Astex Pharmaceuticals Celebrates as Cancer Drug Receives Marketing Approval in Europe

Further Milestone Payment Under Novartis Collaboration as Kisqali® (ribociclib) Receives Approval in Europe as a First-Line Treatment for HR+/HER2- locally Advanced or Metastatic Breast Cancer with an Aromatase Inhibitor
– Kisqali was discovered as part of a strategic research collaboration 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
-Marketing approval in Europe follows US marketing approval announced in March 2017

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 marketing approval in Europe for Kisqali® (ribociclib) 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-) locally advanced or metastatic breast cancer.

Astex is eligible to receive a milestone payment in respect of the European marketing approval, as well as royalty payments on annual sales of Kisqali, under the drug discovery alliance entered into between Astex and Novartis in 2005.

Approval by the European Commission follows a positive opinion granted in June by the Committee for Medicinal Products for Human Use (CHMP). The positive CHMP opinion was based on superior efficacy and demonstrated safety of Kisqali plus letrozole versus letrozole alone in the pivotal Phase III MONALEESA-2 clinical trial of first-line ribociclib plus letrozole in hormone receptor-positive HER2-negative advanced breast cancer which showed that Kisqali plus letrozole reduced the risk of progression or death by over 44% over letrozole alone at interim analysis. In a subsequent analysis of the trial data, after nearly one year of additional follow-up, Kisqali plus letrozole demonstrated median progression-free survival (PFS) of 25.3 months and 16.0 months for letrozole alone.1 The European approval allows for oncologists to prescribe Kisqali with letrozole, anastrozole or with exemestane and to use their discretion to select the treatment choice they believe is best for each individual patient.

Harren Jhoti, President and CEO of Astex, UK, said, “We are delighted that Novartis has received European approval of Kisqali arising from our productive collaboration with the opportunity to bring a new treatment option to many more women in Europe with advanced breast cancer.”

Astex received a milestone payment following the FDA approval of Kisqali in March 2017 and has received a first royalty payment from Novartis based on sales of Kisqali in the US, and is eligible to receive a milestone payment on approval of an additional regulatory filing in Japan.

-ENDS-

Notes to Editors

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. Kisqali is a registered trademark of Novartis AG.

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. Astex is a member of the Otsuka Group, based in Japan. Otsuka 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/

References
1 Hortobagyi G, Stemmer S, Burris H, et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole in hormone receptor-positive HER2-negative advanced breast cancer. Presented at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO), June 4, 2017, Chicago, Illinois (abstract #1038).

At the Company
Jeremy Carmichael
VP Corporate Development
Head of Business Development
Astex Pharmaceuticals
436 Cambridge Science Park
Milton Road, Cambridge
CB4 0QA, UK

Tel: +44(0)1223 226289
Mobile: +44 (0)7786 738066
Email: jeremy.carmichael@astx.com

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

Cambridge, UK, 13th March 2017.  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 PNAS[1].  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 location[2].

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™, 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.

-ENDS-

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/

CONTACT:

At the Company
Jeremy Carmichael
VP Corporate Development
Head of Business Development
Astex Pharmaceuticals
436 Cambridge Science Park
Milton Road,
Cambridge CB4 0QA, UK
Tel: +44(0)1223 226289
Mobile: +44 (0)7786 738066
Email: email_jc

Media Enquiries
Sue Charles/ Daniel Gooch
Instinctif Partners
Tel: +44 (0)20 7866 7905
Email: astex@instinctif.com

[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

Astex to Showcase Its Next-Generation Hypomethylating Agents Being Developed for Treatment of AML/MDS at the 2016 Annual Meeting of the American Society of Hematology

  • New clinical data to be presented in four oral presentations on guadecitabine (SGI-110)
    and ASTX727
  • Two new global Phase 3 studies commencing to investigate the potential of guadecitabine
    in the treatment of relapsed / refractory AML (ASTRAL-2) and relapsed / refractory MDS
    (ASTRAL-3)
  • Enrollment completed into the global Phase 3 clinical study of guadecitabine in adults with
    previously untreated AML who are not considered candidates for intensive induction
    chemotherapy (ASTRAL-1)

Pleasanton, CA, November 29, 2016. Astex Pharmaceuticals, a member of the Otsuka group, announced today that investigators collaborating with Astex will present results from several studies evaluating guadecitabine, its subcutaneous, next-generation hypomethylating agent; and ASTX727, its novel, oral hypomethylating agent at the 2016 Annual Meeting of the American Society of Hematology in San Diego, California, December 3 to 6.

