XIAP

[17-November-2023] Real-world evidence on use of oral decitabine and cedazuridine in the treatment of myelodysplastic syndromes to be featured in an oral presentation; results of several additional studies in hematological malignancies were accepted for poster presentations PRINCETON, N.J. and PLEASANTON, Calif., Nov. 17, 2023 /PRNewswire/ -- Taiho Oncology Inc. and Astex Pharmaceuticals, Inc. announced today details of studies to be presented at the 65th American Society of Hematology (ASH) Annual Meeting, to be held Dec. 9-12, 2023, in San Diego. Among these data are the results of a real-world study of oral decitabine and cedazuridine in patients with myelodysplastic syndromes (MDS), which will be featured in an oral presentation. "Real-world data in healthcare is invaluable as it provides us with a closer look at actual patient experiences outside the clinical trial setting," said Tehseen Salimi, MD, MHA, Senior Vice President Medical Affairs, Taiho Oncology. "This study is the first to explore how an oral therapy may help patients with MDS adhere to their treatment regimen, while reducing both personal and disease burden. Oral decitabine and cedazuridine is a potentially important treatment option for people living with this form of cancer." Below are viewing details of this oral presentation. The above study was sponsored by Taiho Oncology. In addition, investigational compounds from Astex Pharmaceuticals that are currently in various stages of clinical development will be featured in several poster presentations. The above studies are being sponsored by Astex Pharmaceuticals, Inc. About Taiho Oncology, Inc. The mission of Taiho Oncology, Inc. is to improve the lives of patients with cancer, their families and their caregivers. The company specializes in the development and commercialization of orally administered anti-cancer agents for various tumor types. Taiho Oncology has a robust pipeline of small molecule clinical candidates targeting solid tumor and hematological malignancies, with additional candidates in pre-clinical development. Taiho Oncology is a subsidiary of Taiho Pharmaceutical Co., Ltd. which is part of Otsuka Holdings Co., Ltd. Taiho Oncology is headquartered in Princeton, New Jersey and oversees its parent company's European and Canadian operations, which are located in Zug, Switzerland and Oakville, Ontario, Canada. For more information, visit , and follow us on LinkedIn and Twitter. About Astex Pharmaceuticals, Inc. Astex Pharmaceuticals, Inc. is committed to the fight against cancer. Astex is developing a proprietary pipeline of novel therapies for the treatment of solid tumors and hematological malignancies. Astex is a member of the Otsuka group of companies. The group also includes Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Taiho Oncology, Inc. Astex, the Astex logo, Taiho Oncology, and the Taiho Oncology logo are registered trademarks of Otsuka Holdings Co., Ltd. or its subsidiaries. Taiho Oncology Contact: Judy Kay Moore (574) 526-2369 jumoore@taihooncology.com Astex Pharmaceuticals: Martin Buckland Astex Pharmaceuticals, Inc. (+1) 925-560-0100 martin.buckland@astx.com INQ-PM-US-0512 1 Investigational Oral DNA Methyltransferase Inhibitor 2 X-Linked Inhibitor of Apoptosis Protein (XIAP)/Cellular Inhibitor of Apoptosis Protein (cIAP) Antagonist - Astex Pharmaceuticals, Inc. investigational agent being developed in collaboration with Taiho Oncology, Inc.

A research team has published rigorous new research that advances a quest to understand a puzzling -- and heartbreaking -- ultra-rare disease that's found almost exclusively in boys. A University of Ottawa-led research team has published rigorous new research that advances a quest to understand a puzzling -- and heartbreaking -- ultra-rare disease that's found almost exclusively in boys. XLP-2 is a genetic X-linked lymphoproliferative disease first described in 2006. It typically has severe complications among patients who become infected with the Epstein-Barr virus, an exceedingly common virus that infects most people without problems in their teenage years or young adulthood. But when the few individuals with XLP-2 encounter the Epstein-Barr virus the experience is often fatal because it results in immunodeficiency -- a derailing of the immune system. The team aimed to examine how the inactivation of a protein-coding gene called XIAP triggers this immunodeficiency, according to senior author Dr. Subash Sad, whose uOttawa Faculty of Medicine lab studies the mechanisms that maintain a healthy immune system and prevent the development of inflammatory diseases. "How inactivation of XIAP results in immunodeficiency was not clear. It was speculated that an inactivation of XIAP impacts T cells directly. However, our work demonstrates that this is not entirely true. We showed inactivation of XIAP impacts the survival of T cells through direct and indirect effects which comprehensively result in a state of immunodeficiency," says Dr. Sad, a cellular immunologist and professor in the Faculty's Department of Biochemistry, Microbiology and Immunology. First author Parva Thakkar and the other researchers used recombinant bacteria and T cell transgenic cells to monitor the impact of XIAP on the differentiation and memory development of T cells following infection. Most of the experiments were done in vivo with a mouse model. Other mechanistic experiments were done in various cells of the immune system. Ultimately, the team's efforts revealed two underlying mechanisms: 1) Inactivation of XIAP results in poor expression of Interleukin-6 (IL-6) which compromises the proliferation of activated T cells, and 2) inactivation of XIAP compromises the ability of activated T cells to survive long-term. The consequence of this phenomenon is that memory T cells, which patrol the body and are induced during prior infections or vaccinations, survive poorly if there is an inactivating mutation in XIAP. This explains the reasons behind immunodeficiency in XLP-2 patients, Dr. Sad says. The study was recently published in PLOS Pathogens. The work was supported by funding from NSERC and CIHR, and it could not have been done without the expertise of the Faculty's Flow cytometry core facility. As the team explores questions suggested by this study, they are interested in examining downstream mechanisms and pathways that can be targeted for therapy. They are also interested in working with patient samples. Dr. Sad encourages families with such mutations to get in contact with CHEO, an institutional partner of the uOttawa Faculty of Medicine.

