusion with no dose-limiting toxicities. Carisma observed a best overall response of progressive disease in the first two patients and stable disease in the third patient, per RECIST 1.1 criteria. The patient who achieved stable disease presented the greatest increase in peripheral blood T cell clonality seen across all 17 patients treated to date in Study 101 and had one out of two target lesions reduced by approximately 46%. Carisma expects to report data from Regimen Level 2 in the Study 101 sub-study evaluating the co-administration of CT-0508 and pembrolizumab in the second quarter of 2024. CT-1119 (Anti-Mesothelin CAR-Monocyte) In late March 2024, Carisma made the decision to pause further development of CT-1119, pending additional financing. Fibrosis and Immunology Fibrosis On May 8, 2024, during its presentation at the American Society of Gene and Cell Therapy (ASGCT) 2024 Annual Meeting, Carisma reported preclinical proof of concept data of its engineered macrophages for the treatment of liver fibrosis. In the presentation titled "Genetically Engineered Macrophage Cell Therapy Reverses Liver and Lung Fibrosis in Preclinical Models," Carisma presented preclinical proof of concept data for engineered macrophage cell therapy in liver fibrosis. In a CCL4-induced liver fibrosis model, the data showed that a single dose of macrophages co-expressing the anti-fibrotic factor relaxin and the anti-inflammatory cytokine IL10 significantly improved established fibrosis with a 116% reduction in fibrosis relative to untreated control. In addition, systemic administration of engineered macrophages co-expressing relaxin and IL10 significantly reduced liver fibrosis in a high fat diet metabolic dysfunction-associated steatohepatitis (MASH) model, with a 45% reduction in fibrosis relative to untreated control. In both models, the relaxin-IL10 macrophage treatment also resulted in a greater reduction in liver fibrosis compared to non-engineered macrophages. The presentation also included initial preclinical data for the use of engineered macrophages in pulmonary fibrosis. The data showed that a single dose of macrophages expressing a dominant negative TGFβ receptor, which nullified pro-fibrotic TGFβ signaling in the lung, prevented fibrosis in a bleomycin mouse model of pulmonary fibrosis, with a 90% reduction in fibrosis relative to untreated control. Carisma expects to nominate a development candidate for its liver fibrosis program in the first quarter of 2025. Corporate Updates On May 2, 2024, Carisma announced the appointment of Eugene P. Kennedy, M.D., F.A.C.S. as the Company's Chief Medical Officer. Dr. Kennedy brings over 15 years of clinical and industry experience, including cross-functional leadership driving clinical development and regulatory strategies for oncology and immuno-oncology focused organizations. On April 1, 2024, Carisma announced a pipeline reprioritization and corporate restructuring. The pipeline reprioritization includes stopping recruitment of new patients in the Phase 1 clinical study of CT-0508 (Study 101) to focus the Company's efforts and resources on CT-0525 as its lead anti-HER2 product candidate, as well as pausing development of CT-1119 pending additional financing. As a result of the pipeline reprioritization and corporate restructuring, Carisma reduced its workforce by approximately 37% in the second quarter of 2024. On April 1, 2024, Carisma announced the appointment of John Hohneker, M.D. to the Board of Directors of the Company, effective April 1, 2024. Dr. Hohneker brings over 30 years of extensive experience in drug development and leadership across the biotech and pharmaceutical sectors. The Company concurrently announced the resignation of Chidozie Ugwumba from Carisma's Board of Directors, also effective April 1, 2024. First Quarter 2024 Financial Results Cash and cash equivalents as of March 31, 2024 were $56.5 million, compared to $77.6 million as of December 31, 2023. Research and development expenses for the three months ended March 31, 2024 were $17.5 million, compared to $16.6 million for the three months ended March 31, 2023. The increase of $0.8 million was primarily due to a $0.9 million increase in personnel costs due to increased stock-based compensation and payroll, $0.7 million increase in direct costs associated with pre-clinical development of CT-0525, a $0.4 million increase in direct costs associated with the pre-clinical development related to CT-1119, partially offset by a $0.7 million decrease in direct costs associated with CT-0508, a $0.4 million decrease in our facilities and other expenses associated with a decrease in sponsored research agreement fees, and a