The oral presentations are as follows:

  • Initial results of a Phase 2 Study of Guadecitabine (SGI-110), A Novel Subcutaneous (sc) Hypomethylating Agent, for Patients with Previously Untreated Intermediate-2 or High Risk Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML) (Abstract #346). Dr. Guillermo Montalban-Bravo et al. Sunday, December 4, 10:15 am; Manchester
    Grand Hyatt, Grand Hall C.
  • Results of a Phase II study of Guadecitabine (SGI-110) in higher risk MDS, CMML or lowblast- count AML patients refractory to or relapsing after Azacitidine (AZA) treatment
    (Abstract #347). Dr. Marie Sebert et al. Sunday, December 4, 10:30 am; Manchester Grand Hyatt, Grand Hall C.
  • Long Term Survival and Clinical Complete Responses of Various Prognostic Subgroups in 103 Relapsed/Refractory Acute Myeloid Leukemia (r/r AML) Patients Treated with Guadecitabine
    (SGI-110) in Phase 2 Studies (Abstract #904). Dr. Naval Daver et al. Monday, December 5, 3:30 pm; Marriott Marquis San Diego Marina, San Diego Ballroom AB.
  • Successful Emulation of IV Decitabine Pharmacokinetics with an Oral Fixed-Dose Combination of the Oral Cytidine Deaminase Inhibitor (CDAi) E7727 with Oral Decitabine, in Subjects with Myelodysplastic Syndromes (MDS): Final Data of Phase 1 Study (Abstract #114). Dr. Guillermo Garcia-Manero et al. Saturday December 3, 10:45 am; Manchester Grand Hyatt, Grand Hall C.

In addition, a poster presentation entitled: Genetic determinants of response to guadecitabine (SGI- 110) in AML (Abstract #1680), Dr. Patricia L. Kropf et al., will be made on Saturday December 3, 9:30 am to 11 am in the San Diego Convention Center, Hall GH.

Data from the guadecitabine Phase 2 study (www.clinicaltrials.gov, NCT01261312) has helped to inform the design of the 800-patient, global Phase 3 study of guadecitabine in adults with previously
untreated AML who are not considered candidates for intensive induction chemotherapy (ASTRAL-1, www.clinicaltrials.gov, NCT02348489), and the newly announced global Phase 3 studies in relapsed / refractory AML (ASTRAL-2, www.clinicaltrials.gov, NCT02920008), and relapsed / refractory MDS or CMML (ASTRAL-3, www.clinicaltrials.gov, NCT02907359). Astex also announced today that enrollment into the ASTRAL-1 study is now complete. The data on ASTX727 being reported at ASH also informed the design of a Phase 2 randomized, cross-over study comparing ASTX727 to decitabine IV in higher risk MDS, which is ongoing.

“The data from these clinical studies helps to validate the development of these agents for the treatment of AML and MDS, potentially providing new treatment options for patients with these
aggressive hematological malignancies” said Mohammad Azab, President and Chief Medical Officer of Astex. “We are delighted to be working with some of the world’s leading experts in the treatment of hematological malignancies in bringing these next-generation therapies to patients.”

 About Guadecitabine (SGI-110)
Guadecitabine is a novel next-generation, small-molecule DNA hypomethylating agent formulated as a single, small-volume, subcutaneous injection. The product was designed to
deliver longer exposure to the active metabolite, decitabine, compared to IV decitabine, and more efficient delivery into key tissues, including the bone marrow. Guadecitabine
demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML
patients. Guadecitabine is currently being investigated in multiple clinical trials, including the ASTRAL series of studies and an extensive program of investigational studies in combination
with immunotherapy and other anti-neoplastic agents, for the treatment or a range of hematological malignancies and solid tumors.

About ASTX727
ASTX727 is a unique fixed-dose combination of the hypomethylating agent decitabine, the active ingredient in Dacogen®, and the novel cytidine deaminase inhibitor, E7727. ASTX727 was
designed to deliver decitabine by oral administration. By inhibiting cytidine deaminase, E7727 inhibits the major mechanism by which decitabine is degraded in the gut, and the combination
therefore permits the efficient oral delivery of decitabine at a low dose. Astex is completing a Phase 2 clinical study of ASTX727 in the treatment of intermediate and high risk myelodysplastic
syndromes (MDS). Guadecitabine and ASTX727 are investigational agents, and efficacy and safety have not been established. There is no certainty that these agents will become commercially available.

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.

