Centre Hospitalier Universitaire Vaudois

PRESS RELEASE Results from a Phase I clinical trial of a dendritic cell targeting prophylactic HIV vaccine published in the Journal eClinical Medicine Provides important validation of the safety and immunogenicity of EnnoDC’s technology The ANRS VRI06 trial, carried out by Inserm, ANRS MIE and the VRI, shows that the CD40.HIVRI.Env vaccine, is safe and induces early and sustained humoral and cellular immune responses against HIVThe first clinical trial results in humans with this novel type of vaccine, which consists of a monoclonal antibody fused to the HIV envelope, targeting the CD40 molecule expressed at the surface of dendritic cellsResults were published in the Journal eClinical Medicine, an open access clinical journal, published by The Lancet Paris, France, 2 October 2024 – EnnoDC* (or “the Company”), a clinical-stage biotech company pioneering the development of first-in-class dendritic cell-targeting immunotherapies, today notes the publication of positive results from a Phase I trial of its novel Dendritic Cell (DC) targeting prophylactic HIV vaccine in the Journal eClinical Medicine, an open access clinical journal, published by The Lancet. The multicentre, double-blind placebo-controlled dose-escalation trial was conducted at clinical sites in France and Switzerland. The results, published by scientists from the Vaccine Research Institute of Inserm and the Université Paris-Est Créteil, the CHUV in Lausanne and the University of Bordeaux, show that the vaccine, CD40.HIVRI.Env, is safe and induces early and sustained humoral and cellular immune responses against HIV. No serious side effects were observed. General and local reactions at the injection site were mainly mild to moderate. Two severe adverse events were reported, which were found to be unrelated to vaccination after analysis. EnnoDC’s first-in-class approach combines the power of vaccines and immunotherapies to provide targeted immune responses for both cancer and infectious diseases. CD40.HIVRI.Env combines a humanized anti-CD40 monoclonal antibody fused with HIV envelope antigens to stimulate DCs through CD40 and deliver a targeted immune response. Pr. Yves Lévy, co-founder, Chief Medical and Scientific Officer at EnnoDC and Principal Investigator of the trial commented: “These are exciting results for EnnoDC from the first clinical study using our novel dendritic cell targeting technology. The results show that this vaccine is safe and well tolerated and that humoral and cellular immune response were activated against HIV. The results support further development of the program. In addition, the results show that this type of treatment, which specifically targets antigens to the dendritic cells via the CD40 molecule, may be potent in inducing protective immunological responses in prime-boost vaccination strategies.” Christophe Hubert, Chief Executive Officer of EnnoDC, added: “These are very encouraging results which provide further validation of our technology with positive read across to our new immunotherapies, in development for HPV-induced cancers, prostate cancer and infectious diseases.” Last week EnnoDC unveiled the next generation of DC-targeting immunotherapies supported by new leadership and an evolved strategy. EnnoDC has an extensive pipeline of clinical and preclinical stage assets in HPV-induced cancers, prostate cancer and in infectious diseases. Further information on the ANRS VRI06 trial is available in a press release issued by the Vaccine Research Institute (VRI) of Inserm and the Université Paris-Est Créteil (Unit 955 Mondor Institute for biomedical research), the CHUV in Lausanne and the University of Bordeaux through the link below:Preventive vaccine against HIV: promising results in healthy volunteers with a new vaccine technology – Vaccine Research Institute (vaccine-research-institute.fr) The full paper, published in the October 2024 issue of eClinical Medicine, can be accessed through the following link: https://doi.org/10.1016/j.eclinm.2024.102845. Further details about the trial can be found online at https://clinicaltrials.gov/study/NCT04842682. *EnnoDC is the trading name of LinKinVax Europe SAS. -Ends- For more information please contact: EnnoDC Christophe Hubert, CEOinfo@EnnoDC.com ICR Consilium Ashley Tapp / Jonathan Edwards / Kumail Waljee EnnoDC@consilium-comms.comTel: +44 (0) 20 3709 5700 About EnnoDC EnnoDC, the trading name of LinKinVax, is a clinical-stage biotech company pioneering the development of first-in-class Dendritic Cell (DC)-targeting immunotherapies. Through our versatile DC-targeting immunotherapy platform we are developing CD40-specific monoclonal antibodies