BI-764524

Boehringer Ingelheim today presented positive data from the HORNBILL Phase I/IIa study of BI 764524, the first ever study exploring a potential treatment for people living with diabetic macular ischemia (DMI). The study found that BI 764524 was well tolerated following intravitreal administration of single and multiple doses, meeting its primary safety endpoints and showed early signs of potential efficacy.1­ DMI is a common, irreversible complication of diabetic retinopathy (DR) that may lead to blindness.12,3,4­ It can develop when the light sensitive tissues of the central retina do not receive adequate blood supply over a longer time. There are currently no approved treatments for DMI. The current standard of care for advanced DR includes intravitreal anti-VEGF treatment or invasive laser treatment. However, some patients’ conditions progress despite this treatment.5 BI 764524 uses a novel mode of action by inhibiting the Sema3A pathway to re-vascularize ischemic areas and potentially overcome the limitations of anti-VEGF and laser treatments.1 “The results from the HORNBILL study are really encouraging. They suggest there may be a pathway for earlier intervention that could decrease the risk of, and maybe even prevent, people with diabetic retinopathy from developing irreversible and vision-threatening complications, such as DMI,” said Quan Dong Nguyen, MD, MSc, FARVO, FASRS, Professor of Ophthalmology at the Byers Eye Institute, Professor of Medicine and of Pediatrics at Stanford School of Medicine, and Principal and Coordinating Investigator of the trial. “Retinal non-perfusion is a key driver of vision loss in people living with diabetic retinopathy. However, until the HORNBILL study, retinal non-perfusion has not been explored as a potential treatment target.” “Vision loss associated with retinal conditions such as diabetic retinopathy and DMI has a devastating impact on quality of life. Today’s results are an important step towards achieving our aspiration of developing precision therapies delivering the right treatment for the right patient at the right time to prevent vision loss before irreversible damage occurs,” said Ulrike Graefe-Mody, Ph.D., Head of Retinal Health at Boehringer Ingelheim. “We’re looking forward to start a Phase IIb study to further explore the safety and efficacy of BI 764524.” HORNBILL is one of 23 abstracts being presented at the Association for Research in Vision and Ophthalmology (ARVO) Annual meeting 2024, spanning Boehringer Ingelheim’s retinal health portfolio, including other studies of retinal non-perfusion and diabetic retinopathy, geographic atrophy and neovascular age-related macular degeneration. About the HORNBILL study The HORNBILL study consisted of two parts (single rising dose (SRD), N=12 and multiple dose (MD), N=31) both of which met the primary safety endpoints of number of patients with dose-limiting adverse events (SRD) and treatment-related adverse events(MD).1 The study also met its pre-specified criterion for early efficacy of foveal avascular zone area stabilization versus sham at week 16 (p<0.2).1 This suggests that BI 764524 may positively impact retinal non-perfusion and potentially halt the progression of capillary loss.1 The upcoming CRIMSON trial, a Phase IIb trial, will assess safety and efficacy of BI 764524 in patients with DR further and start recruiting later this year. Notes to Editors: About the trial (NCT04424290) This Phase I/IIa trial assessed the tolerability of BI 764524 in people with diabetic retinopathy (DR) with diabetic macular ischemia (DMI) who have previously been treated with panretinal photocoagulation.1 The trial consisted of a single rising dose (SRD) part followed by a multiple dosing (MD) part, with BI 764524 administered via intravitreal injection.1 Single rising dose part In the non-randomized, open-label, SRD part, 12 patients received intravitreal BI 764524 doses: 0.5 (n=3), 1.0 (n=3), or 2.5 mg (n=6).1 The primary endpoint was the number of patients with dose-limiting events (DLEs); secondary endpoints were the number of patients with drug-related adverse events (AEs) and any ocular AEs.1 Patients in the SRD part had a mean age of 61.8 years.1 No DLEs