CARsgen Therapeutics Co.,Ltd

The CAR-T cell therapy involves modifying patients’ T-cells to express a CAR that targets BCMA, a protein found on multiple myeloma cell surface. Credit: Nemes Laszlo / Shutterstock.com. The National Medical Products Administration (NMPA) of China has approved CARsgen Therapeutics’ new drug application for zevorcabtagene autoleucel to treat multiple myeloma. The B cell maturation antigen (BCMA)-targeted autologous chimeric antigen receptor (CAR)-T product candidate is indicated to treat adults with relapsed or refractory multiple myeloma who have not responded to three lines of previous therapies. The therapy involves modifying patients’ T-cells to express a CAR that targets BCMA, a protein commonly found on the surface of multiple myeloma cells. The cells are then infused back into the patient to attack and kill the cancer cells. The approval is based on results from the LUMMICAR STUDY 1, a Phase II clinical trial conducted in China. See Also: Oncology emerges as dominant therapy area for CRISPR technology Nanobiotix files patent for porous, high-z, carbon-free particles for oncology therapy The multicentre open-label, single-arm trial demonstrated that zevorcabtagene autoleucel has “encouraging” efficacy and a favourable safety profile. CARsgen is also conducting a separate Phase Ib/II LUMMICAR STUDY 2 in North America. This trial aims to assess the efficacy and safety of CAR-T therapy in the same patient population. In 2019, the therapy received multiple designations from international regulatory agencies, including regenerative medicine advanced therapy and orphan drug designations from the US Food and Drug Administration. The European Medicines Agency granted priority medicines and orphan medicinal product designations in 2019 and 2020 respectively. The NMPA awarded zevorcabtagene autoleucel breakthrough therapy designation in 2020. In a strategic move to facilitate the marketing of zevorcabtagene autoleucel in mainland China, CARsgen entered into a partnership with Huadong Medicine in January 2023. Huadong Medicine gained sole rights to commercialise the CAR-T therapy within the territory. CARsgen Therapeutics founder, board chairman, CEO and chief scientific officer Dr Zonghai Li stated: “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.” Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva. Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. By Cytiva Thematic By downloading this case study, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy

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

KRAS stands out as the most commonly altered among the trio of RAS genes, with NRAS and HRAS following suit. The human KRAS gene resides on chromosome 12p12.1 and comprises six exons, primarily positioned in exon 1 at sites 12 and 13, though occasionally found in codons 61, 63, 117, 119, and 146. The emergence of KRAS inhibitors marks a notable advancement in the rapidly progressing field of oncology, instilling hope in combating formidable solid tumors. The landscape of treatment for KRAS-mutant cancers is undergoing rapid evolution, marked by several promising advancements in recent years. Forecasts anticipate significant growth in the KRAS inhibitors market in the coming years, propelled by rising cancer incidence rates and the escalating demand for personalized cancer therapies. Ongoing research and clinical trials continue to unveil potential treatment strategies, fostering optimism for improved patient outcomes. According to DelveInsight’s analysis, the market size for KRAS inhibitors across the 7MM and is expected to grow with a tremendous 36% CAGR to reach USD 10 billion by 2032. As per the estimates, the US is set to be the largest market for KRAS inhibitors, with ~70% of the market share among the seven major markets. The KRAS inhibitor market is expected to grow significantly in the coming years, driven by the increasing incidence of cancer and the growing demand for personalized cancer treatments; ongoing research and clinical trials have identified potential treatment strategies. Key players, including Mirati, Novartis Pharmaceuticals, Amgen, Eli Lilly, Verastem, and others, are involved in developing drugs for KRAS mutation for various indications