Brightline-3: A Phase III, Randomized, Open-label, Multi-center Trial of Brigimadlin + Ezabenlimab Compared to Gemcitabine + Docetaxel for Second-line Treatment of Patients With Advanced TP53 Wild-type Soft Tissue Sarcoma Subtypes

This study is open to adults with specific types of advanced soft tissue sarcoma. People with undifferentiated pleomorphic sarcoma (UPS) or myxofibrosarcoma (MFS) can join the study if they have a normal version of the TP53 gene. This is a study for people whose earlier treatment isn't working anymore, and their doctors suggest a new treatment to stop the sarcoma from getting worse.
The purpose of this study is to compare a medicine called brigimadlin in combination with another medicine called ezabenlimab with chemotherapy. Brigimadlin is a so-called MDM2-p53 antagonist that is being developed to treat cancer. Ezabenlimab is an antibody that may help the immune system fight cancer.
Participants are put into 3 groups by chance:
Ezabenlimab group: Participants receive ezabenlimab as an infusion into a vein every 3 weeks
Brigimadlin + ezabenlimab group: Participants take brigimadlin as tablets and receive ezabenlimab as an infusion into a vein every 3 weeks
Chemotherapy group: Participants get chemotherapy as an infusion into a vein on 2 days every 3 weeks. Chemotherapy is a combination of gemcitabine and docetaxel which is often used in the treatment of sarcoma.
There are twice as many participants in the brigimadlin + ezabenlimab group and in the chemotherapy group, compared to those in the ezabenlimab group.
Participants can continue treatment in the study as long as they benefit from it and can tolerate it.
Doctors regularly check the size of the tumor and check whether it has spread to other parts of the body. The doctors also regularly check participants' health and take note of any unwanted effects. Participants in this study use an app on a mobile phone to regularly answer questions about their health and well-being. This is to find out if their quality of life is changing.

Start Date27 Jun 2024

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT06091930 / RecruitingPhase 1

Phase I, Non-randomised, Open-label, Multi-centre Dose Escalation and Expansion Trial of BI 765049 and BI 765049 + Ezabenlimab Administered by Repeated Intravenous Infusion in Asian Patients With Malignant Solid Tumours Expressing B7-H6

This is a study in adults from Asia with different types of advanced cancer (solid tumours). People can join the study if they have cancer of the stomach, large bowel and rectum, pancreas, liver, head and neck or non-small cell lung cancer. This is a study for people for whom previous treatment was not successful or no treatment exists. People can participate if their tumour has the B7-H6 marker.
The purpose of this study is to find the highest dose of BI 765049 that people with advanced cancer can tolerate when taken (alone and) together with ezabenlimab. Another purpose is to check whether BI 765049 taken (alone and) together with ezabenlimab can make tumours shrink. Both medicines may help the immune system fight cancer.
Participants can stay in the study up to 3 years, as long as they can tolerate it and can benefit from it. During this time, they visit the study site about every 3 weeks. At the study site they get BI 765049 alone or in combination with ezabenlimab as an infusion into a vein. BI 765049 is given in 3-week cycles, ezabenlimab is given once every 3 weeks.
The doctors check the health of the participants and note any health problems that could have been caused by BI 765049 or ezabenlimab. Doctors regularly check the size of the tumour and check whether it has spread to other parts of the body.

Start Date31 Jan 2024

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT06084689 / Not yet recruitingPhase 2IIT

Targeting MDMD and PD1 in Tumors With Tertiary Lymphoid Structures

Phase II, multicenter, open-label, multi-cohort proof-of-concept study designed to evaluate the safety and efficacy of Ezabenlimab combined with BI 907828 in patients with unresectable, locally advanced or metastatic solid tumors.

Start Date01 Jan 2024

Sponsor / Collaborator

Institut Bergonié

[+1]

100 Clinical Results associated with Ezabenlimab

100 Translational Medicine associated with Ezabenlimab

100 Patents (Medical) associated with Ezabenlimab

Literatures (Medical) associated with Ezabenlimab

01 Jun 2023·Cancer chemotherapy and pharmacology

Phase I study of the VEGF/Ang-2 inhibitor BI 836880 alone or combined with the anti-programmed cell death protein-1 antibody ezabenlimab in Japanese patients with advanced solid tumors.

