BAY-2965501

Abstracts: ND04, 5047, CT276, 2116, 4035, 433, CT126, 1964, 925, CT228, 311, 5043, CT082 Berlin, April 11, 2023 – Bayer will present latest research across its oncology portfolio at the American Association for Cancer Research (AACR) 2023 Annual Meeting , taking place from April 14-19 in Orlando (FL), USA. Bayer is advancing its oncology R&D efforts in three scientific areas that have the potential to address unmet needs in cancer patients: next-generation Immuno-Oncology, Targeted Radionuclide Therapies and Precision Molecular Oncology. Data from all three areas of scientific focus will be showcased during this year’s meeting. Bayer is progressing novel research around its prostate cancer treatment darolutamide. The presentation highlights the synergistic anti-cancer effects of a PSMA (prostate-specific membrane antigen)-actinium-225 conjugate in combination with darolutamide in preclinical prostate cancer models. Darolutamide, which is jointly developed by Bayer and Orion Corporation, is an oral androgen receptor inhibitor indicated for the treatment of men with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease and for the treatment of men with metastatic hormone-sensitive prostate cancer (mHSPC). Bayer will present the first clinical Phase 1 results on aryl hydrocarbon receptor (AhR) inhibitor BAY 2416964, the company’s most advanced Immuno-Oncology program. A focus of the presentation will be on the target engagement results and pharmacokinetics from its ongoing monotherapy dose-escalation study to explore a potential optimal dose and schedule to effectively inhibit AhR. These results, along with a mathematical model-informed approach have supported the currently ongoing dose expansion for BAY 2416964. In the New Drugs on the Horizon session at AACR, Bayer will present preclinical data on its novel selective diacylglycerol kinase (DGK) zeta inhibitor BAY 2965501, which is under Phase 1 clinical evaluation. The enzyme DGKzeta is a lipid kinase that can down-modulate T-cell activation by catalyzing the conversion of diacylglycerol to phosphatidic acid, thus acting as a ligand-independent, intracellular immune checkpoint. An inhibition of DGKzeta has been demonstrated to enhance T-cell priming against suboptimal tumor antigens and has the potential to overcome multiple immune-suppressive mechanisms in the tumor microenvironment. Based on these data, a first-in-human trial with BAY 2965501 in patients with advanced solid tumors was initiated and is currently enrolling patients. Both small molecule inhibitors in Immuno-Oncology are being jointly developed in a strategic research alliance with the German Cancer Research Center (DKFZ) in Heidelberg, Germany. From its focus area Precision Molecular Oncology, Bayer will show new preclinical data on its mutEGFR/HER2 inhibitor, which was developed in collaboration with the Broad Institute of MIT and Harvard in Cambridge (MA), USA. BAY 2927088 is a reversible small molecule inhibitor that is currently being evaluated in a first-in-human, Phase 1 clinical trial in non-small cell lung cancer (NSCLC) patients with mutations in epidermal growth factor receptors (EGFR & HER2) including exon20 insertions and point mutations. For the first time, Bayer will present the design of the clinical trial and the preclinical activity profile of the inhibitor in human epidermal growth factor receptor 2 ( HER2) mutant NSCLC. Bayer will also report new data looking at larotrectinib, a highly selective and central nervous system (CNS)-active tropomyosin receptor kinase (TRK) inhibitor, approved for the treatment of patients with TRK fusion solid tumors, exploring the concordance between tissue and circulating tumor DNA (ctDNA) testing for neurotrophic tyrosine receptor kinase (NTRK) gene fusions from samples in larotrectinib clinical trials. Additional research to be presented from Bayer’s Targeted Alpha Therapy program evaluates the antitumor efficacy and potential benefit of the combination of radium-223 with 177Lu-PSMA-617 in a preclinical model of bone metastatic prostate cancer. The combination of radium-223 and 177Lu PSMA imaging and therapy (I&T) is currently being investigated in patients with metastatic castration-resistant prostate cancer (mCRPC) in a phase 1/2 trial (AlphaBet, NCT05383079). Key presentations on Bayer research to be presented at AACR 2023 are listed below: Oral presentation: BAY 2965501: A highly selective DGKzeta inhibitor for cancer immuno-therapy with first-in-class potential Abstract ND04, Session DDT001 – New Drugs on the Horizon: Part 1 Sunday, April 16, 2:05 PM – 2:20 PM (EDT), Tangerine Ballroom 2 (WF2) - Convention Center Poster presentations: PSMA-targeted actinium-225 conjugate (225Ac-pelgifatamab) potentiates the antitumor efficacy of darolutamide in hormone-dependent and -independent prostate cancer models Abstract #5047 / 14, Session PO.ET08.02 - Theranostics and Radionuclides/Pharmacologic Approaches Tuesday, April 18, 1:30 PM - 5:00 PM (EDT), Section 19, Convention Center Preliminary analysis of pharmacokinetic (PK) and target engagement biomarkers from a first-in-human Phase I study of immunomodulatory aryl hydrocarbon receptor (AhR) inhibitor BAY2416964 Abstract #CT276 / 16, Session PO.CT01.04 - Phase I Clinical Trials 2 Tuesday, April 18, 1:30 PM - 5:00 PM (EDT), Section 47, Convention Center Phosphorylated extracellular signal-regulated kinase (pERK) activation in T effector cells as a target engagement biomarker for the DGKζ inhibitor BAY 2965501 in clinical trials Abstract #2116 / 19, Session PO.CL01.11 - Biomarkers for Elucidation of Tumor Biology and Metastasis Monday, April 17, 9:00 AM – 12:30 PM (EDT), Section 38, Convention Center Preclinical activity of BAY 2927088 in HER2 mutant non-small cell lung cancer Abstract #4035 / 9, Session PO.ET09.08 - Tyrosine Kinase and Phosphatase Inhibitors 2 Tuesday, April 18, 9:00 AM - 12:30 PM (EDT), Section 21, Convention Center Mechanisms of resistance to BAY 2927088, the first reversible inhibitor targeting EGFR exon 20 insertion mutations in non-small cell lung cancer Abstract #433 / 28, Session PO.ET03.02 - Drug Resistance in Molecular Targeted Therapies 2 Sunday, April 16, 1:30 PM - 5:00 PM (EDT), Section 15, Convention Center An open-label, first-in-human study of BAY2927088 in patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR and/or HER2 mutation Abstract #CT126 / 14, Session PO.CTP01.02 - Phase I Clinical Trials in Progress Monday, April 17, 1:30 PM - 5:00 PM (EDT), Section 46, Convention Center Racial and ethnic trends in next-generation sequencing (NGS) utilization among adult patients with selected advanced tumor types: a large commercial database analysis Abstract #1964 / 5, Session PO.PR01.02 - Cancer Disparities Research Monday, April 17, 9:00 AM - 12:30 PM (EDT), Section 28, Convention Center NTRK gene fusion in adults and pediatrics with solid tumors: a record linkage study of expression frequency and patient characteristics using the Auria Biobank in Finland Abstract #925 / 8, Session PO.CL11.01 - Analyses Using Clinical and Genomic Databases Sunday, April 16, 1:30 PM – 5:00 PM (EDT), Section 38, Convention Center Concordance between tissue and circulating tumor DNA (ctDNA) testing for neurotrophic tyrosine receptor kinase (NTRK) gene fusions in larotrectinib (laro) clinical trials Abstract #CT228 / 18, Session PO.CT02.02 - Phase II Clinical Trials 2 Tuesday, April 18, 9:00 AM - 12:30 PM (EDT), Section 47, Convention Center Optimization of treatment schedule for the combination therapy of ATR inhibitor elimusertib and PARP inhibitor niraparib in preclinical tumor models Abstract #311 / 13, Session: Targeting Replication Stress and the Immune Microenvironment Sunday, April 16, 1:30 PM - 5:00 PM (EDT), Section 11, Convention Center Radium-223 demonstrates increased antitumor activity in combination with 177Lu-PSMA-617 in the intratibial LNCaP xenograft model of bone metastatic prostate cancer Abstract #5043 / 10, Session PO.ET08.02 - Theranostics and Radionuclides/Pharmacologic Approaches Tuesday, April 18, 1:30 PM - 5:00 PM (EDT), Section 19, Convention Center Next-generation sequencing (NGS) and cytokine assessment from a Phase III study of copanlisib in combination with rituximab in patients with indolent non-Hodgkin lymphoma (iNHL) – associations with survival endpoints Abstract #CT082 / 10, Session PO.CT03.01 - Phase III and Pediatric Clinical Trials Monday, April 17, 9:00 AM - 12:30 PM (EDT), Section 47, Convention Center About Oncology at Bayer Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The company has the passion and determination to develop innovative medicines that help improve and extend the lives of people living with cancer. The oncology franchise at Bayer includes six marketed products across various indications and several compounds in different stages of clinical development. Bayer focuses its research activities on first-in-class innovations across the following scientific platforms: Precision Molecular Oncology, Targeted Alpha Therapies, and Immuno-Oncology. Across the areas of focus, we have several prostate cancer treatments on the market or in development, with the goal of extending survival while limiting side effects of treatment throughout the different stages of the disease. Another key focus at Bayer is on innovative precision oncology treatments, with an approved TRK inhibitor exclusively designed to treat tumors that have an NTRK gene fusion, the oncogenic driver of tumor growth and spread. The company’s approach to research prioritizes targets and pathways with the potential to impact the way that cancer is treated. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to www.bayer.com . 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