Ischiopatellar Dysplasia

ADI-001 clinical development program now addresses six autoimmune diseases Patient enrollment for idiopathic inflammatory myopathy and stiff person syndrome cohort expected to be initiated in the first quarter of 2025 Company plans to report initial clinical data from Phase 1 study in multiple autoimmune diseases in the first half of 2025 REDWOOD CITY, CA & BOSTON, MA, USA I October 16, 2024 I Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, today announced that the U.S. Food and Drug Administration (FDA) has agreed to an amendment to the Company’s Investigational New Drug (IND) application to evaluate ADI-001 in idiopathic inflammatory myopathy (IIM) and stiff person syndrome (SPS) as part of the ongoing Phase 1 trial in autoimmune diseases. The Company plans to initiate enrollment for IIM and SPS patients in the first quarter of 2025. This announcement follows the FDA’s recent agreements on amendments to the Company’s ADI-001 IND application to evaluate three additional indications beyond lupus nephritis (LN), including systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). “The FDA’s acceptance of our IND amendment to evaluate ADI-001 in patients with IIM and SPS builds on our recent momentum in autoimmune diseases, expanding our efforts to six autoimmune indications as we aim to bring our differentiated gamma delta T cell therapy candidates to more patients in need of new treatment options,” said Chen Schor, President and Chief Executive Officer at Adicet Bio. “Following our recent announcement highlighting clinical biomarker data which demonstrated robust B-cell depletion and preferential trafficking to tissues and organs, we believe in ADI-001’s best-in-class potential for the treatment of autoimmune diseases, and we look forward to initiating patient enrollment in IIM and SPS in the first quarter of 2025 in our ongoing Phase 1 clinical program.” The ADI-001 Phase 1 program in autoimmune diseases will have four separate arms, enrolling LN and SLE patients into one arm, SSc patients into a second arm, AAV patients into a third arm, and IIM and SPS patients into a fourth arm. The fourth cohort combines several rare autoimmune muscle diseases into a single dose-finding population, including SPS and the following IIM subtypes: dermatomyositis, anti-synthetase syndrome, immune-mediated necrotizing myopathy, polymyositis, and overlap myositis. Enrolled patients will receive a single dose of ADI-001. The dose-limiting toxicity window is 28 days with response and safety assessments conducted on Day 28 and during the follow up period on months 3, 6, 9, 12, 18, and 24. The primary objectives of the study are to evaluate the safety and tolerability of ADI-001. Secondary objectives include measuring cellular kinetics, pharmacodynamics, changes in autoantibody titers, and appropriate disease activity scores in each indication. About Idiopathic Inflammatory Myopathy Idiopathic inflammatory myopathy (IIM, or myositis) refers to a group of rare autoimmune disorders characterized by chronic muscle inflammation and progressive muscle weakness. IIM primarily affects skeletal muscles but can also involve other organs such as the lungs, heart, and skin. Five of the main subtypes include dermatomyositis, anti-synthetase syndrome, immune-mediated necrotizing myopathy, polymyositis, and overlap myositis, all of which can lead to significant functional impairment and have the potential to be life threatening. There is no available cure for IIM and many patients on current treatments have refractory disease and may experience significant side effects. About Stiff Person Syndrome Stiff person syndrome (SPS) is a rare neurological autoimmune disorder characterized by severe muscle stiffness and spasms, primarily affecting the torso and limbs. Muscle stiffness caused by SPS often impairs mobility, making it difficult for patients to walk, bend, or perform daily activities. Muscle spasms can be triggered by sudden stimuli such as loud noises, physical contact, or emotional distress, and can result in a “statue-like” posture when severe. Due to its rarity and overlapping symptoms with other conditions, SPS is frequently misdiagnosed, often as an anxiety disorder or movement disorder. There is currently no available cure for SPS. About ADI-001 ADI-001 is aninvestigational allogeneic gamma delta chimeric antigen receptor (CAR) T cell therapy targeting CD20 for the treatment of autoimmune diseases. ADI-001 