Osemitamab

Phase II results reveal median PFS of 12.6 months in patients with CLDN18.2 high or medium expression, including in patients with PD-L1 CPS<5. PRINCETON, N.J. and SUZHOU, China, May 23, 2024 /PRNewswire/ -- Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a global clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, today announced the results from the Phase I/IIa Cohort-G data for Osemitamab (TST001) plus Nivolumab and CAPOX as the first-line treatment of patients with advanced G/GEJ cancer. The study, which enrolled patients regardless of their CLDN18.2 and PD-L1 CPS expression, indicated encouraging efficacy data for the triple combination, especially in patients with high or medium (H/M) CLDN18.2 expression, regardless of their PD-L1 CPS value. The results showed that median progression-free survival (mPFS) reached 12.6 months in patients with H/M CLDN18.2 expression, any PD-L1 CPS, as well as in the 80% of patients with PD-L1 CPS<5. Using the group of patients with very low/no CLDN18.2 expression as surrogate control, the HR for the triple combination is 0.443 (95%CI, 0.205-0.958) in favor of the H/M expressors and in these patients, the confirmed overall response rate was 68%. The majority (approximately 80%) of CLDN18.2 positive patients are PD-L1 CPS<5. Previous studies have found that the combination of Zolbetuximab+CAPOX in CLDN18.2 positive patients, regardless of the PD-L1 status, leads to an improvement in PFS from 6.80 to 8.21 months (HR = 0.687 (95% CI, 0.544-0.866) (Source: Shah, Manish A et al. Nature Medicine 2023 Aug 29 (8): 2133-2141). However, Nivolumab plus chemotherapy treatment in patients whose PD-L1 CPS is less than 5 produces very little benefit in PFS (median 7.5 vs 8.2 months with an HR of 0.93). (Source: Checkmate-649 study.) This Phase I/IIa Cohort-G data shows that the efficacy from the triple combo therapy of Osemitamab (TST001) plus Nivolumab and CAPOX compares very favorably with the historical data of Nivolumab plus CAPOX combination or Zolbetuximab plus CAPOX combination, including in patients with PD-L1 CPS<5. The first-line Osemitamab (TST001) plus Nivolumab and CAPOX for advanced G/GEJ cancer results of Cohort G Phase I/IIa data will be featured as a poster presentation (Abstract # 4048) on June 1, 2024 at the ASCO 2024 Annual Meeting in Chicago, IL USA. "These Phase II results mark a significant milestone for Osemitamab (TST001) as this data continues to demonstrate significant anti-tumor activities, particularly in patients with high or medium CLDN18.2 expression, including in those with PD-L1 CPS<5, which is consistent with our preclinical data and mechanistic hypothesis," said Dr. Caroline Germa, Executive Vice President, Global Medicine Development and Chief Medical Officer at Transcenta. "In this population, the triple combo treatment delivered significantly better PFS benefits than that of the doublet combinations of checkpoint inhibitor/chemo or CLDN18.2 targeted antibody plus chemo. These results further validate our strategy for the Global Phase III trial, which received FDA and CDE clearance and continue to advance the progression of Osemitamab (TST001) toward becoming a global therapy that elevates the current standard of care for HER2-negative metastatic gastric or gastroesophageal (G/GEJ) adenocarcinoma." "I am excited about these results and the potential they hold for improving the first-line treatment effect and prolonger PFS and OS for patients with HER2-negative metastatic gastric or gastroesophageal (G/GEJ) adenocarcinoma," said Professor Lin Shen, Director, department of Gastrointestinal Oncology and Phase I Clinical Trial Center at Peking University Cancer Hospital; and Principal Investigator of the trial. "We look forward to sharing more detailed data at the upcoming ASCO 2024 Annual Meeting." A brief summary of the study is as follows: Study Design Cohort G from TranStar102 study (NCT04495296) was designed to explore the safety and efficacy of Osemitamab (TST001) plus Nivolumab and CAPOX as the first-line treatment in advanced G/ GEJ cancer, with a safety lead-in and expansion phase. Eligible patients include HER2 negative or unknown, unresectable locally advanced or metastatic G/GEJ cancer, regardless of CLDN18.2 or PD-L1 expression. CLDN18.2 and PD-L1 status are analyzed retrospectively using Claudin 18.2 IHC 14G11 LDT assay and PD-L1 IHC 28-8 pharmDx at a central laboratory. The CLDN18.2 expression was divided into three subgroups: H/M (high/medium), L (low) and R (rest: lower or negative) according to the percentage of tumor cells showing membranous CLDN18.2 staining per Claudin 18.2 IHC 14G11 LDT assay. Encouraging ORR and mPFS As of the cut-off date, 82 patients had been dosed with a median follow-up of 12.6 months. Efficacy analysis was performed in the 66 patients with known CLDN18.2 and PD-L1 expression status. A clear trend between anti-tumor efficacy and CLDN18.2 expression level has been observed, with mPFS of 12.6 months in the patients with high or medium expression (H/M), 8.5 months in patients with low expression (L) and 6.7 months in the rest patients (R) respectively. Confirmed response rate was respectively 68%, 61.1% and 50% respectively. Compared to the R group, the PFS Hazard Ratio (HR) of HM vs R is 0.443 (95% CI 0.205, 0.985), and HML vs R is 0.560 (95% CI 0.292, 1.074). The same trend was observed in patients with PD-L1 CPS<5 patients, and the mPFS of patients with CLDN18.2 H/M expression is 12.6 months too in this subgroup. Manageable Safety Profile The safety profile of the triplet is generally consistent with the safety data of Osemitamab (TST001)/CAPOX combination in 1L G/GEJ cancer patients presented previously (Journal of Clinical Oncology Volume 41, Issue 16, June 1, 2023, Abstract 4046). The main toxicities are on-target-off-tumor effects that are manageable, including nausea, hypoalbuminemia and vomiting, mostly grade 1 or 2. About Osemitamab (TST001) Osemitamab (TST001) is a high affinity humanized anti-CLDN18.2 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity ("ADCC"). It has shown potent anti-tumor activities in tumor xenograft models. Osemitamab (TST001) is the second most advanced CLDN18.2 targeting antibody being developed globally. Osemitamab (TST001) was generated using Transcenta's Immune Tolerance Breaking Technology (IMTB) platform. Osemitamab (TST001) kills CLDN18.2 expressing tumor cells by mechanisms of ADCC. Leveraging advanced bioprocessing technology, the fucose content of Osemitamab (TST001) was significantly reduced during the production, which further enhanced NK cells mediated ADCC activity of Osemitamab (TST001). Clinical trials for Osemitamab (TST001) are ongoing in the U.S. and China (TranStar101/NCT04396821, TranStar102/NCT04495296). Osemitamab (TST001) has been granted Orphan Drug Designation in the U.S. by FDA for the treatment of patients with gastric or gastroesophageal junction (G/GEJ) and pancreatic cancer. About Transcenta Transcenta (HKEX: 06628) is a clinical stage biopharmaceutical company with fully integrated capabilities in antibody-based biotherapeutics discovery, research, development and manufacturing. Transcenta has established global footprint, with Headquarters and Discovery, Clinical and Translational Research Center in Suzhou, Process and Product Development Center and Manufacturing Facility in Hangzhou, and Clinical Development Centers in Princeton, US and in Beijing, Shanghai and Guangzhou of China, and External Partnering Center in Boston and Los Angeles, US. Transcenta has also initiated the construction of the Group Headquarters and the second high-end biopharmaceutical facility with ICB as its core technology in Suzhou Industrial Park. Transcenta is developing 13 therapeutic antibody molecules for oncology and selected non-oncology indications including bone and kidney disorders. All trademarks and registered trademarks in this document are the properties of their respective owners. SOURCE Transcenta Holding Limited

SAN FRANCISCO and SUZHOU, China, May 6, 2024 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, announced that the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for IBI343 as monotherapy for the treatment of claudin18.2-positive advanced gastric/gastro-esophageal junction adenocarcinoma (GC) patients who have progressed after at least 2 lines of prior systematic treatments. The BTD for IBI343 was based on the data from an ongoing Phase 1 study (NCT05458219), in which favorable safety and tolerability and promising antitumor activity of IBI343 monotherapy in advanced GC patients were observed. The study results will be published at an upcoming medical conference later in 2024. Innovent is preparing for a registrational Phase 3 multi-regional clinical trial (MRCT) of IBI343 in patients with claudin18.2-positive, HER2-negative GC (G-HOPE-001, NCT06238843) to be initiated soon. Dr. Hui Zhou, Senior Vice President of Innovent, said, "GC patients tend to progress