On December 9, 2019 Onconova Therapeutics, Inc. (NASDAQ: ONTX) ("Onconova"), a Phase 3-stage biopharmaceutical company discovering and developing novel products to treat cancer, with an initial focus on myelodysplastic syndromes (MDS), reported data presented from INSPIRE related abstracts at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2019 Annual Meeting (Press release, Onconova, DEC 9, 2019, View Source [SID1234552125]). Preliminary genomics data from the INSPIRE Trial was presented. In addition, updated data from the Phase 2 Trial of Oral Rigosertib + Azacitidine (AZA) Versus Single Agent AZA in Treatment-Naive Patients with HR-MDS was presented in an oral presentation. The Company believes these abstracts represent important progress for the development programs of intravenous (IV) and oral rigosertib.

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Abstract #3015. "Genomic Profiling in Patients with Higher Risk Myelodysplastic Syndrome Following HMA Failure: Baseline Results From the INSPIRE Trial." At study entry, 50 different mutations were identified at baseline prior to patients receiving study treatment with either IV rigosertib or physician’s choice (PC). The average number of mutations per patient was 3. The most common mutations identified in patients were ASXL1 39%, TP53 27%, RUNX1 25%, STAG2 21%, SRSF2 19%, TET2 19%, DNM3A 15%, IDH2 13% and U2AF1 12%. In total 31 patients (19%) had mutations that are part of RAS pathway (NRAS, 4 pts; KRAS, 5 pts; CBL, 7 pts; PTPN11, 7 pts; NF1, 8 pts).

"Genomic abnormalities have revolutionized our understanding of the biology and prognosis of patients with MDS. Abnormalities involving the RAS pathway are seen in patients with MDS who have a very poor prognosis. The INSPIRE Trial has catalogued the abnormalities seen in patients with MDS who have failed the standard of care AZA. On-going studies will determine if the research drug rigosertib can target these abnormalities and prolong the lives of patients who have the spectrum of abnormalities that have been identified," said Guillermo Garcia-Manero, M.D., Department of Leukemia, The University of Texas MD Anderson Cancer Center.

Abstract #4249. "Phase II Study of Oral Rigosertib Combined with Azacitidine As First Line Therapy in Patients with HR-MDS." In HMA naïve higher risk MDS patients who require the standard of care with AZA, the combination of oral rigosertib > 840 mg and AZA produced an overall response rate of 90% and a complete response (CR) rate of 34%. CR by definition signifies the patient has a normal appearing bone marrow and the marrow produces a normal peripheral blood count. The median duration of response is 12.2 months. The Company believes these data support the design of a planned Phase 2/3 adaptive trial in HR-MDS.

"Efforts to improve the response rate with single agent AZA is an area of active research. The efficacy and safety data of the doublet of oral rigosertib and AZA warrants further investigation in a pivotal trial of this novel combination compared to AZA alone. If the preliminary efficacy of the doublet is confirmed in a pivotal controlled study and has an acceptable safety profile, patients with HMA naïve higher risk MDS may have an important new treatment option," said Lewis Silverman, M.D., Director of Translational Research Center for MDS, Division of Hematology/Oncology, at the Icahn School of Medicine at Mount Sinai.

Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova, said, "ASH 2019 was a key milestone for Onconova. The five presentations at ASH (Free ASH Whitepaper) showcase the value of our development programs for intravenous and oral rigosertib. The genomic data from the INSPIRE Trial identifies the most common mutations in HR-MDS following AZA failure, including those of the RAS pathway that are targeted by rigosertib. We believe the oral rigosertib in combination with AZA Phase 2 data forms the foundation of a future adaptive trial in HMA naïve HR-MDS patients. We appreciate the recognition by ASH (Free ASH Whitepaper) reviewers of the value of our studies in this field."

Three additional abstracts being presented at the ASH (Free ASH Whitepaper) 2019 Annual Meeting include:

Abstract #4249. "The Inspire Study in HR MDS: A Novel Phase 3 Study Adaptive Design for Hematological Malignancies in Adults."

Abstract #4268. "Phase 3, Multi-Center, International, Randomized, Double-Blind, Placebo Controlled Study of Oral Rigosertib + Injectable Azacitidine (AZA) Versus Injectable Azacitidine in Treatment-Naïve Patients with Higher-Risk Myelodysplastic Syndrome (HR-MDS)."

Abstract #4231. "The Sequenced Combination of Rigosertib and Azacitidine Has Modulatory Effects on CXCL8, RIG-I like Receptor (RLR) and Wnt/β-Catenin Signaling and Downstream Hematopoiesis Pathways in an in Vitro Model of the Myelodysplastic Syndrome."