was granted Fast Track Designation by the FDA for the treatment of relapsed/refractory class III or class IV lupus nephritis (LN), and the ongoing Phase 1 study is also evaluating ADI-001 for the treatment of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), idiopathic inflammatory myopathy (IIM, or myositis), and stiff person syndrome (SPS). In the Phase 1 GLEAN trial, ADI-001 was shown to target B-cells via an anti-CD20 CAR and demonstrated robust exposure and complete CD19+ B-cell depletion both in peripheral blood and secondary lymphoid tissue. About Adicet Bio, Inc. Adicet Bio, Inc. is a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer. Adicet is advancing a pipeline of “off-the-shelf” gamma delta T cells, engineered with chimeric antigen receptors (CARs), to facilitate durable activity in patients. For more information, please visit our website at https://www.adicetbio.com . SOURCE: Adicet Bio

Company symposium to highlight case reports from 11 patients with stiff-person syndrome, myasthenia gravis and multiple sclerosis reinforcing KYV-101's initial efficacy and safety profile and broad potential in B cell-driven neuroinflammatory diseases Key biomarkers indicate potential for KYV-101 to durably modify neuroinflammatory diseases with immune system reset Kyverna to present posters on design and methods for company-sponsored clinical trials in neuroinflammatory diseases EMERYVILLE, Calif., Sept. 18, 2024 /PRNewswire/ -- Kyverna Therapeutics, Inc. (Kyverna), a patient-centered, clinical-stage biopharmaceutical company focused on developing cell therapies for patients suffering from autoimmune diseases, today announced the presentation of three posters outlining the design and methods of Kyverna's clinical trials evaluating KYV-101 in neuroinflammatory diseases at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark, taking place September 18-20, 2024. Also today, Kyverna shared case reports from its ongoing clinical trials in stiff-person syndrome, myasthenia gravis and multiple sclerosis in a company-sponsored symposium. These case reports reinforce emerging clinical data from KYV-101, with individual patient vignettes continuing to demonstrate disease modification across trials and durability in some patients extending beyond one year and a well-tolerated safety profile. "The new data contribute to redefine treatment efficacy and support the safety profile of KYV-101," said Ralf Gold, M.D., professor of Medicine, chair of Neurology at Ruhr University Bochum, St. Josef Hospital, in Germany, and one of the presenters at the company's symposium. "By rapidly adding new data across a wide spectrum of severe neuroinflammatory diseases, we can hope to accelerate the development of potentially life-changing therapies." "We are very proud to lead the field in understanding the impact of deep B-cell reset towards a potential paradigm shift in the treatment of neuroinflammatory diseases," said Warner Biddle, Chief Executive Officer at Kyverna. "As we continue to build on KYV-101's leading position in stiff-person syndrome and myasthenia gravis with these results, we are additionally excited by promising case reports in multiple sclerosis, which represents a significant population with high unmet need. Altogether, these results continue to reinforce the broad potential of KYV-101 to durably modify debilitating symptoms of severe neuroinflammatory diseases, and generate insights that will allow us to bring transformative CAR T treatments to even more patients." Across numerous company- and investigator-sponsored studies, KYV-101 is currently being evaluated in a range of B cell-driven autoimmune diseases. Kyverna is currently conducting three ongoing company-sponsored Phase 2 trials in neuroinflammatory diseases: KYSA-6 in myasthenia gravis, KYSA-7 in multiple sclerosis and KYSA-8 in stiff-person syndrome. At a company symposium titled, "KYV-101 Unlocking the Potential of CAR T-cell Therapy in Neuroinflammatory Diseases," to be held at 5:15 pm CET on September 18, 2024, Kyverna and investigators will highlight case report experience from 11 patients from these studies: In stiff-person syndrome, two patients treated with KYV-101 have demonstrated improved mobility and/or walking speed and reduced autoantibody titers, including one patient at greater than one year post-infusion. A third patient demonstrated reduced autoantibody titers but does not yet have mobility scores available. In myasthenia