Astex is a member of the Otsuka Group, based in Japan. Otsuka 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/

CONTACT:
Martin Buckland
Chief Corporate Officer
Astex Pharmaceuticals, Inc.
4420 Rosewood Drive, Suite 200
Pleasanton, CA 94588
Tel: +1 (925) 560-0100
Email: email_mb

Astex Joins the Dementia Discovery Fund as a Strategic Investor

Astex Joins the Dementia Discovery Fund as a Strategic Investor

Cambridge, UK, 21st November 2016 Astex Pharmaceuticals, a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system (CNS), announced today that it has become a strategic investor in The Dementia Discovery Fund (DDF; www.theddfund.com). DDF is a new venture fund set up to promote innovation in dementia research and to support the next generation of drug discovery approaches for neurodegenerative disease. The fund is managed by SV Life Sciences, a leading venture capital firm with a long track record of successful life science investing.

Astex joins the DDF investor group which includes the UK Government’s Department of Health (DoH) and Alzheimer’s Research UK alongside major pharmaceutical companies including Biogen, GlaxoSmithKline, Johnson & Johnson, Lilly, Pfizer and Takeda. Astex will participate in the Scientific Advisory Board of the DDF, which includes representatives from the other DDF strategic investors as well as world-leading academics, to share expertise, expand the DDF’s collaborative networks and advise the investment team. The DDF’s priorities are to explore and develop novel hypotheses in neurodegenerative diseases which could lead to new disease modifying treatments for dementia.

As part of Otsuka, a major Japanese pharmaceutical company with a strong tradition in developing treatments for disorders of the CNS, Astex has an emerging focus on CNS drug discovery and is using its proprietary fragment-based drug discovery platform to discover new drug candidates. Involvement in DDF provides Astex with a further mechanism to contribute to the identification of new and emerging areas of science for drug discovery with the aim to develop new treatment options for patients with neurodegenerative disease.

-ends-

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. Astex is a member of the Otsuka Group, based in Japan. Otsuka 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/

About the Dementia Discovery Fund

The Dementia Discovery Fund (DDF) is an innovative global investment fund established in October 2015 to deliver new drug approaches for dementia by 2025 to diagnose, intervene early and treat to modify the course and symptoms of the disease. The DDF, managed by SV Life Sciences, has raised more than $100 Million from investors including the UK Government’s Department of Health, Alzheimer’s Research UK and world-leading major pharmaceutical companies: Astex, Biogen, GlaxoSmithKline, Johnson & Johnson, Lilly, Pfizer and Takeda. The DDF will work collaboratively with universities, academic institutes, Government, the regulatory agencies and the biotechnology and pharmaceutical industry internationally to identify and develop novel treatments for dementia.

About SV Life Sciences

SV Life Sciences (SVLS) is a leading international life sciences venture capital firm. SVLS -managed funds have been investing in life sciences companies since the early 1980s and the firm closed its first dedicated life sciences fund in 1994. The SVLS team manages five venture capital funds with approximately $1.9 billion of capital under management. The firm employs a diversified strategy within life sciences in order to selectively capitalise on an expanding opportunity in biotech, medical devices and health-care services. SVLS has offices in Boston, London and San Francisco.

CONTACT:
Jeremy Carmichael
VP Corporate Development
Head of Business Development
Astex Pharmaceuticals
436 Cambridge Science Park
Milton Road,
Cambridge CB4 0QA, UK

Tel: +44(0)1223 226289
Mobile: +44 (0)7786 738066
Email: email_jc

 

Astex Achieves Milestone on US FDA Filing of New Drug Application (NDA) for LEE011 (ribociclib) plus letrozole as a first-line treatment for HR+/HER2- Advanced Breast Cancer

Astex Achieves Milestone on US FDA Filing of New Drug Application (NDA) for LEE011 (ribociclib) plus letrozole as a first-line treatment for HR+/HER2- Advanced Breast Cancer

  • LEE011 (ribociclib) was developed by the Novartis Institutes for BioMedical Research under a research collaboration with Astex Pharmaceuticals
  • LEE011 (ribociclib) plus letrozole significantly extended progression-free survival across all patient subgroups in the pivotal Phase 3 MONALEESA-2 clinical study compared to letrozole alone
  • Separately, Novartis announced today that the US Food and Drug Administration (FDA) accepted the company’s New Drug Application (NDA) for filing and granted Priority Review for LEE011 (ribociclib)
  • A Novartis marketing authorization application for LEE011 (ribociclib) plus letrozole has also been accepted for review by the European Medicines Agency (EMA)

