BI-765063

· BI 765063 in combination with programmed cell death-1 (PD1) inhibitor antibody ezabenlimab + cetuximab demonstrated a well-tolerated safety profile and potentially promising efficacy signals as second-line treatment in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). · Next generation SIRP α inhibitor BI 770371 was shown to be well tolerated alone and in combination with PD1 inhibitor ezabenlimab in a dose escalation trial in patients with advanced solid tumors. BI 770371 is currently being further investigated in a Phase 1b study in first-line patients with R/M HNSCC. Ingelheim, Germany, 22 May 2025 – Boehringer Ingelheim today announced that new clinical data from two early-stage trials targeting the signal regulatory protein α (SIRP α ) innate immune checkpoint will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 - June 3, 2025, in Chicago, IL, USA. In a Phase 1b study conducted by Boehringer, its potential, first-in-class SIRP α monoclonal antibody, BI 765063, demonstrated a manageable safety profile as well as preliminary signs of immune activation and additive antitumor activity when combined with PD-1 inhibitor ezabenlimab and cetuximab in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). [1] Additionally, in an open-label, Phase I trial conducted by Boehringer, its next-generation SIRP α monoclonal antibody, BI 770371, alone and in combination with the PD-1 inhibitor ezabenlimab, was shown to be well tolerated in patients with advanced solid tumors. There were no dose-limiting toxicities in either treatment arm, and the maximum tolerated dose was not reached in either group. [2] “The preliminary results from these early-stage programs are encouraging and further strengthen Boehringer’s robust immuno-oncology pipeline aimed at accelerating next-generation cancer therapies to address high unmet patient needs,” said Mike Akimov, Head of Medicine, Therapy Area Oncology at Boehringer Ingelheim. “Boehringer is developing various complementary approaches to activate the immune system against cancer cells and SIRP α blockade paired with a PD-1 inhibitor is a promising strategy. We look forward to seeing if this dual activation may lead to a broader and more sustained anti-tumor response as the programs progress. ” BI 765063 and BI 770371 are designed to block the “don’t eat me” signal that cancer cells use to hide from the immune system. By targeting SIRP α , these antibodies help immune cells like macrophages recognize and destroy tumor cells, bolstering the body’s natural defenses. [3] Both antibodies have been developed in partnership with OSE, with Boehringer solely responsible for future clinical development and commercialization. Boehringer will move forward with the improved next generation SIRP α inhibitor antibody BI 770371, which will now be tested in a Phase 1b study. Presentation Details: Title: An Open-Label, Phase Ib Trial of the SIRP α Inhibitor BI 765063 in Combination with the PD-1 Inhibitor Ezabenlimab and Cetuximab in Patients (pts) with Head and Neck Squamous Cell Carcinoma ​ Abstract Number: 6019 Session Type/Title: Rapid Oral Abstract – Developmental Therapeutics – Immunotherapy Date/Time: 01 June 2025 – 11:30am – 1:30pm CDT Title: An Open-label, Phase I Trial of the SIRP α Monoclonal Antibody, BI 770371, Alone and in Combination with the PD-1 Inhibitor Ezabenlimab in Patients with Advanced Solid Tumors Abstract Number: 2515 Session Type/Title: Rapid Oral Abstract – Developmental Therapeutics – Immunotherapy Date/Time: 01 June 2025 – 11:15am – 12:45pm CDT Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer Ingelheim takes a long-term perspective, embedding sustainability along the entire value chain. More than 54,500 employees serve over 130 markets to build a healthier, more sustainable and equitable tomorrow. Learn more at https://www.boehringer-ingelheim.com (Global). 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 . Click and follow us on LinkedIn. Intended Audiences Notice This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business. 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 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. Contacts Boehringer Ingelheim Linda Ruckel +1 203-791-6672 linda.ruckel@boehringer-ingelheim.com Reinhard Malin +49 (6132) 77-90815 reinhard.malin@boehringer-ingelheim.com OSE Immunotherapeutics Fiona Olivier fiona.olivier@ose-immuno.com Sylvie Détry sylvie.detry@ose-immuno.com French Media Contact FP2COM Florence Portejoie fportejoie@fp2com.fr +33 6 07 768 283 U.S. Media Contact Rooney Partners LLC Kate Barrette kbarrette@rooneypartners.com +1 212 223 0561 [1] An open-label, phase Ib trial of the SIRP α inhibitor BI 765063 in combination with the PD-1 inhibitor ezabenlimab and cetuximab in patients (pts) with head and neck squamous cell carcinoma. - ASCO [1] An open-label, phase I trial of the SIRP α monoclonal antibody, BI 770371, alone and in combination with the PD-1 inhibitor ezabenlimab in patients with advanced solid tumors. - ASCO [3] Lopez-Yrigoyen, M., et al. (2017). Anti-SIRP α antibody immunotherapy enhances neutrophil and macrophage antitumor activity. Proceedings of the National Academy of Sciences, 114(33), 201710877. https://doi.org/10.1073/pnas.1710877114*:contentReference[oaicite:2]{index=2} Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

