Positive data from Onconova Therapeutics' ON 01910.Na trial for advanced MDS

Dec 8 2009

Onconova Therapeutics, Inc. today announced promising results from two clinical trials in patients with advanced Myelodysplastic Syndrome (MDS) treated with ON 01910.Na. These trials are being conducted at the National Heart, Lung, and Blood Institute (NHLBI) in Bethesda, MD, and St. Vincent’s Comprehensive Cancer Center in New York. In these studies, treatment with ON 01910.Na resulted in significant decrease in blast count (cancer cells) in bone marrow without significant toxicity in these high risk MDS patients. After treatment, MDS patients with cytogenetic abnormalities showed fewer abnormal (aneuploid) cells, and many patients showed improved normal blood cell counts, (i.e., had an improvement in cytopenias). These findings were discussed in an oral presentation (December 6^th) and a poster (December 7^th) at the Annual Meeting of the American Society of Hematology (ASH) in New Orleans.

ON 01910.Na is a novel, targeted small molecule anti-cancer compound in Phase I and II clinical trials for MDS and solid tumors at several major centers in the U.S. and abroad. More than 190 patients have been treated in these clinical trials.

The positive clinical trial data were presented by Elaine Sloand, M.D., lead investigator for the trial at the National Heart, Lung, and Blood Institute. These studies were conducted, in part, with a “bench to bedside” translational award from the NHLBI and exemplify a mechanism and biomarker aided approach to development of new anti-cancer drugs.

“These findings are very promising and reaffirm our efforts to investigate ON 01910.Na for high risk MDS, which is difficult to treat, and for which few therapeutic options are available,” said Azra Raza, M.D., lead investigator for the trial at St. Vincent’s. Dr. Raza’s studies were also featured in a poster presentation.

“We are very pleased to see progress with our lead compound, for which a broad U.S. patent was issued in October,” said Mr. Michael Hoffman, Chairman of Onconova. “These encouraging results have led to the initiation of MDS trials at three additional sites, Mt. Sinai Medical Center, Stanford University Cancer Center and Moffitt Cancer Center. We anticipate additional clinical findings from ongoing trials of ON 01910.Na in single agent and combination therapy for solid tumor patients.”

ON 01910.Na was recently designated an “orphan drug” for treatment of MDS by the Food and Drug Administration. If ON 01910.Na is approved for the treatment of patients with high-risk MDS in the U.S., orphan drug designation could provide Onconova with potential market exclusivity for seven years. In addition, a drug candidate designated by the FDA as an orphan-drug product may qualify for subsidies on regulatory fees and tax incentives and may be eligible for research grant funding to assist in further clinical development.

Mechanism of Action and Biomarker Findings Presented at ASH

Also presented at the ASH meeting were non-clinical findings that further elucidate how ON 01910.Na causes selective cell death in cancer cells.

In an oral presentation, Patricia Perez-Galan, Ph.D. (NHLBI), described mechanism of action studies using human white blood cells from chronic lymphocytic leukemia (CLL) patients and normal donors. CLL, the most common leukemia in Western countries, is characterized by excess accumulation of B-cells. Incubation with ON 01910.Na killed B-cells from the CLL patients, but not their T-cells, nor T- or B-cells from the normal donors. This study revealed that selective killing of CLL cells by ON 01910.Na involved a dual mechanism: up-regulation of certain apoptotic signals, accompanied by down-regulation of the key PI3K/AKT survival/growth pathway. A clinical trial of ON 01910.Na with CLL patients is now accruing patients at the National Heart, Lung, and Blood Institute (Co-investigators: Drs. Mark Roschewski and Adrian Wiestner).

A poster presented by Dr. Wendy Fantl and Dr. David Soper (Nodality, Inc.) showed results of a mechanism of action study of ON 01910.Na aimed at identification of treatment-related biomarkers. Single Cell Network Profiling (SCNP), a new technology, employs flow cytometry to measure multiple parameters in human blood cells. Following treatment with ON 01910.Na, several critical proteins involved in regulating progression through the G2/M phase of the cell cycle were changed by treatment with ON 01910.Na, leading to death of these cells. These potential biomarkers are being tested in samples from an ongoing clinical trial in MDS patients at Stanford University Cancer Center.