Ruijin Hospital, Shanghai Jiaotong University School of Medicine

NANJING, China, SHANGHAI and SAN JOSE, Calif., June 28, 2024 /PRNewswire/ -- IASO Biotechnology ("IASO Bio"), a biopharmaceutical company engaged in discovering, developing, manufacturing, and marketing innovative cell therapies and antibody products, today announces that the investigational new drug (IND) application for RD118, an independently developed, fully human GPRC5D-targeting chimeric antigen receptor T-cell (CAR-T) therapy, has been approved by the National Medical Products Administration (NMPA) for treatment of relapsed/refractory multiple myeloma (RRMM). About RD118 RD118 is an autologous T-cell immunotherapy product targeting G protein-coupled receptor class C group 5 member D (GPRC5D). It can identify and eliminate malignant tumor cells expressing GPRC5D. GPRC5D is highly expressed on multiple myeloma cells. However, in normal tissues, its expression is limited to plasma cells and hair follicle cells. Such a feature has made GPRC5D a promising safe and effective target for the treatment of multiple myeloma. The antigen recognition domain of RD118 is developed from IASO Bio's proprietary fully human single-domain antibody library. It has advantages of high affinity, high specificity, and low immunogenicity. The intracellular domain is a fusion of 4-1BB (CD137) and CD3ζ signaling domains. RD118 has been subjected to extensive development and optimization in terms of antibody screening and structure design. The candidate molecule has demonstrated excellent in vitro cytotoxic activity and in vivo tumor suppression ability. Additionally, it has good expansion capability and persistence in vivo, indicating high development potential. An investigator-initiated clinical trial (IIT) (ClinicalTrials.gov identifier: NCT05759793, NCT05219721) is being conducted to preliminary investigate the safety and efficacy of RD118 injection in patients with RRMM or plasma cell leukemia. The principal investigators are Professor Jianqing Mi from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and Professor Chunrui Li from Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology. The trial enrolled patients with multiple myeloma or plasma cell leukemia who have previously received at least three lines of therapy (must include at least one proteasome inhibitor and one immunomodulator). Patients who have previously received BCMA CAR-T therapy can also be enrolled. The trial investigated RD118 at the doses of 1.0–3.0 × 106 CAR-T cells/kg. As of Nov. 20, 2023, the dose-escalation phase has completed subject enrollment and infusion. The subjects who received infusion have demonstrated good safety and efficacy profiles. Patients with prior BCMA CAR-T therapy have also shown benefits. Professor Mi Jianqing, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, stated: " Studies have shown that malignant plasma cells in almost all multiple myeloma patients express GPRC5D. The GPRC5D-targeting therapy has been demonstrated to effectively control disease progression and prolong overall survival of patients with multiple myeloma, which makes GPRC5D an emerging competitive target. Furthermore, GPRC5D has been shown to be expressed on the surface of myeloma cells independently of BCMA, and its expression is not affected by the loss of BCMA. Patients who experience a relapse after anti-BCMA CAR-T cell therapy may still respond effectively to the treatment with anti-GPRC5D CAR-T cells, further indicating that anti-GPRC5D CAR-T is a candidate therapy with potential." Professor Chunrui Li, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, stated: "The development of CAR-T cell therapy has significantly changed the treatment landscape for multiple myeloma. The current therapies for multiple myeloma are mainly BCMA-targeted. However, the heterogeneous expressions of BCMA on a majority of malignant plasma cells may lead to varying degrees of therapeutic response among different patients. The results of this IIT study demonstrated that RD118 has shown positive therapeutic effects and controllable safety in patients who have experienced target escape from BCMA-targeted therapy, as well as in those with low or unstable BCMA expression. This may provide a new therapeutic approach for patients with RRMM, which is of substantial clinical value. In future clinical studies, we will continue to investigate the optimal treatment sequence and strategy for GPRC5D-targeting therapy." Ms. Jinhua Zhang, Founder and Chairman of IASO Bio, stated, "GPRC5D is expressed on myeloma cells. And just like BCMA, GPRC5D is one of the key targets for treating multiple myeloma. Multiple myeloma is a complex disease and requires different treatment strategies to address various patient conditions. Developed by IASO Bio, RD118 is a GPRC5D-targeting cell product for the treatment of multiple myeloma and has demonstrated significant therapeutic potential in the exploratory clinical trial, offering a new therapeutic approach for both medical professionals and patients. We are excited about the prospects of RD118 and will continue to conduct in-depth research to ensure its safety and efficacy in clinical practice. At the same time, we will continue our collaboration with global medical experts and research institutions to jointly promote the development of this field and bring more benefits to patients." About IASO Bio IASO Bio is a biopharmaceutical company engaged in the discovery and development of novel cell therapies and biologics for oncology and autoimmune diseases. IASO Bio possesses comprehensive capabilities spanning the entire drug development process, from early discovery to clinical development, regulatory approval, and commercial production. The pipeline in the company includes a diversified portfolio of over 10 novel products, including Equecabtagene Autoleucel (a fully human BCMA CAR-T injection). Equecabtagene Autoleucel received New Drug Application (NDA) approval from China's National Medical Products Administration (NMPA) and U.S. FDA IND approval for the treatment of RRMM. Leveraging its strong management team, innovative product pipeline, GMP production, as well as integrated manufactural and clinical capabilities, IASO aims to deliver transformative, curable, and affordable therapies that fulfil unmet medical needs to patients in China as well as around the world. For more information, please visit or . SOURCE IASO Bio

