Zevorcabtagene Autoleucel

SHANGHAI, March 1, 2024 /PRNewswire/ -- 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, announces that today the National Medical Products Administration ("NMPA") of China has approved the New Drug Application ("NDA") for zevorcabtagene autoleucel (R&D code: CT053, an autologous CAR-T product candidate against BCMA), for the treatment of adult patients with relapsed or refractory multiple myeloma who have previously progressed after at least 3 lines of therapy (including a proteasome inhibitor and immunomodulator agent). Zevorcabtagene autoleucel is an autologous BCMA-targeted CAR T-cell product, generated by transducing T cells with a lentivirus encoding a CAR comprising a fully human BCMA-specific single chain variable fragment ("scFv"), the human CD8α hinge domain, CD8α transmembrane domain, 4-1 BB co-stimulatory domain and CD3ζ activation domain. The proprietary novel fully-human scFv has high binding affinity and stability. The approval of zevorcabtagene autoleucel is based on an open-label, single arm, multi-center Phase II clinical trial (LUMMICAR STUDY 1, NCT03975907) conducted in China. The trial results were released at the 2022 Annual Meeting of the American Society of Hematology ("ASH"), and zevorcabtagene autoleucel demonstrated encouraging efficacy and a favorable safety profile. Multiple myeloma is an incurable malignant plasma cell disorder that accounts for approximately 10% of all hematological cancers.[1] With China's ageing population coupled with an increase in life expectancy, the number of patients with multiple myeloma is expected to expand. Frost & Sullivan forecasts that the prevalence of multiple myeloma in China in 2023 is approximately 153,000 per annum, and the number of new cases would be 23,200 per annum. It is estimated that the prevalence of multiple myeloma in China is expected to grow to 266,300 by 2030.[2] Prof. Wenming Chen, the principal investigator of the LUMMICAR STUDY 1, Director of Hematology Department, Beijing Chao-Yang Hospital, Capital Medical University, said, "In the realm of traditional treatments, the prognosis for patients dealing with relapsed or refractory multiple myeloma remains notably grim, given the limitations of available therapeutic alternatives. These individuals confront substantial unmet clinical needs, necessitating an expeditious adoption of an effective, safe, and convenient treatment modalities. The approval of zevorcabtagene autoleucel not only expands the array of choices available to clinical practitioners but also brings new hope to patients." Prof. Chengcheng Fu, the principal investigator of the LUMMICAR STUDY 1, Director of Hematology Department, the First Affiliated Hospital of Soochow University, said, "Based on the published results of the LUMMICAR-1 study, zevorcabtagene autoleucel has demonstrated profound and enduring therapeutic efficacy in patients with relapsed or refractory multiple myeloma, exhibiting overall favorable tolerability. We are pleased to witness the regulatory approval and market launch of zevorcabtagene autoleucel. We look forward to its potential to benefit a larger number of individuals, aiding them in achieving high-quality, long-term survival." Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics, said, "This year marks the tenth anniversary of CARsgen, and I am delighted to announce the NDA approval of zevorcabtagene autoleucel. This achievement stands as a significant milestone in the company's development and serves as a testament to the unwavering dedication of our team. I would like to express heartfelt gratitude to our team members, investigators, patients, and the broader community for their support and trust. We look forward to zevorcabtagene autoleucel bringing renewed hope to adult patients with relapsed or refractory multiple myeloma, thereby improving their survival. Guided by the vision of 'Making Cancer Curable,' we remain committed to exploring new technologies, expanding our product pipeline with global rights to address the major challenges of CAR T-cell therapies, and bringing innovative and differentiated cell therapies to cancer patients worldwide." About Zevorcabtagene Autoleucel Zevorcabtagene autoleucel is a fully human, autologous BCMA CAR T-cell product for the treatment of R/R MM. As informed by the NMPA on March 1, 2024, zevorcabtagene autoleucel was approved on February 23, 2024, for the treatment of adult patients with relapsed or refractory multiple myeloma who have previously progressed after at least 3 lines of therapy (at least one proteasome inhibitor and immunomodulator). CARsgen is conducting a separate Phase 1b/2 LUMMICAR STUDY 2 clinical trial in North America to evaluate the safety and efficacy of zevorcabtagene autoleucel in R/R MM. Zevorcabtagene autoleucel received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations from the U.S. FDA in 2019, as well as Priority Medicines (PRIME) and Orphan Medicinal Product designations from the European Medicines Agency (EMA) in 2019 and 2020, respectively. Zevorcabtagene autoleucel also received Breakthrough Therapy designation from the NMPA in 2020. In January 2023, CARsgen and Huadong Medicine announced a collaboration for the commercialization of zevorcabtagene autoleucel in mainland China. Huadong Medicine was granted the exclusive right to commercialize zevorcabtagene autoleucel in mainland China. 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, . 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. Contact CARsgen For more information, please visit Public Relations: [email protected] Investor Relations: [email protected] SOURCE CARsgen Therapeutics

Pictured: FDA headquarters/iStock, Grandbrothers The FDA has placed a clinical hold on three of CARsgen Therapeutics’ CAR-T cell therapy candidates following an inspection of the Chinese biotech’s manufacturing facility in Durham, North Carolina. CARsgen notified the Hong Kong Stock Exchange that the FDA clinical hold had gone into effect on three of its CAR-T products: CT053, CT071 and CT041. According to CARsgen, the clinical hold on its products are due to chemistry, manufacturing, and controls-related “questions” that arose due to the FDA inspection. The company said in the notice that it plans to conduct a “comprehensive review” and improve its Current Good Manufacturing Practices (cGMP) at the facility, which was opened in February 2022. CARsgen also said in the notice it is “committed to working closely with the FDA to address the findings to ensure the smooth progress and production quality for clinical trials and launching applications.” In a statement emailed to BioSpace, a CARsgen spokesperson said that “lingering concerns” surrounding employee training and “other legacy issues” need to be addressed for the facility to be in compliance. “The FDA's feedback did not pertain to process issues. This provides the company with clear areas of observation, helping us improve in a more targeted manner. We are confident that it will be completed soon and will provide the rectification plan to the FDA as soon as possible, maintain follow-up communication and implement rectifications,” the spokesperson said. The FDA’s clinical hold comes at a time when CARsgen was making headway for its CAR-T products. CARsgen’s CT041 product is a candidate that targets Clauidin18.2 positive solid tumors and is focused on treating gastric, gastroesophageal junction and pancreatic cancer. In August 2023, CARsgen and Moderna announced a partnership to combine an mRNA cancer vaccine with the CT041 CAR-T therapy. Patient enrollment in a Phase II trial for CT041 started in May 2023. The company’s CT071 targets the G protein-coupled receptor Class C group 5 member D and is placed to treat relapsed/refractory multiple myeloma or relapsed/refractory primary plasma cell leukemia. The product received IND clearance from the FDA in December 2023 and already has an investigator-initiated trial underway in China. CT053 is designed to treat refractory and relapsed multiple myeloma. Last year, CARsgen presented data from a Phase I/II trial showing that 14 people treated with the candidate had an objective response rate of 100% and a complete response or stringent complete response rate of 78.6%. CARsgen’s CAR-T cell therapies are not the only ones hit by clinical holds from the FDA. In August 2023, the regulator placed a clinical hold on 2seventy bio’s Phase I trial of its CAR-T therapy for acute myeloid leukemia. Earlier this month, Roche’s BTK inhibitor fenebrutinib was slapped with a clinical hold after two patients enrolled in a Phase III program for relapsing multiple sclerosis had abnormal elevations in hepatic transaminase levels after receiving the drug. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.