GnRHR

– ORGOVYX is the First and Only Oral Gonadotropin-Releasing Hormone (GnRH) Receptor Antagonist Approved for Advanced Prostate Cancer in Canada – MISSISSAUGA, Ontario, Oct. 23, 2023 /PRNewswire/ -- Sumitomo Pharma Canada, Inc., announced today that Health Canada has approved ORGOVYX® (relugolix), an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, for the treatment of men with advanced prostate cancer. The approval is based on efficacy and safety data from the Phase 3 HERO study of ORGOVYX in men with advanced prostate cancer. ORGOVYX is expected to be available for prescription in Canada in Q1 2024. "Roughly 1 in 8 Canadian men will develop prostate cancer in their lifetime, and the ability to suppress testosterone, primarily achieved through androgen deprivation therapy (ADT), is foundational in the treatment of the advanced stages of the disease," said Fred Saad, M.D., FRCS, Professor and Chairman of the Department of Surgery and Director of Genitourinary Oncology at the University of Montreal. "In the HERO study, ORGOVYX demonstrated rapid, sustained, and profound testosterone suppression when compared to leuprolide. ORGOVYX is the first approved ADT in Canada that can be administered orally, and once daily, offering a safe and effective option for advanced prostate cancer patients in the country." "We're pleased that with Health Canada's approval of ORGOVYX, we are helping to expand upon treatment options for Canadian men living with advanced prostate cancer," said Lisa Mullett, General Manager of Sumitomo Pharma Canada, Inc. "We are committed to making ORGOVYX available to patients across Canada early in the new year." The Health Canada approval was based on the results of the Phase 3 HERO study, a randomized, open-label, parallel-group, multinational clinical study evaluating the safety and efficacy of ORGOVYX in over 1,000 men with androgen-sensitive advanced prostate cancer who required at least one year of continuous ADT. In the Phase 3 study, ORGOVYX met the primary endpoint and demonstrated superiority in sustained testosterone suppression to castrate levels (< 50 ng/dL) through 48 weeks compared to those receiving leuprolide acetate injections, the current standard of care. The most frequent adverse events reported in at least 10% of men in the ORGOVYX group were hot flush, musculoskeletal pain, fatigue, constipation, and mild to moderate diarrhea. ORGOVYX was previously approved by the U.S. Food and Drug Administration on December 18, 2020 and granted marketing authorization by the European Commission for advanced hormone-sensitive prostate cancer on April 29, 2022. About Advanced Prostate Cancer Prostate cancer is the most common cancer in Canadian men, and, in 2023 an estimated 24,700 men will be diagnosed.1 Prostate cancer is considered advanced when it has spread or come back after initial treatment and may include biochemical recurrence (rising prostate-specific antigen in the absence of metastatic disease on imaging), locally advanced disease, or metastatic disease. Front-line medical therapy for advanced prostate cancer typically involves androgen deprivation therapy, which reduces testosterone to very low levels, commonly referred to as castrate levels (< 50 ng/dL). Luteinizing hormone-releasing hormone (LHRH) receptor agonists, such as leuprolide acetate, are depot injections and the current standard of care for androgen deprivation therapy. However, LHRH receptor agonists may be associated with mechanism-of-action limitations, including the potentially detrimental initial surge in testosterone levels that can exacerbate clinical symptoms, which is known as clinical or hormonal flare, and delayed testosterone recovery after the drug is discontinued. About ORGOVYX® (relugolix) ORGOVYX (relugolix) is the first and only oral gonadotropin-releasing hormone (GnRH) receptor antagonist approved by the U.S. Food and Drug Administration, the European Commission and Health Canada for the treatment of adult patients with advanced prostate cancer. As a GnRH antagonist, ORGOVYX blocks the GnRH receptor and reduces production of testicular testosterone, a hormone known to stimulate the growth of prostate cancer. About Sumitomo Pharma Sumitomo Pharma Co., Ltd. is a global pharmaceutical company based in Japan with key operations in the U.S. (Sumitomo Pharma America, Inc.), Canada (Sumitomo Pharma Canada, Inc.) and Europe (Sumitomo Pharma Switzerland GmbH) focused on addressing patient needs in psychiatry & neurology, oncology, urology, women's health, rare disease, and cell & gene therapies. With several marketed products in the U.S., Canada, and Europe, a diverse pipeline of early- to late-stage assets, and in-house advanced technology capabilities, we aim to accelerate discovery, research, and development to bring novel therapies to patients sooner. For more information, please visit and LinkedIn to follow us. The Sumitomo Pharma icon is a trademark of Sumitomo Pharma Co., Ltd., used under license. SUMITOMO PHARMA is a trademark of Sumitomo Pharma Co., Ltd., used under license. Sumitomo Pharma America, Inc. is a U.S. subsidiary of Sumitomo Pharma Co., Ltd. ORGOVYX is a trademark of Sumitomo Pharma Switzerland GmbH. © 2023 Sumitomo Pharma America, Inc. All rights reserved. References Fraser M, Mohammad A. The landscape of prostate cancer research in Canada. doi: 10.1200/JCO.2023.41.6_suppl.394 Journal of Clinical Oncology 41, no. 6_suppl (February 20, 2023) 394-394.