fused with pathogenic antigens to induce a highly specific, safe, broad, and long-lasting immune response to combat diseases like cancer and infectious diseases. The Company currently has three active clinical trials in various stages of clinical development, addressing oncology and infectious disease indications. Its lead asset, CD40HVac is currently in a Phase I/IIa clinical trial for HPV16+ oropharyngeal cancer patients. EnnoDC is a spin out from the Vaccine Research Institute (VRI), an institute of INSERM (the French National Institute of Health and Medical Research) and is supported by longstanding investors and internationally renowned key opinion leaders who contribute their expertise in the clinical development of EnnoDC’s assets and help explore the expansive therapeutic potential of its innovative platform. Find out more online at: http://www.EnnoDC.com Follow us on X and LinkedIn About ANRS MIEANRS Emerging Infectious Diseases is an autonomous agency of Inserm (the French National Institute for Health and Medical Research). Its mission is to facilitate, evaluate, coordinate and fund research into HIV/AIDS, viral hepatitis, sexually transmitted infections, tuberculosis and emerging and re-emerging infectious diseases. For more information: https://anrs.fr/en/ About the VRI and Inserm The Vaccine Research Institute (VRI), Laboratory of excellence, was established by Inserm (French National Institute of Health and Medical Research) and the University of Paris-Est Créteil (UPEC) to conduct research to accelerate the development of effective vaccines against HIV/AIDS and (re)-emerging infectious diseases. The VRI's structure strengthens the links between basic research and translational research, patient associations and the socio-economic world. The VRI extends a network of internationally renowned scientists and research teams with multidisciplinary expertise in system biology and clinical immunology, a network of clinical centres, and shared platform.For more information: https://vaccine-research-institute.fr/ Founded in 1964, Inserm is a public scientific and technological institute dedicated to biomedical research and human health and is involved in the entire range of activities from the laboratory to the patient’s bedside. It also partners with the most prestigious research institutions in the world that are committed to scientific challenges and progress in these fields.For more information: https://www.inserm.fr/en/home/ About Université Paris-Est Créteil: With 14 faculties, schools and institutes, 1 observatory and 32 research laboratories, Université Paris-Est Créteil has been active in all fields of knowledge since 1970. Each year, UPEC trains over 42,000 students and working professionals of all ages. A major player in the dissemination of academic, scientific and technological knowledge, the university offers more than 500 training courses in all disciplines and at all levels. UPEC offers personalized support for all successes, thanks to undergraduate and graduate training, recognition of prior learning and lifelong learning opportunities. Furthermore, the university runs a growing number of apprenticeship programs in order to stimulate entrepreneurship and ease professional integration. Université Paris-Est Créteil has built its strategic plan around three strategic orientations: UPEC is an engaged university that aims to match academic excellence with societal relevance. It encourages and supports all paths of students’ success with dedicated programs. UPEC masters its trajectory and is a university open to the world and its diversity. For more information: https://www.en.u-pec.fr/ About the University of Bordeaux With more 54,000 students, 3,200 researchers and teachers, and 2,800 staff members, the University of Bordeaux is one of the leading French public research and higher education institutions, located in a dynamic and culturally rich, fast-developing region. Ranked among the top universities in France, the University of Bordeaux is renowned for the quality of its academic courses and research. It is a multi-disciplinary, research-focused institution with a strong ambition to develop as a leading, international campus. The University of Bordeaux is leading an ambitious, competitive development program in partnership with local higher education institutes and national research organizations, in order to promote Bordeaux as a “Campus of Excellence”. For more information: https://www.inserm.fr/en/home/

CAMBRIDGE, England & BOSTON--( BUSINESS WIRE )--Bicycle Therapeutics plc (NASDAQ: BCYC), a pharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle ® ) technology, today reported recent business progress and financial results for the second quarter ended June 30, 2024. “ In the second quarter, we continued to demonstrate the ongoing progress of our pipeline and highlight the emerging differentiated profiles of our Bicycle Toxin Conjugates ® zelenectide pevedotin and BT5528 compared to antibody drug conjugates. As we enter the second half of the year, we look forward to sharing the first set of data updates from our clinical programs at the upcoming ESMO Congress,” said Kevin Lee, Ph.D., CEO of Bicycle Therapeutics. “ Additionally, I am honored to welcome renowned oncology experts from around the world to our Clinical Advisory Board. Their advice and counsel will be critical as we work to develop therapies that can help patients live longer and live well.” Dr. Lee continued: “ Bicycle Therapeutics also significantly strengthened our balance sheet in the second quarter through the support of leading healthcare investors. Moreover, we have prioritized our pipeline and streamlined our leadership team to enable us to focus on the clinical programs and research areas that we believe have the highest potential for value creation and align with our strategy to support the long-term growth of our company.” Second Quarter 2024 and Recent Events Four abstracts accepted for poster presentation at the European Society for Medical Oncology (ESMO) Congress 2024 being held September 13-17 in Barcelona. Bicycle Therapeutics will present four abstracts containing updated clinical data for zelenectide pevedotin (formerly BT8009) in metastatic urothelial cancer (mUC), BT5528 in advanced solid tumors such as mUC and ovarian, and BT7480 in advanced solid tumors. In June, the company presented two abstracts at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting outlining clinical pharmacokinetics of Bicycle ® Toxin Conjugate (BTC ® ) molecules zelenectide pevedotin and BT5528 compared to antibody drug conjugate enfortumab vedotin and evaluating the emerging safety profile of both BTC molecules, along with an overview of the company’s ongoing Phase 2/3 Duravelo-2 registrational trial of zelenectide pevedotin in mUC. Focused research and development (R&D) pipeline on clinical programs and research areas that the company believes have the highest potential to maximize value creation. Activities include: Prioritizing the clinical development of zelenectide pevedotin and BT5528 in multiple tumor types. Focusing near-term research efforts on advancing the company’s Bicycle Radionuclide Conjugate (BRC™) pipeline and the discovery of next-generation BTC molecules. Except for BT7480, exploring innovative ways to continue development of the company’s immuno-oncology portfolio, including Bicycle Tumor-targeted Immune Cell Agonist ® (Bicycle TICA ® ) molecules, through collaboration. Streamlined leadership team to better align with strategic and pipeline priorities. Michael Skynner, Ph.D., chief technology officer , has assumed leadership of Bicycle Therapeutics’ discovery research team, and all discovery research activities will be consolidated and moved to the company’s headquarters in Cambridge, UK. Jennifer Perry, Pharm.D., promoted to chief strategy officer and head of commercial . Since joining Bicycle Therapeutics in August 2022, Ms. Perry has been instrumental in establishing and growing Bicycle Therapeutics’ commercial organization. In this expanded role, she will oversee the company’s corporate and end-to-end portfolio strategy while also fulfilling her existing commercial responsibilities. Ms. Perry has more than 20 years of experience in pharma and biotech, with 15 years in oncology. Her experience spans commercial and medical roles with a focus on go-to-market strategies for launching oncology medicines at GSK, Tesaro, TG Therapeutics and Pharmacyclics. Nick Keen, Ph.D., chief scientific officer , is transitioning to an advisor role with the company as a distinguished fellow, where he will advise the company as needed. The company also hired Eric Westin, M.D., former vice president of clinical development and translational sciences at ImmunoGen , to an advisor role with the company as a distinguished fellow to help refine the company’s translational and clinical strategy. Formed new Clinical Advisory Board with distinguished global oncology experts to support the advancement of clinical oncology programs. The company expects that the advisors will provide invaluable guidance and insights for the global clinical development of the company’s clinical programs. Inaugural members include: Charles Swanton, M.D., Ph.D., FRS, FMedSci, FRCP, is the chair of Bicycle Therapeutics’ Clinical Advisory Board and Scientific Advisory Board. He leads the Cancer Evolution and Genome Instability Laboratory at the Francis Crick Institute in London. Dr. Swanton’s research is focused on how tumors evolve over space and time, and he has authored over 250 papers developing an understanding of branching evolutionary histories of solid tumors, processes that drive cancer cell-to-cell variation and the impact of cancer diversity on effective immune surveillance and clinical outcome. Toni K. Choueiri, M.D., is the director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School. Dr. Choueiri and colleagues have made seminal observations that have defined and evolved the treatment of kidney cancer and led to the approval of several therapies. He has over 800 PubMed-indexed publications and is the lead investigator of multiple national and international Phase 1-3 trials in GU cancers. Sherene Loi, MBBS (Hons), Ph.D., FRACP, FAHMS, is a medical oncologist specialized in breast cancer treatment and a clinician scientist (lab head) with expertise in genomics, immunology and drug development at the Peter MacCallum Cancer Centre in Melbourne, Australia. She is recognized internationally as a leading clinician scientist whose work has led to new insights into the breast cancer immunology field as well as leading international clinical trials in breast cancer immunotherapy. Professor Loi has published over 330 research articles, co-chairs the International Breast Cancer Study Group and is the Inaugural National Breast Cancer Foundation of Australia Endowed Chair. In 2021, she received the Australian Prime Minister’s Frank Fenner Prize for Life Scientist of the Year. Solange Peters, M.D., Ph.D., is full professor and chair of medical oncology and the chair of the thoracic malignancies program in the Department of Oncology at the University Hospital of Lausanne in Switzerland. She currently oversees teaching and patient care in thoracic malignancies at Lausanne University, and her main fields of interest include new biomarker discovery and validation in preclinical and clinical settings as well as cancer immunotherapy. She is the youngest president of ESMO, serving for an extended period of 2020-2022. Professor Peters has authored over 500 peer-reviewed manuscripts and book chapters and is associate editor of the Annals of Oncology , deputy editor of Lung Cancer and serves on the editorial board of several other oncology journals. She was the deputy editor of the Journal of Thoracic Oncology for 10 years. Raised gross proceeds of $555 million in private investment in public equity (PIPE) financing. The PIPE financing, with participation from leading healthcare investors, is expected to extend the company’s financial runway into the second half of 2027. The company plans to use the net proceeds of $544.1 million to fund the continued development of its proprietary pipeline and for other R&D, as well as for general corporate purposes. Repaid and voluntarily terminated outstanding debt with Hercules. In July 2024, Bicycle Therapeutics announced the repayment of its loan with Hercules Capital, Inc., ahead of its 2025 maturity date, with total payments of $31.9 million, including accrued and unpaid interest, an end-of-term charge and an early repayment fee. Second Quarter 2024 Financial Results Cash and cash equivalents were $961.4 million as of June 30, 2024, compared to $526.4 million as of December 31, 2023. The increase in cash and cash equivalents is primarily due to net proceeds from the PIPE financing and share option exercises, offset by cash used in operating activities. R&D expenses were $40.1 million for the three months ended June 30, 2024, compared to $39.7 million for the three months ended June 30, 2023. The increase in expense of $0.4 million was primarily due to increased clinical program expenses for zelenectide pevedotin development and increased personnel-related expenses, offset by decreased clinical program expenses for Bicycle TICA ® molecule development, decreased discovery, platform and other expenses and incremental U.K. R&D tax credits. General and administrative expenses were $15.9 million for the three months ended June 30, 2024, compared to $14.8 million for the three months ended June 30, 2023. The increase of $1.1 million was primarily due to increased personnel-related costs. Net loss was $39.8 million, or $(0.77) basic and diluted net loss per share, for the three months ended June 30, 2024, compared to net loss of $42.6 million or $(1.41) basic and diluted net loss per share, for three months ended June 30, 2023. About Bicycle Therapeutics Bicycle Therapeutics is a clinical-stage pharmaceutical company developing a novel class of medicines, referred