were reported in the SRD part.1 There were five ocular AEs in four patients in the study eye, none related to the study drug. The highest tested dose (BI 764524 2.5 mg) was considered safe and applied in the MD part.1 Multiple dosing part In the randomized, masked, sham-controlled, MD part, 31 patients received three intravitreal doses of BI 764524 2.5 mg (n=21) or sham injection procedures (n=10) at 4-week intervals (baseline, week 4, and week 8), followed by 14 weeks of follow-up until the end of study at week 22.1 The primary endpoint was the number of patients with drug-related AEs; secondary endpoints included number of patients with ocular AEs, change from baseline in foveal avascular zone (FAZ) area, best corrected visual acuity (BCVA) and central retinal thickness (CRT).1 Patients in the MD part had a mean age of 59.5 years.1 There were seven patients with ocular AEs (study eye; three patients with four AEs for BI 764524, four patients with six AEs for sham), one of which was reported as related to the study drug (vitreous floater).1 In addition, there was one systemic AE (increase deemed related to the study drug by the investigator). There were no cases of intraocular inflammation or occlusive retinal vasculitis.1 At baseline, mean BCVA was 65.2 letters, mean FAZ area was 0.65 mm, and mean CRT was 252 mm.1 The HORNBILL study met its pre-specified criterion for early efficacy of FAZ area stabilization versus sham at week 16 (p<0.2). Over the short trial period, other secondary efficacy endpoints showed no relevant change. About BI 764524 BI 764524 is a humanized monoclonal anti-Sema3A antibody intended to re-vascularize ischemic areas and reduce leakage in the retina, offering the potential to address retinal non-perfusion in retinal diseases. The compound was discovered and developed by Boehringer Ingelheim and is part of its research and development portfolio in retinal conditions. About diabetic retinopathy and diabetic macular ischemia Diabetic retinopathy affects 1 in 3 people with diabetes and is the leading cause of vision loss in adults of working age. It is a growing epidemic that is expected to increase as the incidence of diabetes escalates across the globe. Diabetic macular ischemia (DMI) is a complication of diabetic retinopathy which can lead to slowly progressing, irreversible vision loss. 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 Boehringer Ingelheim’s 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. References 1 Nguyen QD, Jhaveri C, Habib MS. Oral presentation at the Association for Research in Vision and Ophthalmology (ARVO) 2024. Abstract number: 959 2 Marques IP, et al. Diabetes 2019;68:648–653 3 Sim DA, et al. Invest Ophthalmol Vis Sci 2013;54:2353–2360 4 Tey KY, et al. Eye Vis (Lond) 2019;6:37 5 Ip MS, et al. Ophthalmology 2014;122:367–374

The prevalence of diabetic retinopathy has been rising over the past few years, which prompts the growing demand for treatment options. The increasing prevalence of diabetic retinopathy and the growing research and development activities to develop novel therapies to treat diabetic retinopathy to drive the market. The companies developing the potential therapies in the last stage of development include Roche, Kodiak Sciences, Novartis, and several others. LAS VEGAS, May 29, 2023 /PRNewswire/ -- DelveInsight's ' Diabetic Retinopathy Pipeline Insight – 2023 ' report provides comprehensive global coverage of pipeline diabetic retinopathy therapies in various stages of clinical development, major pharmaceutical companies working to advance the pipeline space and future growth potential of the diabetic retinopathy pipeline domain. Key Takeaways from the Diabetic Retinopathy Pipeline Report DelveInsight's diabetic retinopathy pipeline report depicts a robust space with 50+ active players working to develop 55+ pipeline therapies for diabetic retinopathy treatment. Key diabetic retinopathy companies such as Kodiak Sciences, Novartis, Regenxbio Inc., OcuTerra Therapeutics, Ocular Therapeutix, Bayer, RemeGen, Roche, Ocuphire Pharma, Adverum Biotechnologies, Boehringer Ingelheim, Palatin Technologies, Valo Health, EyePoint Pharmaceuticals, Kubota Vision, MingSight Pharmaceuticals, Oxurion, Aerie Pharmaceuticals, AsclepiX Therapeutics, Ocugen, Ashvattha Therapeutics, Stealth BioTherapeutics, and others are evaluating new diabetic retinopathy drugs to improve the treatment landscape. Promising diabetic retinopathy pipeline therapies in various stages of development include KSI-301, Brolucizumab, RGX 314, OTT-166, OTX-TKI, Runcaciguat, RC 28 E, RG7774, APX3330, ADVM-022, Faricimab, BI 764524, PL8331, OPL-0401, EYP-1901, emixustat hydrochloride, MS-553, THR-149, AR-13503, AXT107, OCU200, D 4517.2, Elamipretide, and others. In May 2023, Oculic Holding AG announced positive top-line results from Stage 1 of its Phase III DIAMOND trial of OCS-01 eye drops in diabetic macular edema (DME). According to the company, the DIAMOND trial in diabetic macular edema with topical OCS-01 met its stage 1 objective of validating the loading and maintenance dosing regimen designed to optimize OCS-01 efficacy potential with robust statistical significance. In April 2023, Palatin Technologies announced The International Journal of Molecular Sciences published a manuscript, "Stimulating the Melanocortin System in Uveitis and Diabetes Preserves the Structure and Anti-Inflammatory Activity of the Retina" by Tat Fong Ng and Andrew W. Taylor from Department of Ophthalmology, Boston University Chobanian and Avedisian School of Medicine, in Boston, Massachusetts. The manuscript summarizes data demonstrating the effects of PL8331 in two mouse models of retinal disease, experimental autoimmune uveoretinitis (EAU) and diabetic retinopathy (DR). Palatin and the National Institute of Health (NIH) and the Massachusetts Lions Eye Research Foundation provided funding for the study. In February 2023, Ocugen announced that it had submitted an Investigational New Drug application (IND) with the US Food and Drug Administration (FDA) to initiate a Phase 1 clinical trial of OCU200, a fusion protein with a distinct mechanism of action (MOA), for the treatment of diabetic macular edema (DME). This regulatory milestone fulfills the Company's commitment to file the IND for OCU200 within the first quarter of 2023. In January 2023, Ocuphire Pharma announced topline efficacy and safety results from its ZETA-1 Phase II trial evaluating oral APX3330 for the treatment of diabetic retinopathy (DR). Oral APX3330 demonstrated favorable safety and tolerability allowing for a potential attractive non-invasive option for protection of vision in both eyes in DR patients. In May 2022, EyePoint Pharmaceuticals announced the EYP-1901 license to Betta Pharmaceuticals, to develop and commercialize EYP-1901 in China, Hong Kong, Macau, and Taiwan. EyePoint retains all rights for EYP-1901 in the rest of the world and expands its exclusive rights to local delivery of vorolanib for the treatment of all ophthalmic diseases, including diabetic macular edema (DME). Request a sample and discover the recent advances in diabetic retinopathy drug treatment @ Diabetic Retinopathy Pipeline Report The diabetic retinopathy pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage diabetic retinopathy drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the diabetic retinopathy clinical trial landscape. Diabetic Retinopathy Overview Diabetic retinopathy is a microvascular condition caused by diabetes mellitus's long-term effects. Diabetic retinopathy can cause vision-threatening retinal damage, eventually leading to blindness. It is found in one-third of patients with diabetes and is linked to an increased risk of life-threatening systemic vascular consequences such as stroke, coronary heart disease, and heart failure. Diabetic retinopathy affects an estimated 40% (8% for vision-threatening retinopathy) of people with type 2 diabetes and 86% (42%) of people with type 1 diabetes in the United States. The keys to avoiding diabetic retinopathy blindness are early detection and appropriate intervention. Several large studies have found that the onset of diabetic retinopathy does not usually occur within the first 5 years of type 1 diabetes diagnosis. In contrast, the onset of type 2 diabetes is frequently more subtle, and as a result, retinal damage may be evident at the time of diagnosis. As a result, screening for diabetic