Lusvertikimab

A clinical abstract on the induction results from the CoTikiS Phase 2 trial of anti-IL-7 Receptor Lusvertikimab in Ulcerative Colitis accepted for Oral Presentation and selected amongst the Top 10 oral abstracts for 20th Congress of European Crohn’s and Colitis Organization (ECCO) Highlights. Research highlights OSE Immunotherapeutics’ continued commitment to advancing the treatment and management of IBD. NANTES, France, December 18, 2024 – 6:00pm CET - OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE), today announced that an abstract related to its first in class anti-IL-7 Receptor (IL-7R) Lusvertikimab, has been accepted for Oral Presentation at the 20th congress of the European Crohn’s and Colitis Organization (ECCO) being held February 19-22, 2025, in Berlin (Germany). Details of the presentation: EC25-1892 - "Lusvertikimab, a first-in-class IL7 receptor antagonist, in moderate to severe Ulcerative Colitis: results of a multicenter, randomized, placebo-controlled phase II study" has been accepted as an Oral Presentation in the Scientific Program and selected amongst the Top 10 oral abstracts for the Congress Highlights of ECCO’25 video. Presentation number: OP36Session name: Sustainability in IBD and beyond - Session 10: Hot topics in IBDSession date: 22/02/25; Session time: 08:30 - 10:50; Presentation time: 10:10 - 10:20Session hall: Plenary Hall / Hall B Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, comments: “We are excited to present for the first time at a congress the clinical efficacy and safety data from the induction study in ulcerative colitis. This prestigious scientific meeting gathers the world’s leading specialists in Inflammatory Bowel Diseases (IBD). Lusvertikimab, a pure interleukin-7 receptor antagonist mAb that exclusively blocks IL-7 boasts a differentiated mechanism of action and a favorable tolerance profile. We believe Lusvertikimab is uniquely positioned in IBD, with potential also for a broader spectrum of chronic inflammatory and autoimmune diseases.” Interleukin-7 (IL-7) produced locally by epithelial cells is a crucial survival factor for pathogenic T lymphocytes residing in tissues, such as colitogenic memory T cells1. Lusvertikimab is a unique antagonist of IL-7R targeting the CD127 receptor, the alpha chain of the IL-7R, with a differentiated mechanism of action allowing a selective inhibition of the IL-7 biology while sparing TSLP (Thymic Stromal LymphoPoietin) cytokine and growth factor. This allows potent inhibition of pathogenic memory and effector T lymphocytes expressing high level of CD127, while promoting regulatory T cells (Tregs) biology expressing low level of CD127. The protective role of TSLP in intestinal immunity has been reproducibly described, in particular to instruct Treg generation against commensal bacteria2 and TSLP inhibition has been reported to exacerbate mucosal inflammation and colitis3. This biology together with the results of the CoTikiS study supports the continued clinical development of a pure IL-7 antagonist in IBD, and other diseases where Tregs and microbiota cross-talks are implicated in tissular healing. Interleukin-7 Receptor (IL-7R) overexpression has been associated with numerous diseases4 and therapeutic areas, with preclinical efficacy already demonstrated in IBD5, rheumatoid arthritis6, neuroinflammation7, airways inflammation8, dermatology9, type 1 diabetes10 and lupus11. ABOUT ULCERATIVE COLITIS (UC)Ulcerative colitis is a chronic disease of the large intestine, in which the lining of the colon becomes inflamed and develops tiny open sores, or ulcers. This condition is the result of the immune system’s overactive response. UC affects 3.3 million patients in the US, Europe and Japan (1). Despite broad therapeutic options, remission rates remain only 25-30% (2) leaving most patients without satisfactory treatments. 15% of patients (3) fail to respond to all therapies and undergo surgery as a last option.(1) EvaluatePharma (2) Drugs Context. 2019; 8: 212572 –doi: 10.7573/dic.212572(3) Scientific Reports volume 10, Article number: 12546 (2020)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) that address the unmet patient needs of today and tomorrow. We partner with leading academic institutions and biopharmaceutical companies in our efforts to develop and bring to the market transformative medicines for people with serious diseases. OSE Immunotherapeutics is based between Nantes and Paris and is quoted on Euronext. Additional information about OSE Immunotherapeutics assets is available on the Company’s website: www.ose-immuno.com. Follow us on X and LinkedIn Contacts Fiona Olivierfiona.olivier@ose-immuno.comSylvie Détrysylvie.detry@ose-immuno.comFrench Media Contact FP2COMFlorence Portejoiefportejoie@fp2com.fr+33 6 07 768 283U.S. Media ContactRooney Partners LLCKate Barrettekbarrette@rooneypartners.com+1 212 223 0561 Forward-looking statementsThis 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 considering 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. 1 Markus F. Neurath, Strategies for targeting cytokines in inflammatory bowel disease, Nat Rev Immunol 20242 I Spadoni et al., Dendritic cells produce TSLP that limits the differentiation of Th17 cells, fosters Treg development, and protects against colitis, Mucosal Immunol, 2012 3 Jonathan L Messerschmidt et al., TSLP/dendritic cell axis promotes CD4+ T cell tolerance to the gut microbiome, JCI Insight, 2023 Betsy C Taylor et al., TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis, J Exp Med, 20094 Barata, J. T., S. K. Durum, and B. Seddon. 2019. Flip the coin: IL-7 and IL-7R in health and disease. Nat. Immunol. 20: 1584_1593.5 Belarif, L., R. Danger, L. Kermarrec, V. Nerri`ere-Daguin, S. Pengam, T. Durand, C. Mary, E. Kerdreux, V. Gauttier, A. Kucik, et al. 2019. IL-7 receptor influences anti-TNF responsiveness and T cell gut homing in inflammatory bowel disease. J. Clin. Invest., 2019.Willis, C. R. et al., Interleukin-7 receptor blockade suppresses adaptive and innate inflammatory responses in experimental colitis. J. Inflamm., 2012.6 Sarita A Y Hartgring, Blockade of the interleukin-7 receptor inhibits collagen-induced arthritis and is associated with reduction of T cell activity and proinflammatory mediators, Arthritis Rheum, 2010Zhenlong Chen, The novel role of IL-7 ligation to IL-7 receptor in myeloid cells of rheumatoid arthritis and collagen-induced arthritis, J Immunol, 2013 7 Li-Fen Lee et al., IL-7 promotes T(H)1 development and serum IL-7 predicts clinical response to interferon-β in multiple sclerosis 8 Hoa Le Mai et al., Targeting the interleukin-7 receptor alpha by an anti-CD127 monoclonal antibody improves allergic airway inflammation in mice, Clin Exp Allergy, 2020 9 Lyssia Belarif et al., IL-7 receptor blockade blunts antigen-specific memory T cell responses and chronic inflammation in primates, Nat Commun, 2018Zhenpeng Dai et al., Blockade of IL-7 signaling suppresses inflammatory responses and reverses alopecia areata in C3H/HeJ mice, Sci Adv, 2021 10 Li-Fen Lee et al., Anti-IL-7 receptor-α reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell function, Proc Natl Acad Sci U S A, 2012 Cristina Penaranda, IL-7 receptor blockade reverses autoimmune diabetes by promoting inhibition of effector/memory T cells, Proc Natl Acad Sci U S A, 201211 Rosana Gonzalez-Quintial et al., Systemic autoimmunity and lymphoproliferation are associated with excess IL-7 and inhibited by IL-7Rα blockade PLoS One, 2011 Attachment EN_241218_ECCO Lusvertikimab

NANTES, France I November 4, 2024 I OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE), today reported positive results from the induction period of the CoTikiS randomized, double-blind, placebo-controlled, Phase 2 study of Lusvertikimab (OSE-127) demonstrating a strong efficacy and favorable safety profile in moderate to severe active ulcerative colitis (UC). Topline results from the CoTikiS Phase 2 Study The randomized, double-blind Phase 2 clinical trial CoTikiS has evaluated the efficacy and the safety of Lusvertikimab versus placebo in 136 patients with moderate to severe active UC who failed or lost response to previous treatment(s)*. CoTikiS is a 50-week study, with a 10-week induction period evaluating two doses (450mg or 850mg) of Lusvertikimab against placebo, a 24-week additional open label treatment extension period (OLE) during which all subjects received Lusvertikimab 850mg infusions every 4 weeks and a 16-week safety follow-up period free of treatment. Lusvertikimab (Lusv) met the primary efficacy endpoint defined by the improvement of the Modified Mayo Score (MMS)** at week 10 (W10) at the two doses tested and demonstrated statistically significant and clinically meaningful results on key secondary endpoints. A favorable safety profile was observed during both the induction period and during the 6 months of open-label extension period trial. 