Pancreatic adenocarcinoma metastatic

In addition to cognitive benefit, pepinemab is believed to preserve vascular integrity in brain, a key consideration to avoid toxicity in Alzheimer’s diseaseROCHESTER, N.Y., Oct. 24, 2024 (GLOBE NEWSWIRE) -- Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating Alzheimer’s disease (AD) and cancer through the inhibition of Semaphorin 4D (SEMA4D), today announced that it will present promising new efficacy and safety data for its randomized, double-blind, phase 1b/2 SIGNAL-AD study of pepinemab treatment for Alzheimer’s disease at the Clinical Trials on Alzheimer’s Disease (CTAD) Conference in Madrid, on October 31, 2024. Elizabeth Evans, PhD, Chief Operating Officer and Senior VP Discovery and Translational Medicine, will present results of the study in a podium presentation. Presentation title: Results of SIGNAL-AD, a randomized, phase 1b/2 trial to evaluate safety and efficacy of pepinemab, anti-SEMA4D antibody believed to block reactive astrogliosis, in patients with Mild Cognitive Impairment (MCI) and Mild Dementia due to AD Presenter: Elizabeth Evans, PhD Date: Thursday October 31, 2024, 2:55 PM Central European Time, 9:55 AM EDT. Venue: Madrid Marriott Auditorium Hotel and Conference Center What can we expect to learn from results of this study? Vaccinex scientists discovered and published that Semaphorin 4D (SEMA4D), a molecule that binds to high affinity plexin-B1 receptors expressed on astrocytes in the brain, is highly upregulated on stressed or damaged neurons during progression of Alzheimer’s Disease (AD)Astrocytes, which are key brain cells that support the health and function of neurons, undergo extensive changes in morphology and gene expression when SEMA4D binds to their receptors. They switch from normal supportive functions to neurotoxic inflammatory activity that is believed to aggravate and accelerate progression of AD.The Company’s hypothesis, which is being tested in the SIGNAL-AD study, is that treating with pepinemab antibody that binds SEMA4D can block signaling through astrocyte receptors and slow or prevent the damaging consequences of astrocyte activation.The Company has previously reported that antibody blockade of SEMA4D appears to protect healthy astrocyte functions and to slow disease progression in patients with Huntington’s disease.Key outcomes of the SIGNAL-AD study include the impact of pepinemab treatment on cognitive decline as well as biomarkers of disease progression.Deposition of Aβ amyloid in the brain is currently the earliest recognized event in the pathologic cascade leading to AD. Aggregates of Aβ are believed to trigger a series of subsequent events, including astrocyte reactivity and formation of toxic tau tangles in neurons, which are believed to be key drivers of neurodegeneration. Levels of soluble biomarkers, such as astrocyte protein glial fibrillary acidic protein and phosphorylated tau peptide (p-tau 217), are, therefore, key biomarkers of disease progression, and it is important to characterize expression of these biomarkers in relation to treatment effects.Some currently approved drugs have been reported to compromise the integrity of brain vasculature leading to inflammation and microhemorrhages. Vaccinex will report evidence from new preclinical models suggesting beneficial effects of pepinemab treatment on brain vasculature. The SIGNAL-AD study was funded in part by a grant from the Alzheimer’s Association as well as by investments from the Alzheimer’s Drug Discovery Foundation (ADDF). About PepinemabPepinemab is a humanized IgG4 monoclonal antibody designed to block SEMA4D, which can otherwise bind to plexin-B1 receptors to trigger collapse of the actin cytoskeleton in cells and lead to loss of homeostatic functions of astrocytes and other glial cells in the brain and of dendritic cells in immune tissue. Pepinemab appears to have been well-tolerated with a favorable safety profile in multiple clinical trials in different neurological and cancer indications. About Vaccinex Inc. Vaccinex, Inc. is pioneering a differentiated approach to treating slowly progressive neurodegenerative diseases and cancer through the inhibition of semaphorin 4D (SEMA4D). The Company’s lead drug candidate, pepinemab, blocks SEMA4D, a potent biological effector that it believes triggers damaging inflammation in chronic diseases of the brain and prevents infiltration and activation of immune cells in tumors. Pepinemab is being studied as a monotherapy in the Phase 1b/2 SIGNAL-AD study in