• Guadecitabine did not meet the co-primary endpoints of complete response (CR) rate or overall survival (OS) in the ASTRAL-1 study
• Astex continues to focus on completing the phase 3 ASTRAL-2 and ASTRAL-3 studies evaluating the efficacy and safety of guadecitabine in relapsed and refractory acute myeloid leukemia (AML) and relapsed and refractory myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML)

Otsuka Pharmaceutical Co., Ltd. and our subsidiary Astex Pharmaceuticals, announce top-line results from the ASTRAL-1 study evaluating the efficacy and safety of guadecitabine (SGI-110) in adults with previously untreated AML who are not eligible for intensive induction chemotherapy. The study did not meet its co-primary endpoints: complete response (CR) rate (p>0.04), and overall survival (OS) (p>0.01) as per the protocol analysis plan, compared with the control arm of physician's choice of azacitidine, decitabine, or low-dose cytarabine. Evaluation of the study's secondary endpoints and safety data is ongoing. The full data will be presented at an upcoming scientific meeting.

The company continues to focus on completing the ongoing global phase 3 ASTRAL-2 and ASTRAL-3 studies evaluating guadecitabine in the treatment of relapsed and refractory AML and relapsed and refractory MDS and CMML.

About Guadecitabine (formerly SGI-110)

Guadecitabine is a next-generation DNA hypomethylating agent. Guadecitabine was rationally designed to be resistant to degradation by cytidine deaminase, prolonging the exposure of tumor cells to the active metabolite, decitabine, thus ensuring greater uptake of decitabine into the DNA of rapidly dividing cancer cells. Guadecitabine, through the action of decitabine, inhibits DNA methyl transferase (DNMT), with the potential to reverse aberrant DNA methylation, an epigenetic change characteristic of many cancer cells, and may restore the expression of silenced tumor suppressor genes upregulating tumor-associated antigens. Through this upregulation of tumor associated genes, guadecitabine may have the potential to sensitize tumor cells to other anticancer agents, including immunotherapeutics, as well as re-sensitizing cancer cells previously resistant to chemotherapeutics.

Guadecitabine is currently being tested in two additional phase 3 studies as follows:

• ASTRAL-2: A randomized, open-label study in leukemia patients with relapsed or refractory acute myeloid leukemia (AML) following intensive chemotherapy. See www.clinicaltrials.gov NCT02920008.
• ASTRAL-3: A randomized, open-label study in myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) after failure of prior treatment with azacitidine, decitabine, or both. See www.clinicaltrials.gov NCT02907359.

In addition, guadecitabine is being evaluated in over twenty investigator and company sponsored trials in other hematological malignancies and in solid tumors, both as a single agent, and in combination with chemotherapy or immunotherapy.

Guadecitabine was designed to be administered subcutaneously as a low-volume, stable formulation.

About the ASTRAL-1 Study

The ASTRAL-1 study evaluated the safety and efficacy of guadecitabine (formerly SGI-110) in adults with previously untreated AML who are not eligible for intensive induction chemotherapy (see www.clinicaltrials.gov NCT02348489). The study is the largest global prospective study ever conducted in this specific patient population, with 815 patients randomized from 163 investigator sites in 24 countries worldwide. The study compared guadecitabine, delivered subcutaneously (SC) 60mg/m²/day for 5 days, with physicians' choice of azacitidine IV or SC 75 mg/m²/day for 7 days, decitabine IV 20 mg/m²/day for 5 days, or low-dose cytarabine SC 20 mg bid for 10 days, all administered in 28-day cycles. In addition to the co-primary endpoints of OS and CR, the study evaluated multiple secondary endpoints including progression-free survival, composite CR or CRc (CR + CRi + CRp), days overnight in hospital, red cell / platelet transfusions, QOL (EQ-5D-5L), and duration of response and safety.

About Acute Myeloid Leukemia

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 to 75 percent of AML patients less than 60 years of age will achieve a complete response (CR) with standard intensive induction chemotherapy, approximately 30 to 40 percent of patients will die from their disease. The outlook for patients 60 years of age or more is significantly worse, with response rates less than 50 percent, cure rates following transplant remaining at less than 10 percent and a median survival of less than one year. These figures have not significantly improved during the last three decades. These patients have few therapeutic options available. Effective, less toxic therapies are needed for the treatment of AML, particularly for elderly patients where comorbidities and other consequences of aging may often render them ineligible to receive intensive remission induction chemotherapy, thus denying them a potentially curative transplant.

Otsuka Pharmaceutical Co., Ltd. and our subsidiary Astex Pharmaceuticals, announce top-line results from the ASTRAL-1 study evaluatin

g the efficacy and safety of guadecitabine (SGI-110) in adults with previously untreated AML who are not eligible for intensive induction chemotherapy (NCT 02348489). The study did not meet its co-primary endpoints: complete response (CR) rate (p>0.0, and overall survival (OS) (p>0.01) as per the protocol analysis plan, compared with the control arm of physician's choice of azacitidine, decitabine, or low-dose cytarabine. Evaluation of the study's secondary endpoints and safety data is ongoing. The full data will be presented at an upcoming scientific meetThe company continues to focus on completing the ongoing global phase 3 ASTRAL-2 and ASTRAL-3 studies evaluating guadecitabine in the treatment of relapsed and refractory AML and relapsed and refractory MDS and CMML.