KAT6A

OP-3136 demonstrated potent anti-tumor activity alone and in combination with both palazestrant and CDK4/6 inhibitors in preclinical ER+ breast cancer models Initiating IND-enabling studies with goal to advance into clinical development by end of 2024 Jan. 08, 2024 -- Olema Pharmaceuticals, Inc. (“Olema”, “Olema Oncology”, Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for women’s cancers, today announced the selection of a development candidate for the Company’s program targeting KAT6, an epigenetic target that is dysregulated in breast cancer and other cancers. The compound, named OP-3136, is an orally bioavailable, potent KAT6A/B-selective inhibitor developed by Olema in collaboration with Aurigene Oncology. “We are excited to advance our KAT6 program with the nomination of OP-3136 as a development candidate. OP-3136 has the potential to become a new targeted therapy for breast cancer and other cancers,” said Dr. David C. Myles, Ph.D., Chief Discovery and Non-Clinical Development Officer of Olema Oncology. “Our KAT6 program supports our commitment to discovering and developing new treatment options for women living with cancer and is a natural complement to Olema’s ongoing development of palazestrant in ER+/HER2- breast cancer. We look forward to providing future updates on our progress with OP-3136 development.” Olema presented data regarding the discovery and pre-clinical development of its KAT6 program in a poster session at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (ANE 2023) in Boston, Massachusetts. OP-3136 is orally bioavailable in multiple non-clinical species with desirable pharmacokinetics and has demonstrated highly selective and potent activity against KAT6A and KAT6B versus other KAT family members. In KAT6-amplified and overexpressing estrogen receptor-positive (ER+) breast cancer cell lines, OP-3136 strongly inhibited cell proliferation whereas KAT6-low cell lines were insensitive to the compounds. In a non-clinical xenograft model, OP-3136 caused dose-dependent tumor growth inhibition and tumor regression comparable to or better than a positive-control patented KAT6 inhibitor and demonstrated synergy in combination with CDK4/6 inhibitors or palazestrant (OP-1250). Olema is initiating non-clinical Investigational New Drug (IND) enabling studies in order to support a potential IND submission to the U.S. Food and Drug Administration (FDA) for OP-3136 by the end of 2024. Olema Oncology is a biopharmaceutical company committed to transforming the standard of care and improving outcomes for women living with cancer. Olema is advancing a pipeline of novel therapies by leveraging our deep understanding of endocrine-driven cancers, nuclear receptors, and mechanisms of acquired resistance. In addition to our lead product candidate, palazestrant (OP-1250), a proprietary, orally-available complete estrogen receptor (ER) antagonist (CERAN) and a selective ER degrader (SERD), Olema is developing a potent KAT6 inhibitor. Olema is headquartered in San Francisco and has operations in Cambridge, Massachusetts. For more information, please visit us at www.olema.com. The content above comes from the network. if any infringement, please contact us to modify.

The standard of care for ER+/HER2- breast cancers is endocrine treatments, that may eventually stop working. Credit: Anchiy via Getty Images. Insilico Medicine has joined forces with Menarini through its subsidiary Stemline Therapeutics to develop a small molecule KAT6A inhibitor to treat hormone-sensitive cancers, focusing on ER+/HER2- breast cancer. The collaboration involves an exclusive licensing agreement, providing Stemline with global rights to develop and commercialise a novel KAT6A inhibitor, which is designed using Insilico’s artificial intelligence (AI) platform. The molecule has shown positive results in preclinical studies, demonstrating a potent inhibition in multiple CDX and PDX models, as well as a good safety and efficacy profile. Insilico presented data on this development at the San Antonio Breast Cancer Symposium last month. Insilico will receive $12m in an upfront payment from Menarini, as well as milestone payments with a combined value of more than $500m and sales royalties. In September 2019, Insilico announced its AI-powered drug discovery system GENTRL, which was created in alliance with WuXi AppTec , a global open-access R&D and manufacturing platform, as well as professor Alán Aspuru-Guzik, who works in quantum computing and AI in chemistry. In the announcement accompanying the agreement, Menarini CEO Elcin Barker Ergun said: “Having brought the first innovation in endocrine therapy after almost 20 years to the US and Europe with elacestrant for ER+/HER2- breast cancer patients, our aim is to further augment patient outcomes, and targeting KAT6A can potentially serve that in breast cancer and beyond.” KAT6A proteins play a crucial role in regulating gene expression and are implicated in various cancers, including poor clinical outcomes of ER+/HER- breast cancers. Other companies are also looking at the same protein inhibition. Pfizer ’s PF-07248144 is under development for the treatment of locally advanced or metastatic ER+/HER2- breast cancer, metastatic castration-resistant prostate cancer and metastatic non-small cell lung cancer (NSCLC). According to GlobalData’s Pharmaceutical Intelligence Center, PF-07248144 is currently being investigated in a Phase I clinical trial, with a Phase II trial planned. GlobalData is the parent company of Pharmaceutical Technology.

KAT6 is an emerging target in hormone sensitive breast tumors and other cancers. Overexpression of KAT6A/B correlates with poor clinical outcomes in patients with ER+/HER2- breast cancer – the most common subtype. The molecule has demonstrated strong preclinical activity. Insilico presented data on the novel molecule at the San Antonio Breast Cancer Symposium in early December. This agreement includes upfront and milestone payments with a combined potential value of over $500m and sales royalties. FLORENCE, Italy and NEW YORK, Jan. 4, 2024 /PRNewswire/ -- The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. ("Stemline"), a wholly-owned subsidiary of the Menarini Group focused on bringing transformational oncology treatments to cancer patients, along with clinical stage generative artificial intelligence (AI)-driven biotechnology company Insilico Medicine ("Insilico"), today announced that they have entered into an exclusive licensing agreement granting Stemline the global rights to develop and commercialize a novel, small molecule KAT6A inhibitor designed using Insilico's AI platform, as a potential treatment for hormone sensitive cancers and other oncology indications. Breast cancer is the most commonly diagnosed tumor type and the leading cause of cancer death among women, globally.[1] Approximately 70% of breast cancers are estrogen receptor positive (ER+), and endocrine therapy remains the backbone of therapy for patients with ER+ breast cancer. However, tumors can develop a resistance to endocrine therapy, which in turn can lead to disease progression. This is a significant clinical challenge and highlights the urgent need for novel therapies to help overcome treatment resistance. KAT6A is known to play an important role in several cancers. Overexpression of KAT6A correlates with poor clinical outcomes in patients with ER+/HER2- breast cancer, the most common subtype of breast cancer. In preclinical studies, the molecule has demonstrated potent inhibition against KAT6A in multiple CDX and PDX models with good efficacy and safety. Insilico presented data on the molecule at the San Antonio Breast Cancer Symposium in early December. "We are delighted to enter a collaboration with Insilico that harnesses the power of generative AI as a leader in the field, to explore a promising new treatment approach and potentially unlock transformative new cancer therapies," said Elcin Barker Ergun, CEO of the Menarini Group. "Having brought the first innovation in endocrine therapy after almost 20 years to the U.S. and Europe with elacestrant for ER+, HER2- breast cancer patients, our aim is to further augment patient outcomes, and targeting KAT6A can potentially serve that in breast cancer and beyond." The novel molecule was designed by Insilico's R&D team with the help of its end-to-end Pharma Generative AI platform to inhibit KAT6A and block endocrine receptor (ER) at the transcriptional level, giving it the potential to overcome resistance to endocrine therapies due to mutation or ligand-independent constitutive activation of ER. Currently, endocrine therapy in combination with CDK4/6 inhibitors is the standard treatment for ER+/HER2- breast cancer patients with advanced or metastatic disease. Novel combinations with CDK4/6 inhibitors and/or new oral SERDs are needed to further extend outcomes. "We are excited by the promise of our latest generative AI-designed therapy to provide a new potential treatment option for breast cancer patients," says Alex Zhavoronkov, PhD, founder and co-CEO of Insilico Medicine. "With their innovative vision and deep focus in bringing transformational therapeutics in oncology, Stemline is the ideal partner to lead this molecule into development and through clinical trials." Under the terms of the agreement, Stemline will provide a $12 million upfront payment to Insilico. The combined value of the deal, including all development, regulatory, and commercial milestones, is over $500 million, followed by royalties up to double digits. About The Menarini Group The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4.4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini's products are available in 140 countries worldwide. For further information, please visit menarini.com. About Stemline Therapeutics Inc. Stemline Therapeutics, Inc. ("Stemline") a wholly-owned subsidiary of the Menarini Group, is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics. Stemline commercializes ORSERDU® (elacestrant) in the U.S. and in the E.U., an oral endocrine therapy indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline also commercializes ELZONRIS® (tagraxofusp-erzs), a novel targeted treatment directed to CD123 for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic cancer, in the United States and Europe, which is the only approved treatment for BPDCN in the US and EU to date. Stemline also commercializes NEXPOVIO® (selinexor) in Europe, an XPO1 inhibitor for multiple myeloma. Stemline also has an extensive clinical pipeline of small molecules and biologics in various stages of development for a host of solid and hematologic cancers. About Insilico Medicine Insilico Medicine, a global clinical stage biotechnology company powered by generative AI, is connecting biology, chemistry, and clinical trials analysis using next-generation AI systems. The company has developed AI platforms that utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques for novel target discovery and the generation of novel molecular structures with desired properties. Insilico Medicine is developing breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system diseases, infectious diseases, autoimmune diseases, and aging-related diseases. [1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021 Feb 4. doi: 10.3322/caac.21660. Epub ahead of print. PMID: 33538338. Logo -