Azathioprine

OSE Immunotherapeutics Presents Preclinical Data on mRNA Therapeutic Platform for the Treatment of Inflammatory and Autoimmune Disorders at the FOCIS Annual Meeting, San Francisco (June 18 – 21) NANTES, France, June 20, 2024 – 7:30am CET - OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE), presented a poster on preclinical data on its mRNA (messenger RiboNucleic Acid) therapeutic platform for the treatment of inflammatory and autoimmune disorders at the Federation of Clinical Immunology Societies (FOCIS) annual meeting held in San Francisco (June 18 – 21, 2024). IL-35 (Interleukin-35) is an immunosuppressive cytokine (1) capable of potently inhibiting immune- related inflammation by acting on multiple immune cells (T cells, Myeloid cells, B cells). IL-35 can promote differentiation of T and B cells into regulatory functional state to limit inflammatory response. IL-35 has demonstrated in preclinical studies a key role in controlling several immune related disorders including autoimmune diseases, infectious diseases, and cancer. OSE Immunotherapeutics’ mRNA therapeutic platform has been designed for the local delivery of mRNA into inflammatory tissue using lipid nanoparticles. mRNA encodes for immunotherapy to locally suppress immune response for the treatment of inflammatory and autoimmune diseases. This platform has the potential to deliver innovative immunotherapeutic drugs and to address new biology that cannot be targeted with standard biologic treatments. The poster, entitled: “Local delivery of IL-35 mRNA therapeutic using lipid-based nanoparticles vector demonstrates high efficacy to suppress autoimmune Hepatitis” featured main preclinical data: IL-35 mRNA therapy using lipid nanoparticles vector allows a selective delivery and local expression of IL-35 immunosuppressive cytokine into the liver. IL-35 mRNA therapy can suppress acute and chronic autoimmune hepatitis inflammation in different mouse preclinical models associated with inhibition of T and B cell activation. Specific inhibition of autoantibodies has been observed following mRNA IL-35 treatment in chronic hepatitis inflammatory model. Aurore Morello, Head of R&D of OSE Immunotherapeutics, comments: “We are very pleased to share, for the first time with the international scientific community, our research data on the IL-35 mRNA therapy. Our R&D team is developing next-generation immunotherapy medicines modulating immune cell responses in the field of immuno-inflammation and immuno-oncology. This novel IL-35 mRNA therapeutics is generating potential opportunities for the treatment of inflammatory and autoimmune disorders, in particular in autoimmune hepatitis, a severe immune-mediated inflammatory disorder of the liver with strong unmet medical need”. Hu S. et al Frontiers in Pharmacology 2021: The Role of IL-35 in the Pathophysiological Processes of Liver Disease(1) About Autoimmune Hepatitis Autoimmune hepatitis (AIH) is a severe life threatening chronic progressive immune-mediated inflammatory disorder of the liver. The body's immune system attacks (auto antibodies) the hepatocytes, the cells of the liver, which causes the liver to become inflamed. AIH can cause scarring of the liver and ultimately lead to cirrhosis and liver failure if the treatment is not sufficient. The first line treatment is high dose of corticoids or azathioprine with some specific risks associated as they are chronically used. AIH is an orphan disease. Approximately 10 to 40 percent of people with AIH go into remission. However, most people (75 to 80 %) must eventually restart treatment because the disease becomes active again. Relapse typically occurs within the first 6 to 12 months after treatment is stopped. Relapse is more likely in those who have cirrhosis on the initial liver biopsy. Epidemiology: global pooled incidence and prevalence of AIH were found to be 1.28 cases per 100,000 inhabitant-years and 15.65 cases per 100,000 inhabitants (Global incidence and prevalence of auto-immune hepatitis, 1970-2022: a systematic review and meta-analysis, Hahn et al Lancet 2023). There are approximately 60,000 to 70,000 adults in the United States with a history of AIH approximately 30,000 to 35,000 adults are not responding to current first- and second-line treatments and need new therapeutic options (Current and Emerging Treatments for Autoimmune Hepatitis, Weinberg EM et al. Gastroenterology and Hepatology 2024). Europe analysis have revealed a range of 1.1 to 2.56 incidence and a prevalence of 17.3 to 18.3 per 