such as NSCLC, colorectal cancer, pancreatic cancer, and others. The treatment landscape for KRAS-mutant cancers has rapidly evolved, with several promising advancements in recent years. Keen to know how the KRAS inhibitors market will evolve by 2032? Find out @ KRAS Inhibitors Market Forecast Amgen and Mirati Therapeutics are at the forefront of the race to develop KRAS inhibitors for cancer treatment. However, their current candidates are focused solely on targeting G12C-mutant tumors, leaving a significant gap in addressing other KRAS variants. This represents a major unmet need in the field, as no approved treatments are currently available for other variants. Recognizing this challenge, numerous key players actively explore alternative KRAS variants and expand their research to include other types of cancers beyond NSCLC. This shift in focus holds promising potential for developing effective therapies that can address a wider range of KRAS mutations and target multiple cancer types. Many companies are focusing on developing their candidates in pan-KRAS, like Cardiff Oncology (onvansertib), Gritstone bio (SLATE KRAS), Hookipa Pharma (HB-700), and others. Now, let’s examine the emerging KRAS inhibitor therapies JDQ443: Novartis Pharmaceuticals Phase III JDQ443 represents an experimental KRASG12C inhibitor that is selective, covalent, and can be taken orally. Initial findings from the Phase Ib stage of the KontRASt-01 trial (NCT04699188) indicate a confirmed overall response rate (ORR) of 57% at the recommended dosage of 200 mg twice daily in individuals with advanced non-small cell lung cancer (NSCLC). Presently, JDQ443 is undergoing Phase III evaluation, aiming to compare its effectiveness as a standalone treatment against docetaxel in patients with advanced NSCLC carrying a KRASG12C mutation who have previously undergone platinum-based chemotherapy and immune checkpoint inhibitor therapy, either sequentially or in combination. Novartis intends to New Drug Application (NDA) for NSCLC by 2024 and for colorectal cancer (CRC) post-2026. Avutometinib (VS-6766): Verastem Oncology Phase II Avutometinib (VS-6766) functions as an RAF/MEK clamp, prompting the formation of inactive complexes involving MEK and ARAF, BRAF, and CRAF. This mechanism potentially enhances the anti-tumor response by thoroughly inhibiting the RAS pathway, possibly leading to more sustained effects. Currently, avutometinib is in advanced stages of development. Unlike other MEK inhibitors, it not only blocks MEK kinase activity but also prevents RAF from phosphorylating MEK. This distinctive mode of action enables avutometinib to inhibit MEK signaling effectively without triggering compensatory activation, a limitation observed in other inhibitors. The FDA has recognized the potential of avutometinib in combination with defactinib (a FAK inhibitor) by granting it Breakthrough Therapy designation for treating all patients with recurrent low-grade serous ovarian cancer (LGSOC), irrespective of their KRAS status, after one or more prior lines of therapy, including platinum-based chemotherapy. RAMP 201 is a trial aimed at registering avutometinib, either alone or combined with defactinib, in patients with recurrent LGSOC. RMC-4630 (SAR442720): Revolution Medicines Phase II RMC-4630 (also known as SAR442720) is a highly effective small compound intended for oral use, engineered to specifically hinder the function of SHP2. This essential cellular protein regulates cell survival and proliferation by transmitting signals from receptor tyrosine kinases to RAS. Currently, the company is in the Phase II trial stage, investigating the combination of RMC-4630 with sotorasib for individuals with non-small cell lung cancer harboring a KRAS G12C mutation. These patients have not responded to standard therapies and have not previously undergone treatment with an RAS inhibitor. Discover which therapies are expected to grab major KRAS inhibitors market share @ KRAS Inhibitors Market Report BI 1701963: Boehringer Ingelheim Phase I BI 1701963 is a compound designed to inhibit the activity of KRAS across various oncogenic variants, particularly targeting major G12 and G13 oncoproteins. Its mechanism involves binding to SOS1, a crucial component in activating