Taiho Oncology Announces Agreement with Otsuka to Commercialize Astex Pharmaceuticals’ Drug Candidates

PRINCETON, N.J., June 7, 2019 – Taiho Oncology, Inc. announces that it has assumed commercialization responsibility from Otsuka Pharmaceuticals Co., Ltd., (Otsuka) for the novel fixed-dose combination of cedazuridine and decitabine (ASTX727) and guadecitabine (SGI-110) in the U.S. and Canada, subject to regulatory approvals. Taiho Pharma Canada, Inc., will commercialize these compounds in Canada.

The two candidates are in late-stage clinical development by Astex Pharmaceuticals, a wholly owned subsidiary of Otsuka. Taiho Oncology is also part of the Otsuka group of companies.

“This commercialization agreement is highly significant for Taiho Oncology as it allows us to build on the long-term strategy of expanding our presence in North America,” said Taiho Oncology, Inc. Chief Executive Officer Timothy Whitten. “These investigational therapies have the potential to provide physicians and patients with much-needed treatment options for a range of hematologic malignancies. We look forward to working with Astex as we bring these compounds to market.”

On June 6, 2019, Astex Pharmaceuticals and Otsuka announced top-line results from the Phase III ASCERTAIN study evaluating ASTX727 vs. decitabine IV in adults with intermediate and high-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). The trial met its primary endpoint of decitabine area-under-the-curve (AUC) equivalence of total 5-day dosing between orally administered ASTX727 and IV decitabine. The full data will be presented at an upcoming scientific meeting.

Astex has current studies with guadecitabine (SGI-110) in relapsed and refractory acute myeloid leukemia (R/R AML) and relapsed and refractory myelodysplastic syndromes (R/R MDS) and CMML.

About Taiho Oncology, Inc. (U.S.)
Taiho Oncology, Inc., a subsidiary of Taiho Pharmaceutical Co., Ltd. and an indirect subsidiary of Otsuka Holdings Co., Ltd., has established a world-class clinical development organization that works urgently to develop innovative cancer treatments and has built a commercial business in the U.S.

Taiho has an oral oncology pipeline consisting of both novel antimetabolic agents and selectively targeted agents. Advanced technology, dedicated researchers, and state of the art facilities are helping us to define the way the world treats cancer. It’s our work; it’s our passion; it’s our legacy.

For more information about Taiho Oncology, please visit: https://www.taihooncology.com.

For more information about Taiho Pharmaceutical Co., Ltd., please visit:

https://www.taiho.co.jp/en/.

About Astex Pharmaceuticals, and Otsuka Pharmaceutical
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 multiple partnered products in development under collaborations with leading pharmaceutical companies. Astex became a wholly owned subsidiary of Otsuka in 2013.

Otsuka Pharmaceutical Co., Ltd., based in Tokyo, Japan, 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, visit: http://www.astx.com.

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

###

Contacts for U.S. Media

On behalf of Taiho Oncology:
Craig Heit
GCI Health
Taihooncology@gcihealth.com
646-946-6690

At Astex:
Martin Buckland
Chief Corporate Officer
Astex Pharmaceuticals, Inc.
info@astx.com
925-560-2857

PL-PM-US-0007 06/2019

British Company Behind Groundbreaking Breast Cancer Treatment

Astex welcomes positive, new data showing breast cancer drug, Kisqali® (ribociclib), cuts risk of death by up to a third when given with hormone therapy

Cambridge, UK, 7 June 2019. A new set of statistically significant overall survival (OS) data unveiled at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract# LBA1008), and published in The New England Journal of Medicine, are being heralded as a major breakthrough forpre- and perimenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancerpremenopausal women with advanced breast cancer.

Kisqali was discovered and developed by the Novartis Institutes for Biomedical Research (NIBR) under a research collaboration entered into with Astex in 2005.  Kisqali is a CDK4/6 inhibitor that slows the progression of cancer by inhibiting two proteins (CDK4 & CDK6) which, when over-activated, can enable cancer cells to grow and divide quickly.

Successful results from the phase III MONALEESA-7 clinical trial resulted in Kisqali receiving marketing approval in the US and EU in 2018 in combination with an endocrine-based therapy for pre- and perimenopausal women with (HR+/HER2-) locally advanced or metastatic breast cancer in combination with an aromatase inhibitor.

The UK’s National Institute for Health and Care Excellence (NICE) recommended Kisqali as a cost-effective treatment option for postmenopausal women within England and Wales with advanced breast cancer in November 2017. Advanced breast cancer in premenopausal women is the leading cause of cancer death in women 20-59 years old [1],[2].