Topline pivotal Phase 3 results expected during second half of 2023Potential new treatment option in ultra-rare, life-threatening, primarily pediatric disease with no approved therapies Lausanne (Switzerland), March 7, 2023 -- AB2 Bio Ltd., a biotechnology company developing innovative therapies for the treatment of severe systemic autoinflammatory diseases and conditions driven by IL-18, announced today the completion of enrolment of its ongoing pivotal Phase 3 study of Tadekinig alfa. The study is designed to show the efficacy and safety of Tadekinig alfa (r-hIL-18BP) for the treatment of primary monogenic IL-18 driven HLH, an ultra-rare and life-threatening condition with no approved therapies, mainly affecting children. AB2 Bio anticipates topline results during second half of 2023. “This is a truly exciting time as we pioneer development of the first targeted treatment option for IL18 driven diseases and conditions,” said Dr. Djordje Filipovic, CEO of AB2 Bio. “We are pleased to have completed the targeted enrollment in this pivotal study which represents a significant milestone for AB2 Bio and the patient community. This randomized, placebo-controlled study will provide the dataset required by regulatory authorities to evaluate the efficacy and safety of Tadekinig alfa in patients suffering from primary monogenic IL-18 driven HLH, which will be the basis to support marketing authorization submissions.” “We are grateful to all the patients and their caregivers for participating in this study and the dedication of the investigators and their collaborators,” added Dr. Eduardo Schiffrin, Medical Director of AB2 Bio. “Tadekinig alfa is an important potential new treatment option for patients suffering from IL-18 driven autoinflammatory diseases with no current standard of care. We look forward to communicating top-line data from this study later this year.” About Primary monogenic IL-18 driven HLH in patients with NLRC4 mutation and XIAP deficiency Primary monogenic IL-18 driven HLH (Hemophagocytic lymphohistiocytosis) is a potentially lifethreatening disease characterized by severe systemic inflammation that, if left untreated, may rapidly evolve into multiple-organ failure and death. Mutations in the NLRC4 or XIAP genes are associated with extremely high systemic levels of the pro-inflammatory cytokine IL-18, the therapeutic target of Tadekinig alfa. The excessive release of IL-18 drives the pathology of this clearly defined subgroup of primary HLH, characterized by severe systemic inflammation caused by the detrimental hyperactivation of immune cells leading to a multiorgan pathology and non-reversible organ damage in fatal cases. This ultra-rare disease is most often occurring in infants and young children. About Tadekinig alfa double-blind placebo controlled pivotal Phase 3 trialThe pivotal Phase 3 study conducted in the United States of America, Canada, and Europe, is a multicenter, double-blind, placebo-controlled, randomized withdrawal trial evaluating the efficacy and safety of Tadekinig alfa (r-hIL-18BP) in 15 primary monogenic IL-18 driven HLH patients with verified NLRC4 or XIAP mutations, suffering from severe, life-threatening hyperinflammation despite symptomatic treatment with current care. The study has an overall duration of approximately 34 weeks. During the first 18-week single-arm, open-label (SAOL) phase, Tadekinig alfa is being administered in addition to treatments previously used in an attempt to control inflammation and related sequelae with limited success. Patients who complete the SAOL phase are enrolled in a randomized withdrawal (1:1) phase, during which they receive Tadekinig alfa or placebo for up to 16 weeks. The design, size, and endpoints of the study were validated with the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Further details of the study can be reviewed on www.clinicaltrials.gov website using Identifier NCT03113760. About Tadekinig alfa Tadekinig alfa is a novel, recombinant human interleukin-18 binding protein (IL-18 BP) inhibiting IL18, a major proinflammatory cytokine. In healthy people, a large excess of naturally occurring endogenous IL-18 Binding Protein is keeping levels of systemic free IL-18 undetectable. Dysregulation of this balance results in high systemic free IL-18 levels which leads to pathological hyperinflammation. Tadekinig alfa, captures excess free IL-18 mimicking the normal physiological situation, and therefore represents a well differentiated approach for the treatment of IL-18-opathies (diseases and conditions characterized by high systemic IL-18 levels). Tadekinig alfa has established clinical Proof-of-Concept in three life-threatening orphan diseases and obtained EMA’s Orphan Drug Designation and U.S. FDA’s Orphan Drug Designation, Breakthrough Therapy and Pediatric Rare Disease Designations, making it eligible for a Priority Review Voucher. Tadekinig alfa is presented as a liquid in a vial and is being administered subcutaneously at patient’s homes. About AB2 Bio Ltd AB2 Bio is a Phase 3 clinical-stage biotech company developing innovative therapies for the treatment of severe systemic autoinflammatory diseases and conditions driven by IL-18. The company is advancing Tadekinig alfa in a wide range of IL-18 mediated hyperinflammatory diseases and conditions, including rare orphan diseases with high unmet medical needs, at clinical and preclinical phase. AB2 Bio was founded in 2010 and is headquartered in the Innovation Park at the Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland. More information can be found on www.ab2bio.com. For further information, please contact: AB2 Bio Fernando Cunha CFO, AB2 BioPhone +41 21 694 00 48 info@ab2bio.com Media & Investors Chris Maggos Cohesion Bureau Phone: +41 79 367 62 54 chris.maggos@cohesionbureau.com Attachment PDF Version