Multicenter, multinational Phase 3 Casppian study will evaluate the efficacy, safety, and pharmacokinetics of leuprolide (FP-001) 42 mg-controlled release in patients with central (Gonadotropin-Dependent) precocious puberty (CPP). Foresee's leuprolide injectable emulsion, 42 mg (marketed under the brand name Camcevi®) is currently approved for the treatment of adult patients with advanced prostate cancer and has demonstrated positive efficacy and safety results with statistically significant treatment effects in adult male patients with advanced prostate cancer. Gonadotropin-releasing hormone (GnRH) agonists, including leuprolide, are the most widely used treatment for CPP. TAIPEI, Oct. 13, 2023 /PRNewswire/ -- Foresee Pharmaceuticals (TPEx: 6576), ("Foresee") today announces that the first patient has been dosed in the Casppian Phase 3 registration study. Continue Reading "The Casppian Phase 3 study is an open-label, multicenter clinical trial to evaluate the efficacy, safety, and pharmacokinetics of leuprolide (FP-001) 42 mg-controlled release in patients with central (Gonadotropin- Dependent) precocious puberty (CPP). The study duration is 48 weeks. The study's Primary endpoint is the percentage of patients with serum LH concentration < 4 mIU/mL 30 minutes following a GnRH agonist stimulation test at Week 24. Leuprolide (FP-001) 42 mg will be considered effective for the treatment of children with CPP if ≥ 80% of patients exhibit LH suppression < 4 mIU/mL at Week 24. The Casppian study will also test key secondary endpoints like the changes in bone ages, growth rate, and physical signs of puberty assessed by Tanner stages from baseline to the end of the study at 48 weeks, which the FDA has accepted," said Bassem Elmankabadi, M.D., Senior Vice President Clinical Development at Foresee Pharmaceuticals. "GnRH agonists, including leuprolide, are the standard of care for CPP patients. Foresee's FP-001, 42 mg subcutaneously every 6 months, has the potential to become the only six-month, ready-to-use leuprolide, providing benefit to multiple stakeholders in the CPP community." said Dr. Ben Chien, Foresee's Chairman, and CEO. "It is exciting to be expanding the therapeutic and commercial potential of FP-001 with the initiation of the Casppian study, and we look forward to establishing a commercial partnership for the potential future commercialization of FP-001, specifically in CPP." About CPP GnRH-dependent CPP is a condition that causes early sexual development in girls and boys, as their "hypothalamus - pituitary gland - gonadal axis" is activated prematurely, causing children to enter puberty prematurely, between 2 years and 9 years of age. CPP patients are at risk of having significantly short stature as adults in addition to social, psychological, and emotional issues, including lower self-esteem, stress, anxiety, and depression, which may negatively impact their quality of life. According to the NORD (National Organization for Rare Disorders) website, CPP occurs in 1 out of 5,000 to 10,000 children. It is estimated that approximately 80% - 90% of CPP cases are idiopathic, especially in females, with a female-to-male ratio of around 20: 1. About Foresee Pharmaceuticals Co., Ltd. Foresee is a Taiwan and US-based biopharmaceutical company listed on the Taipei Exchange (TPEx: 6576). Foresee's R&D efforts are focused in two key areas, namely its unique Stabilized Injectable Formulation (SIF) long-acting injectable technology with derived drug products targeting specialty markets and secondly, its transformative preclinical and clinical first-in-class NCE programs targeting rare and severe disease areas with high unmet needs. Foresee's product portfolio includes late and early-stage programs. CAMCEVI® 42 mg, for the treatment of advanced prostate cancer, is now approved in the U.S., Canada, EU and Taiwan and launched in the U.S. in April 2022. Additionally, U.S. and EU regulatory submissions are under preparation for CAMCEVI® 21 mg. The U.S. regulatory submission is anticipated in 