Alzheimer’s Disease, and the Company has previously published promising Phase 2 data in Huntington’s disease. Pepinemab could be an important contributor to combination therapy in AD. In oncology, pepinemab is being evaluated in combination with KEYTRUDA® in the Phase 1b/2 KEYNOTE-B84 study in recurrent or metastatic head and neck cancer (HNSCC) and in combination with BAVENCIO® in a Phase 1b/2 study in patients with metastatic pancreatic adenocarcinoma (PDAC). The oncology clinical program also includes several investigator-sponsored studies in solid tumors including breast cancer and melanoma. Vaccinex has global commercial and development rights to pepinemab and is the sponsor of the KEYNOTE-B84 study which is being performed in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck and Co, Inc. Kenilworth, NJ, USA. Additional information about the study is available at: clinicaltrials.gov. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. BAVENCIO®/avelumab is provided by Merck KGaA, Darmstadt, Germany, previously as part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany and Pfizer. Forward Looking StatementsTo the extent that statements contained in this press release are not descriptions of historical facts regarding Vaccinex, Inc. (“Vaccinex,” “we,” “us,” or “our”), they are forward-looking statements reflecting management’s current beliefs and expectations. Such statements include, but are not limited to, statements about expectations and objectives with respect to the results and timing of the SIGNAL-AD clinical trial; expectations with respect to compliance with Nasdaq listing standards; our plans, expectations and objectives with respect to the results and timing of the SIGNAL-AD and KEYNOTE-B84 clinical trials; the use and potential benefits of pepinemab in R/M HNSCC, lung cancer, metastatic pancreatic adenocarcinoma (PDAC) and other indications; the potential for benefits as compared to single agent KEYTRUDA® or BAVENCIO®; expectations with respect to the collaboration of Merck,; and other statements identified by words such as “anticipate,” “believe,” “plans,” “schedule,” “being,” “will,” “appears,” “expect,” “ongoing,” “potential,” “promising,” “suggest”, and similar expressions or their negatives (as well as other words and expressions referencing future events, conditions, or circumstances). Forward-looking statements involve substantial risks and uncertainties that could cause the outcome of our research and pre-clinical development programs, clinical development programs, future results, performance, or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, uncertainties inherent in the execution, cost and completion of preclinical studies and clinical trials, that interim and preliminary data may not be predictive of final results and does not ensure success in later clinical trials, uncertainties related to regulatory approval, risks related to our dependence on our lead product candidate pepinemab, the possible delisting of our common stock from Nasdaq if the Company is unable to regain and sustain compliance with the Nasdaq listing standards, and other matters that could affect our development plans or the commercial potential of our product candidates. Except as required by law, the Company assumes no obligation to update these forward-looking statements. For a further discussion of these and other factors that could cause future results to differ materially from any forward-looking statement, see the section titled “Risk Factors” in our periodic reports filed with the Securities and Exchange Commission and the other risks and uncertainties described in the Company’s annual year-end Form 10-K and subsequent filings with the SEC. Investor ContactElizabeth Evans, PhDChief Operating Officer, Vaccinex, Inc.(585) 271-2700eevans@vaccinex.com

VYLOY is the first and only CLDN18.2-targeted treatment approved in the U.S. for adults with advanced gastric and gastroesophageal junction cancer whose tumors are CLDN18.2 positive TOKYO, Oct. 18, 2024 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") today announced that the U.S. Food and Drug Administration (FDA) has approved VYLOY™ (zolbetuximab-clzb) in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test.1 VYLOY is the first and only CLDN18.2-targeted therapy approved in the U.S. In the SPOTLIGHT and GLOW clinical trials, approximately 38% of patients screened had tumors that were CLDN18.2 positive.2,3 CLDN18.2 positivity is defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining, as