MDM2

WATERTOWN, Mass., Oct. 23, 2024 (GLOBE NEWSWIRE) -- Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing a new class of small molecule medicines using targeted protein degradation (TPD), today announced that new preclinical data from its innovative TPD platform will be presented across three poster presentations at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics being held October 23-25, 2024, in Barcelona, Spain. The presentations include new data on its preclinical biomarker-based approach for KT-253, its MDM2 degrader. “We have built industry leading knowledge and capabilities that we are leveraging to explore the applicability of our platform, including developing new therapeutic hypotheses to assess the potential of protein degradation to address oncogenic proteins in validated signaling pathways,” said Juliet Williams, PhD, Head of Research, Kymera Therapeutics. “As seen in our presentations at the EORTC-NCI-AACR Symposium, we’ve created a toolbox of integrated approaches to accelerate the discovery and development of transformative degrader medicines.” New data highlights the Company’s research efforts to identify patient populations sensitive to the KT-253 degrader mechanism and define biomarkers associated with an acute apoptotic response in tumors. Using an innovative machine learning framework to develop a predictive signature, the results identified tumor types sensitive to KT-253 that are consistent with preclinical and early clinical findings, including acute myeloid leukemia (AML), neuroendocrine tumors, and subsets of solid tumors with or without neuroendocrine features. KT-253 is in a Phase 1 clinical trial to evaluate its potential as a treatment for solid tumors and hematological malignancies. The Company will also present a poster highlighting its innovative platform capabilities and the case study of the use of targeted protein degradation to provide improved potency and selectivity over traditional small molecule inhibitors for CDK2, a cell cycle regulator and key protein involved in several cancers. Presentations at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics Poster Number: PB283Title: Predictive Markers of Response to the MDM2 Degrader KT-253Presenter: Nancy Dumont, PhD, Director, In Vivo Pharmacology Poster Number: PB032Title: The MDM2 degraders KTX-049 and KT-253 are highly active in wild-type TP53 (WT p53) Merkel cell carcinoma (MCC)Presenter: Yogesh Chutake, PhD, Associate Director, Translational Medicine Poster Number: PB092Title: CDK2 heterobifunctional degraders co-degrade CDK2 and Cyclin E resulting in efficacy in CCNE1-amplified and overexpressed cancersPresenter: Nicholas Kwiatkowski, PhD, Associate Director, Biological Sciences Copies of the EORTC-NCI-AACR poster presentations will be available in conjunction with the conference sessions within the Resource Library section of Kymera's website. About Kymera TherapeuticsKymera is a clinical-stage biotechnology company pioneering the field of targeted protein degradation (TPD) to develop medicines that address critical health problems and have the potential to dramatically improve patients’ lives. Kymera is deploying TPD to address disease targets and pathways inaccessible with conventional therapeutics. Having advanced the first degrader into the clinic for immunological diseases, Kymera is focused on delivering oral small molecule degraders to provide a new generation of convenient, highly effective therapies for patients with these conditions. Kymera is also progressing degrader oncology programs that target undrugged or poorly drugged proteins to create new ways to fight cancer. Founded in 2016, Kymera has been recognized as one of Boston’s top workplaces for the past several years. For more information about our science, pipeline and people, please visit www.kymeratx.com or follow us on X or LinkedIn. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about our expectations regarding its Targeted Protein Degradation platform and the clinical development and outcomes of KT-253. The words "may," "might," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "expect," "estimate," "seek," "predict," "future," "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from any forward-looking statements contained in this press release, including, without limitation, risks associated with: the risk that the results of preclinical studies and clinical trials may not be predictive of future results in connection with current and future clinical trials uncertainties inherent in the initiation, timing and design of future clinical trials, the availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results of early clinical trials will be indicative of the results of later clinical trials, the ability to successfully demonstrate the safety and efficacy of drug candidates, the timing and outcome of planned interactions with regulatory authorities and other factors. These risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in the most recent Quarterly Report on Form 10-Q and in subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our view as of any subsequent date. We explicitly disclaim any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor and Media Contact: Justine KoenigsbergVice President, Investor Relationsinvestors@kymeratx.commedia@kymeratx.com857-285-5300

CAMBRIDGE, United Kingdom, Oct. 21, 2024 (GLOBE NEWSWIRE) -- Astex Pharmaceuticals, a pharmaceutical company based in Cambridge, UK, dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system, announced today that it will make five key data presentations at the 36th EORTC-NCI-AACR Symposium on molecular targets and cancer therapeutics, 23rd-25th October 2024, Barcelona, Spain. The Astex presentations will focus on its novel small-molecule CBP/p300 HAT domain inhibitor, ASTX528 in preclinical development and its Phase II-ready MDM2 antagonist, ASTX295. Astex data presentations at 36th EORTC-NCI-AACR Symposium, 23rd-25th October 2024, Barcelona TitlePresentationDate/Time/Session Title/PresenterPresentation numberA Novel Small-Molecule CBP/p300 HAT Domain Inhibitor Demonstrates PotentIn VivoActivity and a Favourable Safety Profile in Preclinical SpeciesPosterDate: Wed, 23rdOct 2024Time: 12:00 - 19:00Session Title: Molecular Targeted AgentsPresenter: Gianni Chessari, Astex Pharmaceuticals, UKCatalog #42Presentation #PB030Targeting the Catalytic HAT Domain of CBP/p300 for the Treatment of Hormone-Dependent Breast and Prostate CancersPosterDate: Wed, 23rdOct 2024Time: 12:00 - 19:00Session Title: Molecular Targeted AgentsPresenter: John Lyons, Astex Pharmaceuticals, UKCatalog #73Presentation #PB061From a Preclinical Therapeutic Concept to the Clinic. ASTX295: Discovery of a bone marrow sparing MDM2 antagonistOralDate: Wed, 23rdOct 2024Time: 16:55 -17:15Session Title:Optimising of preclinical models for drug developmentPresenter: Maria Ahn, Astex Pharmaceuticals, UKWorkshop 2Room 113+114Identification of Biomarkers Predictive of Response to ASTX295, a Next-Generation MDM2 Antagonist, in Solid Tumors Carrying Wild-type p53PosterDate: Wed, 23rdOct 2024Time: 12:00 - 19:00Session Title: Molecular Targeted AgentsPresenter: Maria Ahn, Astex Pharmaceuticals, UKCatalog #28Presentation #PB016Pulsatile Induction of the p53 Pathway by MDM2 Antagonist ASTX295 Shows an Enhanced Therapeutic Indexin vivoPosterDate: Thu, 24thOct 2024Time: 9:00 - 17:30Session Title: Translational StudiesPresenter: Andrea Biondo, Astex Pharmaceuticals, UKCatalog #289Presentation #PB277 ASTX528 - CBP/p300 HAT Domain Inhibitor - Preclinical ASTX528 is a novel small molecule CBP/p300 HAT domain inhibitor with potent in vivo activity and a favourable safety profile in preclinical species that was discovered by Astex using its proprietary fragment-based drug discovery approach. CREB binding protein (CBP) and its paralog, EP300 (p300), are lysine acetyltransferases and transcriptional cofactors implicated in human cancers. Dose-limiting tolerability issues have been observed with dual CBP/p300 bromodomain (BRD) inhibitors, which may limit their clinical utility. We hypothesised that a dual inhibitor targeting the histone acetyltransferase (HAT) domain may improve the therapeutic window. Our presentations will describe the effects of CBP/p300 HAT domain inhibition in preclinical models of AR- and ER-driven cancers and the characterisation of ASTX528, a potent, fragment-derived CBP/p300 HAT domain inhibitor with a low predicted human dose and promising preliminary toxicity evaluation. Astex is interested in discussing the further development of ASTX528 with potential partners. ASTX295 – Bone Marrow-Sparing MDM2 Antagonist, Phase II-ready ASTX295 is an oral, potent inhibitor of the p53-MDM2 protein-protein interaction that was discovered by Astex using its proprietary structure-based drug design approach. The compound was specifically designed to overcome the on-target toxicity seen in the first generation MDM2 antagonist compounds which have shown dose-limiting haematological toxicities in the clinic. In contrast, ASTX295 is a potent MDM2 antagonist with a clean CYP/hERG profile and a shorter human half-life allowing for pulsatile pathway modulation while avoiding myelosuppression. ASTX295 therefore has bone-marrow sparing characteristics which permit a differentiated safety profile. ASTX295 was discovered by Astex in collaboration with the Cancer Research UK Drug Discovery Unit at Newcastle University. Astex has an exclusive license to research, develop and commercialise ASTX295 under its drug discovery alliance agreement with Newcastle University and Cancer Research Technology Limited. About Astex Pharmaceuticals Astex is a leader in innovative drug discovery and development, committed to the fight against cancer and diseases of the central nervous system. Astex is developing a proprietary pipeline of novel therapies and has several partnered products being developed under collaborations with leading pharmaceutical companies. Astex is a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan. For more information about Astex Pharmaceuticals, please visit: http://www.astx.com For more information about Otsuka Pharmaceutical, please visit: https://www.otsuka.co.jp/en/ Contact At the Company:Jeremy CarmichaelSVP Corporate DevelopmentHead of Business DevelopmentTel: +44(0)1223 226289Email: jeremy.carmichael@astx.comFor Media Enquiries:Sue CharlesCharles ConsultantsTel : +44(0)7968 726585Email: sue@charles-consultants.com

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