Kisqali is the only CDK4/6 inhibitor to show superior overall survival in a clinical trial (alt. “v. placebo”) in advanced breast cancer (HR=0.712; p=0.00973)[3]. In its announcement at ASCO, Novartis noted that the new data from its MONALEESA-7 trial showed that after a median of 42 months follow-up, survival rate for women was 70.2% for women who received Kisqali combination therapy compared to 46.0% for women who received endocrine therapy alone. The breakthrough data has been widely reported in the world’s press.

Harren Jhoti Ph.D., President and CEO of Astex, UK, said, “It’s fantastic to see such a significant advance in cancer treatment. Ultimately as life science entrepreneurs, our goal is to improve lives through the discovery of new therapies. Kisqali was the first new cancer drug discovered and developed from our collaboration with Novartis to reach marketing approval and was a milestone for the company in 2017.  These new data are a real milestone for patients.”
The paper,Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer, was a published in The New England Journal of Medicinetoday and is available online.

See the discovery journey for Kisqali, here: https://astx.com/research-development/partnered-products-and-programs/kisqali-ribociclib-cdk46-inhibitor-oncology/

-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.co.jp/en/

References

[1] Benz CC. Impact of aging on the biology of breast cancer. Crit Rev Oncol Hematol. 2008;66:65-74.
[2] World Health Organization. Top cancer per country, estimated age-standardized mortality rates (World) in 2018, females, all ages. 2018. Available at http://gco.iarc.fr/today/home. Accessed May 2019
[3] Hurvitz S, Seock-Ah I, Yen-Shen L et al. Phase III MONALEESA-7 trial of premenopausal patients with HR+/HER2- advanced breast cancer (ABC) treated with endocrine therapy ± ribociclib: Overall survival (OS) results. Presented at the 2019 ASCO Meeting, June 1, 2019, Abstract# LBA 1008.

CONTACT:

At the Company:
Jeremy Carmichael
VP Corporate Development
Head of Business Development
Tel: +44(0)1223 226289
Email: jeremy.carmichael@astx.com

For Media Enquiries:
Sue Charles / Ashley Tapp
Instinctif Partners
Tel: +44 (0)20 7866 7863
Email: astex@instinctif.com

 

Astex Pharmaceuticals and Otsuka announce results of the phase 3 ASCERTAIN study of the novel oral cedazuridine and decitabine fixed-dose combination (ASTX727) in patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML)

  • Cedazuridine and decitabine, administered orally as a fixed-dose combination (ASTX727), met the primary endpoint of decitabine exposure equivalence of total 5-day dosing between oral ASTX727 and IV decitabine in the phase 3 ASCERTAIN study in MDS and CMML patients
  • The study confirmed that the safety profile and clinical activity of the cedazuridine and decitabine fixed-dose combination was similar to that observed in the phase 1/2 study and similar to the expected clinical profile of decitabine IV
  • Astex plans to file a New Drug Application (NDA) with the US FDA by the end of 2019
  • Astex is continuing to develop cedazuridine and decitabine fixed-dose combination in additional patient populations including those with acute myeloid leukemia (AML) and low-risk MDS

Pleasanton, CA and Tokyo, Japan, June 6th, 2019. Astex Pharmaceuticals, Inc. a member of the Otsuka group of companies, and Otsuka Pharmaceutical Co. Ltd., announce top-line results from the ASCERTAIN phase 3 study evaluating cedazuridine and decitabine fixed-dose combination (ASTX727) vs decitabine IV in adults with intermediate and high-risk MDS or CMML.

The study met its primary endpoint of decitabine exposure equivalence of 5-day dosing between orally administered ASTX727 and IV decitabine as per the protocol analysis plan. Safety and clinical activity were similar to that observed in a previous phase 1/2 study. The full data will be presented at an upcoming scientific meeting.

Astex plans to file an NDA with the US FDA by the end of 2019.

“We are delighted with the outcome of the ASCERTAIN trial, and the demonstration that the fixed dose combination of cedazuridine with decitabine enables successful oral delivery of decitabine, alleviating the significant burden of five days of monthly IV infusions for patients who may continue to benefit from the drug for several months or even years,” said Mohammad Azab, Astex Pharmaceuticals’ president and chief medical officer. “Subject to regulatory review and approvals, ASTX727 could bring a new treatment option to patients with these deadly diseases. We are extremely grateful to all the patients, caregivers, partner research and manufacturing organizations, as well as the healthcare professionals who contributed to this effort.”