Article

Author: Sarashina, Akiko ; Shimizu, Toshio ; Hou, Jianrui ; Koyama, Takafumi ; Kawakami, Takeshi ; Erzen, Damijan ; Yamamoto, Noboru ; Yamazaki, Kentaro ; Li, Bin ; Todaka, Akiko

PURPOSE:

This two-part, open-label, non-randomized dose-escalation study aimed to define the maximum tolerated dose (MTD) of BI 836880 (humanized bispecific nanobody® targeting vascular endothelial growth factor and angiopoietin-2) as monotherapy and in combination with ezabenlimab (programmed death protein-1 inhibitor) in Japanese patients with advanced and/or metastatic solid tumors.

METHODS:

In part 1, patients received an intravenous infusion of BI 836880 at 360 or 720 mg every 3 weeks (Q3W). In part 2, patients received BI 836880 at doses of 120, 360, or 720 mg in combination with ezabenlimab 240 mg Q3W. The primary endpoints were the MTD and the recommended phase II dose (RP2D) of BI 836880 as monotherapy and in combination with ezabenlimab, based on dose-limiting toxicities (DLTs) during the first cycle.

RESULTS:

Twenty-one patients were treated; nine in part 1 and 12 in part 2. No DLTs were reported in either part and the MTD was not reached. The RP2Ds were BI 836880 720 mg Q3W as monotherapy and BI 836880 720 mg plus ezabenlimab 240 mg Q3W. The most common adverse events were hypertension and proteinuria (33.3%) with BI 836880 monotherapy and diarrhea (41.7%) with the combination. Four patients (44.4%) in part 1 had stable disease as best overall tumor response. In part 2, two patients (16.7%) had confirmed partial responses and five had stable disease (41.7%).

CONCLUSION:

MTD was not reached. BI 836880 alone and in combination with ezabenlimab had a manageable safety profile with preliminary clinical activity in Japanese patients with advanced solid tumors.

TRIAL REGISTRATION AND DATE:

NCT03972150, registered on June 3, 2019.

01 Jun 2023·European journal of nuclear medicine and molecular imaging

89Zr-immuno-PET using the anti-LAG-3 tracer [89Zr]Zr-BI 754111: demonstrating target specific binding in NSCLC and HNSCC

Article

Author: van Dongen, Guus A M S ; de Gruijl, Tanja D ; Pitarch, Alejandro Perez ; Menke-van der Houven van Oordt, C Willemien ; Thiele, Andrea ; Zwezerijnen, Gerben J C ; Grempler, Rolf ; Huisman, Marc C ; Bahce, Idris ; Peltzer, Alexander ; Hesse, Raphael ; Vugts, Danielle J ; Miedema, Iris H C ; Elgadi, Mabrouk

Abstract:

Purpose:

Although lymphocyte activation gene-3 (LAG-3) directed therapies demonstrate promising clinical anti-cancer activity, only a subset of patients seems to benefit and predictive biomarkers are lacking. Here, we explored the potential use of the anti-LAG-3 antibody tracer [89Zr]Zr-BI 754111 as a predictive imaging biomarker and investigated its target specific uptake as well as the correlation of its tumor uptake and the tumor immune infiltration.

Methods:

Patients with head and neck (N = 2) or lung cancer (N = 4) were included in an imaging substudy of a phase 1 trial with BI 754091 (anti-PD-1) and BI 754111 (anti-LAG-3). After baseline tumor biopsy and [18F]FDG-PET, patients were given 240 mg of BI 754091, followed 8 days later by administration of [89Zr]Zr-BI 754111 (37 MBq, 4 mg). PET scans were performed 2 h, 96 h, and 144 h post-injection. To investigate target specificity, a second tracer administration was given two weeks later, this time with pre-administration of 40 (N = 3) or 600 mg (N = 3) unlabeled BI 754111, followed by PET scans at 96 h and 144 h post-injection. Tumor immune cell infiltration was assessed by immunohistochemistry and RNA sequencing.

Results:

Tracer uptake in tumors was clearly visible at the 4-mg mass dose (tumor-to-plasma ratio 1.63 [IQR 0.37-2.89]) and could be saturated by increasing mass doses (44 mg: 0.67 [IQR 0.50–0.85]; 604 mg: 0.56 [IQR 0.42–0.75]), demonstrating target specificity. Tumor uptake correlated to immune cell-derived RNA signatures.

