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

Céline Dion, pictured here performing on the Eiffel Tower during the opening ceremony of the Paris 2024 Olympic Games, was diagnosed with stiff-person syndrome in 2022. Céline Dion stands alone as a singer, a chart-topping ballad-belter who recorded some of the most iconic songs of all time, including “My Heart Will Go On” from the “Titanic” soundtrack. But, in 2022, Dion made headlines not for her one-in-a-million voice, but for a one-in-a-million diagnosis: a rare neurological disease called stiff-person syndrome (SPS).Two years on, Dion has staged a “comeback” with the release of a documentary about her health struggles and a widely praised performance to close out the 2024 Paris Olympics opening ceremony last month. But with stiff-person syndrome, looks—and even the name of the disease itself—can be deceiving.“I was so happy for her that she was able to do that,” Tara Zier, founder and CEO of the Stiff Person Syndrome Research Foundation (SPSRF), told Fierce Biotech in an interview. “Does that mean she's cured? No. Does that mean she's OK? No.”A mild name like “stiff-person syndrome” belies the seriousness of the disease, a rare autoimmune neurological disorder that can upend patients’ lives with its broad range of symptoms. Stiffness is a symptom, but so are muscle spasms that can be triggered by emotional distress or environmental stimuli. As Zier explained, “Light touch or a loud noise can set off a full body spasm, and [patients] can freeze like a statue and fall.”Throughout the disease’s progression, patients can struggle with walking and everyday movements, and they also commonly experience depression, anxiety and agoraphobia.As a rare, underdiagnosed disease, SPS is not well understood and currently has no cure. But, in the wake of Dion’s diagnosis, that may finally be changing. Zier’s organization is now working to put together a registry and natural history study of patients living with SPS to facilitate thorough research. And cell therapy biotech Kyverna Therapeutics recently received an FDA designation to test a cell therapy in patients with SPS.“The fact that people are researching it, the fact that we're getting therapies into clinical trials, it's definitely exciting,” Zier said. Even before being diagnosed with SPS, Zier was intimately familiar with the discipline and hard work it takes to cure a rare disease. She was a practicing dentist and third-degree black belt in karate when her husband passed away in 2014. Her own health soon began to spiral, and she developed worsening symptoms of shortness of breath, fatigue, severe pain and difficulty eating.“In 2017, I wasn't able to work, drive, care for myself or my kids,” Zier said, noting that it took years for her to finally receive a diagnosis of stiff-person syndrome. “People just don't know about it, and it's often misdiagnosed.” She founded the SPSRF in 2019 to raise awareness and funds for more research into the disease.“Not all neurologists are familiar with this disease, and so patients go through this diagnostic journey,” Amanda Piquet, M.D., told Fierce Biotech. Piquet is a specialist in autoimmune neurological diseases at the University of Colorado Anschutz Medical Campus and is the physician who diagnosed Dion with SPS. In an epidemiology study of the disease currently under review, Piquet and colleagues found diagnosis typically takes more than four years, with the average across other studies being about seven years. “It's reported even up to 19 years in prior literature,” she said. “Some people can go a very long time suffering before they get to the diagnosis.”One hurdle patients face is the lack of international consensus on diagnostic criteria for the disease, something both Zier and Piquet, who is on the medical advisory board of the SPSRF, are working to address. One critical test, which is what ultimately confirmed Zier’s diagnosis, is for GAD65 antibodies in the blood and spinal fluid.GAD65 antibodies are pumped out by malfunctioning B cells and disrupt a form of the glutamate decarboxylase enzyme. This enzyme plays a key role in making gamma aminobutyric acid (GABA), which is a critical neurotransmitter that inhibits the nervous system. “The way I like to explain it in layman terms with patients is that you have a difficult time putting the brakes on the nervous system,” Piquet said. “You are constantly on the gas pedal.” Normally, GABA would prevent your body from overreacting to mild stimuli like a sudden noise. But with GAD65 antibodies gumming up the works, the excitatory part of the nervous system charges forth unimpeded, leading to seizing and spasms.“In terms of the underlying pathophysiology of the disease, there's still many things that need to be explored,” Piquet said. “However, our thinking of the disease is that this is really a hyper-excitability of the nervous system.” With B cells thought to be the underlying culprit, that makes SPS a prime candidate for cell therapies.“What you're seeing in the [chimeric antigen receptor T cell] space is we've now got very, very effective mechanisms to target certain types of cell lines,” said Sham Dholakia, M.D., Ph.D., head of rare disease at Kyverna Therapeutics, a clinical-stage biotech focused on cell therapies for autoimmune diseases. “CAR T [cells] have really shown a lot of efficacy in the oncology space, and Kyverna’s vision is to use that science and amplify that in the autoimmune disease space, where the disease is a problem being driven by these aberrant B cells that are causing mischief,” Dholakia told Fierce Biotech.By gene editing T cells so that they target the mischievous B cells manufacturing GAD65 antibodies, Kyverna hopes to develop the first-ever treatment for SPS. Their drug candidate, KYV-101, is set to enter a phase 2 trial that aims to enroll about 25 patients and dose the first of them by Dec. 31, Dholakia said.The drug showed its potential in a case report published in the Proceedings of the National Academy of Sciences journal in June, where a 69-year-old patient with SPS showed less muscle stiffness and dramatically improved mobility after receiving an infusion of the CAR T cells. KYV-101 recently received a regenerative medicine advanced therapy designation from the FDA for use in the disease. “What this means is that, potentially, there's an accelerated approval path based on the data that will be generated through this study,” Dholakia said. The cells used in the drug were first developed and tested in B-cell lymphoma by the NIH. Zier is excited about KYV-101’s potential, but sees it as just the first step in the march toward a cure. “It's almost like the start of things, like 101, first day of school,” she said. “If it's not this therapy, maybe it's another therapy.” For Zier, the lack of data and research on SPS is the biggest barrier to a cure. The SPSRF is spearheading an effort, in collaboration with Piquet and others, to create an international patient registry that will “follow patients over time and get the data we need for research,” per Zier. The group has designed a protocol and survey questions to ask the SPSRF’s global patient network, with the resulting data to be hosted by the National Organization for Rare Disorders.With the registry and the research that uses it, as well as the in-progress consensus on diagnostic criteria, Zier is hoping to nail down the basics of a disease that has caused consternation among patients and physicians alike since it was first described in 1956. And though Zier, Piquet and others have been working for years to find a cure, there’s a certain Canadian singer who deserves some credit, too.“She propelled us, like, 50 years with awareness,” Zier said. “We want to focus our efforts. We want to get to a better treatment. Education, awareness—Céline has played a huge part in that.”