Onconova Therapeutics: Rigosertib, An Orphan Designated Preleukemia Drug


Onconova Therapeutics (ONTX)

Lead Compound: Rigosertib

For the treatment of: Preleukemia or MDS

In 2016, 59,000 patients in the US estimated to have MDS. Of this 59,000, only 5,062 qualify or are eligible due to many factors like reception, stage, and risk factor, for rigosertib therapy. While this means demand is small, rigosertib has been granted orphan drug designation (drugs for rare medical conditions) which offers an array of benefits including premium pricing, financial incentives, and other exclusivities. Further, this drug is patented by Onconova through 2026.

Myelodysplastic syndromes are a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells. In a healthy person, the bone marrow makes blood stem cells (immature cells) that become mature blood cells over time.


Ras genes have been known as the “undruggable gene.” This is because there has been so little progress over the last several decades. However, a man named Dr. Reddy and a team of scientists have identified the first small molecule able to simultaneously inhibit the different signaling pathways activated by RAS oncogenes. This small molecule, also called rigosertib or ON01910.Na, acts as a protein-protein interaction inhibitor that prevents binding between RAS and signaling proteins (including RAF, PI3K and others) that turn a cell into a cancer cell.

Ras Pathways – Ras, a small GTP-binding protein, is an important component of the signal transduction pathway used by growth factors to initiate cell growth and differentiation. Cell activation with growth factors such as epidermal growth factor (EGF) induces Ras to move from an inactive GDP-bound state to an active GTP-bound state.

The PI3K/Akt/mTOR pathway plays a key role in the tumorigenesis of many cancers, including preleukemia. Onconova’s drug, Rigosertib, has been shown to inhibit PI3K/Akt/mTOR pathway signaling.

Onconova is using the inhibition of the PI3K/Akt/mTOR pathway to slow/ stop the cell cycle progression/ transformation in a specific cell that occurs when a molecule, such as a hormone or protein (cancer cell), attaches to a receptor on the cell membrane. The pathway is actually a cascade of biochemical reactions inside the cell that eventually reach the target molecule or reaction. Thus, the pathway is a method by which molecules inside the cell can be altered by molecules on the outside.


Rigosertib failed to meet its primary endpoint in 2014. However, post-hoc data showed that there were benefits from the drug in sub-group analysis. Basically, the drug didn’t work the way it was originally intended to, but could work better as an IV medication. The current Ph3 INSPIRE trial is testing Rigosertib as an IV medication versus the Physician’s Choice medication for targeting MDS.

There is now also an oral formulation of Rigosertib that had positive phase 2 data. This data showed that “a complete remission rate among higher-risk MDS patients was higher and with faster responses with oral rigosertib combination versus single agent azacitidine without substantially changing the adverse event profile.”

The combination of rigosertib and cisplatin displayed additivity or synergism at multiple concentrations. This indicates that the administration of both drugs has a greater effect on HNSCC cell viability than either drug alone.

What to look at:

Recent 10k Filing: https://www.sec.gov/Archives/edgar/data/1130598/000104746917002146/0001047469-17-002146-index.htm

Investors buying: http://www.insidercow.com/history/company.jsp?company=ONTX

My take on the insider buying: with the recent public offering, this insider buying shows a significant level of confidence in pipeline drugs passing their respective phases.

Poster data will be released TODAY (5/4/17) so watch for that. I will have BadDoc read it over and update this post accordingly.

Public offering closed: April 26th. The need for additional funding was discussed in their most recent 10k. Onconova’s burn rate is approximately $5.5 million per quarter. This means we can expect another funding coming within the next couple of months.



Onconova has several other products in its pipeline. As of this April, Onconova announced positive results for its pre-clinical CDK4/6 Targeting product.

Additional resources:



Upcoming catalysts:

Poster Presentation at 14th International Symposium on Myelodysplastic Syndromes

May 4th

Oral Presentation at Poster Presentation at 14th International Symposium on Myelodysplastic Syndromes

May 6th

First Quarter Financial Results and Conference Call and Webcast at 9:00 a.m. Eastern Time on Monday, May 15, 2017

May 15th

My take: Consider the financial state of Onconova and more funding needed eventually. The company also has a small market size for this drug because of the small qualified target population. Also, the fact that the company has no completed and marketable drugs under its 18 year old belt, I would only use this company as a swing trading opportunity with all of its upcoming catalysts. While the drug does look promising and useful, the growth potential does not seem to outweigh the risks.

Disclaimer: I do not own any shares of ONTX nor do I plan on opening any positions in the near future. I do not have any options as well. What is written here is solely my own opinion and I am receiving no compensation other than what I may receive from TickHounds.