Conclusions:

[89Zr]Zr-BI-754111 PET imaging shows favorable technical and biological characteristics for developing a potential predictive imaging biomarker for LAG-3-directed therapies.

Trial registration:

ClinicalTrials.gov, NCT03780725. Registered 19 December 2018

31 Dec 2022·Oncoimmunology

Combination of two novel blocking antibodies, anti-PD-1 antibody ezabenlimab (BI 754091) and anti-LAG-3 antibody BI 754111, leads to increased immune cell responses

Article

Author: Lorenz, Ivo C. ; Schaaf, Otmar ; Frego, Lee ; Apfler, Ilse ; Waizenegger, Irene C. ; Oquendo Cifuentes, Elisa ; Vogt, Anne ; Kenny, Cynthia ; Wurm, Melanie ; Moll, Jürgen ; Thibodeau, Michael ; Kraut, Norbert ; Reschke, Markus ; Tirapu, Iñigo ; Mostböck, Sven ; Zettl, Markus ; Sedgwick, Jonathon D.

Upregulation of inhibitory receptors, such as lymphocyte activation gene-3 (LAG-3), may limit the antitumor activity of therapeutic antibodies targeting the programmed cell death protein-1 (PD-1) pathway. We describe the binding properties of ezabenlimab, an anti-human PD-1 antibody, and BI 754111, an anti-human LAG-3 antibody, and assess their activity alone and in combination. Ezabenlimab bound with high affinity to human PD-1 (K_D = 6 nM) and blocked the interaction of PD-1 with PD-L1 and PD-L2. Ezabenlimab dose-dependently increased interferon-γ secretion in human T cells expressing PD-1 in co-culture with PD-L1-expressing dendritic cells. Administration of ezabenlimab to human PD-1 knock-in mice dose-dependently inhibited growth of MC38 tumors. To reduce immunogenicity, ezabenlimab was reformatted from a human IgG4 to a chimeric variant with a mouse IgG1 backbone (BI 905725) for further in vivo studies. Combining BI 905725 with anti-mouse LAG-3 antibodies improved antitumor activity versus BI 905725 monotherapy in the MC38 tumor model. We generated BI 754111, which bound with high affinity to human LAG-3 and prevented LAG-3 interaction with its ligand, major histocompatibility complex class II. In an in vitro model of antigen-experienced memory T cells expressing PD-1 and LAG-3, interferon-γ secretion increased by an average 1.8-fold versus isotype control (p = 0.027) with BI 754111 monotherapy, 6.9-fold (p < 0.0001) with ezabenlimab monotherapy and 13.2-fold (p < 0.0001) with BI 754111 plus ezabenlimab. Overall, ezabenlimab and BI 754111 bound to their respective targets with high affinity and prevented ligand binding. Combining ezabenlimab with BI 754111 enhanced in vitro activity versus monotherapy, supporting clinical investigation of this combination (NCT03156114; NCT03433898).

News (Medical) associated with Ezabenlimab

22 May 2024

·www.biospace.com

OSE Immunotherapeutics and Boehringer Ingelheim expand collaboration to develop first-in-class treatments for cancer and cardio-renal-metabolic diseases