100,000 individuals. About OSE Immunotherapeutics OSE Immunotherapeutics is a biotech company dedicated to developing first-in-class assets in immuno-oncology (IO) and immuno-inflammation (I&I). The Company’s current well-balanced first-in-class clinical pipeline includes: Tedopi® (immunotherapy activating tumor specific T-cells, off-the-shelf, neoepitope-based): this cancer vaccine is the Company’s most advanced product; positive results from the Phase 3 trial (Atalante 1) in Non-Small Cell Lung Cancer patients in secondary resistance after checkpoint inhibitor failure. Other Phase 2 trials, sponsored by clinical oncology groups, of Tedopi® in combination are ongoing in solid tumors. OSE-279 (anti-PD1): first positive results in the ongoing Phase 1/2 in solid tumors. OSE-127 - lusvertikimab (humanized monoclonal antibody antagonist of IL-7 receptor); ongoing Phase 2 in Ulcerative Colitis (sponsor OSE Immunotherapeutics); ongoing preclinical research in leukemia (OSE Immunotherapeutics). FR-104/VEL-101 (anti-CD28 monoclonal antibody): developed in partnership with Veloxis Pharmaceuticals, Inc. in transplantation; ongoing Phase 1/2 in renal transplant (sponsor Nantes University Hospital); successful Phase 1 in the US (sponsor Veloxis Pharmaceuticals, Inc.). Anti-SIRPα monoclonal antibody developed in partnership with Boehringer Ingelheim in advanced solid tumors and cardiovascular-renal-metabolic diseases (CRM); positive Phase 1 dose escalation results in monotherapy and in combination; Phase 2 in CRM diseases planned to be initiated end of 2024. ABBV-230 (ChemR23 agonist mAb) developed in partnership with AbbVie in chronic inflammation. OSE Immunotherapeutics expects to generate further significant value from its four proprietary drug discovery platforms, which are central to its ambitious goal to deliver next-generation first-in-class immunotherapies: Pro-resolutive mAb platform focused on targeting and advancing inflammation resolution and optimizing the therapeutic potential of targeting Neutrophils and Macrophages in I&I. ABBV-230 (licensed to AbbVie) is the first candidate generated by the platform, additional discovery programs ongoing on new pro-resolutive GPCRs. Myeloid Checkpoint platform focused on optimizing the therapeutic potential of myeloid cells in IO by targeting immune regulatory receptors expressed by Macrophages and Dendritic cells. BI 765063 and BI 770371 (licensed to Boehringer Ingelheim) are the most advanced candidates generated by the platform. Ongoing additional discovery programs, in particular with positive preclinical results obtained in monotherapy with new anti-CLEC-1 mAbs. BiCKI® Platform is a bifunctional fusion protein platform built on the key backbone component of anti-PD1 combined with a new immunotherapy target to increase anti-tumor efficacy by “cis-potentiating” tumor-specific T cells. A first program has been acquired by Boehringer Ingelheim. mRNA Therapeutic platform allows local delivery into the inflammatory site of innovative immunotherapies encoded by RNA to locally controls and/or suppress immune responses and inflammation. Additional information about OSE Immunotherapeutics assets is available on the Company’s website: . Follow us on X and LinkedIn Contacts Sylvie Détry sylvie.detry@ose-immuno.com Nicolas Poirier Chief Executive Officer nicolas.poirier@ose-immuno.com French Media: FP2COM Florence Portejoie fportejoie@fp2com.fr +33 6 07 768 283 U.S. Media Contact RooneyPartners LLC Kate Barrette kbarrette@rooneypartners.com +1 212 223 0561 Forward-looking statements This press release contains express or implied information and statements that might be deemed forward-looking information and statements in respect of OSE Immunotherapeutics. They do not constitute historical facts. These information and statements include financial projections that are based upon certain assumptions and assessments made by OSE Immunotherapeutics’ management in light of its experience and its perception of historical trends, current economic and industry conditions, expected future developments and other factors they believe to be appropriate. These forward-looking statements include statements typically using conditional and containing verbs such as “expect”, “anticipate”, “believe”, “target”, “plan”, or “estimate”, their declensions and conjugations and words of similar import. Although the OSE Immunotherapeutics management believes that the forward-looking statements and information are reasonable, the OSE Immunotherapeutics’ shareholders and