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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

CHICAGO, Nov. 22, 2023 /PRNewswire/ -- People with long COVID exhibit patterns of changes in the brain that are different from fully recovered COVID-19 patients, according to research being presented next week at the annual meeting of the Radiological Society of North America (RSNA). "To the best of our knowledge, this is the first study comparing patients with long COVID to both a group without history of COVID-19 and a group that went through a COVID-19 infection but is subjectively unimpaired," said one of the study's lead authors, Alexander Rau, M.D., resident in the Departments of Neuroradiology and Diagnostic and Interventional Radiology at University Hospital Freiburg in Freiburg, Germany. After infection with COVID-19, as many as 10-25% of patients may develop a post-COVID condition commonly referred to as "long COVID." People with long COVID may experience a wide variety of symptoms, including difficulty concentrating ("brain fog"), change in sense of smell or taste, fatigue, joint or muscle pain, shortness of breath, digestive symptoms, and more. These symptoms may persist for weeks, months, or—as is only now becoming apparent—years after COVID-19 infection. However, the basis of this condition is poorly understood. Diffusion microstructure imaging (DMI), a novel MRI technique, is a promising approach to fill this gap. DMI looks at the movement of water molecules in tissues. By studying how water molecules move in different directions and at various speeds, DMI can provide detailed information on the microstructure of the brain. It can detect even very small changes in the brain, not detectable with conventional MRI. For this prospective, cross-sectional study, Dr. Rau and colleagues compared MRI brain scans of three groups: 89 patients with long COVID, 38 patients that had contracted COVID-19 but did not report any subjective long-term symptoms, and 46 healthy controls with no history of COVID-19. The researchers first compared the cerebral macrostructure of these three groups to test for atrophy or any other abnormalities. Next, they used DMI to gain a deeper insight into the brain. The three groups were compared to reveal group differences in the brain's microstructure. DMI parameters were read for the gray matter in the brain. Additionally, whole brain analyses were employed to reveal the spatial distribution of alterations and associations with clinical data, including long-COVID symptoms like fatigue, cognitive impairment or impaired sense of smell. The results showed no brain volume loss or any other lesions that might explain the symptoms of long COVID. However, COVID-19 infection induced a specific pattern of microstructural changes in various brain regions, and this pattern differed between those who had long COVID and those who did not. "This study allows for an in vivo insight on the impact of COVID-19 on the brain," Dr. Rau said. "Here, we noted gray matter alterations in both patients with long-COVID and those unimpaired after a COVID-19 infection. Interestingly, we not only noted widespread microstructural alterations in patients with long COVID, but also in those unimpaired after having contracted COVID-19." The findings also revealed a correlation between microstructural changes and symptom-specific brain networks associated with impaired cognition, sense of smell and fatigue. "Expression of post-COVID symptoms was associated with specific affected cerebral networks, suggesting a pathophysiological basis of this syndrome" Dr. Rau said. The researchers hope to reexamine the patients in the future, recording both clinical symptoms and changes to the brain's microstructure. Despite these brain imaging findings, it remains unclear why some people develop long COVID while others do not, although previous studies have identified risk factors including female sex, older age, higher body mass index, smoking, preexisting comorbidities, and previous hospitalization or intensive care unit admission. Co-authors are Jonas A. Hosp, M.D., Nils Schroter, M.D., Marco Reisert, Ph.D., Horst Urbach, M.D., Cornelius Weiller, M.D., and Elias Kellner, Ph.D. Note: Copies of RSNA 2023 news releases and electronic images will be available online at RSNA.org/press23. RSNA is an association of radiologists, radiation oncologists, medical physicists and related scientists promoting excellence in patient care and health care delivery through education, research and technologic innovation. The Society is based in Oak Brook, Illinois. (RSNA.org) Editor's note: The data in these releases may differ from those in the published abstract and those actually presented at the meeting, as researchers continue to update their data right up until the meeting. To ensure you are using the most up-to-date information, please call the RSNA Newsroom at 1-312-791-6610. For patient-friendly information on brain MRI, visit RadiologyInfo.org. SOURCE Radiological Society of North America (RSNA)