OSE Immunotherapeuticsand Boehringer Ingelheim expand collaboration to develop first-in-class treatments for cancer and cardio-renal-metabolic diseases Nantes, France - Ingelheim, Germany - 22 May 2024, 7:30am CET - Today OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) and Boehringer Ingelheim announced a major expansion of their partnership. Two new projects to develop first-in-class treatments will be added to the ongoing anti-SIRPα immuno-oncology programs. The first involves broadening the therapeutic evaluation of an already partnered asset to reach more patients and the other a new asset acquisition: Reflecting an amendment of the existing collaboration and license agreement for the anti-SIRPα immuno-oncology compounds BI 765063 and BI 770371, which are being investigated in Phase I clinical studies in advanced solid tumors, development will now also be pursued in cardiovascular-renal-metabolic (CRM) diseases. A new preclinical program will be launched to develop immune-cell activating treatments based on OSE’s cis-targeting1 anti-PD1/cytokine platform via an asset acquisition. Affecting over one billion lives globally2, CRM diseases cause 20 million deaths annually. They are interconnected, co-exist, and can amplify one another, resulting in a significant burden on patients’ lives. Cancer accounts for nearly 10 million deaths and for many cancer patients there are no or only limited treatment options. The new development programs bolster Boehringer Ingelheim’s pipeline and reflects the company’s unwavering commitment to explore and progress new therapies to address unmet patient needs, including in CRM diseases and cancer. The cis-targeting anti-PD1/cytokine platform asset will further enrich Boehringer Ingelheim’s array of novel potential immune-modulatory cancer treatments. The development of the ongoing anti-SIRPα compounds for a new indication adds to the company’s comprehensive CRM pipeline with the initiation of a Phase 2 clinical study planned for later this year. “We are very pleased to expand our pipeline of potential first-in-class CRM disease therapies, as well as our pipeline of first-in-class T-cell based anti-cancer therapies,” said Clive R. Wood, Corporate Senior Vice President and Global Head of Discovery Research at Boehringer Ingelheim. “The expansion of our partnership with OSE reflects our joint mission to improving patient outcomes in two of the biggest threats to global health.” Nicolas Poirier, CEO of OSE Immunotherapeutics, commented: “We are excited about adding two highly innovative new development programs to our fruitful collaboration with Boehringer Ingelheim. We look forward to working with the scientists at Boehringer Ingelheim on the new development programs that have the potential to bring new breakthrough therapy options to patients with CRM diseases and cancer.” OSE Immunotherapeutics will receive EUR 13.5. million in upfront payment and a potential near-term milestone of EUR 17.5 million for the purchase of a novel, cis-targeting anti-PD-1/cytokine asset in preclinical stage. Regarding the two ongoing anti-SIRPα programs BI 765063 and BI 770371 the parties agreed on partial royalty buy-out monetizing with a one-time payment of EUR 25.3 million. Furthermore, Boehringer is granted an option for an additional buy-out during further development triggering a one-time payment plus the increase of one sales milestone. All other agreed development, regulatory and sales milestone payments of up to €1.1 billion remain as agreed between the parties under the initial agreement. About Boehringer Ingelheim Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units Human Pharma and Animal Health. Learn more at . 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.). BI 765063 and BI 770371 (anti-SIRPα monoclonal antibody on CD47/SIRPα pathway) developed in partnership with Boehringer Ingelheim in advanced solid tumors; positive Phase 1 dose escalation results in monotherapy and in combination, in particular with anti-PD-1 antibody ezabenlimab; international Phase 1b ongoing clinical trial in combination with ezabenlimab alone or with other drugs in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and hepatocellular carcinoma (HCC). 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. Cytokine platform focused on leveraging the Cis-Delivery of cytokine in IO and I&I. BiCKI® is a bispecific fusion protein platform built on the key backbone component of anti-PD1 combined with a new immunotherapy target to increase anti-tumor efficacy. BiCKI®-IL-7v is the most advanced BiCKI® candidate targeting anti-PD1xIL-7. Ongoing additional discovery programs on Cis-Demasking technologies. Additional information about OSE Immunotherapeutics assets is available on the Company’s website: . Follow us on X and LinkedIn Contacts Boehringer Ingelheim T +49 (6132) 77-90815 reinhard.malin@boehringer-ingelheim.com Boehringer Ingelheim Binger Str. 173 55218 Ingelheim am Rhein More information boehringer-ingelheim.com OSE Immunotherapeutics 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. 1 Cis-targeting: Bispecific antibodies have the capability to target cells either in a cis- or in a trans-binding orientation. During trans-binding, the antibody recognizes two different antigens, each expressed on a different cell population, and can link two different cell populations with each other (e.g. T-cell engagers). Cis-binding bispecific antibody targets two antigens expressed on the very same cell enabling preferential activation of the desired immune cell types while minimizing the activation of others (Segués A. et al. International Review of Cell and Molecular Biology 2022). 2 Schechter M, Melzer Cohen C, Yanuv I, et al. Epidemiology of the diabetes-cardio-renal spectrum: a cross-sectional report of 1.4 million adults. Cardiovascular Diabetology. 2022;21(1):104. doi:10.1186/s12933-022-01521-9 Attachment EN_240522_OSE BI_agreement

