The First Affiliated Hospital, Zhejiang University School of Medicine

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

WUXI, China, Feb. 25, 2024 /PRNewswire/ -- BioCity Biopharma is pleased to announce the completion of enrollment of all 120 participants in the IgA nephropathy (IgAN) cohort in a randomized, double-blind, placebo-controlled Phase 2 clinical study of the novel, oral endothelin A (ETA)-receptor selective antagonist SC0062, currently under development for chronic kidney disease (CKD), including IgAN and diabetic kidney disease (DKD). The enrollment of DKD cohort is ongoing with expected completion by the end of Q2 2024. "We appreciate the dedication of our colleagues and collaborators. The IgAN cohort enrollment was initiated in June 2023, and we enrolled all 120 subjects in less than 9 months. Thanks to the investigators, their teams, patients, and related BioCity colleagues", Dr. Ivy Wang, co-founder and executive vice president of BioCity, stated. This accomplishment highlights BioCity's ability to coordinate resources and operate efficiently in clinical trials, and further solidifies its leading position in the field of CKD. Dr. Wang emphasized that this achievement aligns well with the company's strategic objectives and establishes a solid foundation for further corporate development. Dr. Yong jiang Hei, CEO of BioCity, noted the clear trend of drug development focus on chronic diseases globally, with CKD gaining significant attention. The early entry in this field by BioCity reflects its thoughtful vision. There are approximately 700 million potential CKD patients worldwide with 82 million in China. The vast CKD market is growing rapidly, and the unmet medical needs are significant. Proteinuria is a key prognostic indicator of disease progression in CKD and can serve as an end point to evaluate the effectiveness of interventions intended to treat CKD. Of note, the US FDA granted accelerated approval of the first treatment for IgAN using proteinuria as a surrogate clinical endpoint. "CKD (including DKD and IgAN) with proteinuria is the primary indication under development for SC0062 which has demonstrated significant safety advantages in preclinical and Phase 1 studies. Leveraging our efficient clinical operation capabilities, we plan to accelerate the phase 2 study and initiate Phase 3 trials in 2024. Our goal is to bring this innovative medicine to patients and improve their quality of life at the earliest possible time." Dr. Hei says. About SC0062 SC0062 is one of the most unique ETA receptor small molecule antagonists globally to enter clinical development for CKD, which designed with high selectivity for ETA receptors with the objective of ensuring efficacy while avoiding the potential safety risks associated with other molecules in the same class. Preclinical studies have shown that SC0062 improved pathological scores in models of acute kidney injury and CKD. In the completed Phase I study, SC0062 demonstrated favorable safety profile, good tolerability, and predictable pharmacokinetic characteristics. Fluid retention, an adverse event presumable associated with ETB blockade, was not observed in the phase 1 trial in healthy volunteers. SC0062 is potentially a best-in-class ETA receptor-selective antagonist. About the Phase 2 Clinical Study of SC0062 (CTR20230689) The ongoing Phase 2 clinical study is designed to evaluate the efficacy and safety of SC0062 in patients with CKD with proteinuria. It is a multi-center, randomized, double-blind, placebo-controlled study with two parallel cohorts (IgAN and DKD). The trial is led by professor Jianghua Chen, director of the Kidney Disease Center at the First Affiliated Hospital of Zhejiang University School of Medicine and former Chairman of the Chinese Medical Association Nephrology Branch. The study is being conducted simultaneously at over 40 study sites nationwide. Currently, the IgAN cohort enrollment is completed, and the DKD cohort continues to enroll patients. About BioCity Founded in December 2017, BioCity is a clinical-stage biopharmaceutical company committed to developing novel and highly differentiated, modality-independent therapeutics for cancer and autoimmune disorders including chronic kidney diseases (CKD). The company has established a pipeline of more than 10 innovative drug candidates including small molecules, monoclonal and bispecific antibodies as well as antibody-drug conjugates (ADCs). Currently, BioCity Biopharma has 6 oncology assets in Phase 1 development, including the first-in-class CDH3-targeting ADC, WEE1 and ATR inhibitors targeting the DNA damage response (DDR) pathway, and agents targeting the immune system including a T cell engager (CD3/EGFR BsAb), an immune checkpoint inhibitor (TIM-3 mAb), and a T cell activator (4-1BB mAb). In addition, an endothelin A (ETA)-receptor selective antagonist for CKD is in phase 2 clinical development. For more information, please visit . Contact: [email protected] [email protected] SOURCE BioCity Biopharma

A new study identifies numerous pathways by which the gut microbiome may change the immune system. During pregnancy, a woman's immune system changes dramatically but researchers don't yet understand all the underlying mechanisms. A new study shows how the gut microbiota may play a role. In a paper published this week in mSystems, researchers in China report that during pregnancy, changes in levels of cytokines -- immune system proteins important in inflammation -- may be linked to specific alterations in the mother's gut microbiome and in plasma and fecal metabolites. "To the best of our knowledge, these associations were first explored in our study," said first author Ting Huang, M.D., from the First Affiliated Hospital of Jinan University in Guangzhou, China. Pregnancy brings a raft of changes, including fluctuations in hormones, changes to a woman's body structure, and variations in the immune system. Previous studies have identified changes to the gut microbiome that can occur during pregnancy; they have also suggested that those changes may influence physiological processes in the mother through metabolites. Disturbances in the microbiota, for example, have been connected to the promotion of preeclampsia, a dangerous pregnancy complication characterized by high blood pressure. However, it remains unclear how alterations in the gut microbiota during pregnancy affect maternal immunity. To investigate these connections, the researchers at the First Affiliated Hospital of Jinan University compared the gut microbiota, metabolite profiles and immune system status of 30 healthy pregnant women to 15 healthy women who weren't pregnant. All the women in the study were between 18 and 34 years old. Fecal and blood samples were collected from the pregnant women during or after the 37th week of pregnancy, and samples from non-pregnant women were collected on the 14th day of the menstrual cycle. Analyses of the fecal samples showed that Firmicutes was the most dominant phylum of bacteria in both groups of women. However, Bacteroidota bacteria accounted for a smaller relative share of the microbial population in pregnant women than in non-pregnant women. Pregnant women also showed a higher relative abundance of both Actinobacteriota and Proteobacteria, compared to non-pregnant women. The researchers similarly found a distinct difference in the cytokine levels in the 2 groups. Pregnant women had lower levels of cytokines that promote inflammation, and they showed higher levels of cytokines that act against inflammation. These results suggest that the immune system may be suppressed during pregnancy, the authors noted. The researchers then identified hundreds of metabolites found in the plasma and fecal samples. They found that each group -- pregnant and non-pregnant women -- had its own distinct collection of metabolites, or metabolome. Notably, many of those metabolites were connected to bile acid secretion and metabolism, and bile acids have previously been tied to inflammation. In further analyses, they found that some enriched metabolites in pregnant women were associated with lower levels of pro-inflammatory cytokines. Similarly, some of the depleted metabolites are associated with increases in pro-inflammatory cytokines. Finally, the group identified a total of 46 connections among microbes, metabolites and cytokines. They found that some microbes enriched in pregnant women, for example, may inhibit an immune response by inhibiting pro-inflammatory metabolites. Overall, Huang said, the results support the idea that gut microbes interact with host metabolites to change cytokine levels in the blood. However, Huang cautioned that the study doesn't establish causation. In addition, the small sample size may amplify errors arising from individual differences, and the design of the study doesn't account for cofounding factors, like diet. More clinical trials are needed, the researchers said, to confirm and better elucidate the connections.