This year will be a pivotal and likely very successful year for the company:
First off, Ziopharm is scheduled to have final data completed for primary outcome measure in June 2014 on Human IL-12 to treat melanoma. The main goal of this study is to evaluate the safety and tolerability of tumor injections of the drug.
With what has been seen thus far in the Phase I trial last year, in my opinion results should show that the drug works precisely well and that side effects can be controlled by the ability to turn on and off the drug by the Intrexon (NYSE:XON) trademarked RheoSwitch. So what is RheoSwitch? Intrexon's RheoSwitch® technology is a gene switch turned on by an activator ligand which can be used to regulate the gene expression with many applications.
To simplify, the engineered IL-12 drug is missing a component that when the ligand drug is orally given, it will fit into the IL-12 drug(previously injected into tumor site), in such a way as to supply the missing component that it activates the drug for a certain period of time close to 24 hours. So that if any unusual side effects would occur, they would be easier to control by either stopping continued therapy or temporarily pausing the therapy at any future point in time. Another advantage of this activator ligand drug (Veledimex) is its ability to cross the Blood brain barrier in the treatment of Glioblastoma. Animals treated with Ad-RTS-IL-12 survived throughout the duration of the study (100% survival at 75 days) with no significant adverse clinical signs observed. There is a posted journal article from a few months ago demonstrating the pre-clinical effectiveness of IL-12 in Glioblastoma but using a different vector system (adenoviral), and not quite as effective as the study that Ziopharm recently unveiled. It did demonstrate though that the IL-12 gene-based therapy can possibly be an effective way to treat glioblastoma and study the immune response with IL-12 treatment.
Of course we will need to see the human clinical trial results to start this summer, and how well that translates from murine model to human trials, but the preclinical evidence is most remarkable. I did search the internet to see if anything was as impressive on various other newer type investigation drugs, but was unable to find similar results. Of course it may be that the best future drug treatment could end up being a combo drug and human trial results will have to be proven, but the pre-clinical results are extraordinary. In the most recently released report it was revealed that they can control gene expression that leads to a sytemic immune response. The expression of Veledimex(activator ligand) is tightly controlled and showed high amounts of lymphocytes in not just injected tumors but in systemic ones as well. Even the apparent mild toxicity was fully reversible, and most impressive was the ability to reduce brain cancer stem cells.
So, in summary, of the IL-12 drug trials this year, there is the melanoma Phase II results update likely released soon, and the new Glioblastoma Phase I trial to start this June, as well as breast cancer Phase II update results due by year end.
Also, unknown or forgotten about by many Ziopharm investors and analysts alike is the Phase III (or Phase II spoken of by some) of the Palifosfamide drug in the Matisse study (small cell lung cancer) and the Phase II Germ cell (independent) clinical trial being conducted by Principal Investigator Dr. Lawrence H. Einhorn, both of which could have updates this year.
Some former investors were upset that Ziopharm chose not to wait for the OS results of Palifosfamide on the STS trial and to downgrade the Palifosfamide drug from the pipeline on the website, but in my opinion was a good strategy, since all along, if you do your research on RJ Kirk and Intrexon as well as Ziopharm, you will learn that it was always going to be that their primary future interest was to sell off the Palifosamide (old technology drug) and focus on the new Synthetic Biology platform. And, that way, if by surprise the Palifosfamide results turn out to be stellar in the future, a larger monetary sale can be completed. It was confirmed to me via email response from Ziopharm that their intention is to sell the drug Palifosfamide, irregardless of how these future trial results turn out. However, surely with good results, they would likely fare better with a sale than with poor results.
RJ Kirk and Dr. Broder and Dr. Reed are some of the most impressive minds behind Ziopharm and Intrexon:
RJ Kirk, is the man involved in quite a many successful biotech ventures and often successful buyouts by a major pharmaceutical company. It was my first biotech company that I invested in, Scios that was taken over by J&J in 2003, that I first learned about Mr. Kirk. He would later be rewarded in New River and Clinical Data, both companies taken over by a major pharmaceutical company. But as Mr. Kirk has spoken publicly, he is now more amazed than ever about his present venture, as mentioned by him in a respected journal article a few years back - that this new Synthetic Biology science is the most remarkable thing he has seen, and implies that we have seen nothing compared to what is coming in the future. And he has assembled some of the greatest minds of scientists on his team, such as Dr. Thomas Reed and Dr. Samuel Broder. One may want to read more about them to find out more about the brains behind the ZIOP/XON operation.