ImmunotherapyPhase 1Clinical ResultLicense out/inPhase 3

16 Apr 2024

·www.biospace.com

OSE Immunotherapeutics’ Global License to Develop a Novel Monoclonal Antibody for the Treatment of Chronic Inflammation Becomes Effective

OSE Immunotherapeutics’ Global License to Develop a Novel Monoclonal Antibody for the Treatment of Chronic Inflammation Becomes Effective NANTES, France, April 16, 2024 – OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE), a clinical-stage immunotherapy company, today announced that the Hart-Scott-Rodino waiting period has expired with respect to its global license with AbbVie to develop OSE-230, a monoclonal antibody designed to resolve chronic and severe inflammation, currently in the pre-clinical development stage. As part of the partnership agreement announced on February 28, 2024, AbbVie received from OSE Immunotherapeutics an exclusive global license and collaboration agreement to develop OSE-230, a monoclonal antibody designed to resolve chronic inflammation. Under the terms of this agreement, AbbVie will now make an upfront payment of $48 million to OSE Immunotherapeutics. In addition, OSE Immunotherapeutics will be eligible to receive up to an additional $665 million in clinical development, regulatory and commercial milestones and potential tiered royalties on global net sales of OSE-230. 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.). BI 765063 and BI 770371 (anti-SIRPα monoclonal antibody on CD47/SIRPα pathway) developed in partnership with Boehringer Ingelheim in advanced solid tumors; positive Phase 1 dose escalation results in monotherapy and in combination, in particular with anti-PD-1 antibody ezabenlimab; international Phase 1b ongoing clinical trial in combination with ezabenlimab alone or with other drugs in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and hepatocellular carcinoma (HCC). 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. Cytokine platform focused on leveraging the Cis-Delivery of cytokine in IO and I&I. BiCKI® is a bispecific fusion protein platform built on the key backbone component of anti-PD1 combined with a new immunotherapy target to increase anti-tumor efficacy. BiCKI®-IL-7v is the most advanced BiCKI® candidate targeting anti-PD1xIL-7. Ongoing additional discovery programs on Cis-Demasking technologies. Additional information about OSE Immunotherapeutics assets is available on the Company’s website: . Follow us on X and LinkedIn 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 May 2, 2023, including the annual financial report for the fiscal year 2022, 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. 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 Attachment EN_240416_OSE-230

License out/inImmunotherapyPhase 1Phase 2Phase 3

10 Apr 2024

·www.globenewswire.com

OSE Immunotherapeutics Receives €8.4 M in Public Funding to Support the Registration Phase 3 Clinical Trial of Cancer Vaccine Tedopi® in Lung Cancer

