Brigimadlin

RIDGEFIELD, Conn., Aug. 27, 2024 /PRNewswire/ -- Data from the Phase Ib Beamion LUNG-1 trial selected for late-breaking oral presentation in the Presidential Symposium at WCLC on Monday, September 9. The U.S. FDA and China's CDE have granted zongertinib Breakthrough Therapy Designation for patients with HER2-mutated NSCLC and who have received prior systemic therapy. Phase I trial data of a novel DLL3-targeting T-Cell Engager, which has already secured FDA Fast Track as well as FDA and EMA Orphan Drug Designations, will also be presented. At the IASLC 2024 World Conference on Lung Cancer (WCLC) Boehringer Ingelheim will present encouraging data from across its oncology pipeline, illustrating its aspiration to transform the lives of people with cancer by delivering meaningful advances. Carinne Brouillon, Head of Human Pharma at Boehringer said: "Every year, about 40,000 people worldwide are diagnosed with non-small cell lung cancer (NSCLC) with a HER2 mutation.i While targeted therapy is available for some cancers driven by HER2, people living with HER2-mutated NSCLC have few options. We are proud to be sharing new data evaluating our investigational zongertinib in this hard-to-treat setting. Our strong oncology pipeline underscores our strategic approach in advancing novel targeted treatments and cancer cell-directed therapies that have a potential to transform lives for generations of patients." Late-breaking results from the Beamion LUNG-1 trial, which is a Phase Ia/b trial evaluating the safety and efficacy of zongertinib (BI 1810631), a HER2-specific tyrosine kinase inhibitor (TKI), will be presented at WCLC. This includes new data from a primary analysis of the first Cohort of Phase Ib in pre-treated patients with HER2m+ NSCLC to be presented in a Presidential Symposium on Monday, September 9, from 8:30AM - 10:00AM PDT (Location: Plenary Hall) and featured in the official WCLC Press Program. Highlighting the potential of zongertinib, the investigational oral therapy was recently granted Breakthrough Therapy Designation by the U.S. FDA and China's CDE for the treatment of adult patients with advanced, unresectable or metastatic NSCLC whose tumors have activating HER2 mutations, and who have received a prior systemic therapy. Investigating the potential of DLL3 targeted immunotherapy to transform the treatment of neuroendocrine carcinomas Exploring the promise of DLL3-targeted immunotherapy in transforming the treatment of neuroendocrine carcinomas, Boehringer will present data from the Phase I trial of its novel DLL3-targeting T-Cell Engager, BI 764532 in an Oral Presentation on Monday, September 9, from 2:22 PM-2:32 PM PDT (Location: 20A). This investigational treatment, which has been granted FDA Fast Track as well as FDA and EMA Orphan Drug Designations, is currently being evaluated in patients with large-cell neuroendocrine carcinoma of the lung (LCNEC-L), small cell lung cancer (SCLC) and extrapulmonary neuroendocrine cancer (epNEC). BI 764532 is designed to redirect T-cells to target tumors that express the DLL3 protein. In addition to the five abstracts to be presented at WCLC, Boehringer will also host a symposium titled "Emerging Therapies in Clinical Practice: What are the Patient Perspectives on the Future of Lung Cancer Treatment?" on Saturday, September 7, from 3:45PM to 4:45PM PDT (Location: 30DE). At Boehringer, cancer care is personal, which is why this event will explore patient viewpoints and expectations regarding the evolving landscape of lung cancer therapy. Data from Boehringer's oncology pipeline to be presented at WCLC: About non-small cell lung cancer (NSCLC) Lung cancer claims more lives than any other cancer type and the incidence is set to increase to over 3 million cases worldwide by 2040.ii NSCLC is the most common type of lung cancer.iii The condition is often diagnosed at a late stage,iv and fewer than 3 in 10 patients are alive five years after diagnosis.v 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. Around 4.7% of lung cancers are driven by HER2 mutations (or gene alterations).i,vi About zongertinib Zongertinib (also known as BI 1810631) is an investigational oral HER2-specific tyrosine kinase inhibitor (TKI) that is highly selective and being developed as a potential treatment for non-small cell lung cancer (NSCLC). Zongertinib was granted FDA Fast Track Designation in 2023, then in 2024 it was granted Breakthrough Therapy Designation by the U.S. FDA and China CDE for the treatment of adult patients with advanced NSCLC whose tumors have activating HER2 mutations, and who have received a prior systemic therapy. HER2 is a member of the ErbB family of receptor tyrosine kinases (enzymes that act like chemical messengers). 