after second-line systematic therapies with poor prognosis and have only a half year of survival expectancy. They are in urgent need of effective third-line treatment options. We are glad to see the NMPA granted BTD for IBI343 monotherapy based on the PoC clinical results in GC, and we will continue to validate its efficacy and safety in the registrational MRCT trial. Innovent has a comprehensive and robust oncology pipeline, and, particularly in GC, we have PD-1 inhibitor (TYVYT®) for first-line GC treatment and anti-angiogenic drug (CYRAMZA®) for second-line GC treatment. We will further explore IBI343's potential in combination therapy as well as in other solid tumors such as pancreatic cancer." NMPA Breakthrough Therapy Designation is intended to facilitate and expedite the development and review of an investigational drug to treat a serious disease or condition when preliminary clinical evidence indicates that the drug has demonstrated substantial improvement over current therapies. The BTD will not only qualify a drug candidate to receive status for rapid review by the CDE, but it will also allow the sponsor to obtain timely advice and communication from the CDE to accelerate the approval and launch to address the unmet clinical need of patients at an accelerated pace. Click here for the published list of drugs that have been granted BTD by NMPA. About Gastric/ Gastroesophageal Junction Adenocarcinoma Gastric cancer is one of the most common malignant tumors in the world and is one of the leading causes of cancer-related deaths globally. The 5-year survival rate of patients with metastatic gastric cancer is less than 5%[i]. China and Japan are countries with highest incidence of gastric cancer[ii]. Currently, chemotherapy combination of fluoropyrimidine and platinum and immune checkpoint inhibitor therapy are the standard-of-care treatments for patients with advanced metastatic gastric cancer. However, systemic therapy has limited efficacy in advanced gastric cancer. In particular, the prognosis for patients with third-line or higher gastric cancer is usually poor, with fewer treatment options and shorter survival expectations. The median survival times for these patients is only about 0.5 year[iii]. Claudin, a member of the tight junction molecule family, is a key structural and functional component of epithelial tight junctions. Among them, CLDN18.2 is normally buried in the gastric mucosa, but the development of malignancy leads to disruption of tight junctions and exposure of CLDN18.2 epitopes on the membrane of tumor cells[iv]. CLDN18.2 is expressed in up to 80% of patients with gastric cancer. About IBI343 (Claudin18.2 ADC) IBI343 is an antibody-drug conjugate composed of an anti-claudin18.2 antibody, and a cytotoxic drug exatecan. As a topoisomerase I inhibitor, exatecan effectively kills tumor cells by inhibiting DNA synthesis. Binding of IBI343 to claudin18.2-expressing tumor cells results in claudin18.2-dependent internalization of IBI343. Degradation of the cleavable linker will release the drug that causes DNA damage, leading to apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring tumor cells, resulting in a strong "bystander killing effect" of IBI343. About Innovent Innovent is a leading biopharmaceutical company founded in 2011 with the mission to provide high-quality biologics that are affordable to all. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 10 products in the market. It has 3 new drug applications under regulatory review, 5 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center. Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit , or follow Innovent on Facebook and LinkedIn. Note: TYVYT® (sintilimab injection) is not an approved product in the United States. BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States. TYVYT® (sintilimab injection, Innovent) BYVASDA® (bevacizumab biosimilar injection, Innovent) HALPRYZA® (rituximab biosimilar injection, Innovent) SULINNO® (adalimumab biosimilar injection, Innovent) Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan. CYRAMZA® (ramucirumab, Eli Lilly). Cyramza® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China. Retsevmo® (selpercatinib, Eli Lilly). Retsevmo® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China. Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s). Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions. Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. References: SOURCE Innovent Biologics