OSE Immunotherapeutics Receives €8.4 M in Public Funding to Support the Registration Phase 3 Clinical Trial of Cancer Vaccine Tedopi® in Lung Cancer Nantes, France – April 10, 2024 – 6:00 pm CET – OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) today announced the Company has received €8.4 million in non-dilutive funding under the “i-Démo” call for projects as part of the plan “France 2030” operated by Bpifrance on behalf of the State. This plan aims at developing industrial companies in growth markets that create value and competitiveness for the French economy and also contribute to energy, ecological and digital transitions. This financial support applies from the feasibility study to marketing. This public funding will support the registration Phase 3 clinical trial of neoepitope-based cancer vaccine Tedopi®, in second line treatment in HLA-A2 positive non-small cell lung patients with secondary (acquired) resistance to anti-PD-(L)1 immunotherapy. This new national support adds up to the €1.5 million funding from Bpifrance * announced in June 2023 to support the development of a companion diagnostic test (HLA-A2) associated with Tedopi®’s registration in the same indication. Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, comments: « We thank the State and Bpifrance for renewing their confidence and supporting us with this funding. It will enable the Company to accelerate the last step of clinical development of our cancer vaccine Tedopi®. This innovation will meet the important medical need of non-small cell lung cancer patients who are failing after immunotherapy, and who do not have today any approved therapeutic options. Following FDA approval on the trial protocol in early 2024, we will be able to start this confirmatory Phase 3 in the United States in the coming weeks and then, once we receive approval from the EMA, in Europe and in France where many clinical sites will be set up. We thank particularly the international groups of clinical investigators and lung cancer experts who, from the beginning, support us and are committed to advance the clinical development of Tedopi® towards a potential new standard treatment in second line of metastatic or advanced lung cancer”. Based on positive final survival, safety and quality of life results from the Phase 3 clinical trial in the third line of treatment in non-small cell lung cancer published in September 2023 in the internationally renowned Journal ‘Annals of Oncology’, a confirmatory pivotal Phase 3 trial in second line treatment is being prepared for launch. This trial is associated with the development of a unique companion diagnostic test (collaboration with the company GenDx) to identify positive HLA-A2 patients eligible for treatment with Tedopi®. The clinical trial application dossier to initiate the new confirmatory Phase 3 of Tedopi®, including the study protocol and the specific “diagnostic companion test” dossier, was approved by the Food & Drug Administration (FDA) in mid-January 2024, which should allow the trial to start in the United States in Q2 2024, after approval from the Ethic committees. The submission of the dossier to the European Medicines Agency (single European portal) is planned in the coming weeks to extend this study to a large number of clinical investigator sites in Europe, particularly in France. * As part of an “R&D Innovation Loan” program The management of lung cancer is a major public health issue: 1st cause of cancer mortality for all populations combined (33,100 deaths in 20181 in France and 1.8 million per year worldwide2).-2nd most common cancer among solid tumors.Non-Small Cell Bronchial Cancer (NSCLC) is a serious disease with a short-term life-threatening prognosis. NSCLC represents 85% of lung cancers.Stage IV metastatic NSCLC: 2-year survival between 10% and 23%; 5-year survival <10%3.Targeted population of patients identified as responders to Tedopi®4: HLA-A2+ patients (45% of stage IV patients with secondary resistance to anti-PD-(L)1 (approximately 50% of patients failing immunotherapy in NSCLC). Lapôtre-Ledoux, B., Benedicte, L.-L., Dantony, E., Grosclaude, P., Molinié, F., Woronoff, A.-S., Lecoffre-Bernard, C., Lafay, L., Defossez, G., & D’Almeida, T. (s. d.). // MAIN CANCERS INCIDENCE IN METROPOLITAN FRANCE IN 2023 AND TRENDS SINCE 1990.WHO. Globocan 2020 Fact SheetDetterbeck, F. C., Boffa, D. J., Kim, A. W., & Tanoue, L. T. (2017). The Eighth Edition Lung Cancer Stage Classification. Chest, 151(1), 193-203. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.chest.2016.10.010Mezquita, L., Charrier, M., Faivre, L., Dupraz, L., Lueza, B., Remon, J., Planchard, D., Bluthgen, M. V., Facchinetti, F., Rahal, A., Polo, V., Gazzah, A., Caramella, C., Adam, J., Pignon, J. P., Soria, J.