KRAS by facilitating the exchange of RAS-bound GDP for GTP. This selective inhibition of SOS1 presents a promising therapeutic approach, enabling KRAS suppression regardless of mutation type. Preclinical studies demonstrate the efficacy of this pan-KRAS inhibitor in impeding tumor growth across numerous tested G12 and G13 KRAS mutations, which are commonly observed in the protein. Additionally, the compound exhibits selectivity towards cancer cell lines bearing mutations in the KRAS gene. Currently undergoing Phase I trials, BI 1701963 is being assessed both as a standalone treatment and in combination with trametinib for patients with advanced or metastatic solid tumors carrying KRAS mutations. Boehringer Ingelheim has initiated a clinical collaboration with Amgen to explore the potential of BI 1701963 in combination with LUMAKRAS. Divarasib/GDC-6036: Roche Phase I Divarasib/GDC-6036, an orally administered small molecule, exhibited strong and specific inhibition of the KRAS G12C protein in preclinical trials. Engineered to target the switch II pocket of the KRASG12C protein, it interacts specifically with the cysteine at position 12, effectively locking it in an inactive GDP-bound state irreversibly. Results from a Phase Ib study presented at AACR 2023 showed that combining GDC-6036 with cetuximab effectively treated colorectal cancer (CRC), displaying notable clinical efficacy and tolerable safety levels. LY353798: Eli Lilly Phase I LY353798 is a specific covalent blocker of KRASG12C, exhibiting efficacy both alone and when paired with other anti-cancer treatments in preliminary studies. Its pharmacokinetic pro well, prompting its progression to clinical trials. In laboratory settings, LY3537982 has displayed the ability to target the KRAS G12C mutation, hindering mutant KRAS-driven signaling. Phase I clinical trials are underway, focusing on patients with non-small cell lung cancer, colorectal cancer, or other advanced solid tumors. For further information on the most promising KRAS inhibitors, reach out @ KRAS Inhibitors Treatment Pipeline Related Reports PD-1 and PD-L1 Inhibitors Competitive Landscape PD-1 and PD-L1 Inhibitors Competitive Landscape – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug pro including clinical and non-clinical stage products, and the key PD-1 and PD-L1 inhibitors companies, including Merck, Laekna Therapeutics, Genentech, Tracon Pharmaceuticals Inc., Celgene, MedImmune, Hangzhou Sumgen Biotech, among others. Non-Small Cell Lung Cancer Market Non-Small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NSCLC companies, including EMD Serono, Merck, Cellular Biomedicine Group, Inc., Celgene, CellSight Technologies, Inc., BeyondSpring Pharmaceuticals Inc., J Ints Bio, Forward Pharmaceuticals Co., Ltd., AstraZeneca, Bristol-Myers Squibb, Teligene US, Rain Oncology Inc, ReHeva Biosciences, Inc., Amgen, Novartis, RedCloud Bio, Parexel, Vitrac Therapeutics, LLC, Mythic Therapeutics, Instil Bio, Mirati Therapeutics Inc., Daiichi Sankyo, Inc., AstraZeneca, Precision Biologics, Inc, Promontory Therapeutics Inc., Palobiofarma SL, Regeneron Pharmaceuticals, Revolution Medicines, Inc., Cullinan Oncology, LLC, Iovance Biotherapeutics, Inc., Innate Pharma, among others. Multiple Myeloma Market Multiple Myeloma Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key multiple myeloma companies, including Johnson & Johnson (Janssen), Pfizer, AbbVie and Roche (Genentech), Regeneron Pharmaceuticals, Bristol-Myers Squibb, Celgene, Roche (Genentech), Arcellx, Novartis, Regeneron Pharmaceuticals, BeiGene, CARsgen Therapeutics, Cartesian Therapeutics, C4 Therapeutics, Heidelberg Pharma, Bristol-Myers Squibb, RAPA Therapeutics, AbbVie (TeneoOne), Takeda, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve. Conference Coverage Solutions: DelveInsight’s Conference Coverage Solutions delivers a comprehensive examination of conference outcomes from a range of prominent events, such as ASCO, ESMO, ASH, AACR, ATS, ERS, EULAR, ELCC, and IPF Summit 2023. This in-depth analysis equips businesses with the insights they need for effective competitive intelligence and forecasting market trends, aiding in the development of future strategies. Contact Us Shruti Thakur info@delveinsight.com +14699457679