About Cedazuridine and Decitabine Fixed-Dose Combination (ASTX727)

ASTX727 is a novel, orally administered fixed dose combination of cedazuridine, an inhibitor of cytidine deaminase, with the anti-cancer DNA hypomethylating agent, decitabine.1  By inhibiting cytidine deaminase in the gut and the liver, ASTX727 allows for oral delivery of the approved DNA hypomethylating agent, decitabine at exposures which are equivalent to the approved intravenous form of decitabine administered over 5 days.

ASTX727 has been evaluated in a phase 1/2 pharmacokinetics-guided dose escalation and dose confirmation study in patients with MDS and CMML to define appropriate doses of the individual components of ASTX727 (cedazuridine and decitabine) so that decitabine exposure after oral administration of ASTX727 is similar to exposure after IV decitabine at the approved daily dose of a 1-hour infusion at 20 mg/m2 (see https://www.clinicaltrials.gov NCT02103478). This study demonstrated that ASTX727 allowed decitabine to be delivered orally at a dose that emulates parenteral pharmacokinetics, as measured by 5-day area-under-the-curve (AUC).3 The drug’s safety profile was similar to that of IV decitabine. Of particular note was the low level of gastrointestinal adverse events.3

The concept of using cedazuridine to block the action of cytidine deaminase is also being evaluated in a low dose formulation of cedazuridine and decitabine for the treatment of lower risk MDS (see https://www.clinicaltrials.gov NCT03502668). ASTX727 may also have potential in all-oral combination regimes for the treatment of a range of different tumor types.

Astex is also expanding the evaluation of cedazuridine – decitabine combinations through a program of investigator-sponsored trials.

ASTX727 is an investigational compound and is not currently approved in any country.

About the ASCERTAIN Study

The ASCERTAIN study was designed to demonstrate that the cedazuridine and decitabine fixed-dose combination (ASTX727) could deliver orally a pharmacokinetically equivalent exposure of decitabine compared to IV decitabine in adults with previously untreated or treated MDS, including all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and CMML), and subjects with MDS International Prognostic Scoring System (IPSS) int-1, int-2, or high-risk MDS. (see https://www.clinicaltrials.gov NCT03306264). The study was designed as a randomized, open-label cross-over study in which patients were randomized in a 1:1 ratio to receive ASTX727 daily x 5 in the first 28-day cycle followed by IV decitabine daily x 5 in the second 28-day cycle, or the converse order. Following completion of the first two cycles, patients continued to receive treatment with ASTX727 in 28-day cycles until disease progression, unacceptable toxicity, or the subject decided to discontinue treatment or withdrew from the study. The primary endpoint of the study was total 5-day AUC exposures of decitabine after treatment with ASTX727 versus IV decitabine as measured across the first two cycles. Secondary endpoints included safety assessments, pharmacodynamic measurements, secondary PK parameters, clinical responses, red blood cell transfusion independence, leukemia-free survival, and overall survival. The study was conducted in 138 patients at 46 sites in the US and Canada.

About Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias affecting one or more of the three lineages. US incidence of MDS is estimated to be 10,000 cases per year, although the condition is thought to be under-diagnosed.4,5 The prevalence has been estimated to be from 60,000 to 170,000 in the US.6 MDS may evolve into acute myeloid leukemia (AML) in one-third of patients.7 The prognosis for MDS patients is poor; patients die from complications associated with cytopenias (infections and bleeding) or from transformation to AML. CMML is a clonal hematopoietic malignancy characterized by accumulation of abnormal monocytes in the bone marrow and in blood. The incidence of CMML in the US is approximately 1,100 new cases per year,8 and CMML may transform into AML in 15% to 30% of patients.9 The hypomethylating agents decitabine and azacitidine are effective treatment modalities for hematologic cancers and are FDA-approved for the treatment of higher risk MDS and CMML. These agents are administered by IV infusion, or by large-volume subcutaneous injections.

About Astex Pharmaceuticals, and Otsuka Pharmaceutical

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 multiple partnered products in development under collaborations with leading pharmaceutical companies. In October 2013 Astex became a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in 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 Details

Martin Buckland
Chief Corporate Officer
Astex Pharmaceuticals, Inc.
4420 Rosewood Drive, Suite 200
Pleasanton 94588, CA, USA
Tel: +1-925-560-2857
Email: info@astx.com

 