determined by the VENTANA® CLDN18 (43-14A) RxDx Assay from Roche.2,3 Astellas collaborated with Roche on the newly approved immunohistochemistry (IHC) companion diagnostic (CDx) test to identify patients who may be eligible for VYLOY.4 Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development, Astellas "The approval of VYLOY as the first and only targeted therapy for CLDN18.2-positive patients in the U.S. further delivers on our relentless pursuit of scientific progress for devastating diseases like gastric and GEJ cancers, which are often only discovered at the advanced stage. This achievement is the result of years of dedicated research and development focused on targeting a novel biomarker, and we are grateful to the patients, investigators, and Astellas team members who have made this important advancement for patients a reality." Samuel J. Klempner, M.D., Associate Professor, Harvard Medical School, M edical Oncologist at Massachusetts General Hospital, Boston "While there have been advances in the first-line treatment of locally advanced unresectable and metastatic gastric and GEJ cancers in the last several years, there is still a tremendous unmet need among our patients. The approval of VYLOY, based on the pivotal Phase 3 SPOTLIGHT and GLOW trials, brings forward a novel biomarker and new therapy for patients whose tumors are CLDN18.2 positive, and for those on the frontlines of treatment decision-making." The approval is based on results from the Phase 3 SPOTLIGHT and GLOW clinical trials.2,3 The SPOTLIGHT study evaluated VYLOY plus mFOLFOX6 (a combination chemotherapy regimen that includes oxaliplatin, leucovorin, and fluorouracil) compared to placebo plus mFOLFOX6. The GLOW study evaluated VYLOY plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX. Both trials met their primary endpoint, progression-free survival (PFS), as well as a key secondary endpoint, overall survival (OS), in patients treated with VYLOY plus chemotherapy compared to placebo plus chemotherapy. Across the SPOTLIGHT and GLOW trials, the most common all-grade treatment-emergent adverse events (TEAEs) reported in the VYLOY treatment arms were nausea, vomiting and decreased appetite.2,3 An FDA-approved test is used to identify patients who may be eligible for VYLOY.1 The VENTANA CLDN18 (43-14A) RxDx Assay from Roche is an FDA-approved IHC test used to help determine CLDN18.2 status. Testing is available in the U.S. at multiple reference laboratories nationwide and is expected to expand to additional laboratories over time. To see where testing for CLDN18.2 status is available, please visit VYLOYhcp.com.* Following today's FDA decision, VYLOY is now approved in five markets worldwide — Japan, the United Kingdom, the European Union, South Korea and the U.S. Japan's Ministry of Health, Labour and Welfare approved VYLOY for use on March 26, 2024, representing the first global approval of this treatment. In August, VYLOY was approved by the UK Medicines and Healthcare products Regulatory Agency. In September, the European Commission granted marketing authorization to VYLOY in the European Union, and the Ministry of Food and Drug Safety approved the therapy in South Korea. Astellas has submitted other applications for VYLOY to regulatory agencies around the world, with reviews ongoing. Astellas has already reflected the impact from this approval in its financial forecast for the current fiscal year ending March 31, 2025. *VYLOYhcp.com is in the process of being deployed. If you cannot access the site right away, please try again soon. About VYLOY™ (zolbetuximab-clzb) VYLOY™ (zolbetuximab-clzb) is a claudin 18.2-directed cytolytic antibody that is approved by the U.S. Food and Drug Administration (FDA) in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test. As a first-in-class monoclonal antibody (mAb), VYLOY targets and binds to CLDN18.2, a transmembrane protein. VYLOY depletes CLDN18.2-positive cells via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).1 VYLOY (zolbetuximab-clzb) U.S. Indication & Important Safety Information INDICATION VYLOY, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test. IMPORTANT SAFETY INFORMATION Warnings and Precautions Hypersensitivity reactions, including serious anaphylaxis reactions, and serious and fatal infusion-related reactions (IRR) have been reported in clinical studies when VYLOY has been administered. Any grade hypersensitivity reactions, including anaphylactic reactions, occurring with VYLOY in combination with mFOLFOX6 or CAPOX