Cambridge, UK, 1st November 2016. Astex Pharmaceuticals, 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 it has received  a milestone payment from Novartis in relation to the US FDA NDA filing by Novartis for  LEE011 (ribociclib) plus letrozole as a first-line treatment for HR+/HER2- advanced breast  cancer. Novartis also announced that it had received FDA Priority Review for the NDA  application of LEE011 as first-line treatment of postmenopausal women with hormonereceptor  positive, human epidermal growth factor receptor-2 negative (HR+/HER2-)  advanced or metastatic breast cancer in combination with letrozole.
LEE011 (ribociclib) was developed by the Novartis Institutes for BioMedical Research  (NIBR) under a research collaboration with Astex. Under the collaboration, which  commenced in 2005, NIBR scientists worked with Astex on a programme of early drug  discovery research resulting in the discovery of LEE011. Novartis then led LEE011 into  preclinical and later clinical development. Under terms of the agreement, Astex is eligible to  receive further milestone payments in respect of additional regulatory filing and approvals in  Europe and Japan, as well as royalty payment on annual sales of ribociclib should the drug  be approved.  Harren Jhoti, President and CEO of Astex, said, “We are absolutely delighted that Novartis  has reached such a significant stage in the development of LEE011. If the product is  approved, it will provide an important treatment option for many patients with advanced  disease. We congratulate Novartis for an excellent job in developing LEE011 and on the  achievement of US FDA Priority Review of the NDA filing.”

About LEE011 (ribociclib)

LEE011 (ribociclib) is   selective cyclin dependent kinase inhibitor, a class of drugs that help  slow the progression of cancer by inhibiting two proteins called cyclin dependent kinase 4  and 6 (CDK4/6). These proteins, when over-activated in a cell, can enable cancer cells to  grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in  ensuring cancer cells do not grow uncontrollably.

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/

CONTACT:

Jeremy Carmichael
VP Corporate Development
Head of Business Development
Astex Pharmaceuticals
436 Cambridge Science Park
Milton Road, Cambridge
CB4 0QA, UK
Tel: +44(0)1223 226289
Mobile: +44 (0)7786 738066
Email: email_jc

Positive Phase III Clinical Trial Results for Ribociclib (LEE011), an Investigational Compound for Advanced Breast Cancer in Development by Major Pharmaceutical Company under a Research Collaboration with Otsuka’s Subsidiary Astex Pharmaceuticals

Positive Phase III Clinical Trial Results for Ribociclib (LEE011), an Investigational Compound for Advanced Breast Cancer in Phase III Development by Major Pharmaceutical Company under a Research Collaboration with Otsuka’s Subsidiary Astex Pharmaceuticals

Otsuka Pharmaceutical Co., Ltd., which is active in the discovery of new medicines in the fields of cancer and central nervous system diseases announces positive phase III trials results for a drug compound in development by Novartis related to its subsidiary Astex Pharmaceuticals.

Positive clinical trial results on ribociclib (LEE011) plus letrozole as first-line treatment for advanced or metastatic breast cancer, compared to letrozole alone, were presented by Novartis at the European Society for Medical Oncology (ESMO) 2016. (The contents of this press release were announced earlier by Novartis in an October 8 press release. See the press release on the trial results including full safety and efficacy data here.)

In the trial (MONALEESA-2 study), patients with HR+ (hormone receptor positive)/HER2- (human epidermal growth factor receptor 2-negative), advanced or metastatic breast cancer were assigned to treatment with ribociclib (LEE011) and letrozole or to the standard of care: letrozole alone. Progression-free survival (the length of time during which cancer does not progress) was significantly extended in the experimental group treated with ribociclib plus letrozole. Trial results were published simultaneously in an online article in The New England Journal of Medicine.

Ribociclib (LEE011) was developed by the Novartis Institutes for BioMedical Research under a research collaboration with Astex Pharmaceuticals.

Otsuka’s subsidiary Astex undertakes drug discovery in the U.K. directed at unmet medical needs in the field of oncology and diseases of the CNS, thereby contributing to the lives of patients and their families.

Astex Pharmaceuticals Enters Clinical Trial Collaboration to Explore the Potential of Combining Guadecitabine (SGI-110) with Atezolizumab in the Treatment of Acute Myeloid Leukemia

Astex Pharmaceuticals Enters Clinical Trial Collaboration to Explore the Potential of Combining Guadecitabine (SGI-110) with Atezolizumab in the Treatment of Acute Myeloid Leukemia

Pleasanton, CA, USA, April 19th, 2016. Astex Pharmaceuticals, Inc., a pharmaceutical company dedicated to the development of novel small molecule oncology therapeutics, announced today that it has entered into a clinical collaboration with Genentech. The collaboration will evaluate the potential for combining Astex’s next generation hypomethylating agent, guadecitabine (SGI-110), with Genentech’s investigational anti-PD-L1 monoclonal antibody, atezolizumab, in the treatment of acute myeloid leukemia (AML). An initial Phase 1b study will investigate the safety and pharmacology of the combination.