other investors are cautioned that the completion of such expectations is by nature subject to various risks, known or not, and uncertainties which are difficult to predict and generally beyond the control of OSE Immunotherapeutics. These risks could cause actual results and developments to differ materially from those expressed in or implied or projected by the forward-looking statements. These risks include those discussed or identified in the public filings made by OSE Immunotherapeutics with the AMF. Such forward-looking statements are not guarantees of future performance. This press release includes only summary information and should be read with the OSE Immunotherapeutics Universal Registration Document filed with the AMF on April 30, 2024, including the annual financial report for the fiscal year 2023, available on the OSE Immunotherapeutics’ website. Other than as required by applicable law, OSE Immunotherapeutics issues this press release at the date hereof and does not undertake any obligation to update or revise the forward-looking information or statements. Attachment EN_240620_FOCIS_IL-35

-- The United States FDA Clears Initiation of Efficacy Trial in Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (AAV) Patients APhase II, Efficacy Trial in adult AAV patients has been approved by the FDA. Ruxoprubart is a first-in-class treatment for sustaining remission in AAV patients as a conjunctive therapy along with Standard of Care (SOC) which includes corticosteroids plus Cyclophosphamide/Azathioprine or Rituximab. Ruxoprubart demonstrated an anticipated safety pro Phase I trial in healthy subjects in 2022. TAVNEOS® (avacopan) was approved by the FDA in 2022 for treating AAV. Ruxoprubart is being positioned as the next-generation AAV treatment based on its mechanism of action. NovelMed’s Ruxoprubart drug blocks the alternative pathway (AP) without blocking the complement classical pathway (CP), an important advantage in maintaining a healthy lifestyle. Recent commencement of Ruxoprubart proof-of-concept Phase II trial through intravenous (IV) administration in naïve PNH patients shows promising results with a clean safety and efficacy profile. The Subcutaneous (SC) route of administration is under regulatory review and is expected to start soon. Ruxoprubart is a multi-indication platform. Given the role of the alternative pathway in rare diseases, the antibody drug has the potential to treat multiple diseases, including ocular, inflammatory, renal, neurological, and hematological. CLEVELAND, June 17, 2024 (GLOBE NEWSWIRE) -- NovelMed Therapeutics, Inc. proudly announces the U.S. Food and Drug Administration's (FDA) clearance on Ruxoprubart, the investigational drug, for commencing an efficacy trial targeting patients with ANCA Associated Vasculitis (AAV), a rare autoimmune chronic ailment characterized by inflammation in small blood vessels. Currently, the standard of care (SOC) for AAV requires high doses of Glucocorticoids, along with prolonged administration of other immunosuppressive drugs. However, this approach comes with severe side effects, including general immune suppression and toxicity from glucocorticoids, leaving unmet needs in managing the disease's impact on vital organs and associated adverse events (AEs). Results from Phase I and II trials of Ruxoprubart in PNH patients demonstrate the drug's selective blocking of the alternative pathway (AP) without affecting the classical pathway (CP), which is crucial for maintaining immunity. This selectivity presents a significant advantage over existing complement blockers approved by the FDA or under development, potentially eliminating the need for a Black Box Warning. In a forthcoming twelve-patient AAV study, Ruxoprubart will be evaluated alongside the SOC, akin to the trial conducted for TAVNEOS. Ruxoprubart is anticipated to outperform TAVNEOS due to its comprehensive control over the pathway responsible for generating three major toxins contributing to the disease pathology: C3a, C5a, and MAC. While TAVNEOS only targets C5a, Ruxoprubart aims to neutralize two powerful toxins including C3a and C5a, offering a potentially superior treatment approach. "We are thrilled to have gained FDA approval to address AAV in patients with an inadequate response to standard of care. Through this study, we aim to compare Ruxoprubart with historical data on TAVNEOS, hoping to improve AAV patients' lives substantially" says Dr. Rekha Bansal, Chief Executive Officer of NovelMed. Joseph Jankowski, Ph.D., VP, Business