134 patients were analyzed in the W0-W10 period [group 850mg (50 patients); group 450mg (35 patients); drug group pooled 850mg + 450mg (85 patients); group placebo (49 patients)]. A total of 120 patients treated with Lusvertikimab participated to the additional 24-week OLE treatment period. Final analysis of the primary endpoint at W10*** Improvement of the global Disease Activity Index of UC (MMS) Key secondary endpoint results at W10 Clinical remission**** Endoscopic remission (endoscopic score at 0) Endoscopic improvement (endoscopic score ≤ 1 point) Ulcerative Colitis Endoscopic index of Severity***** (UCEIS score decreases at week 10) Safety Profile Lusvertikimab displayed a good safety profile and was well tolerated, with no difference between both dose groups and placebo in the incidence of drug related serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, severe drug-related AEs, opportunistic infections or infusion reactions during the induction period. In addition, no safety signal was observed in the patient population who received 850mg of Lusvertikimab for an additional 24-week period in the OLE, regardless of the initial randomization groups. Pr. Arnaud Bourreille, Associate professor in Gastroenterology, Institut des Maladies de l’Appareil Digestif, Nantes University Hospital, Principal/ Scientific coordination of the CoTikiS study , said: “We are very excited to share these positive topline efficacy results which could establish Lusvertikimab as a potential new breakthrough therapeutic option for UC patients. We are beyond enthusiastic with the very high endoscopy efficacy and what it could mean for patients suffering from chronic ulcerative colitis. This promising drug-candidate with a differentiated mode of action and very good safety profile needs to be further actively explored in ulcerative colitis and in other indications. We are grateful to all the investigators and patients for their participation in this study and we are eager to present a more complete clinical and biomarkers data set in future medical congresses.” Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics , adds: “These impressive efficacy and safety results represent a major milestone in the clinical development of Lusvertikimab and a strong catalyst for the subsequent steps. Lusvertikimab has clearly demonstrated meaningful clinical proof-of-efficacy in UC and we are now looking forward to further evaluating it in additional studies with the ultimate goal of making this innovative therapy accessible to millions of patients in need of more efficacious and safe treatments. Lusvertikimab is a pure interleukin-7 receptor antagonist mAb and we believe it has a broad first-in-class potential in various chronic inflammatory and autoimmune diseases. We look forward to making progress on this strategy and to go ahead with the most relevant partners.” * Previous corticosteroids, immunosuppressive agents or previous biological treatments. ** Ulcerative Colitis is a chronic inflammatory disease of the rectum and colon characterized by mucosal inflammation, abdominal pain associated with symptoms and frequency of diarrhea and rectal bleeding. The moderate to severe UC is measured by a Modified Mayo Score (MMS) between 4 and 9, inclusive. The primary endpoint is the mean change at Week 10 from baseline in the Modified Mayo Score, a Disease Activity Index for UC defined by the addition of the stool frequency and the rectal bleeding sub-scores (two patient’s clinical elements as Patient Reported Outcomes) and the endoscopic sub-score (mucosal endoscopy activity), assessed by an endoscopist through a central reading platform. *** An interim Futility analysis performed early (about 30% of patients) by the IDMC proposed interruption of the 450 mg group for risk of futility. The 850 mg group was initially considered as primary analysis, in the final analysis the futility of the 450mg was not confirmed. SAP (Statistical Analysis Plan) Addendum: Results of 450mg group reconsidered with all patients already included in this group. In addition, the two groups have been pooled for the drugs cohort to a global treatment effect. **** Clinical remission at Week 10, a modified Mayo score of ≤ 2 points with no individual sub-score of > 1 point and a rectal bleeding at 0, therefore a stool frequency score of 0 or 1 and an endoscopic score of 0 or 1. ***** Ulcerative Colitis Endoscopic Index of Severity, UCEIS, is a validated endoscopic scoring tool with lower interobserver variability, score change at Week 10 from baseline measuring specific subscores: vascular pattern/ presence of bleeding/ erosions and ulcerations (Pabla B S et al Gastroenterol Clin North Am. 2020). 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: OSE Immunotherapeutics expects to generate further significant value from its three proprietary drug discovery platforms, which are central to its ambitious goal to deliver next-generation first-in-class immunotherapies: Additional information about OSE Immunotherapeutics assets is available on the Company’s website: www.ose-immuno.com . Follow us on X and LinkedIn SOURCE: OSE Immunotherapeutics