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. Read more here. About BI 764532 BI 764532 is an investigational DLL3/CD3 IgG-like T-Cell Engager under development as a potential new targeted immunotherapy for patients with large-cell neuroendocrine carcinoma of the lung (LCNEC-L), small cell lung cancer (SCLC) & extrapulmonary neuroendocrine cancer (epNEC). The therapy is designed to directly redirect T-cells, potentially resulting in the selective killing of tumor cells by the body's own immune system. Pre-clinical in-vivo data suggests administration of DLL3/CD3 bispecific T-cell engager (ITE) monotherapy induces T-cell infiltration into tumor tissues, transforming a non-inflamed (cold) tumor microenvironment into an inflamed (hot) state. This process triggers tumor cell apoptosis, resulting in significant tumor regression. BI 764532 has been granted FDA Fast Track as well as FDA and EMA Orphan Drug Designations. Read more here. About brigimadlin Brigimadlin (also known as BI 907828) is an investigational oral MDM2-p53 antagonist being developed as a potential treatment for certain types of cancer. The small molecule compound may inhibit the interaction between MDM2 and p53, restoring p53 wild type function. Inactivation of the tumor suppressor protein p53 is a central mechanism by which cancer cells drive tumor growth. Increased levels of the protein MDM2, a key negative regulator of p53, is a well-characterized inactivation mechanism, seen in about 5-7% of all cancer cases. 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. Read more here. 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. Lean more at boehringer-ingelheim.com/us. i Chia, P. et al. Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors. Clinical Epidemiology. . ii International Agency for Research on Cancer – World Health Organization. Rates of trachea, bronchus and lung cancer. Available at: (Accessed August 2024). iii Zappa C & Mousa Non-small cell lung cancer: current treatment and future advances, Transl Lung Cancer Res. 2016 Jun; 5(3): 288–300. iv Polanco D et al. Prognostic value of symptoms at lung cancer diagnosis: a three-year observational study. J Thorac Dis 2021;13:1485–1494 v National Cancer Institute Surveillance, Epidemiology, and End Results (SEER). (Accessed: August 2024). vi Arcila, 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). MPR-US-103284 8/24 SOURCE Boehringer Ingelheim

On July 29, Boehringer Ingelheim announced a major acquisition, with plans to buy Nerio Therapeutics for $1.3 billion. Nerio Therapeutics, a pharmaceutical company focused on phosphatase research, has successfully developed highly selective phosphatase PTPN2/N1 inhibitors for an innovative regimen of tumor immunotherapy. With a leading position in the global oncology market, Boehringer Ingelheim has continuously strengthened its strategic presence in oncology in recent years. According to preliminary statistics, the company has established cooperative relationships with a number of well-known pharmaceutical companies in recent years to accelerate the construction of tumor research and development pipelines: In December 2020, Boehringer Ingelheim acquired NBE Therapeutics for 1.18 billion euros to acquire novel antibody-coupled drugs to address the challenge of refractory solid tumors. In the same month, Boehringer Ingelheim acquired Labor Dr. Merk & Kollegen to increase its research and development and clinical manufacturing capabilities to support its next generation cancer immune drug development program. In January 2021, the company entered into a strategic partnership with Enara Bio to develop innovative cancer immunotherapies using its Dark Antigen™ platform. In September 2021, Boehringer Ingelheim acquired Abexxa Biologics to gain expertise in targeting cancer-specific proteins within cells, expanding the range of potential cancer antigen targets. In June 2022, the company entered into A global licensing agreement with the Agency for Science, Technology and Research of Singapore (A*STAR) to acquire the development and commercialization rights for A*STAR's series of innovative tumor-specific antibodies. In January 2023, Boehringer Ingelheim and 3T Biosciences entered into a strategic collaboration and licensing agreement to jointly explore and develop the next generation of cancer therapies. In March 2023, the company partnered with Covant Therapeutics to develop a covalent drug candidate for the ADAR1 cancer target. In November 2023, Boehringer Ingelheim acquired T3 Pharmaceuticals for CHF 450 million (approximately $508 million), which specializes in innovative therapeutic platforms that enhance immunotherapy with live bacteria. In the same month, Boehringer Ingelheim established a strategic collaboration and licensing agreement with Phenomic AI to jointly discover key targets in rich stromal cancers. In February 2024, Boehringer Ingelheim and CBmed entered into a long-term strategic partnership to accelerate the development of first-of-its-kind oncology drugs using translational medicine to improve the lives of patients. In May 2024, Boehringer Ingelheim and OSE expanded their collaboration to jointly develop first-of-its-kind therapies for tumor and cardio-renal metabolic diseases, including the anti-SIRRP α tumor Immunity program and the cis targeted anti-PD1 / cytokine platform. While Boehringer Ingelheim does not yet have a significant oncology product in the market, its oncology pipeline includes several promising candidates, such as Zongertinib(Phase 1), Brigimadlin (Phase two-thirds) and BI-764532 (Phase 2). Zongertinib is an innovative covalently bound, orally effective and selective HER2 small molecule inhibitor. It covalently binds to the tyrosine kinase domain (TKD) of both wild-type and mutant HER2 receptors, including exon 20 mutations, while preserving the wild-type signal of EGFR, thereby demonstrating good tolerability and safety while ensuring efficacy. Data from the Phase 1a/1b clinical study of Zongertinib monotherapy for HER2-variant advanced solid tumors (NCT04886804), presented at the ASCO meeting in 2024, showed that Zongertinib demonstrated superior efficacy and was well tolerated in patients with HER2-mutation-positive advanced NSCLC. Brigimadlin is a mouse dual microhomologous gene 2 (MDM2) -p53 antagonist targeting MDM2-amplified tumors such as biliary adenocarcinoma, non-small cell lung cancer, and pancreatic cancer. Currently, Brigimadlin's first-line treatment of dedifferentiated liposarcoma (DDLPS) has entered phase 2/3 of clinical trials. New results from the Phase 1a/1b study (NCT03449381) presented at the ASCO Meeting in 2024 show that Brigimadlin induces proteomic changes in DDLPS that may serve as potential biomarkers for predicting treatment response and adverse events. BI 764532 is a first-in-class T cell-mediated bisspecific antibody developed at Boehringer Ingelheim that induces a patient's own T cells to attack cancer cells expressing DLL3. BI 764532 has received fast track approval from the FDA for the treatment of advanced SCLC and advanced or metastatic extrapulmonary neuroendocrine carcinoma. In both DLL3-positive cell and xenograft models, BI 764532 showed potential preclinical antitumor activity. PTPN2 and PTPN1 (also known as PTP-1B) are phosphatases that negatively regulate multiple cytokine signaling pathways and T cell receptor (TCR) signaling pathways. They inhibit inflammation by dephosphorylation of JAK and STAT family members, and reduce T-cell sensitivity to antigens by phosphorylation of LCK and FYN. PTPN2 deletion was found to increase the number of activated cytotoxic CD8+T cells in the tumor, improve antigen presentation and sensitivity to IFNγ, and thus enhance tumor sensitivity to CD8+T cells. Given the critical role of PTPN2/N1 in tumor and immune cells and its highly conserved active sites, researchers are developing PTPN2/N1 inhibitors. Currently, there are several PTPN2/N1 inhibitors, such as ABBV-CLS-579 and ABBV-CLS-484 (AC484). AC484 is an oral PTPN2/N1 active site inhibitor that enhances the response to interferon and promotes the activation and function of immune cell subsets. In a PD-1-resistant mouse model, AC484 monotherapy showed significant antitumor effects. Currently, a Phase 1 clinical trial of AC484 is underway to evaluate its efficacy alone or in combination with PD-1 inhibitors or VEGFR tyrosine kinase inhibitors (TKI) in the treatment of advanced or metastatic solid tumors. In addition, using Chemistry42, its generating-AI platform, Insili has also developed a novel PTPN2/N1 inhibitor that has drug-like properties, good oral bioavailability in vivo, and strong in vivo anti-tumor activity, demonstrating nanoscale inhibitory efficacy.