Claudins

Although a US rejection earlier this year tempered some of the enthusiasm surrounding Astellas’ CLDN18.2-targeting antibody, Tuesday’s approval in Japan for gastric cancer may help to course-correct the treatment’s trajectory.The Ministry of Health, Labour and Welfare (MHLW) cleared Vyloy (zolbetuximab) to treat patients with CLDN18.2-positive, unresectable, advanced or recurrent gastric cancer. The approval was driven by data from the Phase III SPOTLIGHT and GLOW studies, which evaluated Vyloy plus chemotherapy as first-line treatment for patients with CLDN18.2-positive, HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma, versus chemotherapy alone. Both trials met the primary endpoint of progression-free survival as well as the key secondary endpoint of overall survival.Last year, a FirstWord poll of oncologists showed a bullish opinion on the monoclonal antibody (mAb), with the majority of participants projecting for Vyloy to quickly become a new standard of care in this population of gastric cancer patients. For more, see KOL Views Q&A: Leading oncologist excited to get to work learning how to use zolbetuximab in gastric cancer.However, in January, the FDA declined to approve the mAb following a priority review, citing third-party manufacturing deficiencies. While Astellas hasn’t provided an update since receiving the complete response letter, it’s possible the Japanese pharma will be able to quickly resolve the agency’s manufacturing concerns, especially since no issues regarding efficacy or safety data were raised.The antibody is also under review in China and the EU.

VYLOY approved in combination with chemotherapy for patients with human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2 positive, unresectable, advanced or recurrent gastric cancer MHLW approval makes VYLOY the first and only CLDN18.2-targeted therapy approved in the world TOKYO, March 26, 2024 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") today announced that on March 26, 2024, Japan's Ministry of Health, Labour and Welfare (MHLW) approved VYLOY™ (zolbetuximab), an anti-claudin 18.2 (CLDN18.2) monoclonal antibody for patients with CLDN18.2 positive, unresectable, advanced or recurrent gastric cancer. VYLOY is the first and only CLDN18.2-targeted therapy approved by any regulatory agency in the world. Gastric cancer is frequently diagnosed in the advanced or metastatic stage due to overlapping early-stage symptoms with other more common stomach conditions.1 Despite efforts to reduce its impact, gastric cancer is the third deadliest cancer in Japan, with 126,724 cases diagnosed in 2022.2 Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development, Astellas "The approval of VYLOY by the MHLW marks a new era in the treatment of gastric cancer, offering the first and only targeted therapy option for CLDN18.2-positive patients living with this devastating disease. Astellas is proud to help address the urgent therapeutic need for this hard-to-treat cancer in Japan, where incidence rates are among the highest globally. Importantly, this approval holds the potential to provide eligible patients with more precious time with their loved ones, delivering on our commitment to improve patient outcomes." Kohei Shitara, MD, Primary Investigator for the SPOTLIGHT Trial and Head, Department of Gastrointestinal Oncology, the National Cancer Center Hospital East in Kashiwa, Japan "Developing new targeted therapies is critical for diseases like advanced gastric adenocarcinoma, which has had very limited treatment options and is often discovered at an advanced stage. As the primary investigator for the Phase 3 SPOTLIGHT clinical trial, I witnessed firsthand the significant improvement in progression-free survival and overall survival for patients treated with VYLOY in combination with chemotherapy compared to those treated with placebo plus chemotherapy. These results support VYLOY as a new treatment option for the CLDN18.2-positive population in Japan, where there were nearly 44,000 deaths caused by gastric cancer in 2022 alone." The approval is based on results from the Phase 3 SPOTLIGHT and GLOW clinical trials for first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors were CLDN18.2 positive.3,4 