The collaboration will test the hypothesis that upfront “priming” of patients’ immune systems with guadecitabine, an epigenetic investigational drug, may result in enhanced responses to immunotherapy. The hypothesis is based on the observation that guadecitabine demethylates and induces re-expression of tumor associated antigens, as well as inducing or upregulating the expression of immune checkpoints such as programmed death 1 (PD-1), and programmed deathligand 1 (PD-L1) and 2 (PD-L2), rendering the tumor more immunogenic, and more susceptible to treatment with a checkpoint inhibitor antibody such as atezolizumab (Maio et al, Clin. Cancer Research, 2015; 21:4040-47).

Guadecitabine has been evaluated in multiple Phase 1 and Phase 2 trials to investigate its potential in the treatment of a range of cancers. Astex has recently completed a large (over 400 patients) randomized Phase 1/2 study in patients with myelodysplastic syndromes (MDS) or AML. The trial included a Phase I dose escalation stage (93 patients) and a randomized Phase 2 stage (308 patients) that investigated four different patient populations: treatment naïve and relapsed/refractory AML and MDS. The trial demonstrated that guadecitabine was clinically active and well tolerated in all four patient groups. The results from the Phase 1 portion of the trial were recently published in Lancet Oncology (http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2900038-8/abstract). Additional information about the study can be found online at http://clinicaltrials.gov/ct2/show/NCT01261312.

Guadecitabine is now being evaluated in the ASTRAL-1 trial, a large, global, randomized 800-patient study in treatment naïve AML patients who are unfit to receive, or unsuitable for, intensive induction chemotherapy. The trial compares guadecitabine with physician’s choice of low-dose cytarabine, decitabine or azacitidine. Additional information about the study can be found online at: https://www.clinicaltrials.gov/ct2/show/NCT02348489.

Mohammad Azab, Astex’s President and Chief Medical Officer said: “We are delighted that Genentech has chosen to partner with Astex on this exciting study. The idea of combining epigenetic therapies such as guadecitabine with immune checkpoint inhibitors such as atezolizumab, has the potential to open up new therapeutic options with enhanced outcomes for patients with a range of cancer types. Astex is committed to exploring the broad potential of guadecitabine as a “backbone” therapy for use in immunotherapy combinations.

About Acute Myeloid Leukemia (AML)

AML is the most common form of leukemia in adults. Over 20,000 new cases of AML are diagnosed annually in the US. Although 60%-75% of AML patients <60 years of age will achieve complete response (CR) with standard intensive induction chemotherapy, approximately 30%-40% of patients will die from their disease. The outlook for patients >60 years old is significantly worse with response rates < 50%, cure rates remaining at <10% and a median survival of <1 year. These figures have not significantly improved within the last 3 decades. These patients have few therapeutic options. Effective, less toxic therapies are needed for the treatment of AML, particularly for elderly patients whose comorbidities make them unfit for intensive therapy.

About Guadecitabine (SGI-110)

Guadecitabine is a novel next-generation, small molecule DNA hypomethylating agent formulated as a single, small volume, subcutaneous injection. The product was designed to deliver longer exposure to the active metabolite, decitabine, compared to iv decitabine, and more efficient delivery into key tissues, including the bone marrow. Guadecitabine demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML patients. Guadecitabine is wholly owned by Astex Pharmaceuticals.

About Atezolizumab

Atezolizumab (also known as MPDL3280A) is an investigational humanized monoclonal antibody designed to target and bind to a protein called PD-L1, which is expressed on tumor cells and tumorinfiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, thereby inhibiting T cell function. By blocking this interaction, atezolizumab may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. Atezolizumab is being developed by Genentech (South San Francisco, CA, USA), a member of the Roche Group.

About Astex Pharmaceuticals, Inc.

Astex Pharmaceuticals, Inc. is a leader in innovative oncology drug development, committed to the fight against cancer. Astex is developing a proprietary pipeline of novel anti-cancer 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. The Otsuka Group employs approximately 43,000 people globally, and its products are available in more than 80 countries worldwide.

