Two Cases of Pancreatic Cancer Treatment with CARsgen's CT041 Published in Journal of Hematology & Oncology

SHANGHAI,Sept. 21,2023 -- CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK),a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors,announced the publication of two cases of the treatment of metastatic pancreatic cancer with CARsgen's CT041,an innovative Claudin (CLDN) 18.2 CAR T-cell Therapy,in Journal of Hematology & Oncology (IF 23.186),titled "CT041 CAR T cell therapy for Claudin18.2–positive metastatic pancreatic cancer" (https://jhoonline.biomedcentral.com/articles/10.1186/s13045-023-01491-9)[1] (NCT04581473 and NCT03874897).

For case 1,a 58-year-old woman was diagnosed with pancreatic cancer with lung and lymph nodes metastasis. First-line nab-paclitaxel plus gemcitabine and second-line irinotecan-liposome plus 5-flurouracil were failed before she was enrolled in CT041 clinical trial,after confirming CLDN18.2 expression as 2+/70%. After lymphodepletion consisting of fludarabine,cyclophosphamide,and nab-paclitaxel,a CT041 dose of 250 × 106 cells was administered to the patient in September 2021. Grade 2 cytokine release syndrome (CRS) occurred,which was later controlled by tocilizumab. Partial response (PR) was achieved according to RECIST v1.1,with great shrinkage of lung metastasis.

For case 2,a 75-year-old woman was diagnosed as pT2N0 pancreatic cancer after she underwent surgery in May 2019. Lung metastasis was found after 5 months during routine post-surgery follow-up. S-1 monotherapy was given as the first-line chemotherapy starting from December 2019. During the surgical area palliative radiation,tumor progression was observed in the lung. Since the CLDN18.2 expression was determined as 3+/60%,the patient was enrolled in CT041 clinical trial. After receiving lymphodepletion consisting of fludarabine,cyclophosphamide and nab-paclitaxel,the patient was infused with a CT041 dose of 250 × 106 cells in July 2021. Patient experienced grade 2 CRS,which was further controlled with tocilizumab. PR was reached since the first evaluation 4 weeks after infusion. Target lesions of lung metastasis subsequently disappeared and achieved complete response. The tumor was still under well control until the last follow-up in July 2023. The peripheral blood CLDN18.2 CAR copy number in both patients exhibited a rapid post-infusion increase,peaking within 2 weeks. Concurrently,fluorescence-activated cell sorting results indicated an increase in peripheral blood CD8+ T cells and Treg cells,alongside a reduction in CD4+ T cells and B cells. These shifts in immune cell phenotypes demonstrated greater persistence compared to alterations in cytokine levels.

Raffaele Baffa,MD,PhD,Chief Medical Officer of CARsgen Therapeutics,remarked that,"I am delighted to see the publication of two cases on our CT041's treatment of metastatic pancreatic cancer cases in the Journal of Hematology & Oncology. The fact that both patients achieved partial response after receiving CT041 infusion is truly encouraging. Pancreatic cancer remains one of the most challenging malignancies in the field of oncology,with extremely poor prognosis and limited treatment options. Therefore,the development of innovative therapy is crucial in providing hope to pancreatic cancer patients. Our preliminary data from the treatment of pancreatic cancer with CAR T-cell therapy indicate its potential in achieving significant anti-tumor responses,even in patients who have failed multiple previous treatment regimens. We believe that CT041 has the potential to transform the treatment landscape of pancreatic cancer and other solid tumors,offering new hope to patients and their families."

About CT041

CT041 is an autologous CAR T-cell product candidate against the protein Claudin18.2 that has the potential to be the first-in-class globally. CT041 targets the treatment of Claudin18.2 positive solid tumors with a primary focus on GC/GEJ and PC. Trials in CARsgen include investigator-initiated trials (NCT03874897),a Phase Ib clinical trial for advanced GC/GEJ and PC and a confirmatory Phase II clinical trial for advanced GC/GEJ in China (CT041-ST-01,NCT04581473),a Phase I clinical trial for PC adjuvant therapy in China (CT041-ST-05,NCT05911217),and a Phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America (CT041-ST-02,NCT04404595). CT041 was granted Regenerative Medicine Advanced Therapy (RMAT) Designation by U.S. FDA for the treatment of advanced GC/GEJ with Claudin18.2-positive tumors in January 2022 and was granted PRIME eligibility by the EMA for the treatment of advanced gastric cancer in November 2021. CT041 received Orphan Drug designation from the U.S. FDA in 2020 for the treatment of GC/GEJ and Orphan Medicinal Product designation from the EMA in 2021 for the treatment of advanced gastric cancer.

About CARsgen Therapeutics Holdings Limited

CARsgen is a biopharmaceutical company with operations in China and the U.S. and is focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors. CARsgen has established a comprehensive CAR T-cell research and development platform,encompassing target discovery,innovative CAR T-cell development,clinical trials,and commercial-scale production. CARsgen has internally developed novel technologies and a product pipeline with global rights to address major challenges of CAR T-cell therapies,such as improving the safety profile,enhancing the efficacy in treating solid tumors,and reducing treatment costs. CARsgen's vision is to become a global biopharmaceutical leader that brings innovative and differentiated cell therapies to cancer patients worldwide and makes cancer curable.

Forward-Looking Statements

All statements in this press release that are not historical fact or that do not relate to present facts or current conditions are forward-looking statements. Such forward-looking statements express the Group's current views,projections,beliefs and expectations with respect to future events as of the date of this press release. Such forward-looking statements are based on a number of assumptions and factors beyond the Group's control. As a result,they are subject to significant risks and uncertainties,and actual events or results may differ materially from these forward-looking statements and the forward-looking events discussed in this press release might not occur. Such risks and uncertainties include,but are not limited to,those detailed under the heading "Principal Risks and Uncertainties" in our most recent annual report and interim report and other announcements and reports made available on our corporate website,https://www.carsgen.com. No representation or warranty is given as to the achievement or reasonableness of,and no reliance should be placed on,any projections,targets,estimates or forecasts contained in this press release.

Reference

1. Qi,C.,Xie,T.,Zhou,J. et al. CT041 CAR T cell therapy for Claudin18.2-positive metastatic pancreatic cancer. J Hematol Oncol 16,102 (2023). https://doi.org/10.1186/s13045-023-01491-9

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