The SPOTLIGHT study evaluated VYLOY plus mFOLFOX6 (a combination chemotherapy regimen that includes oxaliplatin, leucovorin, and fluorouracil) compared to placebo plus mFOLFOX6.4 The GLOW study evaluated VYLOY plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX.3 Both trials met their primary endpoint, progression-free survival (PFS), as well as a key secondary endpoint, overall survival (OS), showing statistical significance in patients treated with VYLOY plus chemotherapy compared to placebo plus chemotherapy. The most frequent treatment-emergent adverse events (TEAEs) ≥20% for VYLOY in combination with mFOLFOX6 or CAPOX were nausea, vomiting, decreased appetite, neutropenia, and decreased weight. In clinical trials, adverse reactions were managed by antiemetics, dose interruptions, and infusion rate adjustments.3,4 In both SPOTLIGHT and GLOW, approximately 38% of patients screened had tumors that were CLDN18.2 positive.3,4 CLDN18.2 positivity is defined as ≥75% of tumor cells showing moderate-to-strong membranous CLDN18 staining, which should be confirmed by a pathologist or laboratory with adequate experience using the approved in-vitro diagnostic agent or medical device.3,4 Astellas collaborated with Roche Diagnostics on the newly approved VENTANA® CLDN18 (43-14A) RxDx Assay, an immunohistochemistry (IHC) companion diagnostic (CDx) test, to identify patients who may be eligible for VYLOY.5 Testing will be available in Japan at multiple central laboratories and is expected to expand to additional laboratories over time. Astellas has also submitted applications for VYLOY to regulatory agencies around the world, and review is ongoing. Astellas has already reflected the impact from this approval in its financial forecast for the current fiscal year ending March 31, 2024. About VYLOY™ VYLOY™ (zolbetuximab) is an anti-claudin 18.2 (CLDN18.2) monoclonal antibody that is approved by Japan's Ministry of Health, Labour and Welfare (MHLW) for patients with CLDN18.2 positive, unresectable, advanced or recurrent gastric cancer. VYLOY is used in combination with chemotherapy for patients whose tumors are human epidermal growth factor receptor 2 (HER2)-negative. VYLOY is the first and only CLDN18.2-targeted therapy approved by any regulatory agency in the world. CLDN18.2 positivity should be confirmed by a pathologist or laboratory with adequate experience using the approved in-vitro diagnostic agent or medical device. As an antibody directed against human CLDN18.2, VYLOY binds to CLDN18.2 expressed on cell membrane in cancer cells such as gastric cancer and shows antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), leading to tumor growth inhibition.3,4 Important Safety Information For Important Safety Information for VYLOY, please see the Package Insert. About Unresectable, Advanced or Recurrent Gastric Cancer Gastric cancer, also known as stomach cancer, is the fifth most commonly diagnosed cancer worldwide.6 Gastric cancer killed 43,807 people in Japan in 2022, making it the third deadliest cancer by number of deaths in the country.2 Signs and symptoms can include indigestion or heartburn, pain or discomfort in the abdomen, nausea and vomiting, diarrhea or constipation, bloating of the stomach after meals, loss of appetite, and sensation of food getting stuck in the throat while eating.1 Signs of more advanced gastric cancer can include unexplained weight loss, weakness and fatigue, and vomiting blood or having blood in the stool.7 Risk factors associated with gastric cancer can include older age, male gender, family history, H. pylori infection, and smoking.8 Because early-stage gastric cancer symptoms frequently overlap with more common stomach-related conditions, gastric cancer is often diagnosed in the advanced or metastatic stage, or once it has spread from the tumor's origin to other body tissues or organs.1 The five-year relative survival rate for patients at the metastatic stage is 6.6%.9 INVESTIGATIONAL STUDIES About SPOTLIGHT Phase 3 Clinical Trial SPOTLIGHT is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab plus mFOLFOX6 (a combination chemotherapy regimen that includes oxaliplatin, leucovorin, and fluorouracil) compared to placebo plus mFOLFOX6 as a