References

  1. Oganesian A, Redkar S, Taverna P, Choy G, Joshi-Hangal R, Azab M. Preclinical data in cynomolgus (cyn) monkeys of ASTX727, a novel oral hypomethylating agent (HMA) composed of low-dose oral decitabine combined with a novel cytidine deaminase inhibitor (CDAi) E7727 [ASH Abstract]. Blood 2013;122(21): Abstract 2526.
  2. Ferraris D, Duvall B, Delahanty G, Mistry B, Alt, J, Rojas C, et al. Design, synthesis, and pharmacological evaluation of fluorinated tetrahydrouridine derivatives as inhibitors of cytidine deaminase. J Med Chem 2014; 57:2582-2588.
  3. Savona MR, Odenike O, Amrein PC, Steensma DP, DeZern AE, Michaelis LC, et al. An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Lancet Haematol [Internet]. 2019;6(4):e194-e203.
  4. Garcia-Manero G. Myelodysplastic syndromes: 2015 update on diagnosis, risk-stratification and management. Am J Hematol 2015; 90(9) 831-841.
  5. Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: Incidence and survival in the United States. Cancer 2007;109(8):1536–1542.
  6. Cogle C. Incidence and burden of the myelodysplastic syndromes. Curr Hematol Malig Rep 2015; 10(3): 272-281.
  7. Shukron O, Vainstein V, Kündgen A, Germing U, Agur Z. Analyzing transformation of myelodysplastic syndrome to secondary acute myeloid leukemia using a large patient database. Am J Hematol 2012;87:853–860.
  8. What are the key statistics about chronic myelomonocytic leukemia? American Cancer Society Web site. https://www.cancer.org/cancer/chronic-myelomonocytic-leukemia/about/key-statistics.html. Accessed 08 April 2019.
  9. About chronic myelomonocytic leukemia (CMML). Cancer Research UK Web site. https://www.cancerresearchuk.org/about-cancer/other-conditions/chronic-myelomonocytic-leukaemia-cmml/about. Accessed 08 April 2019.

 

Astex Pharmaceuticals Celebrates as Second New Cancer Drug Receives US Marketing Approval

Astex Pharmaceuticals Celebrates as Second New Cancer Drug Receives US Marketing Approval
  • Further Milestone from Janssen on NDA Approval by the US FDA of BALVERSA™ (erdafitinib) for the Treatment of Urothelial Cancer

Cambridge, UK, 12 April 2019. 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 it has received a milestone payment from Janssen Pharmaceutica N.V. (Janssen). This follows the United States Food and Drug Administration’s (FDA) accelerated review and approval of a Janssen New Drug Application (NDA) for BALVERSA™ (erdafitinib) for the treatment of adults with locally advanced or metastatic urothelial carcinoma (mUC) which has susceptible fibroblast growth factor receptor (FGFR)3 or FGFR2 genetic alterations and who have progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

BALVERSA™ (erdafitinib) is a once-daily, oral pan-FGFR inhibitor that was discovered by Astex and Janssen as part of a 2008 exclusive worldwide collaboration and licence agreement to identify novel, small molecule inhibitors of FGFR kinase, including for the treatment of cancer. Under the ongoing collaboration, Janssen is responsible for the clinical development and commercialisation of all products, including erdafitinib. Astex is eligible to receive further milestone payments on additional regulatory filings and approvals in the US and Europe and for additional indications, as well as tiered double-digit royalty payments on annual sales of erdafitinib.

BALVERSA™ (erdafitinib) received Breakthrough Therapy Designation from the FDA for the treatment of patients with metastatic urothelial cancer in March 2018 and Janssen announced submission of an NDA seeking its approval to the US FDA in September 2018. Urothelial cancer, particularly of the bladder, is the sixth most common type of cancer in the USA.

Before entering into its exclusive worldwide collaboration and licence agreement with Janssen, Astex performed pioneering work on FGFR with the Cancer Research UK Drug Discovery Group at the Newcastle Cancer Centre, Northern Institute for Cancer Research, Newcastle University, UK, underlining the quality of UK science and strengths in academic-biotech collaboration.

Harren Jhoti Ph.D., President and CEO of Astex, UK, said, “‘We are delighted with the approval of BALVERSA™ and congratulate our valued colleagues at Janssen for their determination and excellent work in the discovery and development of this new medicine. We also congratulate our academic collaborators at Newcastle University for their contribution to our pioneering early collaboration on FGFR that aided in its discovery. Astex continues to strive to discover new medicines for cancer patients and is very proud that BALVERSA™ is the second of our Pharma-partnered products to have been approved in the last two years.’

-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.co.jp/en/

BALVERSA is a trademark of Janssen Biotech, Inc.

Contact

At the Company:
Jeremy Carmichael
VP Corporate Development
Head of Business Development

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

For Media Enquiries:
Sue Charles / Ashley Tapp
Instinctif Partners

Tel: +44 (0)20 7866 7863
Email: astex@instinctif.com