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/

CONTACT:

Martin Buckland
Chief Corporate Officer Astex Pharmaceuticals, Inc.
4420 Rosewood Drive, Suite 200
Pleasanton, CA 94588
Tel: +1 (925) 560-0100
Email: email_mb

Astex Pharmaceuticals Announces Orphan Drug Designation for Guadecitabine (SGI-110) in the Treatment of Acute Myeloid Leukemia

Astex Pharmaceuticals Announces Orphan Drug Designation for Guadecitabine (SGI-110) in the Treatment of Acute Myeloid Leukemia

  •  FDA has granted an orphan drug designation for Astex Pharmaceuticals’ investigational drug, guadecitabine (SGI-110), in the treatment of acute myeloid leukemia (AML). 
  • Over 20,000 new cases of AML are diagnosed annually in the US, and the prognosis for patients who are unfit to receive standard intensive induction chemotherapy is poor. Currently, there is no drug specifically approved for these patients in the US.
  • Guadecitabine is a novel, next-generation hypomethylating agent (HMA) which reverses aberrant DNA methylation, one of the key mechanisms associated with AML and other malignancies, by inhibiting DNA methyltransferase enzymes.
  • Guadecitabine is currently being evaluated in a large global Phase 3 study (ASTRAL- 1) in treatment naïve AML patients who are unfit to receive, or unsuitable for, intensive induction chemotherapy.

Pleasanton, CA, USA, October 6th, 2015. Astex Pharmaceuticals, a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics, announced today that its novel hypomethylating agent, guadecitabine (SGI-110), has been granted an orphan drug designation by the US FDA.

Guadecitabine has been evaluated in multiple Phase 1 and Phase 2 trials to investigate its potential in the treatment of a range of cancers. The company has recently completed a large (over 400 patients) randomized Phase 1/2 study in patients with myelodysplastic syndromes (MDS) or AML. The trial included a Phase I dose escalation stage (93 patients) and a randomized Phase 2 stage (308 patients) that investigated four different patient populations: treatment naïve and relapsed/refractory AML and MDS. The trial demonstrated that guadecitabine was clinically active and well tolerated in all four patient groups. The results from the Phase 1 portion of the trial were recently published in Lancet Oncology (http://www.thelancet.com/journals/lanonc/article/PIIS1470- 2045%2815%2900038-8/abstract). Additional information about the study can be found online at http://clinicaltrials.gov/ct2/show/NCT01261312.

Guadecitabine is now being evaluated in the ASTRAL-1 trial, a large, global, randomized 800- patient study in treatment naïve AML patients who are unfit to receive, or unsuitable for, intensive induction chemotherapy. The trial compares guadecitabine with physician’s choice of low-dose cytarabine, decitabine or azacitidine. Additional information about the study can be found online at: https://www.clinicaltrials.gov/ct2/show/NCT02348489.

Mohammad Azab, Astex’s President and Chief Medical Officer said: “We are delighted that FDA has granted orphan drug status to guadecitabine for the treatment of AML. This designation supports our conviction that new therapies are desperately needed for patients who are diagnosed with AML, particularly those for whom standard intensive induction chemotherapy is unsuitable, and helps underpin the rationale for commencing the ASTRAL-1 trial, the largest clinical study ever conducted in this group of patients.”

About Orphan Drug Designation

Orphan Drug designation is granted to drugs or biologics that treat a rare disease or condition affecting fewer than 200,000 people in the US. Orphan Drug designation by the FDA qualifies the sponsor for incentives provided for in the Orphan Drug Act, which can include protocol assistance for clinical trials, prescription drug user fee waivers, tax incentives and seven years of market exclusivity.

About Acute Myeloid Leukemia (AML)

AML is the most common hematological malignancy in adults. Over 20,000 new cases of AML are diagnosed annually in the US. Although 60%-75% of AML patients <60 years of age will achieve complete response (CR) with standard intensive induction chemotherapy, approximately 30%-40% of patients will die from their disease. The outlook for patients >60 years old is significantly worse with response rates < 50%, cure rates remaining at <10% and a median survival of <1 year. These figures have not significantly improved within the last 3 decades. These patients have few therapeutic options. Effective, less toxic therapies are needed for the treatment of AML, particularly for elderly patients whose comorbidities make them unfit for intensive therapy.

About guadecitabine (SGI-110):

Guadecitabine is a novel next-generation, small molecule DNA hypomethylating agent formulated as a single, small volume, subcutaneous injection. The product was designed to deliver longer exposure to the active moiety, decitabine, compared to iv decitabine and more efficient delivery into key tissues, including the bone marrow. Guadecitabine demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML patients. Guadecitabine is wholly owned by Astex Pharmaceuticals.

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. The Otsuka Group employs approximately 43,000 people globally, and its products are available in more than 80 countries worldwide.