Development of NovelMed, expressed enthusiasm regarding the FDA’s clearance, stating, "The FDA's clearance of the Phase II clinical trial for AAV marks a significant milestone for Ruxoprubart, which harbors potential as a versatile platform for multiple indications." Ruxoprubart is positioned to compete with TAVNEOS with its potential for a superior safety and efficacy profile. Acquisition of TAVNEOS by Amgen for 3.7 Billion dollars underscores the value placed on treatments for AAV patients. Ruxoprubart is expected to be a next-generation product that can replace TAVNEOS. Ruxoprubart's selectivity and specificity, based on the clinical data from ongoing trials, hold promise not only for AAV, but also for several other renal disorders, including aHUS, and IgAN. The drug's potential to offer a superior safety and efficacy pro it apart and places it in a strong position within the market. The alternative pathway (AP) plays a pivotal role in managing anemia, inflammation, and tissue damage in various complement-mediated disorders, including AAV. NovelMed is committed to advancing the development of Ruxoprubart and addressing the unmet medical needs of patients with AAV and other complement-mediated disorders. The FDA's clearance of the Phase II trial represents a significant step forward in our mission to bring innovative and effective treatments to the market. We are actively exploring licensing, partnership, and acquisition opportunities to advance Ruxoprubart's development and approval across multiple rare disease indications. For further details, please visit . About ANCA Associated Vasculitis (AAV) Anti-Neutrophil Cytoplasmic Antibody-associated vasculitis (ANCA Vasculitis or AAV), is a rare autoimmune condition causing inflammation in blood vessels, often leading to swelling, narrowing, and sometimes blockage of blood vessels. It is characterized by the presence of Anti-Neutrophil Cytoplasmic Antibodies (ANCAs), targeting certain proteins within white blood cells, particularly neutrophils. It often causes a specific type of inflammation called crescentic glomerulonephritis, which can lead to kidney failure. Diagnosis of AAV involves a comprehensive assessment of medical history, physical examination, specific laboratory tests, imaging studies, and sometimes tissue biopsies. The current treatment approach primarily focuses on immune system suppression to alleviate inflammation and prevent further organ damage, utilizing corticosteroids and immunosuppressants. Despite being a rare and complex disease, advancements in treatment strategies are a must for continued improvement in the outcome of AAV patients. The prevalence of AAV in the United States is approximately 66,600 to 133,200 patients. TAVNEOS costs $75,051 annually per patient, with the potential to generate over 4 Billion in annual sales. About Ruxoprubart Ruxoprubart is a high affinity, humanized monoclonal antibody to Bb, selectively blocking the initiation and propagation of the alternative pathway (AP). By targeting the AP and sparing the CP pathway, Ruxoprubart holds promise for treating renal disorders, including ANCA vasculitis (AAV). Furthermore, Ruxoprubart shows therapeutic potential across a broad spectrum of rare diseases and disorders, including but not limited to hematological (PNH), renal (aHUS, IgAN), neurological (NMOSD), and ocular (GA and Uveitis). Clinical trials for Ruxoprubart can be found at , showing its potential to address various complement-mediated and associated illnesses where treatment options are inadequate or absent. About NovelMed NovelMed is a clinical-stage biopharmaceutical company dedicated to developing antibody treatments for numerous complement-mediated disorders, particularly rare (orphan) diseases. We aim to innovate and develop novel biologics to address unmet needs in rare disease treatment. NovelMed boasts a robust portfolio of intellectual property with broad applications in rare and common diseases. This includes Ruxoprubart's potential to treat a range of complement-mediated disorders associated with uncontrolled AP activation. As part of its antibody platform, NovelMed also offers humanized antibodies to C3b and Factor P (Properdin), effectively targeting the AP. NovelMed actively seeks licensing, partnership, and acquisition opportunities to advance antibody development through Phase III and approval in multiple rare disease indications. For more information, please visit News (novelmed.com). Ya Gao Email: bd@novelmed.com Tel: (216) 440 2696 Follow NovelMed on LinkedIn