gravis, three patients treated with KYV-101 have shown reduced pathogenic anti-AChR antibody titers and sustained disease control, including two patients at more than one year post-infusion and all three at greater than 8 months post-infusion. In multiple sclerosis, five patients treated with KYV-101 who failed prior anti-CD20 medications have shown a significant and unprecedented average reduction in oligoclonal bands in the central nervous system (CNS), a potential surrogate biomarker for reduced disease progression. Across 41 autoimmune disease patients treated to date with KYV-101, no severe CRS or ICANS has been observed. In addition, the Company will present three posters featuring additional detail on the design and methods used in Kyverna's sponsored clinical trials of KYV-101: "Activity and manufacturing of KYV-101 anti-CD19 chimeric antigen receptor T cells derived from patients with neurologic autoimmune diseases" "Design of KYSA-6, a phase 2, open-label, multicenter study of KYV-101, a novel fully human anti-CD19 chimeric antigen receptor T-cell therapy in refractory generalized myasthenia gravis" "Design of KYSA-7, a phase 2, open-label, randomized, multicenter study of KYV-101, an autologous fully human anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in treatment refractory primary and secondary progressive multiple sclerosis" The posters presented at ECTRIMS will be available on the publications page of Kyverna's website, and highlights from the case studies presented at Kyverna's symposium will be included in the company's updated corporate presentation, which will be available on the investor relations section of Kyverna's website. About Stiff-Person Syndrome (SPS) SPS is a rare, progressive neurological autoimmune disorder causing debilitating muscle stiffness in the torso, arms, and legs, impacting the ability to walk or move. Patients typically present with muscle spasms and stiffness, resulting in difficulty turning and bending. When stiffness is severe, the patients' posture resembles a statue. Muscle spasms and stiffness can be precipitated by unexpected stimuli, including sounds, like a phone ring or a siren, sudden touches or conditions triggering anxiety and emotional upset which, when severe, are misdiagnosed as a primary anxiety disorder1. About Myasthenia Gravis (MG) Myasthenia gravis is an autoimmune disorder associated with muscle weakness in tissues throughout the body, potentially manifesting in partial paralysis of eye movements, problems in chewing and swallowing, respiratory problems, speech difficulties and weakness in skeletal muscles. MG patients develop antibodies that lead to an immunological attack on critical signaling proteins at the junction between nerve and muscle cells, thereby inhibiting the ability of nerves to communicate properly with muscles. The symptoms of the disease can be transient and in the early stages of the disease can remit spontaneously. However, as the disease progresses, symptom-free periods become less frequent and disease exacerbations can last for months. Disease symptoms reach their maximum levels within two to three years in approximately 80% of patients. Up to 20% of MG patients experience respiratory crisis at least once in their lives2. About Multiple sclerosis (MS) Multiple sclerosis is a chronic neurodegenerative autoimmune disease affecting over 2.8 million individuals worldwide3. It affects more frequently women, people of Northern European descent, and is also associated with certain environmental and genetic factors. Patients with MS can experience a range of symptoms including blurred vision, slurred speech, tremors, numbness, extreme fatigue, problems with memory and concentration, and, in severe cases, the inability to walk or stand. Current disease-modifying treatments for MS aim to reduce the frequency of disease relapses and delay progression of disability, but the disease remains a chronic condition that will progressively worsen for most patients. About KYV-101 KYV-101 is an autologous, fully human CD19 CAR T-cell product candidate for use in B cell-driven autoimmune diseases. The CAR in KYV-101 was designed by the National Institutes of Health (NIH) to improve tolerability and tested in a 20-patient Phase 1 trial in oncology. Results were published by the NIH in Nature Medicine4. KYV-101 is currently being evaluated in sponsored, open-label, Phase 1/2 and Phase 2 trials in the United States and Germany across