PIPELINE

Product Pipeline

Onconova is focused on discovering and developing targeted, small molecule product candidates for the treatment of cancer.

Program	Indication	Preclinical	Phase 1	Phase 2	Phase 3

Corporate Programs
Narazaciclib (Daily)	Solid Tumors
Narazaciclib (3 wk. on 1 wk. off)	Solid Tumors
Narazaciclib + Letrozole (Both daily)	2L / 3L Low Grade Endometrioid Endometrial Cancer

Investigator-initiated Programs
Oral Rigosertib + Nivolumab	CPI Resistant KRAS-mutated NSCLC
Oral/IV Rigosertib	RDEB-associated SCC
Oral Rigosertib + Pembrolizumab	CPI Resistant Melanoma

NSCLC: Non-small cell lung cancer;, RDEB: Recessive dystrophic epidermolysis bullosa; SCC: Squamous cell carcinoma; CPI: checkpoint inhibitors

PLATFORM

Our product candidates, designed for targeting cancer, are derived from a novel chemistry platform and cell-based differential screening, which together define our discovery approach. Most are simple two-ring or three-ring structures that are built around a common core or signature element. Most kinase enzymes require the binding of adenosine triphosphate, or ATP, to function. Our proprietary libraries consist of ATP mimetics that act as inhibitors by competing with ATP at the ATP binding site as well as at the non-ATP binding sites of kinases. We believe that this approach provides a more selective way to inhibit these important enzymes which are deregulated in cancer cells.

The Onconova platform has yielded an internal pipeline of experimental clinical product candidates.

NARAZACICLIB
(ON 123300)

Narazaciclib is a multi-targeted kinase inhibitor targeting cyclin-dependent kinases (CDK) 4 and 6, AMPK-related protein kinase 5 (NUAK1/ARK5), colony-stimulating factor 1 receptor (CSF1R), tyrosine-protein kinase kit (Kit), and additional kinases. These kinases are key to cellular pathways involved in DNA synthesis and normal cell cycle functions. Due to Narazaciclib’s broad kinase inhibitory profile, it has been shown to not only result in cell cycle arrest but also to induce apoptosis. As a result, Narazaciclib may be able to treat a broad range of cancers.

Notable kinase targets include CSF1R and ARK5. When the CSF1R ligand is bound, it promotes the accumulation of immunosuppressive tumor associated macrophages (TAMs) in the tumor microenvironment. High levels of TAMs in tumors are associated with poorer patient outcomes. Therefore, inhibition of CSF1R can promote an anti-tumor immune response. Narazaciclib also inhibits ARK5, making it more difficult for the tumor to grow in hypoxic conditions.

Because Narazaciclib differs from other CDK4/6 inhibitors in that it inhibits a different set of kinases, its toxicity profile may be reduced, thereby limiting the adverse effects. Narazaciclib also has the potential to be administered as a single daily dose with no breaks, limiting the ability of cancer cell regrowth. Narazaciclib may be used where other CDK4/6 inhibitors have failed or where tumors have become resistant to other drugs.

RIGOSERTIB

Rigosertib is a small molecule that inhibits multiple cell signaling pathways that drive cancer growth while having little effect on normal cells. In contrast to many kinase inhibitors, Rigosertib is a protein inhibitor that does not interact at the ATP binding site, but acts via allosteric inhibition. Its inhibitory profile enables it to target multiple growth and survival pathways, providing an opportunity to treat multiple cancer types. Rigosertib appears to be an immuno-modulator that can turn “cold” tumor microenvironments “hot”, meaning it can change the tumor environment from immunosuppressive to immuno-stimulatory by increasing neoantigen expression like CD40 on the tumor cells and thereby recruiting host T cells.

Rigosertib interferes with the RAS/RAF/MEK/ERK and PI3K/AKT pathways in several ways. First, Rigosertib can act via the RAS-binding domain — independent of RAS mutations — disrupting the RAS/RAF heterodimers and the MEK pathway, reducing the phosphorylation of ERK which is necessary for cancer cell division. This binding can also cause increased reactive oxygen species (ROS) in the cell, inhibiting a second pathway which activates the ERK pathway. Rigosertib also inhibits cell mitosis, most likely due to the inhibition of the PLK-1 pathway and interference with microtubule formation, which is critical to proper spindle assembly and mitotic cell division. These mechanisms result in apoptosis of the tumor cells.

