Menarini Group and Insilico Medicine Enter Global Exclusive License Agreement for Novel KAT6 Inhibitor for Potential Breast Cancer Treatment and Other Oncology Indications

• 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. www.Insilico.com

[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.

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