first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors were CLDN18.2 positive. The study enrolled 565 patients at 215 study locations in the U.S., Canada, United Kingdom, Australia, Europe, South America, and Asia, including Japan. The primary endpoint is progression-free survival (PFS) of participants treated with the combination of zolbetuximab plus mFOLFOX6 compared to those treated with placebo plus mFOLFOX6. Secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), safety and tolerability, and quality-of-life parameters. Data from the SPOTLIGHT clinical trial were presented during the 2023 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium in an oral presentation on January 19, 2023, and were subsequently published in The Lancet on April 14, 2023.4 For more information, please visit clinicaltrials.gov under Identifier NCT03504397. About GLOW Phase 3 Clinical Trial GLOW is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX as a first-line treatment in patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive. The study enrolled 507 patients at 166 study locations in the U.S., Canada, United Kingdom, Europe, South America, and Asia, including Japan. The primary endpoint is PFS in participants treated with the combination of zolbetuximab plus CAPOX compared to those treated with placebo plus CAPOX. Secondary endpoints include OS, ORR, DOR, safety and tolerability, and quality-of-life parameters. Data from the GLOW study were initially presented at the March 2023 ASCO Plenary Series with an updated oral presentation at the 2023 ASCO Annual Meeting on June 3, 2023, and were subsequently published in Nature Medicine on July 31, 2023.3 For more information, please visit clinicaltrials.gov under Identifier NCT03653507. Investigational Pipeline in Targeting CLDN18.2 An expanded Phase 2 trial of zolbetuximab in metastatic pancreatic adenocarcinoma is in progress. The trial is a randomized, multi-center, open-label study, evaluating the safety and efficacy of investigational zolbetuximab in combination with gemcitabine plus nab-paclitaxel as a first-line treatment in patients with metastatic pancreatic adenocarcinoma with CLDN18.2 positive tumors (defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining based on a validated immunohistochemistry assay). For more information, please visit clinicaltrials.gov under Identifier NCT03816163. In addition to zolbetuximab, ASP2138 is under development in our Primary Focus Immuno-Oncology. ASP2138 is a bispecific monoclonal antibody that binds to CD3 and CLDN18.2, and it is currently in a Phase 1/1b study in participants with metastatic or locally advanced unresectable gastric or GEJ adenocarcinoma or metastatic pancreatic adenocarcinoma whose tumors have CLDN18.2 expression. The safety and efficacy of the agent under investigation have not been established for the uses being considered. For more information, please visit clinicaltrials.gov under Identifier NCT05365581. There is no guarantee that the agent will receive regulatory approval and become commercially available for the uses being investigated. About Astellas Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients. For more information, please visit our website at . Cautionary Notes In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice. References 1 American Cancer Society. Signs and symptoms of stomach cancer (01-22-2021). Available at . Accessed 01-09-2024. 2 Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2024). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available at . Accessed 02-06-2024. 3 Shah, M.A., Shitara, K., Ajani, J.A. et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med (2023). . 4 Shitara K, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. The Lancet. Published online April 14, 2023; S0140-6736(23)00620-7. 5 DATA ON FILE. 6 Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49. 7 National Cancer Institute. Gastric cancer treatment (PDQ®): patient version (08-24-2021). Available at . Accessed 01-18-2024. 8 American Cancer Society. Stomach cancer risk factors (01-22-2021). Available at . Accessed 01-09-2024. 9 National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: stomach cancer. Available at . Accessed 01-16-2024. SOURCE Astellas Pharma Inc.