Rigosertib is available in both oral and IV formulations and is being investigated as a single agent therapy for recessive dystrophic epidermolysis bullosa (RDEB)-associated squamous cell carcinoma and in combination with PD1 checkpoint inhibitors in immune oncology-refractory KRAS mutated non-small cell lung cancer and malignant melanoma.

PARTNERING OPPORTUNITIES:

Onconova technologies and products are developed utilizing our proprietary chemistry platform. Some of our product candidates are partnered with pharmaceutical or biotechnology companies for advanced development. We endeavor to retain a participating role as we expand our competency horizon to include commercialization capabilities.

To discuss partnering opportunities with Onconova please contact info@onconova.us.

CURRENT PARTNERSHIPS:

SPECIALISED THERAPEUTICS ASIA

December 18, 2019 – Onconova entered into a Distribution, License and Supply Agreement with Specialised Therapeutics Asia (“STA”). Headquartered in Singapore, STA is an international biopharmaceutical company established to commercialize new therapies and technologies to patients throughout South East Asia, as well as in Australia and New Zealand. The Agreement grants STA the exclusive rights to commercialize rigosertib in Australia and New Zealand.

For more information please refer to the Press Release of Dec. 18, 2019

KNIGHT THERAPEUTICS INC.

November 21, 2019 – Onconova entered into a Distribution, License and Supply Agreement with Knight Therapeutics Inc., a Canadian-based specialty pharmaceutical company focused on acquiring, in-licensing, selling and marketing innovative prescription and over-the-counter pharmaceutical products. According to the Agreement, Knight shall have the exclusive rights to commercialize rigosertib in Canada.

For more information please refer to the Press Release of Nov. 21, 2019

MISSION BIO

Aug. 12, 2019 – Onconova entered into a Partnership with Mission Bio to advance precision oncology clinical trials employing single-cell genomics. The alliance will leverage Mission Bio’s Tapestri Platform to investigate Onconova’s novel cancer therapy rigosertib, through clinical trials.

For more information please refer to the Press Release of Aug. 12, 2019

PINT PHARMA

March 5, 2018 – Onconova entered into a License Agreement with Pint Pharma GmbH to commercialize rigosertib in Latin America. Pint Pharma is a Europe based pharmaceutical company focused on the development, registration and commercialization of specialty-based treatments for the Latin American market.

For more information please refer to the Press Release of March 5, 2018

NATIONAL CANCER INSTITUTE/NATIONAL INSTITUTES OF HEALTH

Jan 04, 2018 – Onconova entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). Under the terms of the CRADA, the NCI will conduct research, including preclinical laboratory studies and a clinical trial, on rigosertib in pediatric cancer associated RASopathies.

For more information please refer to the Press Release of Jan. 4, 2018

HANX BIOPHARMACEUTICALS, INC.

Dec 19, 2017 – Onconova entered into a License and Collaborative Development Agreement with HanX Biopharmaceuticals, Inc. for the further development, registration, and commercialization of narazaciclib (ON 123300) in China. Narazaciclib (ON 123300) is a first-in-class dual inhibitor of CDK4/6 + ARK5, which is currently in a dose-escalation and expansion Phase 1 trial in China. This compound has the potential to overcome the limitations of current generation CDK 4/6 inhibitors.

For more information please refer to the Press Release of Dec. 19, 2017

SYMBIO PHARMACEUTICALS LIMITED

July 2011 – Onconova and SymBio Pharmaceuticals began a collaboration to develop and commercialize rigosertib in Japan and Korea. Under the terms of the agreement, SymBio has an exclusive license for Japan and Korea and will develop and commercialize rigosertib in these countries. Onconova received an upfront payment and will receive milestone payments tied to the progress of rigosertib development, as well as sales milestone payments plus royalties on net sales. Onconova supplies drug product for clinical trials conducted by SymBio in Japan.

PIPELINE

Product Pipeline

Program

Indication

Preclinical

Phase 1

Phase 2

Phase 3

PARTNERING OPPORTUNITIES:

CURRENT PARTNERSHIPS:

Onconova Therapeutics

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