was 18%. Severe (Grade 3 or 4) hypersensitivity reactions, including anaphylactic reactions, occurred in 2% of patients. Seven patients (1.3%) permanently discontinued VYLOY for hypersensitivity reactions, including two patients (0.4%) who permanently discontinued VYLOY due to anaphylactic reactions. Seventeen (3.2%) patients required dose interruption, and three patients (0.6%) required infusion rate reduction due to hypersensitivity reactions. All grade IRRs occurred in 3.2% in patients administered VYLOY in combination with mFOLFOX6 or CAPOX. Severe (Grade 3) IRRs occurred in 2 (0.4%) patients who received VYLOY. An IRR led to permanent discontinuation of VYLOY in 2 (0.4%) patients and dose interruption in 7 (1.3%) patients. The infusion rate was reduced for VYLOY for 2 (0.4%) patients due to an IRR. Monitor patients during infusion with VYLOY and for 2 hours after completion of infusion or longer if clinically indicated, for hypersensitivity reactions with symptoms and signs that are highly suggestive of anaphylaxis (urticaria, repetitive cough, wheeze and throat tightness/change in voice). Monitor patients for signs and symptoms of IRRs including nausea, vomiting, abdominal pain, salivary hypersecretion, pyrexia, chest discomfort, chills, back pain, cough and hypertension. If a severe or life-threatening hypersensitivity or IRR reaction occurs, discontinue VYLOY permanently, treat symptoms according to standard medical care, and monitor until symptoms resolve. For any Grade 2 hypersensitivity or IRR, interrupt the VYLOY infusion until Grade ≤1, then resume at a reduced infusion rate for the remaining infusion. Follow Grade 2 management for Grade 3 infusion-related nausea and vomiting. Premedicate the patient with antihistamines for the subsequent infusions, and closely monitor the patient for symptoms and signs of a hypersensitivity reaction. The infusion rate may be gradually increased as tolerated. Severe Nausea and Vomiting. VYLOY is emetogenic. Nausea and vomiting occurred more often during the first cycle of treatment . All grade nausea and vomiting occurred in 82% and 67% respectively of patients treated with VYLOY in combination with mFOLFOX6 and 69% and 66% in combination with CAPOX, respectively. Severe (Grade 3) nausea occurred in 16% and 9% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX respectively. Severe (Grade 3) vomiting occurred in 16% and 12% of patients treated with VYLOY in combination with mFOLFOX6 or CAPOX. Nausea led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 18 (3.4%) patients and dose interruption in 147 (28%) patients. Vomiting led to permanent discontinuation of VYLOY in combination with mFOLFOX6 or CAPOX in 20 (3.8%) patients and dose interruption in 150 (28%) patients. Pretreat with antiemetics prior to each infusion of VYLOY. Manage patients during and after infusion with antiemetics or fluid replacement. Interrupt the infusion, or permanently discontinue VYLOY based on severity. ADVERSE REACTIONS Most common adverse reactions (≥15%): Nausea, vomiting, fatigue, decreased appetite, diarrhea, peripheral sensory neuropathy, abdominal pain, constipation, decreased weight, hypersensitivity reactions, and pyrexia. Most common laboratory abnormalities (≥15%): Decreased neutrophil count, decreased leucocyte count, decreased albumin, increased creatinine, decreased hemoglobin, increased glucose, decreased lymphocyte count, increased aspartate aminotransferase, decreased platelets, increased alkaline phosphatase, increased alanine aminotransferase, decreased glucose, decreased sodium, increased phosphate, decreased potassium, and decreased magnesium. SPOTLIGHT Study: 279 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with mFOLFOX6 Serious adverse reactions occurred in 45% of patients treated with VYLOY in combination with mFOLFOX6; the most common serious adverse reactions (≥2%) were vomiting (8%), nausea (7%), neutropenia (2.9%), febrile neutropenia (2.9%), diarrhea (2.9%), intestinal obstruction (3.2%), pyrexia (2.5%), pneumonia (2.5%), respiratory failure (2.2%), pulmonary embolism (2.2%), decreased appetite (2.1%) and sepsis (2.0%). Fatal adverse reactions occurred in 5% of patients who received VYLOY in combination with mFOLFOX6 including sepsis (1.4%), pneumonia (1.1%), respiratory failure (1.1%), intestinal obstruction (0.7%), acute hepatic failure (0.4%), acute myocardial infarction (0.4%), death (0.4%), disseminated intravascular coagulation (0.4%), encephalopathy (0.4%), and upper gastrointestinal hemorrhage (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 20% of patients; the most common adverse reactions leading to discontinuation (≥2%) were nausea and vomiting. Dosage interruptions of VYLOY due to an adverse reaction occurred in 75% of patients; the most common adverse reactions leading to dose interruption (≥5%) were nausea, vomiting, neutropenia, abdominal pain, fatigue, and hypertension. GLOW Study: 254 patients with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors were CLDN18.2 positive who received at least one dose of VYLOY in combination with CAPOX Serious adverse reactions occurred in 47% of patients treated with VYLOY in combination with CAPOX; the most common serious adverse reactions (≥2%) were vomiting (6%), nausea (4.3%), decreased appetite (3.9%), decreased platelet count (3.1%), upper gastrointestinal hemorrhage (2.8%), diarrhea (2.8%), pneumonia (2.4%), pulmonary embolism (2.3%), and pyrexia (2.0%). Fatal adverse reactions occurred in 8% of patients who received VYLOY in combination with CAPOX including sepsis (1.2%), pneumonia (0.4%), death (0.8%), upper gastrointestinal hemorrhage (0.8%), cerebral hemorrhage (0.8%), abdominal infection (0.4%), acute respiratory distress syndrome (0.4%), cardio-respiratory arrest (0.4%), decreased platelet count (0.4%), disseminated intravascular coagulation (0.4%), dyspnea (0.4%), gastric perforation (0.4%), hemorrhagic ascites (0.4%), procedural complication (0.4%), sudden death (0.4%), and syncope (0.4%). Permanent discontinuation of VYLOY due to an adverse reaction occurred in 19% of patients; the most common adverse reaction leading to discontinuation (≥2%) was vomiting. Dosage interruption of VYLOY due to an adverse reaction occurred in 55% of patients; the most common adverse reactions leading to dose interruption (≥2%) were nausea, vomiting, neutropenia, thrombocytopenia, anemia, fatigue, infusion-related reaction, and abdominal pain. SPECIFIC POPULATIONS Lactation Advise lactating women not to breastfeed during treatment with VYLOY and for 8 months after the last dose. For more information, please see the U.S. full Prescribing Information for VYLOY here. About Locally Advanced Unresectable Metastatic Gastric and Gastroesophageal Junction Cancer Gastric and gastroesophageal junction (G/GEJ) cancer is the fifth most commonly diagnosed cancer worldwide.5 GEJ adenocarcinoma is a cancer that starts at the area where the esophagus joins the stomach.6 In the U.S., it is estimated that 130,263 people are living with G/GEJ cancer, classifying it as a rare disease.7,8 In 2024, it is estimated that 26,890 people will be diagnosed with G/GEJ cancer and 10,880 will die from the disease in the U.S.7 Signs and symptoms can include indigestion or heartburn, pain or discomfort in the abdomen, nausea and vomiting, bloating of the stomach after meals and loss of appetite.9 Signs of more advanced G/GEJ cancer can include unexplained weight loss, weakness and fatigue, and vomiting blood or having blood in the stool.10 Risk factors associated with gastric and GEJ cancer can include older age, male gender, family history, H. pylori infection, smoking, and gastroesophageal reflux disease (GERD).11,12 Because early-stage gastric cancer symptoms frequently overlap with more common stomach-related conditions, G/GEJ 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.10 The five-year relative survival rate for patients at the metastatic stage is 7%.7 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 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. The primary endpoint is progression-free survival (PFS) in 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, 2023.2 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. 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 CLDN18.2 A 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 area and is currently recruiting patients. 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 these agent(s) 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 VYLOY [package insert]. Northbrook, IL: Astellas Inc. 2 Shitara K, Lordick F, Bang YJ, 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. Lancet 2023;401(10389):1655-1668. Errata in: Lancet 2023;402(10398):290; Lancet 2024;403(10421):30. 3 Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med 2023;29(8):2133-2141. 4 DATA ON FILE. 5 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. 6 American Cancer Society. About esophagus cancer (03-20-2020). Available at . Accessed 11-13-2023. 7 National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: stomach cancer. Available at . Accessed 04-26-2024. 8 National Institutes of Health National Center for Advancing Translational Sciences. About - Genetic and Rare Diseases Information Center. . Accessed 11-13-2023. 9 American Cancer Society. Signs and symptoms of stomach cancer (01-22-2021). Available at . Accessed 11-13-2023. 10 National Cancer Institute. Stomach Cancer Symptoms (05-31-2023). Available at . Accessed 08-28-2024. 11 American Cancer Society. Stomach cancer risk factors (01-22-2021). Available at . Accessed 11-13-2023. 12 American Cancer Society. Esophageal cancer risk factors (06-09-2020). Available at . Accessed 11-13-2023. SOURCE Astellas Pharma Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

- Zolbetuximab is currently the first and only therapy approved in the European Union to target claudin 18.2, a biomarker positively expressed by 38% of patients with advanced gastric cancer1,2 - Treatment with the claudin 18.2-targeted monoclonal antibody shown to significantly extend both progression-free survival and overall survival in Phase 3 trials1,2 TOKYO, Sept. 20, 2024 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") today announced that the European Commission (EC) has approved VYLOY™ (zolbetuximab) in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive. The European Medicines Agency has recommended that zolbetuximab's designation as an orphan medicinal product be maintained in recognition of the poor survival outcomes associated with gastric and GEJ cancers. Zolbetuximab is currently the first and only approved monoclonal antibody specifically designed to target gastric tumor cells that express the biomarker CLDN18.2, offering a more personalized approach to cancer treatment. In the zolbetuximab Phase 3 clinical trials, approximately 38% of adult patients with advanced and metastatic gastric and GEJ cancers had tumors that were CLDN18.2 positive.1,2 By binding to CLDN18.2 expressed on tumor cell membranes, zolbetuximab results in antibody-dependent cellular cytotoxicity, complement dependent cytotoxicity and tumor growth inhibition.3 Zorana Maravic, Chief Executive Officer of Digestive Cancers Europe (DiCE): "Sadly, due to similar symptoms to more common stomach conditions, gastric and gastroesophageal junction cancers are often diagnosed at the advanced or metastatic stage when treatment options have traditionally been relatively limited. Ensuring timely diagnosis, followed by personalized treatment and care, will be essential to better survival and quality of life for patients." Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development, Astellas: "We are delighted to bring zolbetuximab, a first-in-class targeted treatment option, to patients in Europe where gastric and gastroesophageal cancers are the sixth leading cause of cancer-related death. With zolbetuximab, we're entering a new era in precision medicine for these advanced cancers, underpinning our ongoing commitment to pioneering scientific discovery that can advance patient outcomes." Data from the Phase 3 SPOTLIGHT and GLOW clinical trials, which supported the European Marketing Authorization, showed that treatment with zolbetuximab provided statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared to other standard of care chemotherapies in eligible patients with gastric and GEJ cancers.1,2 In the SPOTLIGHT trial, a median PFS of 10.61 months was achieved with zolbetuximab plus mFOLFOX6 as first-line treatment, versus 8.67 months with placebo plus mFOLFOX6. The median OS was 18.23 months versus 15.54 months in the respective treatment groups.1 Similar efficacy findings were seen in the GLOW trial where median PFS was 8.21 months versus 6.80 months, and median OS 14.39 months versus 12.16 months, with zolbetuximab plus CAPOX, compared to placebo plus CAPOX, respectively.2 In both the SPOTLIGHT and GLOW trials, the incidence of serious treatment emergent adverse events (TEAEs) was similar in the zolbetuximab treatment groups compared to the controls. The most common all-grade TEAEs reported in the zolbetuximab treatment groups were nausea, vomiting and decreased appetite.1,2 The European Marketing Authorization for zolbetuximab is valid in all 27 EU member states as well as Iceland, Liechtenstein, and Norway, and is aligned to the recently updated ESMO Gastric Cancer Living Guidelines which state that the addition of zolbetuximab to chemotherapy can be considered for patients with CLDN18.2 positive, HER-2 negative tumors in