Cambridge-based Astex Pharmaceuticals Celebrates as Cancer Drug Receives US Marketing Approval

Further Milestone Payment Under Novartis Collaboration as Kisqali® (ribociclib) Receives FDA approval as a First-Line Treatment for HR+/HER2- Advanced Breast Cancer with an aromatase inhibitor

• Novartis drug Kisqali® (ribociclib, LEE011) receives marketing approval by the US FDA as a first-line drug for HR+/HER2- advanced breast cancer in combination with an aromatase inhibitor
• Astex's scientific expertise was instrumental in the drug's discovery by solving the crystal structure of the key cancer target CDK4
• A strategic research collaboration with Novartis under which Astex and Novartis Institutes for BioMedical Research (NIBR) scientists jointly developed and optimised the chemical structure of Kisqali, which was then progressed through clinical trials by Novartis
• In a clinical trial, Kisqali, plus drug letrozole, has shown significant clinical benefit in all patient subgroups when compared with letrozole alone, for treatment of HR+/HER2- advanced breast cancer

Astex Pharmaceuticals ("Astex"), a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system, announced today that its long-standing pharmaceutical collaborator, Novartis, has received US Food and Drug Administration (FDA) marketing approval for Kisqali® (ribociclib, formerly known as LEE011) plus an aromatase inhibitor as a first-line treatment in post-menopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced (metastatic) breast cancer.

Astex is eligible to receive a milestone payment in respect of this FDA marketing approval and on approval of additional regulatory filings in Europe and Japan, as well as royalty payments on annual sales of Kisqali, under the drug discovery alliance entered into between Astex and Novartis in 2005. The partnership was struck to discover cell cycle inhibitors which represented a novel class of compounds that target the mechanisms of cell division in order to prevent or interfere with cancer growth.

Under the collaboration, Astex scientists, based at the company's research laboratories in Cambridge UK, were responsible for solving the crystal structure of the key cancer target protein CDK4. This was an important scientific breakthrough that no other group had previously been able to achieve, leading to a peer-reviewed publication in PNAS¹. Working with the Novartis team at the Novartis Institutes for BioMedical Research (NIBR), Cambridge, Mass., USA, Astex then applied its structure-based drug discovery technology, part of its Pyramid™ platform, in the collaboration that led to the discovery of LEE011, (now known as Kisqali) which was then taken forward by Novartis into clinical trials. In total, a team of some 25 Astex scientists were involved in this research program.

Kisqali® (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drug that helps slow the progression of cancer by inhibiting two proteins (CDK4 CDK6) which, when over-activated, can enable cancer cells to grow and divide quickly.

Novartis received the approval under the FDA Breakthrough Therapy Designation and Priority Review programs, based on data from a first-line Phase III trial that met its primary endpoint at interim analysis, due to its superior efficacy compared to letrozole alone. The combination of Kisqali plus letrozole reduced the risk of disease progression or death by 44% over letrozole alone. There was a sustained separation of the progression free survival curves evident as early as 8 weeks and more than 53% of patients with measurable disease who took Kisqali plus letrozole saw their tumour size shrink by at least 30%. The combination also showed significant clinical benefit in all patient subgroups regardless of disease burden or tumour location²

Harren Jhoti, President and CEO of Astex, UK, said, "We're committed to the fight against cancer and so we are absolutely delighted that Novartis has received this first approval of a cancer drug arising from our productive collaboration. This milestone further validates the power of our Pyramid™ platform and the excellence of our science. It's a moment to celebrate when such ground-breaking scientific work results in a new treatment option for women with advanced breast cancer."

Astex was formed in 1999 in Cambridge, UK, and was a pioneer in the development of fragment-based drug discovery technology. Backed by leading venture capital firms, including Abingworth, it has established multiple partnerships with major pharmaceutical companies including AstraZeneca, Janssen (Johnson Johnson) and GSK as well as Novartis to use the Company's drug discovery platform, Pyramid^TM, to identify novel small molecule drugs addressing key disease targets. Today it is a wholly-owned subsidiary of Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan, with a focus on cancer and diseases of the central nervous system. It employs about 200 staff at its research headquarters in Cambridge UK and its clinical development headquarters in Pleasanton, California, USA.

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 a number of partnered products being developed under collaborations with leading pharmaceutical companies. In October 2013 Astex became a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan. Otsuka Pharmaceutical is a global healthcare company with the corporate philosophy: "Otsuka people creating new products for better health worldwide." Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.

For more information about Astex Pharmaceuticals, please visit http://www.astx.com

For more information about Otsuka Pharmaceutical, please visit http://www.otsuka.com/en/

¹ "Crystal structure of human CDK4 in complex with a D-type cyclin", 4166-4170 PNAS, March 17, 2009, vol. 106, no. 11 www.pnas.org/cgi/doi/10.1073/pnas.0809645106

² "Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer" Gabriel N. Hortobagyi et al., NEJM, 2016, DOI: 10.1056/NEJMoa1609709

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