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/

CONTACT:

Martin Buckland
Chief Corporate Officer
Astex Pharmaceuticals, Inc.
4420 Rosewood Drive, Suite 200
Pleasanton, CA 94588 Tel: +1 (925) 560-0100
Email: email_mb

Astex Pharmaceuticals Announces Publication of Key Clinical Data for Guadecitabine (SGI-110) in The Lancet Oncology

Astex Pharmaceuticals Announces Publication of Key Clinical Data for Guadecitabine (SGI-110) in The Lancet Oncology

  • Guadecitabine (SGI-110) is a novel, next-generation hypomethylating agent (HMA) which reverses aberrant DNA methylation by inhibiting DNA methyltransferase enzymes.
  • This publication describes a first-in-human pharmacokinetic and pharmacodynamic guided dose-escalation study of guadecitabine (SGI-110) in adults with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), refractory to, or relapsed after, standard treatment.

Pleasanton, CA, USA, August 18, 2015. Astex Pharmaceuticals, a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics, announces the publication of key clinical data for the novel hypomethylating agent (HMA) guadecitabine (SGI-110) in the prestigious journal, The Lancet Oncology. The publication, entitled “Pharmacokinetic and Pharmacodynamic-guided Phase 1 study of the novel hypomethylating drug guadecitabine (SGI-110) in myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML)”, was released online on August 18, 2015 at http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00038-8/abstract.

The publication describes the first-in-human clinical trial of 93 heavily pre-treated patients (74 AML and 19 MDS) treated with guadecitabine and reports that the drug is welltolerated, easily administered, and biologically and clinically active in both MDS and AML patients who relapsed after standard of care. Importantly, potent dose-related DNA demethylation is associated with clinical responses in patients treated with guadecitabine, with responders showing significantly more demethylation than non-responders. The study was conducted at 13 leading cancer centers in the US and Canada.

The results described in this publication were used to inform the design of a large Phase 2 study in both treatment naïve and relapsed / refractory AML and MDS, in which over 300 patients were treated with guadecitabine, and a recently-commenced 800-patient global Phase 3 study (ASTRAL-1), in which guadecitabine is being compared with physician’s choice of decitabine, azacitidine, or low-dose cytarabine in treatment naïve AML patients unfit to receive, or unsuitable for, intensive induction chemotherapy.

Lead Author, Jean-Pierre Issa, MD of Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine said “This study demonstrates that guadecitabine is safe, and showed that the drug resulted in improved PK exposure and PD demethylation over what has been reported for the first-generation HMAs. It also confirmed the importance of DNA demethylation as a PD marker for clinical response”. Dr. Issa added “Guadecitabine’s improved PK and PD profile may improve clinical outcomes in patients with hematologic malignancies, and may also make the drug useful in the treatment of solid tumors, an area in which first generation HMAs are not currently approved .”

Hagop Kantarjian, MD, of The University of Texas MD Anderson Cancer Center, the senior author of the study said: “In this study we observed induced clinical responses in heavily pre-treated patients including prior treatment with current HMAs. Together with the results of a large Phase 2 study to be published later, these data support further investigation, including the recently commenced global Phase 3 study in treatment-naïve AML patients”.

About guadecitabine (SGI-110): Guadecitabine is a novel next-generation small molecule, DNA hypomethylating agent designed to be administered as a single, small volume, subcutaneous injection. Guadecitabine demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML patients. Guadecitabine is wholly owned by Astex Pharmaceuticals.

About the SGI-110 study in MDS and AML patients (Study SGI-110-01): The SGI-110-01 trial is a large (over 400 patients) randomized Phase 1/2 study in patients with MDS or AML. The trial included a Phase I does escalation stage (93 patients) and a randomized Phase 2 stage (308 patients) that investigated four patient populations: treatment naïve and relapsed / refractory AML and MDS, and also explored both a dailyx5 and a dailyx10 regimen. Additional information about the study can be found online at http://clinicaltrials.gov/ct2/show/NCT01261312.

About the ASTRAL-1 SGI-110 study (Study SGI-110-04) ASTRAL-1 is a large, global, randomized 800-patient study of guadecitabine (SGI-110) in treatment naïve AML patients who are unfit to receive, or unsuitable for, intensive induction chemotherapy. The trial commenced in March 2015, and compares guadecitabine with physician’s choice of low-dose cytarabine, decitabine or azacitidine. Additional information about the study can be found online at https://www.clinicaltrials.gov/ct2/show/NCT02348489.