the first-line metastatic disease setting.4 Astellas is working closely with local regulatory authorities and health technology assessment bodies across the EU to ensure that patients who may gain benefit from zolbetuximab are able to access the novel treatment as soon as possible. This regulatory approval for zolbetuximab follows the August 2024 approval by the UK Medicines and Healthcare products Regulatory Agency and the March 2024 approval by Japan's Ministry of Health, Labour and Welfare.5,6 Astellas has submitted further applications for zolbetuximab to other regulatory agencies around the world with reviews ongoing. Astellas has already reflected the impact from this result in its financial forecast for the current fiscal year ending March 31, 2025. About Zolbetuximab Zolbetuximab is a claudin 18.2-directed cytolytic antibody investigated in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive. In both the SPOTLIGHT and GLOW Phase 3 clinical trials, approximately 38% of patients screened had tumors that were CLDN18.2 positive, defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 immunohistochemical staining, assessed and confirmed using an in-vitro companion diagnostic test or medical device.1,2 Astellas collaborated with Roche on the VENTANA® CLDN18 (43-14A) RxDx Assay that, upon approval, is intended to be used by a pathologist or laboratory to identify patients eligible for targeted treatment with zolbetuximab.7 This immunohistochemistry based companion diagnostic test is currently under review by the notified body. As an investigational first-in-class monoclonal antibody (mAb), zolbetuximab targets and binds to CLDN18.2, a transmembrane protein expressed on cancer cells. In pre-clinical studies, zolbetuximab reduced the number of CLDN18.2-positive cells via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, leading to tumor growth inhibition.3 About Locally Advanced Unresectable Metastatic Gastric and Gastroesophageal Junction Cancer Gastric and gastroesophageal junction (G/GEJ) cancers are known to be histologically similar, are recommended to be managed in the same way in treatment guidelines, and frequently display aligned responses to treatment.2,8 Across Europe, over 135,000 new cases of G/GEJ cancer were diagnosed in 2022.9 G/GEJ cancer is the sixth most common cause of cancer-related mortality in Europe, responsible for 95,431 deaths in 2022.9,10 GEJ adenocarcinomas start in the first two inches (5 cm) where the esophagus joins the stomach.11 The average five-year survival rate for patients in Europe with G/GEJ cancer is 26% across all stages of the disease, driving the need for new therapeutic options that can slow disease progression and extend lives.12 Because early-stage cancer symptoms frequently overlap with more common stomach-related conditions, G/GEJ cancers are often diagnosed in the advanced or metastatic stage, or once they have spread from the tumor's origin to other body tissues or organs.13 Early signs and symptoms can include indigestion or heartburn, pain or discomfort in the abdomen, nausea and vomiting, bloating of the stomach after meals, and loss of appetite.13,14 Signs of more advanced G/GEJ cancer can include unexplained weight loss, weakness and fatigue, sensation of food getting stuck in the throat while eating, vomiting blood or having blood in the stool.13,14,15 Risk factors associated with G/GEJ cancer can include older age, male gender, family history, H. pylori infection, smoking, and gastroesophageal reflux disease (GERD).16,17 INVESTIGATIONAL STUDIES About the 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 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. 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.1 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, 2023.1 For more information, please visit clinicaltrials.gov under Identifier NCT03504397. About the 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.2 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, 2023.2 For more information, please visit clinicaltrials.gov under Identifier NCT03653507. Investigational Pipeline in CLDN18.2 An expanded Phase 2 trial of zolbetuximab in metastatic pancreatic adenocarcinoma is in progress and recruiting patients. 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 area and is currently recruiting patients. 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(s) 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. SOURCE Astellas Pharma Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED