Survodutide

Milestones reached in cardiovascular, renal, metabolic health (CRM), and oncologyFurther data read-outs expected in 2024 in oncology, mental health, and pulmonary fibrosisStrong first half net sales growth of 7.4%* year on year Boehringer Ingelheim, a leading research-driven biopharmaceutical company, reported on Thursday significant progress in its pipeline across key therapeutic areas as it reached major milestones in the first half of the year. “We are stepping up our investments in R&D beyond our plans announced in April,” said Hubertus von Baumbach, Chairman of the Board of Managing Directors. “The data read-outs that we received in MASH and will receive for oncology, mental health, and pulmonary fibrosis give us reason to accelerate our launch preparedness for these late-stage assets. We are pleased to see our pipeline developing at such pace.” Boehringer advanced its pipeline across clinical phases with five new phase I, II, or III initiations in cardiometabolic diseases, mental health, and oncology, and achieved two additional fast track designations for programs in inflammation. At the same time, the company announced nine R&D partnership agreements, significantly bolstering its human pharma portfolio across all therapeutic areas and tech platforms. “As our pipelines continue to expand, both in depth and breadth, we need to apply a rigorous focus where we allocate our resources,” said Frank Hübler, Member of the Board of Managing Directors with responsibility for Finance. “We want to accelerate our pipeline where we can, to deliver innovative medicines to patients ever faster.” Net sales rose by 7.4%* year-on-year to EUR 12.9 billion in the first six months of 2024, driven by ongoing high patient demand for Boehringer’s medications, especially for the JARDIANCE® product family and OFEV® in Human Pharma, and NEXGARD® in Animal Health. Human Pharma As Boehringer prepares for its future portfolio and ongoing and upcoming launches, the past months were marked by developments across all focus therapy areas. For the remainder of the year, more news is expected across the portfolio with data read-outs in oncology (Zongertinib), mental health (Iclepertin) and pulmonary fibrosis (Nerandomilast). The company’s efforts to advance holistic cardiovascular, renal and metabolic (CRM) health met some major milestones. Positive Phase II data for survodutide in metabolic dysfunction-associated steatohepatitis (MASH) showed groundbreaking results in liver disease due to MASH, with 83.0% of adults treated with survodutide achieving significant improvements versus 18.2% for placebo (response difference: 64.8%; CI 51.1%-78.6%, p<0.0001). Also, a sub analysis demonstrated that up to 64.5% of adults with fibrosis stages F2 and F3 (moderate to advanced scarring) achieved an improvement in fibrosis without worsening of MASH vs placebo, 25.9% [response difference: 38.6% (95% CI 18.1% - 59.1%), p=0.0005].1 The company initiated a Phase III trial in chronic heart failure for its novel selective aldosterone synthase inhibitor (ASi) in combination with empagliflozin. In an upcoming Phase III trial in chronic kidney disease for ASi, Boehringer will collaborate with Oxford Population Health. Boehringer has joined a multi-year sponsorship of the American Heart Association's Cardiovascular-Kidney-Metabolic Health Initiative. The initiative, which was announced recently, will allow the company to better understand the burden of people affected by diseases in these interconnected areas and enable better care. Boehringer is committed to re-entering oncology with targeted investments. Phase Ia/Ib trial of Zongertinib, a HER2-specific tyrosine kinase inhibitor in patients with HER2 aberration-positive solid tumors, showed that Zongertinib was well tolerated and demonstrated promising efficacy. 2 The Brightline-1 trial investigating Brigimadlin in dedifferentiated liposarcoma did not meet its primary endpoint, though the benefit-risk assessment remains positive. Data for both oncology trials will be presented at conferences in the coming months. In the first six months of 2024, the Human Pharma business grew by 9.3%* year on year. Net sales stood at EUR 10.3 billion. Growth was driven primarily by the JARDIANCE® family and OFEV®. To meet growing demand, the company continues high investments in its production and supply network. In January, Boehringer announced a further expansion and upgrade of its plant in Koropi, Greece. With an investment of EUR 120 million, the company will increase the manufacturing capacity of new and existing medications, some of them in the late-stage development. Animal Health In livestock, the VAXXITEK® portfolio of poultry vaccines continues to expand and grew by 15.9%*. The company launched BULTAVO 3™, a new vaccine that protects cattle and sheep against bluetongue virus serotype 3 (BTV-3). It is the first BTV-3 vaccine that prevents clinical signs and mortality. BULTAVO 3™ has been licensed for emergency use in the Netherlands, Belgium, and Germany. Recent outbreaks of BTV-3 in the three countries caused severe losses for farmers and are threatening neighboring countries. In the Animal Health business, growth was slower than expected in the first six months, with sales up 0.9%* compared to the same period last year to EUR 2.5 billion. This was primarily due to lower-than-expected sales in the U.S. pet business and challenging market conditions in China, especially impacting the swine vaccine business. Most other markets delivered solid growth. With the recent launches of NEXGARD® PLUS for dogs and NEXGARD® COMBO for cats, sales of the NEXGARD® parasiticides brands grew by 15.9%*. FRONTPRO®, the first approved over-the-counter chewable tablet against ticks and fleas for dogs, is now available in most countries in Europe and continues to drive growth in the region. In pet therapeutics, sales of VETMEDIN®, indicated for use in dogs with congestive heart failure, grew by 16.1%*. Pipeline Outlook Looking ahead, the company aims for up to 25 new treatment launches in Human Pharma until 2030. In Animal Health, 20 additional launches are expected across markets until 2026, including product updates, indication expansion and new products. 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 www.boehringer-ingelheim.com. * currency-adjusted 1 Sanyal, Arun J. "Glucagon and GLP-1 receptor dual agonist survodutide improved liver histology in people with MASH and fibrosis: Results from a randomized, double-blind, placebo-controlled phase 2 trial”. Oral presentation at European Association for the Study of the Liver Congress, Milan, Italy. 7June 2024. Abstract #LB117, presentation #GS-006. 2 Heymach, John. "Phase Ia/Ib trial of zongertinib (BI 1810631), a HER2-specific tyrosine kinase inhibitor in patients with HER2 aberration-positive solid tumors: updated Phase Ia data from Beamion LUNG-1, including progression-free survival data”. Oral presentation at American Society of Clinical Oncology, United States, Chicago. 1 June 2024. Abstract #8514 Attachment Boehringer_Workplace_Lab_Research

Boehringer Ingelheim and partner Gubra on Monday launched a Phase I study of experimental obesity treatment BI 3034701, the second weight-loss candidate from the partners to enter the clinic. In the announcement, BI 3034701 is described as a “long-acting triple agonist peptide” with first-in-class potential. The German drugmaker did not respond to an inquiry regarding whether the candidate acts on the same three receptors as Eli Lilly’s weight-loss therapy retatrutide, commonly referred to as a “triple G” agonist because it targets GLP-1, GIP, and glucagon. Last year, retatrutide set the triple agonism standard by demonstrating an average weight loss of about 24% in a Phase II trial.Weight loss pipelineThe Phase I study of BI 3034701 is expected to enrol 124 participants and will be divided into two parts. The first half will recruit healthy men between the ages of 18 and 55 to establish the candidate’s safety, and the second portion will administer several subcutaneous doses of the experimental treatment to individuals between 18 and 65 years old with overweight or obesity who are otherwise healthy.The trial is expected to wrap up in the second half of 2025.The study launch triggered an undisclosed milestone payment to Gubra, who has now helped bring two obesity candidates to the clinic with Boehringer. Last year, the partners kicked off a Phase I study of BI 1820237, a long-acting NPY2 agonist.Boehringer’s most advanced weight loss hopeful is survodutide, a glucagon/GLP-1 receptor dual agonist it’s co-developing with Zealand. While Phase II data released last year showed that the candidate achieved about 19% weight loss in patients at 46 weeks, nearly a quarter of participants who received the investigational treatment dropped out due to gastrointestinal adverse events. For more analysis, see ADA23: Tolerability clouds Boehringer, Zealand Pharma's obesity ambitions for survodutide.Despite the tolerability concerns, the pair moved survodutide into a Phase III trial last August. The candidate is also in Phase III testing for metabolic dysfunction-associated steatohepatitis (MASH).