-C., Chaput, N., & Besse, B. (2017). Prognostic value of HLA-A2 status in advanced non-small cell lung cancer patients. Lung Cancer, 112, 10-15. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.lungcan.2017.07.004Molinier, O., Besse, B., Barlesi, F., Audigier-Valette, C., Friard, S., Monnet, I., Jeannin, G., Mazières, J., Cadranel, J., Hureaux, J., Hilgers, W., Quoix, E., Coudert, B., Moro-Sibilot, D., Fauchon, E., Westeel, V., Brun, P., Langlais, A., Morin, F., … Girard, N. (2022). IFCT-1502 CLINIVO : Real-world evidence of long-term survival with nivolumab in a nationwide cohort of patients with advanced non-small-cell lung cancer. ESMO Open, 7(1), 100353. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.esmoop.2021.100353 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.).BI 765063 and BI 770371 (anti-SIRPα monoclonal antibody on CD47/SIRPα pathway) developed in partnership with Boehringer Ingelheim in advanced solid tumors; positive Phase 1 dose escalation results in monotherapy and in combination, in particular with anti-PD-1 antibody ezabenlimab; international Phase 1b ongoing clinical trial in combination with ezabenlimab alone or with other drugs in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and hepatocellular carcinoma (HCC).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.Cytokine platform focused on leveraging the Cis-Delivery of cytokine in IO and I&I. BiCKI® is a bispecific fusion protein platform built on the key backbone component of anti-PD1 combined with a new immunotherapy target to increase anti-tumor efficacy. BiCKI®-IL-7v is the most advanced BiCKI® candidate targeting anti-PD1xIL-7. Ongoing additional discovery programs on Cis-Demasking technologies. Additional information about OSE Immunotherapeutics assets is available on the Company’s website: www.ose-immuno.com. Follow us on X and LinkedIn ABOUT FRANCE 2030 INVESTMENT PLAN Reflects a double ambition: sustainably transform key sectors of our economy (health, energy, automotive, aeronautics or space) through technological innovation, and position France not only as a player, but as a leader in the world of tomorrow. From basic research to the emergence of an idea to the production of a new product or service, France 2030 supports the entire life cycle of innovation until its industrialization.Is unpublished by its magnitude: €54 billion will be invested to ensure that our companies, universities and research organisations are fully successful in their transitions in these strategic sectors. The challenge: to enable them to respond competitively to the ecological and attractiveness challenges of the coming world, and to bring out the future leaders of our sectors of excellence. France 2030 is defined by two cross-cutting objectives consisting in dedicating 50% of its expenditure to the decarbonisation of the economy, and 50% to emerging players, who are the bearers of innovation without spending that is unfavourable to the environment (in the sense of the principle Do No Significant Harm).Will be implemented collectively: designed and deployed in consultation with economic, academic, local and European stakeholders to determine their strategic orientations and flagship actions. Project leaders are invited to submit their application via open, demanding and selective procedures to benefit from the support of the State. Is led by the General Secretariat for Investment on behalf of the Prime Minister and implemented by the Agence de la transition écologique (ADEME), the Agence nationale de la recherche (ANR), Bpifrance and the Banque des Territoires. More information on: france2030.gouv.fr | @SGPI_avenir ABOUT BPIfrance Bpifrance finances companies – at each stage of their development – with credit, guarantees and equity. Bpifrance supports them in their innovation projects and internationally. Bpifrance also support their export activity through a wide range of products. Consulting, university, networking and an acceleration program for start-ups, SMEs and mid-caps are also part of the support proposed to entrepreneurs. Thanks to Bpifrance and its 50 regional locations, entrepreneurs benefit from a close, unique and efficient contact to help them face their challenges.www.bpifrance.fr www.presse.bpifrance.fr/ @BpifrancePresse @Bpifrance Contacts OSE ImmunotherapeuticsSylvie 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 General Secretariat for Investment presse.sgpi@pm.gouv.fr Bpifrancepresse@bpifrance.fr 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 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 May 2, 2023, including the annual financial report for the fiscal year 2022, 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 OSE_Bpifrance_I_Demo_EN