retinopathy is advised in type 2 diabetics at the time of diagnosis. Find out more about drugs for diabetic retinopathy @ New Diabetic Retinopathy Drugs A snapshot of the Diabetic Retinopathy Pipeline Drugs mentioned in the report: Learn more about the emerging diabetic retinopathy pipeline therapies @ Diabetic Retinopathy Clinical Trials Diabetic Retinopathy Therapeutics Assessment The diabetic retinopathy pipeline report proffers an integral view of diabetic retinopathy emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Diabetic Retinopathy Pipeline Report Coverage: Global Diabetic Retinopathy Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Diabetic Retinopathy Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Diabetic Retinopathy Therapeutics Assessment By Route of Administration: Oral, Intravenous, Subcutaneous, Parenteral, Topical Diabetic Retinopathy Therapeutics Assessment By Molecule Type: Recombinant fusion proteins, Small molecule, Monoclonal antibody, Peptide, Polymer, Gene therapy Diabetic Retinopathy Therapeutics Assessment By Mechanism of Action: Vascular endothelial growth factors inhibitors, Angiogenesis inhibitors, Vascular endothelial growth factor A inhibitors, Gene transference, Integrin alphaVbeta3 antagonists, Integrin alphaVbeta6 inhibitors, Integrin alphavbeta8 inhibitors, Platelet-derived growth factor beta receptor antagonists, Protein tyrosine kinase inhibitors, Proto oncogene protein c-kit inhibitors, Vascular endothelial growth factor receptor 3 antagonists, Vascular endothelial growth factor receptor-1 antagonists, Vascular endothelial growth factor receptor-2 antagonists, Guanylate cyclase stimulants, APEX1 protein inhibitors, DNA apurinic apyrimidinic site lyase inhibitors Key Diabetic Retinopathy Companies: Kodiak Sciences, Novartis, Regenxbio Inc., OcuTerra Therapeutics, Ocular Therapeutix, Bayer, RemeGen, Roche, Ocuphire Pharma, Adverum Biotechnologies, Boehringer Ingelheim, Palatin Technologies, Valo Health, EyePoint Pharmaceuticals, Kubota Vision, MingSight Pharmaceuticals, Oxurion, Aerie Pharmaceuticals, AsclepiX Therapeutics, Ocugen, Ashvattha Therapeutics, Stealth BioTherapeutics, and others. Key Diabetic Retinopathy Pipeline Therapies: KSI-301, Brolucizumab, RGX 314, OTT-166, OTX-TKI, Runcaciguat, RC 28 E, RG7774, APX3330, ADVM-022, Faricimab, BI 764524, PL8331, OPL-0401, EYP-1901, emixustat hydrochloride, MS-553, THR-149, AR-13503, AXT107, OCU200, D 4517.2, Elamipretide, and others. Dive deep into rich insights for new drugs for diabetic retinopathy treatment; visit @ Diabetic Retinopathy Medications Table of Contents For further information on the diabetic retinopathy pipeline therapeutics, reach out @ Diabetic Retinopathy Drug Treatment Related Reports Diabetic Retinopathy Market Diabetic Retinopathy Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key diabetic retinopathy companies, including Genentech, Inc., Regeneron Pharmaceuticals, Roche, Opthea Limited, Regenxbio, Kodiak Sciences Inc, Ocuphire Pharma, Eisai Co Ltd, Apexian Pharmaceuticals, Oculis, among others. Diabetic Retinopathy Epidemiology Forecast Diabetic Retinopathy Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and diabetic retinopathy epidemiology trends. Proliferative Diabetic Retinopathy Pipeline Proliferative Diabetic Retinopathy Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key proliferative diabetic retinopathy companies, including Kubota Vision, among others. Diabetic Neuropathy Pipeline Diabetic Neuropathy Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key diabetic neuropathy companies, including Goldfinch Bio, Novartis, Serodus, CURACLE, Daiichi Sankyo, NeuroBo Pharmaceuticals, Dong-A Pharmaceutical, among others. Diabetic Neuropathy Market Diabetic Neuropathy Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key diabetic neuropathy companies, including Goldfinch Bio, Novartis, Serodus, CURACLE, Daiichi Sankyo, NeuroBo Pharmaceuticals, Dong-A Pharmaceutical, among others. Related Healthcare Services Healthcare Consulting Healthcare Competitive Intelligence Services Healthcare Asset Prioritization Services About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . 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