Submitted a New Drug Application (NDA) of Stapokibart (CM310) for the treatment of moderate-to-severe AD in adults. The NDA was accepted by the China's NMPA and granted priority review. Advanced a Phase III clinical study of Stapokibart for the treatment of CRSwNP in 2023. The results of the clinical trial are positive with co-primary endpoints both achieved. We expect to NDA for CRSwNP indication in 2024. Launched and advanced Phase III clinical studies respectively to evaluate the efficacy and safety of Stapokibart in patients with seasonal allergic rhinitis under background therapy and in adolescent subjects with moderate-to-severe AD. Entered into a global exclusive license agreement with AstraZeneca for the research, development, registration, manufacturing and commercialization of CMG901 and received an upfront payment of US$63 million in 2023. As of the date of this announcement, AstraZeneca has conducted multiple clinical studies regarding CMG901/AZD0901 for the treatment of advanced solid tumors. Rapidly expanded manufacturing capacity and continue to recruit talents to meet the growing needs of commercialized sales of products, research and development, clinical, production and operation of the Company. CHENGDU, China, March 26, 2024 /PRNewswire/ -- Keymed Biosciences Inc. (HKEX: 02162) today announced its 2023 annual results, along with recent pipeline highlights and corporate updates. "We made solid advances across our business in 2023 toward our goal to become a fully-integrated innovative biopharmaceutical company," said Dr. Bo Chen, Chairman, Executive Director, and Chief Executive Officer of Keymed Biosciences. "We successfully filed for NDA for Stapokibart (CM310), gaining priority review status, and have reported positive results from multiple clinical studies. We continued to develop our innovative and differentiated pipelines, actively explored value-accretive strategic partnerships, further expanded our cGMP-compliant manufacturing capacity and efficiently prepared for the company to become a commercial organization. The year 2024 is set to be an exciting one for Keymed, as the commercialization of our first product will propel us from being a clinical-stage biotech to a commercial-stage biopharmaceutical company. We will build on our plans to enable the successful launch of our product, as we continually strive to develop, manufacture and commercialize innovative biological therapies for patients worldwide." Pipeline Highlights The progress of core pipeline products: Stapokibart (CM310) (IL-4Rα antibody) Submitted a New Drug Application (NDA) of Stapokibart (CM310) for the treatment of moderate-to-severe AD in adults. The NDA was accepted by the China's NMPA and granted priority review. Launched a randomized, double-blinded, placebo-controlled Phase III clinical study to evaluate the efficacy and safety of Stapokibart in adolescent subjects with moderate-to-severe AD in February 2024, and the patient enrollment is currently in progress. Advanced a Phase III clinical study of Stapokibart for the treatment of CRSwNP and completed the unblinding of data from the double-blind treatment period and the preliminary statistical analysis in December. The results of the Phase III clinical trial are positive with co-primary endpoints both achieved. We expect to NDA for CRSwNP indication in 2024. Launched and advanced a Phase III clinical study to evaluate the efficacy and safety of Stapokibart in patients with seasonal allergic rhinitis under background therapy in 2023, and a multi-center, single-arm Phase II clinical study to evaluate the safety of Stapokibart in patients with seasonal allergic rhinitis. Our partner, CSPC, has initiated the critical Phase II/III clinical study for the treatment of moderate-to-severe asthma, and the patient enrollment is currently in progress. CMG901/AZD0901 (Claudin 18.2 antibody conjugated) Entered into a global exclusive license agreement with AstraZeneca for the research, development, registration, manufacturing and commercialization of CMG901 and received an upfront payment of US$63 million in 2023. As of the date of this announcement, AstraZeneca has conducted multiple clinical studies regarding CMG901/AZD0901 for the treatment of advanced solid tumors. In November 2023, the latest data from Phase I clinical study of CMG901 in the treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer has been presented by way of oral presentation at the American Society of Clinical Oncology (ASCO) Plenary Series. Among 89 evaluable patients with claudin 18.2-positive G/GEJ cancer confirmed objective response rate (ORR) and confirmed