Phase 3ImmunotherapyPhase 2Clinical ResultPhase 1

100 Deals associated with Ezabenlimab

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Indication	Highest Phase	Country/Location	Organization	Date
Malignant Fibrous Histiocytoma	Phase 3	-	Boehringer Ingelheim GmbH	27 Jun 2024
myxoid MFH	Phase 3	-	Boehringer Ingelheim GmbH	27 Jun 2024
Soft Tissue Sarcoma	Phase 3	-	Boehringer Ingelheim GmbH	27 Jun 2024
Biliary Tract Neoplasms	Phase 2	FR	Boehringer Ingelheim GmbH	16 Oct 2023
Colorectal Cancer	Phase 2	FR	Boehringer Ingelheim GmbH	16 Oct 2023
Non-Small Cell Lung Cancer	Phase 2	FR	Boehringer Ingelheim GmbH	16 Oct 2023
Triple Negative Breast Cancer	Phase 2	FR	Boehringer Ingelheim GmbH	16 Oct 2023
Neuroendocrine Tumors	Phase 2	JP	Boehringer Ingelheim GmbH	31 May 2023
Neuroendocrine Tumors	Phase 2	BE	Boehringer Ingelheim GmbH	31 May 2023
Neuroendocrine Tumors	Phase 2	FR	Boehringer Ingelheim GmbH	31 May 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04839471 (BEAR, ESMO_ASIA2022) Manual	Phase 2	Esophageal Squamous Cell Carcinoma	19	afatinib 30 mg+BI-754901 240 mg	qdqieoquvg(uvqcjwecie) = bqzymxvmqk ljwbcfygad (gwvxgenzlx, 3.8 - 6.1) View more	Positive	03 Dec 2022
NCT03964233 (ASCO2022) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	26	BI 907828+ezabenlimab+BI 754111	jrpxrsvcuv(ogupzrtznd) = gfglwtqexj atykuidrco (czvifokqkc ) View more	Positive	02 Jun 2022
				BI 907828+ezabenlimab	jrpxrsvcuv(ogupzrtznd) = bkkahuptvp atykuidrco (czvifokqkc ) View more
NCT03697304 (ASCO_GI2022)	Phase 2	Advanced Colorectal Adenocarcinoma	30	BI 836880 720 mg plus Ezabenlimab 240 mg	ypizechonb(trgvinxgmr) = ilmjpxstxv txqslcivtm (loohvqigqq ) View more	Negative	19 Jan 2022
NCT03697304 (ESMO2021) Manual	Phase 2	Advanced Malignant Solid Neoplasm	60	BI 836880 720 mg+Ezabenlimab 240 mg (locally advanced/metastatic gastric/gastroesophageal adenocarcinoma with ≥1 prior treatment (anti-PD-[L]1 naïve))	xbvwmymjip(gyyahowien) = yfjsztijwf kltpehpgfz (dqrrpxcvlg ) View more	Positive	16 Sep 2021
				BI 836880 720 mg+Ezabenlimab 240 mg (any advanced/metastatic solid tumours (except non-squamous NSCLC or melanoma) with prior anti-PD-(L)1 treatment, which progressed following at least stable disease (SD) for ≥4 months)	xbvwmymjip(gyyahowien) = eknnmshyhw kltpehpgfz (dqrrpxcvlg ) View more
NCT03468426 (ESMO2021) Manual	Phase 1	Neoplasms	215	BI 836880+ezabenlimab	fsgnjpusni(zqtglzmpkl) = wwuihhtoiu furthlycft (lmyipkfahv ) View more	Positive	16 Sep 2021
NCT03433898 \| NCT02952248 \| NCT03780725 (ESMO2021)	Phase 1	Advanced Malignant Solid Neoplasm	111	Ezabenlimab 240 mg	ohacriruyn(beddwnmafl) = wwcfxphibd rgcuqhtpyg (vyqktquids ) View more	-	16 Sep 2021
NCT04046445 (KISIMA-01, ESMO_GI2021)	Phase 1	Colorectal Cancer CEA \| Survivin \| Achaete-scute complex homolog 2 (ASCL2)	9	ATP128 alone	wourzwozvc(tqdlzcuevl) = lailbwoqwj kikrmfrjkg (cmrvxghhmc, 25.3) View more	Positive	03 Jul 2021
				ATP128 + ezabenlimab	wourzwozvc(tqdlzcuevl) = fengtbrdvj kikrmfrjkg (cmrvxghhmc, 14.11) View more
NCT03433898 (ASCO_GI2021) Manual	Phase 1	Esophageal Carcinoma \| Gastrooesophageal junction cancer \| Stomach Cancer	73	BI 754091+BI 754111 (gastric/gastroesophageal junction cancer (Cohort A))	ntnupizadr(rtratfzyyy) = pjerkagcto dvkvicqmeb (aamuzbtbwf ) View more	Positive	20 Jan 2021
				BI 754091+BI 754111 (esophageal cancer (Cohort B))	ntnupizadr(rtratfzyyy) = tbwpymqoae dvkvicqmeb (aamuzbtbwf ) View more
NCT03433898 (ASCO2020) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	121	BI 754091+BI 754111 (gastric/esophagogastric junction cancer)	sbihsqqzpk(fqemgwabba) = bimaivyhat nshdowdffh (ypngwczbgc ) View more	Positive	29 May 2020
				BI 754091+BI 754111 (esophageal cancer)	sbihsqqzpk(fqemgwabba) = bcqmqdqose nshdowdffh (ypngwczbgc ) View more
NCT03468426 (ASCO2020) Manual	Phase 1	Advanced Lung Non-Small Cell Carcinoma	12	BI 836880+BI 754091	xlckniowvy(bywanhamym) = 1 pt (360 mg; G3 pulmonary embolism) hzyccfrrtc (aszyjvfdvv ) View more	Positive	29 May 2020

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