About Astex Pharmaceuticals

Astex Pharmaceuticals is dedicated to the discovery and development of novel small molecule therapeutics with a focus on oncology. 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 was acquired by Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan, and operates as a wholly owned subsidiary. The Otsuka Group employs approximately 43,000 people globally, and its products are available in more than 80 countries worldwide.

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/

CONTACT:
Martin Buckland
Chief Corporate Officer
Astex Pharmaceuticals, Inc.
4420 Rosewood Drive, Suite 200
Pleasanton, CA 94588
Tel: +1 (925) 560-0100
Email: email_mb

Astex Pharmaceuticals Presents Final Results of Phase 2 Study of SGI-110 in Treatment Naive Elderly Acute Myeloid Leukaemia at the European Hematology Association Meeting

Astex Pharmaceuticals Presents Final Results of Phase 2 Study of SGI-110 in Treatment Naïve Elderly Acute Myeloid Leukemia at the European Hematology Association Meeting

Dublin, CA, USA and Cambridge, UK, June 16, 2014 – Astex Pharmaceuticals, a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics, presented the final results of a Phase 2 study of SGI-110, a novel hypomethylating agent in elderly Acute Myeloid Leukemia (AML) in an oral session on June 14 at the European Hematology Association meeting held in Milan, Italy (June 12-15).

The results focused on clinical responses as well as safety of 2 doses of SGI-110 (60 and 90 mg/m2 /d) given as a subcutaneous injection daily x5 every 28 days in treatment naïve elderly AML patients not suitable for intensive chemotherapy enrolled in study SGI-110-01.

The study enrolled and treated 51 patients. The primary endpoint of Overall Complete Remission (CR or CR with incomplete normal count recovery (CRi)) was achieved in 28 of 51 patients (55%). The CR rate was achieved in 17 of 51 patients (33%). There were no major differences between the clinical responses and safety of the two doses of SGI-110. The most common Grade ≥ 3 Adverse Events were the expected and reversible myelosuppression adverse events: febrile neutropenia, thrombocytopenia, and anemia. All patients achieved potent DNA demethylation, and patients with CR or CRi had better Overall Survival than non-responders.

“We are pleased with the promising clinical activity and safety profile of SGI-110 as a next generation hypomethylating agent” said Mohammad Azab, MD, President and Chief Medical Officer of Astex Pharmaceuticals, Dublin, CA, USA. “These results support the Phase 3 development of SGI-110 in treatment naive elderly AML not suitable for intensive chemotherapy.”

About SGI-110:

SGI-110 is a novel small molecule, DNA-hypomethylating agent administered as a single small volume subcutaneous injection. SGI-110 demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML patients. SGI-110 is wholly owned by Astex Pharmaceuticals.

About the SGI-110 study in MDS and AML patients (Study SGI-110-01):

The SGI-110-01 trial is a randomized Phase 1/2 study in patients with Myelodysplastic Syndromes (MDS) and AML. The trial completed its Phase 1 dose escalation segment showing extended half-life and prolonged exposure window to the active ingredient decitabine compared to decitabine IV as well as potent DNA demethylation and multiple clinical responses in heavily pretreated MDS and AML patients.

This study is currently in a Phase 2 dose expansion segment with several cohorts including refractory/relapsed AML and treatment naïve elderly AML ineligible for intensive chemotherapy treated with dailyx5 and dailyx10 regimens. Additional information about the study can be found online at http://clinicaltrials.gov/ct2/show/NCT01261312.

About Astex Pharmaceuticals Astex Pharmaceuticals is dedicated to the discovery and development of novel small molecule therapeutics with a focus on oncology. Astex is developing a proprietary pipeline of novel therapies and has a number of partnered products being developed under collaborations with leading pharmaceutical companies. Astex is a subsidiary of Otsuka America, Inc. (OAI), a holding company established in the U.S. in 1989. OAI is wholly owned by Otsuka Pharmaceutical Co., Ltd. The Otsuka Group employs approximately 42,000 people globally, and its products are available in more than 80 countries worldwide. Otsuka welcomes you to visit its global website at https://www.otsuka.co.jp/en.

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

CONTACT:

Jeremy Carmichael
Senior Director of Business Development Astex Pharmaceuticals
436 Cambridge Science Park
Milton Road
Cambridge CB4 0QA
United Kingdom
Tel: +44 (0) 1223 226200
Email: email_jc

Peggy Bickerton
Corporate Communications Astex Pharmaceuticals
4140 Dublin Blvd.
Suite 200
Dublin,CA 94568
USA Tel: +1 (925) 560-2803
Email: email_pb