disease control rate (DCR) were 33% and 70%, respectively. Among others,CMG901 showed a 42% confirmed ORR in 2.2 mg/kg dose cohort, with median progression free survival (mPFS) of 4.8 months. CM313 (CD38 antibody) Continuously proceeded with a Phase I clinical trial of CM313 to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy of CM313 monotherapy in hematological malignancies including relapsed/refractory multiple myeloma (RRMM) and lymphoma. In June 2023, we presented, in the form of a poster, the latest data from the Phase I clinical study of CM313 for the treatment of RRMM and relapsed/refractory lymphoma at the 28th European Hematology Association (EHA) Congress 2023. CM313 exhibited a good safety pro general in this study for it at dose levels of ≥2.0 mg/kg and yielded preliminary efficacy in patients with RRMM. Continuously proceeded with a Phase Ib/IIa clinical study in 2023 to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy of CM313 injection in subjects with systemic lupus erythematosus (SLE). In December 2023, the latest data from the investigator-initiated single-arm, open-label, exploratory clinical study to evaluate CM313, which aimed to evaluate the safety and preliminary efficacy of CM313 for the treatment of primary immune thrombocytopenia in adults, were presented in a poster form at the 65th American Society of Hematology (ASH) Annual Meeting. As of June 30, 2023, a total of 21 patients were enrolled in the study. 7 subjects completed 8 treatments with follow-up period of more than 8 weeks. Among the 7 patients, 100.0% (7/7) achieved a platelet count ≥50 × 109/L within 8 weeks after administration with the first dose, with a median time to response of 1 week (range from 1 to 3). CM326 (TSLP antibody) Continuously proceeded with a Phase II clinical study to evaluate the efficacy and safety of CM326 in adult patients with moderate-to-severe AD. Continuously proceeded with a Phase Ib/IIa clinical trial to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, immunogenicity, and preliminary efficacy of CM326 in subjects with CRSwNP. Our partner, CSPC, has initiated the Phase II clinical study for the treatment of moderate-to-severe asthma. Progress of other pipeline products: CM355/ICP-B02 (CD20xCD3 bispecific antibody) Continuously proceeded with a Phase I/II clinical trial to assess the safety, tolerability, PK, and the preliminary anti-tumor activity of CM355 in relapsed or refractory non-Hodgkin's lymphoma (r/r NHL). As of the date of this announcement, all the 13 patients who were treated CM355 at dose ≥6mg achieved response with the ORR of 100%. CM336 (BCMAxCD3 bispecific antibody) Continuously proceeded with a Phase I/II clinical study in 2023 to assess the safety, tolerability, pharmacokinetics, and the anti-tumor activity of CM336 in RRMM. CM350 (GPC3xCD3 bispecific antibody) Continuously proceeded with a Phase I/II clinical study in 2023 to assess the safety, tolerability, pharmacokinetics, and the preliminary efficacy of CM350 in patients with advanced solid tumors. CM338 (MASP-2 antibody) Continuously proceeded with a Phase II clinical study in 2023 to evaluate the efficacy and safety of CM338 injection in subjects with immunoglobulin A nephropathy (IgAN). CM369/ICP-B05 (CCR8 antibody) Continuously proceeded with a Phase I trial to evaluate the safety, tolerability, pharmacokinetic characteristics, and efficacy of CM369 in subjects with advanced solid tumors and relapsed or refractory NHL. We will explore the combination of CM369 with other immunotherapies in various cancer indications after collecting the safety data of monotherapy. CM383 (Aβ protofibrils antibody) Submitted an IND application for CM383 in February 2024, and we are about to conduct a Phase I clinical study of the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of single dose-escalation administration in healthy subjects. Financial and Business Highlights Revenue amounted to RMB354 million for the year ended December 31, 2023, mainly representing collaboration income from AstraZeneca in respect of granting the relevant license; R&D expenses increased by RMB89 million to RMB596 million; As at December 31, 2023, our time deposits, cash and cash equivalents and bank wealth management products amounted to RMB2,719 million. The production capacity of the production base in Chengdu has reached 18,600 litres in total, and all the designs thereof are in compliance with the requirements of cGMP of the NMPA and FDA. Continue to recruit talents to meet the growing needs of commercialized sales of products, research and development, clinical, production and operation of the Company.