two broad areas of autoimmune diseases, rheumatologic and neuroinflammatory, as well as in investigator-initiated trials for multiple indications in multiple geographies. The clinical experience to date with KYV-101 in both oncological and autoimmune diseases highlight the differentiated properties of KYV-101 and the potential to treat autoimmune patients. About Kyverna Therapeutics Kyverna Therapeutics, Inc. (Nasdaq: KYTX) is a patient-centered, clinical-stage biopharmaceutical company focused on developing cell therapies for patients suffering from autoimmune diseases. Our lead CAR T-cell therapy candidate, KYV-101 is advancing through clinical development with sponsored clinical trials across two broad areas of autoimmune disease: rheumatology and neurology, including Phase 2 trials for stiff-person syndrome, multiple sclerosis and myasthenia gravis, a Phase 1/2 trial for systemic sclerosis, and two ongoing multi-center, open-label Phase 1/2 trials in the United States and Germany for patients with lupus nephritis. Kyverna's pipeline includes next-generation CAR T-cell therapies in both autologous and allogeneic formats with properties intended to be well suited for use in B cell-driven autoimmune diseases. Forward-Looking Statements Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements." The words, without limitation, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these or similar identifying words. Forward-looking statements in this press release include, without limitation, those related to: the potential impact of the clinical outcomes from the ongoing clinical programs; the potential impact of the new data on the treatment efficacy and safety profile of KYV-101; the potential that the results of the ongoing trials could drastically change the treatment landscape for the targeted autoimmune diseases; Kyverna's goals to develop certain paradigm-shifting treatment options; the potential for KYV-101 to provide durable, immunosuppressant-free remission for autoimmune disease patients; Kyverna's beliefs about the differentiated properties of KYV-101; and Kyverna's clinical trials and named-patient activities. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties related to market conditions, and other factors discussed in the "Risk Factors" section of Kyverna's most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q that Kyverna has filed or may subsequently file with the U.S. Securities and Exchange Commission. Any forward-looking statements contained in this press release are based on the current expectations of Kyverna's management team and speak only as of the date hereof, and Kyverna specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. For more information, please visit . Contact: Precision AQ on behalf of Kyverna Therapeutics Investors: [email protected] Media: [email protected] 1 Dalakas, M.C., Neurotherapeutics 2022; 19, 832–847. 2 Payus et al., Am J Case Rep. 2021; 22: e928419-1–e928419-4. 3 Walton C, et al., Mult Scler. 2020; 26:1816-1821. 4 Brudno et al., Nature Medicine 2020; 26:270-280. SOURCE Kyverna Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

今年的奥运会，席琳·狄翁的回归无疑是其中亮点，要知道2年前，她刚刚被检出患有罕见的僵人综合征（SPS），病如其名患者会出现全身弥漫性肌僵硬，今年6月发布的纪录片显示，发病时，她无法控制呼吸，筋挛长达10分钟。 目前来看，SPS这一疾病几乎无法被治愈，大部分治疗手段为维持治疗，然而近期，僵人综合征研究基金会(SPSRF)的创始人兼CEO Tara Zier表示，这一疾病还是有治愈希望的。 SPS的疾病特性 Tara Zier现年53岁，她是一名执业牙医和空手道三级黑带，自2014年前夫去世后，她开始出现相关症状，并在经历了多年的误诊后，最终于2017年被诊断为患有SPS。此后，她创立了SPSRF，以支持患者群体并为治疗筹款。 Tara Zier的例子并不是个例，误诊情况普遍出现在SPS上，科罗拉多大学安舒茨医学院的自体免疫神经疾病专家Amanda Piquet就表示，在以前的文献中，甚至有患者长达19年时间被误诊为其他疾病。 这位专家同时也是诊断迪翁患有SPS的医生。他表示，在目前正在审查的疾病流行病学研究中，Piquet和他的同事发现患者被诊断出SPS通常需要四年以上，而其他研究去诊断SPS的平均时间约为七年。 患者面临的一个障碍是对该疾病的诊断标准缺乏国际共识，这是身为SPSRF的医学顾问委员会的Zier和Piquet正在努力解决的问题。 目前最为关键的测试是血液和脊髓液中的GAD65抗体，GAD65抗体是由功能失常的B细胞分泌出来的破坏谷氨酸脱羧酶的一种形式。这种酶在制造γ-氨基丁酸(GABA)中起着关键作用，γ-氨基丁酸是一种抑制神经系统的关键神经递质。 通常情况下GABA对神经系统有调节作用，可以防止兴奋过度，例如说γ-氨基丁酸会防止你的身体对像突然的噪音这样的轻微刺激做出过度反应，但随着GAD65抗体对GABA的破坏，神经系统的兴奋部分不受阻碍地被激活，导致身体痉挛。 这大概就像是一辆车刹车失灵了，踩着油门一路向前冲。 CAR-T治疗SPS 不过，既然B细胞被认为是潜在的罪魁祸首，正好CAR-T等细胞疗法不就是靶向B细胞的吗？ Kyverna Therapeutics就想在这一疾病上试试身手。通过基因编辑T细胞，使它们针对制造GAD65抗体的有害B细胞，Kyverna有望开发出有史以来第一种治愈SPS的方法。 根据该公司罕见病负责人Sham Dholakia的说法，他们的候选药物KYV-101将进入二期试验，旨在招募约25名患者，并在12月31日之前给第一批患者用药。 目前KYV-101在发表于《美国国家科学院学报》的病例报告中显示了其潜力，一名69岁的SPS患者接受了CAR T细胞的输注后，肌肉僵硬减少，身体灵活度提升。 这一病例报告后紧跟着KYV-101成为获得了再生医学高级治疗的称号。 当然……SPS这一疾病本身因为患者稀少，目前还是非常缺乏临床数据的，Tara Zier表示，SPSRF正在与Piquet和其他人合作，率先努力创建一个面向全世界的国际患者注册中心，该中心将随着时间的推移跟踪患者，并获得他们进行研究所需的数据。通过注册和使用它的研究，以及在诊断标准上正在取得的共识，Zier希望确定这种疾病的基本情况。