2024. The second indication of CAMCEVI® 42 mg – central precocious puberty (CPP), the Casppian phase 3 clinical study, has been initiated. FP-025 – a highly selective oral MMP-12 inhibitor targeting inflammatory and fibrotic diseases, a Phase 2 proof-of-concept study in allergic asthmatic patients has been completed with positive outcomes, with future development in rare immune-fibrotic diseases. FP-045 – a highly selective oral small molecule allosteric activator of ALDH2, a mitochondrial enzyme, for which the FuschiA Phase 1b/2 Fanconi Anemia study is currently being initiated, and a Phase 2 study in pulmonary hypertension-interstitial lung disease (PH-ILD) patients is in planning. SOURCE Foresee Pharmaceuticals Co., Ltd.

Phase 3 aims to demonstrate cardiovascular benefit of Teverelix versus GnRH agonists.Up to 30% of advanced prostate cancer patients on Androgen Deprivation Therapy have pre-existing Cardiovascular Disease. Phase 3 top-line results expected in 2027. LONDON, March 08, 2023 (GLOBE NEWSWIRE) -- Antev Ltd., a late clinical-stage biotech company developing a novel gonadotrophin-releasing hormone (GnRH) antagonist, Teverelix trifluoroacetate (Teverelix), announces that the US Food & Drug Administration (FDA) has provided written guidance on the company’s proposed Phase 3 pivotal trial design. This would be the first Phase 3 trial for a specific label to treat prostate cancer in patients with increased cardiovascular risk, addressing a significant need for prostate cancer drugs with a better cardiac toxicity profile. Prostate cancer is the second most common cause of cancer death in men[1], with around 5 million men living with the disease in the US and Europe. Current treatments using GnRH agonists have been shown[2] to have between two and four times increased risk of cardiovascular events in patients with a medical history of cardiovascular disease than antagonist treatments, a conclusion supported by the American Heart Association in a 2021 scientific statement[3][4]. Prior to initiating androgen deprivation therapy (ADT), a common form of hormone therapy, an estimated 30% of men have known cardiovascular disease (CVD)[5]. Teverelix, a decapeptide, has the potential to be the first hormone therapy specifically approved to treat advanced prostate cancer patients with a history of cardiovascular disease. “We are delighted to reach this critical milestone in Antev’s journey to secure regulatory guidance to develop Teverelix in advanced prostate cancer patients with increased cardiovascular risk,” commented Amit Kohli, Chief Executive Officer of Antev. “This written acceptance by the US FDA on our proposed Phase 3 pivotal trial design provides great visibility and supports the company’s clinical plans for our innovative treatment that could combine profound castration, improved tolerability, and significantly reduced cardiovascular risk compared to GnRH agonists, which generate over US$ 3 billion in annual sales globally. Cardio-oncology is an important new therapeutic area, and Antev is leading the way to deliver improved patient and payor outcomes.” Antev’s Chief Medical Officer, Dr Steve van Os, added, “Having worked on the global development and registration of Xtandi® for late-stage prostate cancer patients, I am very satisfied with the progress we are making at Antev in developing a novel GnRH antagonist that could help the many earlier-stage prostate cancer patients with an increased cardiovascular risk. With cardiovascular diseases being now the leading cause of death in men with prostate cancer and with up to 30% of prostate cancer patients having a history of CVD, there is a clear and urgent need for safer therapies that treat prostate cancer, yet do not increase cardiovascular risk.” Antev's Scientific Adviser, Dr Neal Shore MD FACS, CMO of Surgery and Oncology at GenesisCare USA, said, “There is an unmet medical need for a new specific ‘cardio-oncology’ indication for androgen deprivation therapy which will effectively treat the patient’s cancer while not