to as Bicycle ® molecules, for diseases that are underserved by existing therapeutics. Bicycle molecules are fully synthetic short peptides constrained with small molecule scaffolds to form two loops that stabilize their structural geometry. This constraint facilitates target binding with high affinity and selectivity, making Bicycle molecules attractive candidates for drug development. The company is evaluating zelenectide pevedotin (formerly BT8009), a Bicycle ® Toxin Conjugate (BTC ® ) targeting Nectin-4, a well-validated tumor antigen; BT5528, a BTC molecule targeting EphA2, a historically undruggable target; and BT7480, a Bicycle Tumor-Targeted Immune Cell Agonist ® (Bicycle TICA ® ) targeting Nectin-4 and agonizing CD137, in company-sponsored clinical trials. Additionally, the company is developing Bicycle ® Radio Conjugates (BRC™) for radiopharmaceutical use and, through various partnerships, is exploring the use of Bicycle ® technology to develop therapies for diseases beyond oncology. Bicycle Therapeutics is headquartered in Cambridge, UK, with many key functions and members of its leadership team located in Cambridge, Mass. For more information, visit bicycletherapeutics.com . Forward Looking Statements This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Bicycle’s anticipated progress across its R&D pipeline and the advancement of its product candidates, including zelenectide pevedotin, BT5528 and BT7480; the anticipated progression of Bicycle’s clinical trials and the method and timing of announcement of data from clinical trials and program updates for clinical candidates; Bicycle’s beliefs regarding the clinical programs and research areas with the highest potential to maximize value creation and the company’s activities to focus on such programs and areas; the guidance and insights provided by the Clinical Advisory Board; the development of potential radiopharmaceutical or other product candidates using Bicycle’s technology through various partnerships; the therapeutic potential for Bicycles in oncology and other applications; and Bicycle’s expected financial runway. Bicycle may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in research and development and in the initiation, progress and completion of clinical trials and clinical development of Bicycle’s product candidates; the risk that Bicycle may not realize the intended benefits of its technology or partnerships; timing of results from clinical trials; whether the outcomes of preclinical studies will be predictive of clinical trial results; the risk that trials may have unsatisfactory outcomes; potential adverse effects arising from the testing or use of Bicycle’s product candidates; the risk that Bicycle’s management have not focused the company’s activities on the clinical programs and research areas with the highest potential to maximize value creation; the risk that the Clinical Advisory Board does not provide guidance or insights or that such guidance turns out to be deficient; the risk that Bicycle’s projections regarding its expected cash runway are inaccurate or that its conduct of its business requires more cash than anticipated; and other important factors, any of which could cause Bicycle’s actual results to differ from those contained in the forward-looking statements, are described in greater detail in the section entitled “Risk Factors” in Bicycle’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 2, 2024, as well as in other filings Bicycle may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Bicycle expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. Bicycle Therapeutics plc Condensed Consolidated Statements of Operations and Comprehensive Loss (In thousands, except share and per share data) (Unaudited) Three Months Ended Six Months Ended June 30, June 30, 2024 2023 2024 2023 Collaboration revenues $ 9,361 $ 11,397 $ 28,891 $ 16,293 Operating expenses: Research and development 40,059 39,720 74,923 71,931 General and administrative 15,949 14,788 32,331 29,276 Total operating expenses 56,008 54,508 107,254 101,207 Loss from operations (46,647 ) (43,111 ) (78,363 ) (84,914 ) Other income (expense): Interest income 7,774 812 13,398 3,741 Interest expense (824 ) (821 ) (1,645 ) (1,629 ) Total other income (expense), net 6,950 (9 ) 11,753 2,112 Net loss before income tax provision (39,697 ) (43,120 ) (66,610 ) (82,802 ) Provision for (benefit from) income taxes 115 (517 ) (235 ) (1,135 ) Net loss $ (39,812 ) $ (42,603 ) $ (66,375 ) $ (81,667 ) Net loss per share, basic and diluted $ (0.77 ) $ (1.41 ) $ (1.40 ) $ (2.71 ) Weighted average ordinary shares outstanding, basic and diluted 51,992,034 30,191,693 47,276,062 30,097,234 Condensed Consolidated Balance Sheets Data (In thousands) (Unaudited) June 30, December 31, 2024 2023 Cash and cash equivalents $ 961,364 $ 526,423 Working capital 958,645 492,331 Total assets 1,057,355 595,344 Total shareholders’ equity 873,813 370,932

OSE Immunotherapeutics and Nantes University Hospital Present Positive Phase 1/2 Study Evaluating FR104/VEL-101 Immunotherapy in Renal Transplant At the American Transplant Congress 2024 (June 1-5 Philadelphia) Nantes, France – June 5, 2024, 7:30am CET – OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) and Nantes University Hospital present positive Phase 1/2 analysis from first use of anti-CD28 FR104/VEL-101 in kidney transplantation in oral presentation at the Annual American Transplant Congress (ATC) held in Philadelphia (June 1-5, 2024). A total of three oral presentations on FR104/VEL-101 were presented at this congress. A first oral communication, entitled “First use of FR104, an anti-CD28 molecule in human kidney transplantation”, presented by Pr. Gilles Blancho, Head of the ITUN* at the University Hospital in Nantes / Nantes University and Principal Investigator of the study, reported on the positive data from the completed Phase 1/2 clinical trial FIRsT evaluating FR104/VEL-101 in patients undergoing renal allotransplant. This study is sponsored and conducted by the University Hospital of Nantes as part of a collaboration agreement with OSE Immunotherapeutics. A second oral communication, entitled “Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Fixed-Dose, Subcutaneous (SQ) Administration of VEL-101, an Anti-CD28 Pegylated Monoclonal Antibody Fragment, in Healthy Participants”, presented by OSE Immunotherapeutics partner Veloxis Pharmaceuticals, featured the results from the Company’s Phase 1 dose escalation clinical trial evaluating the safety, tolerability, pharmacodynamics and pharmacokinetics of single ascending doses of subcutaneous administration of FR104/VEL-101 in healthy participants. A third oral communication, entitled “Combined blockade of the CD154 and CD28 co-stimulation pathways attenuates pathogenic alloimmunity and prolongs survival in cynomolgus cardiac allografts”, presented by the group of Pr. Richard Pierson (Massachusetts General Hospital, Harvard university, Boston, USA), reported on the positive preclinical efficacy data of FR104/VEL-101 injection in monotherapy or in combination with anti-CD40L antibody to protect from acute and chronic heart allograft rejection. Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, said: “We thank the University Hospital of Nantes for this important step with the first clinical study evaluating FR104/VEL-101 in transplanted patients. Our partner Veloxis presented its positive subcutaneous Phase 1 clinical trial results in oral session, which will facilitate dose selection in preparation for a Phase 2 study in kidney transplant recipients. At last, we are excited about the promising preclinical results of our academic collaborator in the field of cardiac transplantation, further enhancing the future market potential.” Pr. Gilles Blancho commented: « We are very pleased to share the positive results of the FIRsT study at international congress on post-transplant immune response and one-year safety in patients treated with FR104/VEL-101, developed for years in our own research laboratory, CR2TI**/UMR Inserm 1064. The data presented show the safety of the product used in combination and the first signs of efficacy in kidney transplant recipients with no episodes of acute rejection after one year follow-up in all patients of the study. The exploration of FR104/VEL-101’s safety profile seems promising and encourages moving to a Phase 2 trial for patients undergoing renal transplant who require innovative solution.” The purpose of the FIRsT Phase 1/2 clinical trial is to investigate the safety, tolerability, and pharmacokinetics of FR104/VEL-101, a novel antagonist pegylated anti-CD28 Fab’ antibody fragment, as well as its potential clinical efficacy on acute rejection prophylaxis and renal function in a de novo renal transplant population receiving an allograft from standard criteria donors (NCT number: NCT04837092). A one-year safety and efficacy of FR-104/VEL-101 treatment assessment was performed after transplantation, including renal function, incidence of rejection and suspected reported adverse events. Ten patient candidates eligible to a first kidney transplant at low risk of rejection, as planned in the protocol, have been included in the FIRsT study for eight analyzable patients (two patients were screened and enrolled but not transplanted for technical reasons). Tacrolimus (a