Data to be presented at ASCO reflect Boehringer's broad pipeline and growing body of evidence supporting innovative therapies for various cancers Patient-reported outcomes from the Beamion LUNG-1 study in previously treated patients with HER2 (ERRB2)-mutant advanced non-small cell lung cancer (NSCLC) reported physical function and disease-related symptom improvement while being treated with zongertinib1 New data from a study of T-cell engager, obrixtamig, show encouraging findings in the treatment of extrapulmonary neuroendocrine carcinomas in patients with high DLL3 expression2 RIDGEFIELD, Conn., May 22, 2025 /PRNewswire/ --Boehringer Ingelheim will present the latest data in its robust oncology pipeline at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, including patient-reported outcomes (PRO) from the Beamion LUNG-1 study evaluating zongertinib as an orally administered targeted therapy for previously treated patients with HER2 (ERBB2)-mutant advanced non-small cell lung cancer (NSCLC). In addition, new data evaluating the efficacy and safety of obrixtamig for the treatment of extrapulmonary neuroendocrine carcinomas with high or low DLL3 expression will be featured in an oral session. "Tackling difficult-to-treat cancers requires a multi-pronged approach, which is why we're exploring multiple pathways to address key cancer drivers, including HER2 and DLL3, to deliver meaningful advancements for the patients who need them most," said Vicky Brown, U.S. Senior Vice President and Head of Oncology, Immunology & Eye Health, Boehringer Ingelheim. "Our data at ASCO underscore our generational commitment to pioneering critical innovations that address patients' greatest needs." Developing zongertinib for the treatment of HER2-mutant advanced NSCLC Patient reported outcomes (N=30) from the Beamion LUNG-1 study (NCT04886804) evaluating zongertinib, showed improvements in physical functioning and disease-related symptoms in previously treated patients with HER2 (ERBB2)-mutant advanced NSCLC, identified through the following surveys: EORTC IL46/Q168 Survey (side effect burden): 80% to 90% (24 to 27) of patients reported "not at all" or "a little" side-effect trouble across all visits.1 PRO-CTCAE: Patient-reported symptomatic adverse events assessed were in line with the previously reported safety profile of zongertinib in the Beamion LUNG-1 study; the majority of patients who reported they experienced diarrhea stated "rarely" or "occasionally".1 NSCLC Symptom Assessment Questionnaire: At weeks 15 and 27, over 50% of patients reported "no coughing at all" – a key disease-related symptom – double the proportion at baseline with remaining patients responding with "mild to moderate" coughing.1 EORTC QLQ-C30 Physical Functioning: After 15 weeks of treatment with zongertinib, participants showed a 60% improvement in physical functioning from baseline (95% CI: 6.3-12.9).1 This improvement was sustained throughout the PRO data collection period.1 Physical functioning was measured by the ability to complete strenuous activities, go on long or short walks, ability to sit in a chair (versus need to stay in bed), and need for assistance completing daily tasks.1 "In treating HER2-mutant advanced non-small cell lung cancer – a disease with limited options and a poor prognosis – patient reported outcomes are critical in understanding not only how well a treatment works, but also how it is received by patients," said Dr. Joshua K. Sabari, study investigator and Associate Professor, Department of Medicine, New York University (NYU) Grossman School of Medicine; Medical Director, Thoracic Medical Oncology, NYU Langone Health's Perlmutter Cancer Center. "The study's reported outcomes provide further confidence in the potential of zongertinib to have a meaningful impact on the lives of patients living with this aggressive disease." Exploring precision medicine through DLL3 targeted therapy, obrixtamig New data will be presented from the ongoing, Phase I dose escalation study (NCT04429087) evaluating T-cell engager, obrixtamig, in previously treated patients with extrapulmonary neuroendocrine carcinomas with high or low DLL3 expression (N=60). In the study, obrixtamig demonstrated efficacy in patients with high DLL3 expression.2 The objective response rate was 40% (95% CI: 24.6-57.7) in patients with high DLL3 expression compared to 3.3% (95% CI: 0.6-16.7) in patients with low DLL3 expression.2 The median duration of response was 7.9 months (95% CI: 6.2-not calculable [NC]) in patients with high DLL3 expression