MOG

LIEGE, BELGIUM / ACCESSWIRE / September 13, 2023 / Imcyse a clinical-stage biopharmaceutical company pioneering the development of a new class of active and specific immunotherapies for the treatment of severe autoimmune diseases, today announced completion of enrollment and initial dosing in the Phase 1 portion of its adaptive Phase 1/2 clinical trial, IMCY-MS-001. The Phase 1 open-label, dose escalation part of the study is assessing the safety of three doses of Imotope™ IMCY-0141 in patients with relapsing-remitting multiple sclerosis (RRMS). "Completing enrollment in the Phase 1 trial with IMCY-0141 is an important step towards bringing this therapy to patients suffering from RRMS, a disease with devastating and often unpredictable symptoms," said Denis Bedoret, CEO of Imcyse . "IMCY-0141 is now the second Imotope™ from Imcyse's proprietary platform to progress to the next clinical stage, demonstrating our commitment to finding new therapies for patients suffering from severe, chronic autoimmune diseases." Jean Van Rampelbergh, CCDO of Imcyse , added: "The pre-specified Independent Data Monitoring Committee analyses to date have found no safety concerns, and we expect the final outcome of the IDMC's review of the data from the third and highest dose level from our Phase 1 trial by the end of this year. The results from the Phase 1 portion of the trial will allow further refining of the Phase 2 protocol design and selection of the most appropriate doses to be evaluated. We look forward to continuing to explore the role of IMCY-0141 in the treatment of multiple sclerosis, which, if applied early-on in the course of disease, could slow down or even halt its progression, leading to a potentially curative approach." IMCY-0141 is being evaluated in an ongoing Phase 1/2 trial, IMCY-MS-001, in adult patients with RRMS. Following the Phase 1 dose escalation portion, the Phase 2 expansion arm of the trial will be designed to assess immune responses, while continuing to evaluate disease marker activity. In addition, it will allow for dose optimization in preparation for registration studies. For more information on this clinical trial, please visit: , NCT05417269. ABOUT IMCY-0141 IMCY-0141 is the Company's second clinical-stage compound. This Imotope™ is designed based on MOG (Myelin Oligodendrocyte Glycoprotein) with the aim to halt the progression of multiple sclerosis (MS) by stopping the body's immune system from attacking the central nervous system and disrupting undesirable autoimmune responses that drive the destruction of the myelin sheath protecting the nerves. IMCY-0141 has shown promising results in several MS preclinical models, demonstrating an immune response that supports the proposed mode of action and inducing a memory response so that the treatment effect is long-lasting and requires less frequent dosing regimens. Also, if treatment is begun early enough, it has the potential to allow patients to live with minimal impact from the disease. ABOUT MULTIPLE SCLEROSIS (MS) Multiple sclerosis (MS) induces damage to the proteins protecting the nerves, also called nerve sheath demyelination, which exposes the underlying nerves and can lead to paralysis. Symptoms include muscle weakness, weak reflexes, tremors, and muscle spasms. More than three million people globally have been diagnosed with MS. The disease can affect people as young as 15 years old, and women are twice as likely as men to contract MS. The true cause of the disease is unknown; however, a combination of hereditary and environmental factors is believed to enable the autoimmune attack. There is no cure for MS. MS treatments typically focus on speeding recovery from attacks, slowing disease progression and managing symptoms. Although current medications are effective in reducing the frequency of disease relapse, they are also associated with significant side effects and compliance challenges. Thus, there remains a major need for new treatments with a more favourable safety pro can slow or even stop disease progression. ABOUT IMCYSE Imcyse is a clinical-stage biopharmaceutical company pioneering the development of a new class of active specific immunotherapies for the treatment of severe chronic autoimmune diseases. The Company's unique technology platform allows the local targeting of immune cells involved in the destruction of the diseased organ. This platform is based on the administration of Imotopes™, which are synthetic peptides encompassing a T-cell epitope and an active thioredox motif. Imotopes™ generate cytolytic CD4 T-cells that specifically eliminate autoantigen-presenting cells and autoantigen-specific lymphocytes involved in the disease pathways. Imcyse's approach, sustained over time, may help to prevent and treat diseases with no current therapeutic options and to potentially cure patients without impairing their immune defenses. The Company has established proof of concept in several indications, has completed its first clinical trial in type 1 diabetes with promising results and is expecting top-line data from the fully enrolled Phase 2 study in this indication in 2024. A Phase 1/2 clinical trial in multiple sclerosis (MS) was initiated in April 2022. Beyond type 1 diabetes and MS, Imcyse is developing a pipeline of Imotopes™ for the treatment of several autoimmune diseases in large and rare disease indications. Imcyse was founded as a spin-off from the Catholic University of Leuven and is headquartered in Liège, Belgium. CONTACT: Imcyse S.A. Andrew Mackie Chief Business Officer Mail: contact@imcyse.com Investor Relations: Life Sci Advisors Chuck Padala, Managing Director Mail: chuck@lifesciadvisors.com Tel: +1-646-627-8390 For Media Inquiries: MC Services AG Anne Hennecke / Lydia Robinson-Garcia Mail: imcyse@mc-services.eu Tel.: +49 (0) 170 7134018 SOURCE: Imcyse View source version on accesswire.com:

LONDON, UK I September 06, 2023 I The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) regarding the supplemental Biologics License Application (sBLA) for long-acting C5 complement inhibitor Ultomiris (ravulizumab-cwvz) for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive (Ab+). The CRL did not request additional analysis or reanalysis of the Phase III CHAMPION-NMOSD trial data included in the sBLA submission and did not raise concerns about the efficacy or safety data from the trial. 1 The FDA requested modifications to enhance the Ultomiris Risk Evaluation and Mitigation Strategy (REMS) to further validate patients’ meningococcal vaccination status or prophylactic administration of antibiotics prior to treatment. Alexion, AstraZeneca Rare Disease is working closely with the FDA regarding next steps for the REMS modifications and remains committed to bringing Ultomiris to people living with NMOSD in the US as quickly as possible. Ultomiris is currently approved for the treatment of certain adults with NMOSD in the European Union (EU), Japan and other countries. Ultomiris is approved by the FDA for the treatment of adult patients with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) Ab+, and certain adults and children with paroxysmal nocturnal haemoglobinuria (PNH) or atypical haemolytic uraemic syndrome (aHUS). Notes NMOSD NMOSD is a rare disease in which the immune system is inappropriately activated to target healthy tissues and cells in the central nervous system (CNS). 2,3 Approximately three-quarters of people with NMOSD are anti-AQP4 Ab+, meaning they produce antibodies that bind to a specific protein, aquaporin-4 (AQP4). 4 This binding can inappropriately activate the complement system, which is part of the immune system and is essential to the body’s defence against infection, to destroy cells in the optic nerve, spinal cord and brain. 2,5,6 It most commonly affects women and begins in the mid-30s. Men and children may also develop NMOSD, but it is even more rare. 7,8 People with NMOSD may experience vision problems, intense pain, loss of bladder/bowel function, abnormal skin sensations (e.g., tingling, prickling or sensitivity to heat/cold) and impact on coordination and/or movement. 9-13 Most people living with NMOSD experience unpredictable relapses, also known as attacks. Each relapse can result in cumulative disability including vision loss, paralysis and sometimes premature death. 10,11,14 NMOSD is a distinct disease from other CNS diseases, including multiple sclerosis. The journey to diagnosis can be long, with the disease sometimes misdiagnosed. 15-17 CHAMPION-NMOSD CHAMPION-NMOSD is a global Phase III, open-label, multicentre trial evaluating the safety and efficacy of Ultomiris in adults with NMOSD. The trial enrolled 58 patients across North America, Europe, Asia-Pacific and Japan. Participants were required to have a confirmed NMOSD diagnosis with a positive anti-AQP4 antibody test, at least one attack or relapse in the twelve months prior to the screening visit, an Expanded Disability Status Scale Score of 7 or less and body weight of at least 40 kilograms at trial entry. Participants could stay on stable supportive immunosuppressive therapy for the duration of the trial. 18 Due to the potential long-term functional impact of NMOSD relapses and available effective treatment options, a direct placebo comparator arm was precluded for ethical reasons. The active treatment was compared to an external placebo arm from the pivotal Soliris PREVENT clinical trial. Over a median treatment duration of 73 weeks, all enrolled patients received a single weight-based loading dose of Ultomiris on Day 1, followed by regular weight-based maintenance dosing beginning on Day 15, every eight weeks. The primary endpoint was time to first on-trial relapse, as confirmed by an independent adjudication committee. The end of the primary treatment period could have occurred either when all patients completed or discontinued prior to the Week 26 visit and two or more adjudicated relapses were observed, or when all patients completed or discontinued prior to the Week 50 visit if fewer than two adjudicated relapses were observed. In the trial, there were zero adjudicated relapses, so the end of the primary treatment period occurred when the last enrolled participant completed the 50-week visit. Patients who completed the primary treatment period were eligible to continue into a long-term extension period, which is ongoing. Ultomiris Ultomiris (ravulizumab-cwvz), the first and only long-acting C5 complement inhibitor, provides immediate, complete and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Ultomiris is administered intravenously every eight weeks in adult patients, following a loading dose. Ultomiris is approved in the US, EU and Japan for the treatment of certain adults with generalised myasthenia gravis. Ultomiris is also approved in the US, EU and Japan for the treatment of certain adults with paroxysmal nocturnal haemoglobinuria (PNH) and for certain children with PNH in the US and EU. Additionally, Ultomiris is approved in the US, EU and Japan for certain adults and children with atypical haemolytic uraemic syndrome to inhibit complement-mediated thrombotic microangiopathy. Further, Ultomiris is approved in the EU and Japan for the treatment of certain adults with neuromyelitis optica spectrum disorder (NMOSD). As part of a broad development programme, Ultomiris is being assessed for the treatment of additional haematology and neurology indications. Alexion Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca focused on rare diseases, created following the 2021 acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare diseases for more than 30 years, Alexion is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialisation of life-changing medicines. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on haematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca . References 1. Pittock SJ, et al. Efficacy and safety of ravulizumab in adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: outcomes from the phase 3 CHAMPION-NMOSD trial. Oral Presentation at: American Academy of Neurology Annual Meeting, April 23, 2023; Presentation S5.002 . 2. Wingerchuk DM, et al. The spectrum of neuromyelitis optica. Lancet Neurol . 2007;6(9):805-815. 3. Wingerchuk DM. Diagnosis and treatment of neuromyelitis optica. Neurologist . 2007;13(1):2-11. 4. Wingerchuk DM, et al. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology . 1999;53(5):1107-1114. 5. Cossburn M, et al. The Prevalence of Neuromyelitis Optica in South East Wales. Eur J Neurol . 2012;19(4): 655-659. 6. Papadopoulos MC, et al. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. Nat Rev Neurol . 2014;10(9):493. 7. Takata K, et al. Aquaporins: water channel proteins of the cell membrane. Prog Histochem Cytochem . 2004;39(1):1-83. 8. Mori M, et al. Worldwide prevalence of neuromyelitis optica spectrum disorders. J Neurol Neurosurg Psychiatry . 2018;89(6):555-556. 9. Hamid SHM, et al. What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients. J Neurol . 2017;264(10):2088-2094. 10. Wingerchuk DM, Weinshenker BG. Neuromyelitis optica. Curr Treat Options Neurol . 2008;10(1):55-66. 11. Kitley J, et al. Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan. Brain. 2012;135(6):1834-1849. 12. Quek AML, et al. Effects of age and sex on aquaporin-4 autoimmunity. Arch Neurol 2012;69:1039–43. 13. Tüzün E, et al. Enhanced complement consumption in neuromyelitis optica and Behcet’s disease patients. J Neuroimmunol . 2011;233(1-2):211-215. 14. Jarius S, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14. 15. Jarius S, Wildemann B. The History of Neuromyelitis Optica. J Neuroinflammation . 2013;10, 797. 16. Kuroda H, et al. Increase of complement fragment C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica. J Neuroimmunol . 2013;254(1-2):178-182. 17. Mealy MA, et al. Assessment of Patients with Neuromyelitis Optica Spectrum Disorder Using the EQ-5D. Int J MS Care . 2019;21(3), 129-134. 18. ClinicalTrials.gov. An Efficacy and Safety Study of Ravulizumab in Adult Participants With NMOSD. NCT Identifier: NCT04201262. Available here . Accessed August 2023. SOURCE: AstraZeneca

It has been known for several years that the diagnosis 'multiple sclerosis' conceals a whole range of different illnesses, each requiring customized treatment. Researchers have now described a possible new MS-like disease and explained how to diagnose it. It has been known for several years that the diagnosis "multiple sclerosis" conceals a whole range of different illnesses, each requiring customized treatment. Researchers at the University of Basel and the University Hospital of Basel have now described a possible new MS-like disease and explained how to diagnose it. Multiple sclerosis (MS) is characterized by areas of inflammation in the central nervous system. The immune system attacks the body's own structures and destroys the covering of nerve cells, known as the myelin sheath. The picture research has painted of the illness is somewhat more complicated, however. It can cause a variety of neurological symptoms, like paresthesia and paralysis of the limbs, which progressively or abruptly worsen. Which parts of the nervous system are affected varies substantially between individuals. A treatment may work for some patients -- but make the condition worse in others. "There's a huge amount of diversity in how inflammatory autoimmune diseases of the central nervous system like multiple sclerosis present," explains Professor Anne-Katrin Pröbstel of the University of Basel and University Hospital Basel. Researchers have been gradually discovering the key distinctive features of "atypical" cases of MS for the past ten years. A few of these autoimmune diseases have been given different names to better distinguish them from MS even though they also destroy the myelin sheath. Victims of these diseases often have inflammation in their spinal cords or optic nerves. In a study of roughly 1,300 patients, Pröbstel's team has now discovered a biomarker that may make it possible to differentiate another MS-like illness from the others. The researchers have reported their findings in the journal JAMA Neurology. Antibodies as biomarkers The team discovered a specific antibody, a type of immunoglobulin A (IgA), in one group of patients. The antibody attacks a component of the myelin sheath called "MOG" (which stands for "myelin oligodendrocyte glycoprotein"). IgA antibodies are typically responsible for protecting mucous membranes. The precise role of MOG-IgA in this autoimmune disease remains unclear, however. "Victims experience inflammation particularly in their spinal cords and brain stems," Pröbstel explains. This group of patients was missing other typical biomarkers related to MS or similar diseases. Next, the researchers want to decipher the role of MOG-IgA and the clinical characteristics arising from it in more detail. "By distinguishing between myelin-destroying autoimmune diseases that were previously all called MS, we're taking an important step towards a better understanding of the causes of these illnesses and towards individualized treatments," says the neurologist. Ultimately, the researchers hope to discover what treatments are most effective under what conditions. About the project The study was conducted in collaboration with the Universidade de São Paulo in Brazil and several German universities (Charité Berlin, Heinrich Heine University Düsseldorf, Ruhr University Bochum). The research team from the Departments of Biomedicine and Clinical Research of the University of Basel, the Department of Neurology at the University Hospital, and the Research Center for Clinical Neuroimmunology, which is affiliated with both institutions, received funding for the study from the University Hospital of Basel's Propatient Foundation, the Goldschmidt-Jacobson Foundation, the Fondation Pierre Mercier pour la Science, the National Multiple Sclerosis Society and the Swiss National Science Foundation. The two lead authors received grants from the European Committee for Treatment and Research in Multiple Sclerosis Clinical Fellowship, as well as the Swiss Government Excellence Scholarship (Ana Beatriz A.G.R. Gomes) and the Trygve Tellefsens Legat Scholarship (Laila Kulsvehagen).