This official launch marks a significant advancement in patient care in mainland China, introducing a new era in the treatment of IgA nephropathy ​ (IgAN). IgA nephropathy (IgAN) is a common chronic kidney disease which mainly affects young adults. In IgAN a protein called immunoglobulin A (IgA) becomes trapped in the very fine filters of the kidney (glomeruli), causing damage and scarring to the whole kidney. China has the highest prevalence of primary glomerular diseases globally, with IgAN accounting for about 35% to 50% of cases. Most IgAN patients risk progressing to end-stage renal disease during their lifetime, often requiring dialysis or kidney transplantation. Current treatments, like renin-angiotensin system (RAS) inhibitors, fail to address the underlying disease progression, highlighting a significant unmet medical need. Rogers Yongqing Luo, chief executive officer of Everest Medicines, said the commercialization of Nefecon in the Chinese market represents a significant milestone for Everest and a breakthrough for IgAN patients in China. Nefecon has undergone a 20-year research and development process, becoming the first non-oncology therapeutic to receive Breakthrough Therapy Designation in China by the China National Medical Products Administration (NMPA), and the first treatment for IgAN to receive full approval from the US Food and Drug Administration (FDA). Five million IgAN patients in China He said: “It is also the first approved medicine with an IgAN indication by the NMPA in China. On behalf of the company, I would like to extend my gratitude to all parties who have assisted in obtaining the approval for Nefecon’s market entry and clinical use in mainland China, especially the clinical investigators and the 62 Chinese patients who participated in the global phase 3 clinical trials. With approximately 5 million IgAN patients in China and over 100,000 newly diagnosed patients annually, there is a significant unmet clinical demand. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Professor Zhang Hong is from Peking University First Hospital, a member of the global steering committee for the phase 3 clinical study NefIgArd. He said: “We will actively engage with all stakeholders to improve the accessibility and affordability of this innovative therapy for IgAN. Moreover, we will contribute to improving nephropathy diagnosis, treatment, and disease management, ultimately benefiting more patients. As we advance the commercialization of Nefecon in China and Asia, we will also actively promote the development of other innovative drugs in the nephropathy field, extending benefits to more patients.” “IgAN is the most common primary glomerular disease, occurring at a young age with a high possibility of progressing to end-stage renal disease. Compared to European and American populations, Chinese IgAN patients experience faster disease progression and poorer prognosis, imposing a heavy burden on patients and society. The full results of the NefIgArd study demonstrate that Nefecon can protect renal function, delay progression to dialysis or kidney transplantation, and significantly reduce urinary protein and hematuria. It is also safe and well-tolerated.” “Data analysis of the Chinese population shows that Nefecon reduces kidney function decline by 66%, and delays disease progression to dialysis or kidney transplantation by 12.8 years. The approval of Nefecon fills the gap in targeted therapy for IgAN in China, benefiting Chinese patients, improving disease prognosis, and providing clinicians with new treatment options.” Nefecon - even greater benefit in delaying kidney function decline The company says the latest analysis, presented at the World Congress of Nephrology 2024, provides further evidence that Nefecon may offer even greater benefit in delaying kidney function decline in Chinese patients with more rapidly progressing disease, without compromising patients' quality of life. Positive results from the global Open Label Extension (OLE) study based on the NefIgArd phase 3 study validated the efficacy and safety of re-treatment with Nefecon independent of prior treatment cycles, providing a solid scientific basis for future long-term maintenance regimens of Nefecon. "IgAN is highly prevalent in Asia and is one of the main causes of kidney failure in young adults in China. Among IgAN patients, the risk of progressing to end-stage renal disease in Asian populations is 56% higher compared to other populations, and the disease progresses more rapidly, imposing a significant medical burden on patients, families, and society. Therefore, more proactive treatment is needed to intervene and control the risk of disease progression, delaying the need for dialysis or kidney transplantation. “For a long time, this disease has lacked targeted treatment options, resulting in significant unmet clinical needs," said Professor Xie Jingyuan, chief physician of the Department of Nephrology, Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine. “Nefecon, as the world's first-in-disease therapy for IgAN, has treated over one hundred patients in total through its early-access program in Boao last April. During the follow-up period, Nefecon was found to be effective in stabilizing renal function, reducing proteinuria and hematuria, and was well tolerated by the patients. It is of great significance for Nefecon to be officially commercialized in mainland China, helping patients with IgAN to initiate treatment as early as possible.” Nefecon received approval from the China NMPA in November 2023 for the treatment of primary IgAN in adults at risk of disease progression. Additionally, Nefecon has been approved in multiple countries and territories across Europe, the US, and Asia.