calcineurin inhibitor) was withdrawn after 6 months post-transplantation. The eight patients completed 1-year treatment with FR104/VEL-101. No safety alert was detected for FR104/VEL-101. Adverse events were those conventionally observed in kidney transplantation. Pharmacological monitoring made it possible to optimize exposure to FR104/VEL-101 and to maintain high receptor occupancy during the one-year follow-up. With a follow-up of 1 year in all patients, not only no acute rejection under FR104/VEL-101 was observed, and notably no acute rejection episodes occurred after discontinuation of tacrolimus, but also no immunization against the donor occurred. One of the key challenges in organ transplantation remains calcineurin inhibitors alternatives with effective immunosuppressive treatments and minimal side effects, particularly on renal function in order to preserve patients’ quality of life, and long-term control of post-transplant immune reaction. * Urology and Nephrology Transplant Institute (ITUN) ** Center for Research in Transplantation and Translational Immunology (CR2TI) DETAILS OF THE PRESENTATIONSOSE IMMUNOTHERAPEUTICS“First Use of FR104, an Anti-CD28 Molecule in Human Kidney Transplantation, Interim Analysis” Rapid Fire Oral Abstract SessionAbstract 1050Tuesday, June 04 - 3:50PM – 4 :00PM G. J. Blancho, Institute of Transplantation - Urologie - Nephrologie (ITUN), Centre Hospitalier Universitaire, Nantes, FranceVELOXIS PHARMACEUTICALS“Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Fixed-Dose, Subcutaneous (SQ) Administration of VEL-101, an Anti-CD28 Pegylated Monoclonal Antibody Fragment, in Healthy Participants” Rapid Fire Oral Abstract SessionAbstract 1049Tuesday, June 04 - 3:40PM 3:50PM S. Tremblay {1}, A. Abaigar{2}, P. Allton{1}, D. Sardinha{1}, S. Patel{1}, U. Meier-Kriesche{1}, K. Shah{1}, J. Maynard{3}, B. Otulana{1}, {1}Veloxis Pharmaceuticals, Cary, NC, {2}CTI Clinical Trial & Consulting Services, Bilbao, Spain, {3}CTI Clinical Trial & Consulting Services, Cincinnati, OHCENTER FOR TRANSPLANTATION SCIENCES, MASSACHUSETTS GENERAL HOSPITAL, HARVARD UNIVERSITY, BOSTON“Combined blockade of the CD154 and CD28 co-stimulation pathways attenuates pathogenic alloimmunity and prolongs survival in cynomolgus cardiac allografts” Rapid Fire Oral Abstract Session Abstract 860Tuesday, June 04 - 9:45AM 9:55PM Kohei Kinoshita1, A Maenaka1, Z Habibabady1, I Ileka1, M Ma1, V Diaz1, T Zhang3, N O’Neill3, I Rosales2, S Fogarty4, P Maguire4, B Daugherty4, S Lederman4, U Meier-Kriesche5, N Poirier6, A Azimzadeh1,3, R Pierson III1, 1Center for Transplantation Sciences, Massachusetts General Hospital, Boston, 2 Department of Pathology, Massachusetts General Hospital, Boston, , 3 University of Maryland School of Medicine, Baltimore, 4 Tonix Pharmaceuticals, 5 Veloxis Pharmaceuticals, 6 OSE Immunotherapeutics ABOUT FR104/VEL-101 FR104/VEL-101 is a pegylated monoclonal antibody fragment that binds to and blocks CD28-mediated effector-T cell co-stimulation, without blocking CTLA-4, an important protein receptor found on T cells that acts as a natural brake on the body’s immune responses. FR104/VEL-101 is, therefore, expected to have a dual-mechanism of action where in a direct manner, it blocks CD28-mediated T cell activation, and in an indirect way, it allows for CTLA-4 mediated immunosuppressive functions. ABOUT VELOXIS PHARMACEUTICALS Veloxis Pharmaceuticals, an Asahi Kasei company, is a fully integrated specialty pharmaceutical company committed to improving the lives of transplant patients. Headquartered in Cary, N.C., USA, Veloxis is focused on the global development and commercialization of medications utilized by transplant patients and by patients with serious related diseases. For further information, please visit www.veloxis.com. 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.OSE-230 (ChemR23 agonist mAb) developed in partnership with AbbVie in chronic inflammation. 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: Pro-resolutive mAb platform focused on targeting and advancing inflammation resolution and optimizing the therapeutic potential of targeting Neutrophils and Macrophages in I&I. OSE-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. Additional information about OSE Immunotherapeutics assets is available on the Company’s website: www.ose-immuno.com. Follow us on X and LinkedIn. Contacts Sylvie Détrysylvie.detry@ose-immuno.comNicolas PoirierChief Executive Officer nicolas.poirier@ose-immuno.comFrench Media: FP2COMFlorence Portejoiefportejoie@fp2com.fr+33 6 07 768 283U.S. Media ContactRooneyPartners LLCKate Barrettekbarrette@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_240605_FR104 ATC