worsening cardiovascular safety. This proposed Phase 3 trial is designed to provide the level one evidence that this GnRH antagonist could be the treatment of choice for prostate cancer patients with cardiovascular risks.” Both GnRH agonists and antagonists are approved for the treatment of prostate cancer and although both bind to the same therapeutic target, the GnRH receptor in the pituitary gland, they have distinct mechanisms of action. While the GnRH agonist stimulates the GnRH receptor, leading to overexpression of Follicle Stimulating Hormone and Luteinizing Hormone, which in turn leads to an initial increase in the production of testosterone but then rapidly inhibited through a negative feedback loop, the GnRH antagonists directly suppress the production of sex hormones by competitively blocking the GnRH receptors at the pituitary gland, and thus do not create a testosterone surge. Antev’s proposed ANT-1111-04 is a global Phase 3 trial in up to 1,500 advanced prostate cancer patients with increased CV risk with a 1:1 randomization against standard of care (GnRH agonist) that aims to read out by 2027. References 1 – Bray et al. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), pp.394-424 2 – Studies by Margel et al. in 2019 (n=80) and Shore et al. 2020 (n=930). https://ic-os.org/wp-content/uploads/2020/04/2019-CV-morbidity-in-a-RCT-comparing-GnRH-agonist-and-GnRH-antagonist.pdf https://pubmed.ncbi.nlm.nih.gov/32469183/ 3 – AAH Scientific Statement, published in Genomic and Precision Medicine (Vol 14, No. 3. 26 April 2021) “Impact of Hormonal Therapies for Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart” Association https://www.ahajournals.org/doi/10.1161/HCG.0000000000000082 4 – Accompanying AAH press release: https://newsroom.heart.org/news/close-monitoring-for-heart-risk-needed-if-breast-prostate-cancer-treatment-includes-hormones 5 – PCN194 Prevalence of Major Adverse Cardiac Events (MACE) in Patients with Prostate Cancer (PC) Receiving Androgen Deprivation Therapy (ADT) in the United States: https://www.valueinhealthjournal.com/article/S1098-3015(20)32587-0/fulltext For more information, please contact: Antev Limited Amit Kohli, CEO Email: amitkohli@antev.co.uk Scius CommunicationsKatja Stout +44 778 943 5990 katja@sciuscommunications.com Daniel Gooch +44 774 787 5479 daniel@sciuscommunications.com About Teverelix and GnRH antagonists Teverelix is an injectable, long-acting GnRH antagonist. In a novel and unique microcrystal formulation which can overcome the well documented safety issues associated with other GnRH antagonist candidates in the treatment of prostate cancer. With good injection site tolerance and a six-week dosing interval, Teverelix is likely to secure better patient compliance and therefore better clinical outcomes. Teverelix also has the potential to be developed for BPH (Benign Prostate Hyperplasia), AUR (Acute Urinary Retention), Endometriosis and Uterine Fibroids. About Antev Limited Antev Limited, based in London, is a late clinical-stage biopharmaceutical company, focused on the development of a robust registration-ready data package for the treatment of advanced prostate cancer in patients with high cardiovascular risk. Prostate cancer affects an estimated 1.3 million new patients annually around the globe and is the second most common cause of cancer death in men. Gonadotrophin-releasing hormone (GnRH) agonists and antagonists represent the foundation of prostate cancer treatment. The Company acquired the intellectual property rights for the decapeptide Teverelix, a novel GnRH antagonist, from LifeArc, one of the UK’s leading medical research charities. Teverelix is formulated as a teverelix TFA salt. It forms a microcrystalline suspension at the concentration used for injection, allowing a small injection volume. This very rare property allows for a highly injectable drug product that exhibits a sustained release. Antev is backed by private investors and was founded in 2013. For more details see our website and follow us on LinkedIn.