SHENZHEN, China, April 30, 2024 /PRNewswire/ -- Shenzhen Chipscreen Biosciences Co., Ltd. (Chipscreen Biosciences, Stock Symbol: 688321.SH) announced that the company's lead innovative product Chidamide (Epidaza®) , an oral subtype-selective histone deacetylase (HDAC) inhibitor, combined with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), has been officially approved by the National Medical Products Administration (NMPA) for treatment of previously untreated diffuse large B-cell lymphoma (DLBCL) with positive MYC and BCL2 expression. Up to now, Chidamide has been approved for multiple indications globally. (For more information, please review the global commercialization situation). Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, with approximately 30000 new cases occurring annually in China. Clinical diagnosis and treatment guidelines and consensus both domestically and internationally recommend the R-CHOP regimen as the standard first-line treatment for DLBCL. However, about one-third or more of patients in the overall population still experience ineffective or early recurrence of first-line R-CHOP treatment. Meanwhile, approximately 30% of patients with DLBCL exhibit simultaneous overexpression of MYC/BCL2 protein (referred to as "double expression" lymphoma, DEL), and their efficacy and prognosis after R-CHOP treatment are significantly lower than those of non double expression patients. Therefore, how to combine new drugs based on R-CHOP regimen to provide a more effective and safer treatment to our patients is a significant unmet medical need. The approval of this new indication is based on a randomized, double-blind, placebo-controlled, multicenter Phase III clinical trial DEB trial (NCT04231448). The DEB trial is the first Phase III registered clinical study in the world as first line treatment of MYC/BCL2 dual expression diffuse large B-cell lymphoma. This trial is to evaluate the efficacy and safety of Chidamide combined with R-CHOP compared to R-CHOP in primary treatment and MYC/BCL2 dual expression DLBCL subjects. Based on the interim analysis conducted by the Independent Data Monitoring Committee (iDMC), the efficacy and safety indicators set by the protocol were achieved. Compared with the R-CHOP regimen, the Chidamide combination regimen significantly improved the complete response rate (CRR) of the study's key secondary endpoint, and the study's primary endpoint, event free survival (EFS), also showed a clear trend of benefit. The experimental safety profile is consistent with known risks, and no new significant safety signals were found. The results of the interim analysis of the DEB Phase III study were selected as the Late breaking Abstract (LBA) for the American Society of Clinical Oncology (ASCO) Annual Meeting on April 24, 2024. Dr. Xianping Lu, Chairman and General Manager of Chipscreen Biosciences, stated, "The classic R-CHOP regimen has been used as a first-line treatment for diffuse large B-cell lymphoma (DLBCL) for nearly 20 years, but its therapeutic effect is not satisfactory in populations with dual expression of BCL2 and MYC proteins. The combination of Chidamide and R-CHOP is the world's first phase 3 registered clinical study that focuses on first line therapy of dual expressed DLBCL, and also the world's first R-CHOP improvement study with significant benefits in complete remission rate. We believe that the approval of the new indication will bring new hope and better survival benefits to patients." About Chidamide (Epidaza®) Chidamide (Tucidinostat, Trade name: Epidaza®), a Class 1.1 innovative drug, is a novel molecular entity with global patent protection and the first marketed product developed independently by Chipscreen Biosciences. The first original chemical new drug approved in China, Chidamide is also the first oral subtype-selective histone deacetylase (HDAC) inhibitor in the world, Since its approval in China in December 2014 for the treatment of peripheral T-cell lymphoma, Chidamide has achieved significant commercialization worldwide and continuously explored new indications. Global commercialization situation: In December 2014, Chidamide was approved for use in patients with recurrent or refractory peripheral T-cell lymphoma (PTCL) in China; In November 2019, Chidamide was approved to combine aromatase inhibitors to treat locally advanced or metastatic breast cancer patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, postmenopausal, and endocrine therapy relapse or progress in China; In June 2021, Chidamide was approved for monotherapy in the treatment of recurrent or refractory (R/R) adult T-cell leukemia (ATL) in Japan; In December 2021, Chidamide was approved for monotherapy for recurrent or refractory (R/R) peripheral T-cell lymphoma (PTCL) in Japan; In March 2023, Chidamide was approved to be used for postmenopausal women with locally advanced or metastatic breast cancer who are hormone receptor positive, type II human epidermal growth factor receptor (HER2) negative, and relapse or worsen after endocrine therapy (in combination with exemestane) in Taiwan, China; In April 30, 2024, Chidamide was approved to use in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for previously untreated diffuse large B-cell lymphoma (DLBCL) patients with positive MYC and BCL2 expression in China. Global exploration of other indications: In addition to ongoing global multicenter phase III clinical trial for the first-line treatment of melanoma in comniation with Opdivo, Chidamide is also conducting multiple clinical trials in China and internationally in combination with different anti-tumor immunotherapies. In November 2023, the Phase II clinical trial of the first-line treatment of non-small cell lung cancer with Chidamide combined with Tislelizumab was completed and enrolled. On March 4, 2024, Professor Ruihua Xu and Professor Feng Wang from the Cancer Prevention and Treatment Center of Sun Yat sen University led the research on CAPAbility-01, which was published on the world's top academic journal Nature Medicine (IF=82.9). As one of the most valuable sub journals under Nature, the publication of Nature Medicine reflects the academic authority's recognition of CAPAbility-01 research. This study indicates that for patients with microsatellite stable/mismatched repair function intact (MSS/pMMR) type metastatic colorectal cancer (mCRC), a three drug regimen led by Chidamide (Chidamide+sintilimab antibody+bevacizumab) for third line and above treatment, with an 18 week PFS rate of 64.0%, an ORR of 44.0%, and a median PFS of 7.3 months, is considered a promising treatment option for MSS/pMMR advanced CRC patients. On April 24, 2024, an abstract entitled "Tucidinostat plus R-CHOP in previously untreated diffuse large B-cell lymphoma with double expression of MYC and BCL2: An interim analysis from the phase III DEB study" was selected the American Society of Clinical Oncology (ASCO) LBA list for the 2024 ASCO, which submitted by Professor Weili Zhao's team from Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine About Chipscreen Chipscreen Biosciences is an innovative drug company driven by core technologies with globally competitive pipelines. As a pioneer in drug innovation & development in China, adhering to the concept of "Constant Innovation for Life", we focus on developing revolutionary innovative drugs with new mechanisms of action, to address patients' pressing clinical needs. Our complete industry chain that covers early exploratory discovery through commercialization allows us to provide innovative Chinese drugs for patients worldwide. With a global development strategy based on early-stage research in China, Chipscreen Biosciences has leveraged the top scientists and teams with extensive experience in related fields from the Shenzhen Small Molecule Early R&D Center and Chengdu Small Molecule Early R&D Center to create an integrated technology platform based on AI-driven design and chemical genomics, which spanned the whole process from basic science to clinical translation. We have successfully developed first-in-class and best-in-class innovative drugs. Currently, we have marketed two drugs for threeindications in Mainland China, two indications in Japan, and one indication in Taiwan, China. In addition, we have launched a number of R&D projects with differentiated advantages and global competitiveness in the five major areas, including malignant tumors, metabolic diseases, autoimmune diseases, central nervous system diseases, and antivirals. Chipscreen Biosciences has formed a global industrial layout consisting of Shenzhen Head Office/R&D Center/GMP production base, Chengdu Regional Head Office/R&D Center/GMP production base, Beijing Branch, Shanghai Branch, and Chipscreen Biosciences (USA) Co., Ltd. Meanwhile, as one of the first batches of national "innovative drug incubation bases" and national high-tech enterprises, Chipscreen Biosciences has independently undertaken many national "863" plans and national major science and technology projects, such as "10th five-year plan", "11th five-year plan", "12th five-year plan" and "13th five-year plan", and National Science and Technology primary Project for Innovative Drug Development. We have filed over 660 invention patents in China and worldwide, with over 180 granted. SOURCE Shenzhen Chipscreen Biosciences Co., Ltd.