There is proof that IL-12 can be efficacious as a valid treatment option:
Turning to the previous history of IL-12 as a therapy, I located a particular article, Interleukin 12: Stumbling Blocks and Stepping Stones to Effective Anti-Tumor Therapy
The article goes into grand detail as to the many benefits of IL-12 and the many possible mechanisms that can benefit anti-tumor immune responses. Also the article mentions the various stumbling blocks and the main reasons for why the therapy did not work very well for Roche and others - primarily due to systemic administration, to include a single IL-12 infused loading dose given 2 weeks prior in consecutive treatments, that made side effects worse. This resulted in the FDA halting the trials of Roche in IL-12 at the time.
Since then, it was discovered that by administering the IL-12 directly into the tumor site and not systemically and no large loading dose, resulted in better side effect results, and a renewed excitement in the potential treatment using IL-12.
A much higher price level is coming relatively soon:
There have been several analysts reports out with opinions that the price of Ziopharm at present could easily exceed $10 by year end. One may want to seek out and research these reports on their own. One in particular is very excited about the increasing chatter of a partnership relatively soon, in part due to the present on/off technology and the future expansion of the pipeline by year end to include new cancer therapies with exosomes, T cells with chimeric antigen receptors, and stem cells, to be used for treating hematological cancers and solid tumors. Ziopharm has also mentioned on occasion that no others are as far along as they are and have mentioned the capability of developing multigenic type drugs that can target more than one gene at the same time with precision. Ziopharm has also revealed that they plan to file eight new INDs to start at year end and into 2015, immensely increasing their existing drug pipeline.
In summary, we can conclude the IL-12 drug does have anti-tumor immune stimulatory properties and is likely to be a therapy to be utilized in the future. The Phase I clinical trials in breast cancer and melanoma were such that it was shown that the engineered IL-12 drug with activator ligand can be efficacious with precise control, and with acceptable control of side effects too. While the optimal dose may have needed to be discovered in Phase II, there is a good likelihood (in my opinion) that future results will prove to be as good as expected. Also, while the human trials may not prove to be close to 100% survival in the glioblastoma after 80 days as in the murine trial, something close to that would be received as astounding in the medical community. Superior results to other treatments with a favorable side effect profile could elevate IL-12 into a combo treatment regimen (with a likely PD-1 drug), that could prove to be a major success. It would also accelerate a partnership in place with a major pharmaceutical company near any future positive data point this year, if not before.
Of course time will tell and we will need to see the human trial results as confirmation, but then again, with Ziopharm you have 3 good chance opportunities this year with the IL-12 trials. Also, one thing I keep hearing at the Ziopharm presentations from the CEO and others is that "no one can do what we can" and from what I have heard is that they are very confident with the present drug treatments and even more about what they have in store with certain multigenic (many targets at once) treatment INDs to come by next year. The addition of the new INDs could also add much value to the pipeline and therefore lift the stock price. It would depend on what future value discounted to present market cap that an analyst would apply. If it were say $50 million per IND added(or higher), one could easily visualize why it might be a good idea to purchase the stock well ahead of that pipeline addition.
And finally, this present stock price could turn out to be a very ideal price and time to own a good size position, looking back, in my opinion. Due to the recent likely bottoming in price action of many biotech stocks, along with the various biotech indexes(IBB/XBI), we could see a return to higher prices to where we were back in March. If that is to occur, ZIOP could easily return back to $5 on just what they have in the pipeline at present. However, as we get closer to data, and other mentioned potential catalysts, the stock price could easily go much higher. I highly recommend buying the stock at these price levels now under $4, in anticipation of many catalysts that could propel the stock price much higher.
Disclosure: I am long ZIOP, XON. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.