Ziopharm Oncology(ZIOP) - Get Report and Oncosec Medical(ONCS) - Get Report are developing similar but competing gene therapies to deliver interleukin-12, a protein which stimulates the immune system to kill cancer cells, directly into tumors.

Ziopharm's current enterprise value is almost $800 million, while Oncosec has a negative enterprise value of $2 million. But guess which company has better clinical data, to date?


Ziopharm is also developing other anti-cancer therapies using engineered T cells, commonly referred to as CAR-T. Does this research justify Ziopharm's valuation?

No, because Ziopharm's CAR-T pipeline is inferior and straggling behind competitors like Novartis (NVS) - Get Report , KitePharma (KITE) and Juno Therapeutics (JUNO) . All three companies are expected to secure regulatory approvals and reach the commercial market with their CAR-T products years ahead of Ziopharm.

Ziopharm is its own mini biotech bubble, held aloft unjustifiably because of its interlocking relationship with Intrexon(XON) - Get Report , the synthetic biology company majority owned by R.J. Kirk, the deal-making health care billionaire.

If tracking stocks were still in vogue like they were in the late 1990s, Ziopharm would be the biotech tracking stock of Intrexon. Ziopharm is dependent on Intrexon scientifically and financially. Ziopharm's interleukin-12 gene therapy technology was licensed from Intrexon. Kirk is a major investor in Ziopharm and helps the company raise additional money. Ziopharm acquired its CAR-T platform in partnership with Intrexon.

The Intrexon relationship has been beneficial to Ziopharm so far because Kirk spins a good story about using synthetic biology to invent new drugs to fight cancer. Ziopharm owes a lot of its $800 million enterprise value to Kirk's ability to woo investors.

But the Kirk-Intrexon cancer-fighting story doesn't hold up to scrutiny when you examine Ziopharm's clinical data compared to its competitors like the much smaller Oncosec.

Ziopharm's lead anti-cancer gene therapy Ad-RTS-hIL-12 uses a virus encoded with DNA to express interleukin-12, or IL-12, a powerful protein known to stimulate T cells in the immune system to kill cancer cells. This virus is injected directly into a patient's tumor. Once there, the gene and the production of IL-12 are controlled using an oral drug, veledimex. By raising or lowering the veledimex dose swallowed by patients, Ziopharm says it can control the production of IL-12 to optimize the killing of cancer cells in both injected and non-injected tumors, while also limiting the dangerous side effects (sometimes fatal) caused when IL-12 is administered systemically.

Melanoma is known to be a cancer most susceptible to immune-stimulating drugs, so this is where Intrexon first focused the development of Ad-RTS-hIL-12 + veledimex. Ziopharm took over that work when it licensed the gene therapy from Intrexon in January 2011.

Last September, Ziopharm and Intrexon presented results from a phase II study of Ad-RTS-hIL-12 + veledimex in melanoma patients at a cancer immunotherapy conference in New York City. In a press release, Ziopharm described the results this way:

Ad-RTS-hIL-12 and veledimex in patients with melanoma was found to increase in the immune cytokine IL-12 and downstream cytokines, IFNg, IP-10 and IL-10, resulting in a significant increase in tumor infiltrating lymphocytes both locally, in injected lesions, and systemically, in non-injected lesions.

The actual poster presented at the meeting tells a much different, more negative story: Ad-RTS-hIL-12 and veledimex was almost completely ineffective at shrinking melanoma tumors in patients enrolled in the study.

Ziopharm and Intrexon enrolled 26 melanoma patients into the study. All were treated with Ad-RTS-hIL-12 and veledimex. Inexplicably, seven patients were omitted from the efficacy analysis. Of the remaining 19 patients, only two patients achieved a partial response following treatment with Ad-RTS-hIL-12 and veledimex.

Two melanoma patients with objective tumor shrinkage out of 19 is a 10% partial response rate. Adding back the seven missing patients into the denominator (a truer, more conservative way to measure efficacy) lowers the partial response rate to 8%.

Based on these results, Ziopharm and Intrexon discontinued clinical work on Ad-RTS-hIL-12 and veledimex in melanoma.

Oncosec also injects DNA encoded to produce IL-12 into tumors, but instead of an activating pill, the company uses short pulses of electricity through small needles to get the DNA into the cancer cells and start production of IL-12.

Results from a phase II study of OncoSec's ImmunoPulse DNA therapy in 30 melanoma patients were presented at medical meeting in 2014. In 28 evaluable patients, the objective response rate was 32%, including an 11% complete response rate.

Neither of these phase II studies provide definitive proof of efficacy and it can be challenging to compare results across two different studies, but based on available data, Oncosec's IL-12 gene therapy looks more effective than anything produced by Ziopharm and Intrexon in melanoma.

After giving up on melanoma, Ziopharm and Intrexon have shifted Ad-RTS-hIL-12 and veledimex to breast cancer and glioblastoma, a type of brain cancer.

In a study of 12 breast cancer patients treated with Ad-RTS-hIL-12 and veledimex, there was a single patient with a partial response, according to data presented alongside the melanoma results at the same November 2015 cancer immunotherapy meeting.

On Wednesday, Ziopharm disclosed interim results from a phase II study of Ad-RTS-hIL-12 and veledimex in 11 patients with recurrent glioblastoma. Ten of the 11 patients are still alive with a median follow-up of six months.

Ziopharm called the interim survival results promising because all the enrolled patients had failed standard therapy and nine of the 11 had failed salvage therapies.

However, interpreting survival results from a single-arm study lacking a comparator arm is challenging, at best. Ziopharm makes it even more difficult by failing to disclose any specific information about the baseline characteristics, prior therapies or subsequent therapies used to treat the enrolled patients. The study is also set up to assess the ability of Ad-RTS-hIL-12 and veledimex to shrink brain tumors, but Ziopharm declined to provide those data on Wednesday.

Additional data from the Ad-RTS-hIL-12 and veledimex study in glioblastoma will be presented at the American Society of Clinical Oncology annual meeting in June.

Ziopharm plans to study Ad-RTS-hIL-12 and veledimex in combination with other cancer immunotherapy drugs like the PD-1/PD-L1 checkpoint inhibitors. But here, too, the company is well behind competitors who are already testing hundreds of different combination cancer immunotherapies.

Ziopharm's $800 million enterprise value makes little sense when judged against the poor performance of its cancer therapy pipeline to date. Only the R.J. Kirk/Intrexon lifeline keeps the stock price as high as it is.

Adam Feuerstein writes regularly for TheStreet. In keeping with company editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback; click here to send him an email.