compared to 2.8 months (95% CI: NC-NC) in patients with low DLL3 expression.2 The disease control rate was 66.7% (95% CI: 48.8-80.8) in patients with high DLL3 expression compared to 26.7% (95% CI: 14.2-44.4) in patients with low DLL3 expression.2 Most treatment-related adverse events (AEs) were mild to moderate in both groups. Grade ≥3 treatment-related AEs occurred in 23.3% of patients with high DLL3 expression and 20% of those with low DLL3 expression.2 "Neuroendocrine carcinomas are a relatively rare form of cancer that are unfortunately often diagnosed at advanced stages, leading to poor outcomes for patients due to both the nature of the disease and the lack of standard of care, with limited treatment options," said Dr. Jonathan Strosberg, Professor and Medical Oncologist, Neuroendocrine Tumor Division & Department of Gastrointestinal Oncology Research Program, Moffitt Cancer Center. "DLL3 is highly expressed in neuroendocrine carcinomas, making DLL3 an important biomarker in precision medicine. Findings from this study, including a 40% objective response rate, underscore the potential of obrixtamig to produce an effective and durable response in patients with high DLL3 expression, and offer a targeted approach to treating this cancer." An ongoing Phase II DAREON®-5 trial (NCT04429087) is assessing obrixtamig in patients with relapsed/refractory DLL3-high extrapulmonary neuroendocrine carcinomas.2 Additionally, new clinical data from two early-stage trials evaluating BI 765063 and BI 770371 will be presented, strengthening Boehringer's partnership with OSE Immunotherapeutics. Presentations at ASCO 2025 from Boehringer Ingelheim's innovative pipeline highlight vision of transforming cancer care: About non-small cell lung cancer (NSCLC) Lung cancer claims more lives than any other cancer type3 and the incidence is set to increase to over 3 million cases worldwide by 2040.4 NSCLC is the most common type of lung cancer.5 The condition is often diagnosed at a late stage,6 and fewer than 3 in 10 patients are alive five years after diagnosis.7 People living with advanced NSCLC can experience a detrimental physical, psychological, and emotional impact on their daily lives. There remains a high unmet need for additional treatment options for people living with advanced NSCLC. Up to 4% of lung cancers are driven by HER2 mutations (or gene alterations).8 Mutations in HER2 can lead to overexpression and overactivation, which can in turn result in uncontrolled cell production, inhibition of cell death and promotion of tumor growth and spread.9 About zongertinib Zongertinib is an investigational irreversible tyrosine kinase inhibitor (TKI) that selectively inhibits HER2 while sparing wild-type EGFR, thereby limiting associated toxicities. This orally administered, targeted therapy was granted FDA Fast Track Designation in 2023, followed by Breakthrough Therapy Designation in the U.S. and China for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 mutations and who have received prior systemic therapy. An application for accelerated approval was granted Priority Review status by the FDA in February 2025. In addition, Japan's Pharmaceuticals and Medical Devices Agency granted Orphan Drug Designation to zongertinib. A recent study has shown pre-clinically that the investigational compound zongertinib has potential for further clinical study in HER2 dependent solid cancers as monotherapy and as concurrent treatment with ADC therapy. In addition, zongertinib is being evaluated in Beamion LUNG-2 (NCT06151574)4, a global Phase III trial, compared to standard of care as first-line treatment in patients with unresectable, locally advanced or metastatic NSCLC who have activating HER2 TKD mutations. About the Beamion clinical trial program Beamion LUNG-1 (NCT04886804) is an open-label, Phase I dose escalation trial, with dose confirmation and expansion of zongertinib as monotherapy in people with advanced or metastatic solid tumors and NSCLC with activating HER2 alterations. The study has 2 parts. The first part is open to adults with different types of advanced cancer (solid tumors with changes in the HER2 gene) for whom previous treatment was not successful. The second part is open to people with advanced non-small cell lung cancer with a specific mutation in the HER2 gene. Beamion LUNG-2 is a Phase III, open label, randomized, active-controlled study in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring HER2 TKD mutations to evaluate zongertinib compared with standard of care. About obrixtamig Obrixtamig is an investigational novel Immunoglobin G (IgG)-like bispecific T-cell engager designed to bind concomitantly to DLL3 on tumor cells and CD3 on T-cells.10 By creating a physical link between T-cells and tumor cells, the T-cell engager could potentially activate T-cells against DLL3-expressing tumor cells, potentially resulting in their destruction by the body's own immune system. Activated T-cells could indirectly stimulate other immune cells to broaden the immune response against the tumor tissue. NCT04429087 is a Phase I trial evaluating obrixtamig in patients whose tumors are positive for DLL3. The aim of the study is to determine the highest dose of obrixtamig that can be tolerated by patients before reaching the maximum tolerated dose. The study also aims to assess the side effects of obrixtamig to evaluate early evidence of antitumor activity. In addition, obrixtamig is being evaluated in additional tumor types, including an ongoing Phase II trial (DAREON®-5) in patients with relapsed/refractory DLL3-high epNECs. About extrapulmonary neuroendocrine carcinomas Extrapulmonary neuroendocrine carcinomas (epNECs) are rare, aggressive cancers arising outside the lungs, from neuroendocrine cells present in various organs such as the gastrointestinal tract, pancreas, and others.11 Delta-like ligand 3 (DLL3) is a protein that is expressed specifically on the surface of up 77% of NECs. In normal tissue, DLL3 is minimally expressed, which makes it an ideal therapeutic target. These cancers are often diagnosed at an advanced stage, leading to poor survival rates. Like other aggressive cancers, epNECs can significantly impact patients' physical, psychological, and emotional well-being.12 There remains a high unmet need for effective treatment options for individuals with advanced epNECs. Research is ongoing to identify molecular targets and develop new therapies.13 About Boehringer Ingelheim in Oncology We have a clear aspiration – to transform the lives of people with cancer by delivering meaningful advances, with the ultimate goal of curing a range of cancers. Boehringer Ingelheim's generational commitment to driving scientific innovation is reflected by the company's robust pipeline of cancer cell-directed and immuno-oncology investigational therapies, as well as the smart combination of these approaches. Boehringer's ambition in oncology is to take a diligent and broad approach, creating a collaborative research network to tap into a diversity of minds, which is vital in addressing some of the most challenging, but potentially most impactful, areas of cancer research. Simply put, for Boehringer Ingelheim, cancer care is personal, today and for generations. About Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry's top investors in Research and Development, the company focuses on developing innovative therapies in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. Learn more at . 1Sabari JK, Ruiter G, Nadal E, et al. Patient-reported outcomes evaluating physical functioning and symptoms in patients with pretreated HER2-mutant advanced non-small cell lung cancer (NSCLC) – results from the Beamion LUNG-1 trial. Presented at: 2025 American Society of Clinical Oncology (ASCO) Annual Meeting; Chicago, IL. 2Capdevila J. Efficacy and safety of the DLL3/CD3 T-cell engager obrixtamig in patients with extrapulmonary neuroendocrine carcinomas with high or low DLL3 expression: results from an ongoing phase I trial . The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Published online 2025. 3World Health Organization Cancer Factsheet. (Accessed April 2025). 4International Agency for Research on Cancer – World Health Organization. Rates of trachea, bronchus and lung cancer. Available at: (Accessed August 2024). 5Zappa C & Mousa Non-small cell lung cancer: current treatment and future advances, Transl Lung Cancer Res. 2016 Jun; 5(3): 288–300. 6Polanco D et al. Prognostic value of symptoms at lung cancer diagnosis: a three-year observational study. J Thorac Dis 2021;13:1485–1494 7National Cancer Institute Surveillance, Epidemiology, and End Results (SEER). (Accessed: August 2024). 8Arcila, M. E. et al. Prevalence, clinicopathologic associations, and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin. cancer Res. an Off. J. Am. Assoc. Cancer Res. 18, 4910–4918 (2012). 9Galogre M, et al. A review of HER2 overexpression and somatic mutations in cancers, Critical Reviews in Oncology/Hematology, Volume 186, 2023, 103997. 10Hallet, J. et. al. 2015 Feb 15;121(4):589-97. doi: 10.1002/cncr.29099. Epub 2014 Oct 11Liu Y, Li X, Zhang Y, et al. A novel approach to cancer therapy: targeting the tumor microenvironment. Cancer Res. 2024;84(2):123-134. doi:10.1158/0008-5472.CAN-23-4567. 12Pellegrini CA, Bodei L, Papi M, et al. Impact of neuroendocrine tumors on patients' personal and work lives. J Global Oncol. 2015;1(1):37-42. doi:10.1200/JGO.2015.002980. 13Muğlu H, Sünger E, Mıldanoğlu MM, Engin Delipoyraz E, Yücel MH, Özçelik H, Hamdard J, Açıkgöz Ö, Ölmez ÖF, Yıldız Ö, et al. Clinicopathological Characteristics of Extrapulmonary Neuroendocrine Carcinomas: Treatment Responses and Survival Outcomes: Single-Center Experience. Journal of Clinical Medicine. 2025;14(7):2264. doi:10.3390/jcm14072264. SOURCE Boehringer Ingelheim WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED