Onconova Therapeutics is developing new drugs for treating cancer and protecting against radiation injury.

Onconova Therapeutics®, Inc., founded in 1998, is a private biopharmaceutical company located in Newtown, PA and Pennington, NJ.

The Company is focused on targeting cancer and protecting healthy cells. Based on a proprietary medicinal chemistry library of over 140 novel chemotypes, Onconova has discovered and optimized a number of small molecule therapeutics aimed at novel molecular and biological targets.

ONCONOVA OVERVIEW

Onconova currently has one Phase III clinical-stage compound, two Phase I products in clinical development, and more than a half-dozen, well-differentiated preclinical compounds. The most advanced product, ESTYBON® (rigosertib, ON 01910.Na), is now in a pivotal trial being conducted under a Special Protocol Assessment (SPA) from the United States Food & Drug Administration for myelodysplastic syndrome (MDS), as well as a Phase II trial for ovarian cancer and a Phase II/III trial for pancreatic cancer.

The anti-cancer agents ESTYBON (rigosertib) and ON 013105, exploit differences in cell cycle regulation between normal and cancerous cells. This process allows for the destruction of tumor cells without effecting normal cells. In doing so, these agents are capable of overcoming several barriers associated with conventional cancer medicines with respect to:

• Improving efficacy
• Overcoming drug resistance
• Reducing the burden of toxicity

Ex-RAD® (ON 01210.Na), in clinical development for protection from radiation injury, reduces the damaging effects of radiation exposure by enhancing cell survival and DNA repair pathways.

The broad-based capabilities of Onconova span drug discovery and clinical development, from medicinal chemistry through Phase III clinical trials. All compounds are developed internally by leveraging expertise in state-of-the-art chemistry and cellular biology. These in-house capabilities are enhanced through several productive academic collaborations, government institutions, and by engaging in various high gain outside development activities.

Onconova has created a diversified proprietary library of novel chemotypes. Most of these new chemical entities are small, two- or three-ring molecules. These chemotypes provide a platform for identifying inhibitors of defined molecular and cellular targets. Many of our drug candidates are non-ATP competitive protein kinase inhibitors. Examples of some cellular mechanisms impacted by these compounds are described in the following pages.

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