For a little biopharmaceutical company, Ziopharm Oncology has attracted capital from some heavy hitters—a coup in an industry hit particularly hard by the financial market crunch. The two largest stakeholders are seasoned biotech investors: Fidelity Management, with a 13.75 percent stake, and Intrexon’s Randal J. Kirk, a well-known deal-maker and founder of several successful biotechs, with a 12 percent stake. So how did a 2004 startup build a $130 million bankroll during a tight capital market?
CEO Jonathan Lewis, M.D., Ph.D., a former surgeon at Memorial Sloan-Kettering Cancer Center, attributes his company’s appeal to a rigorous focus on developing lower-cost, more effective, cutting-edge anti-cancer drugs. “Coming up with products that will work in people is the real key here, but we also envision being able to get there in a straighter line and ultimately at a lower cost,” says Lewis, who likens Ziopharm’s approach to drug development to Henry Ford’s vision for revolutionizing manufacturing. “Ford was able to take a very expensive, artisanal automobile manufacturing process, copy that science and simplify it in terms of applying automated rules of manufacturing. We believe that the same or similar principles can be applied here again to control and bring costs down.”
Ultimately, of course, efficacy is the primary goal for Ziopharm, which is pursuing both small-molecule and synthetic-biology cancer treatments but cherry picking products with optimal potential. “The possibilities are vast, but we’re not going after every single option,” explains Lewis. “We’re taking a very disciplined approach to prioritizing those products that we think have the greatest chance of success, understanding that there’s always an element of randomness.”
In screening prospective treatments, the company seeks those that can meet what Lewis describes as a “high unmet need”—drugs that target a group of cancer patients for whom there are currently no real treatment options. For example, its small-molecule Palifosfamide is geared toward advanced sarcoma patients whose cancer is not responsive to surgery. “If it’s successful, it won’t replace anything, but rather be an additional new treatment in a high unmet-need niche,” says Lewis, who notes that Palifosfamide is currently in Phase III clinical testing and may receive FDA approval as soon as year-end 2013.
But Ziopharm’s real investor appeal may well be its efforts in synthetic biology, where the company is pursuing DNA-based therapies that trigger cells to produce powerful cancer-fighting proteins precisely where they are needed in the body. Ziopharm is currently testing a gene that will trigger a patient’s own cells to produce Interleukin-12 (IL-12), a potent, naturally occurring anticancer protein instrumental to the initiation and regulation of cellular immune responses. “We’ve taken the DNA for IL-12 and put it into people with melanoma, and we’ve shown that the protein made inside these people turns on the immune system in a way similar to Ipilimumab, a drug used to treat melanoma,” says Lewis. “This is early data, but the proof of principle is there. We can show that we can make the protein inside of people, using their own cells, and it’s working quite well—and that that’s having an effect on their immune system and then on their cancer.”
An important element of these treatments is that the protein production can be switched on and off, which is key because cancer therapies often involve striking a balance between fighting cancer and managing the toxicity of the treatment itself. For example, Ipilimumab treatment can cause severe and even potentially fatal adverse immunological effects due to T cell activation and proliferation. “Some of these proteins have been used before and proved too toxic, but we now have exquisite control over how much we deliver,” says Lewis. “That control enables us to increase effectiveness while reducing toxicity. With these protein therapies, we’re at the beginning of being able to radically change the treatment of many different kinds of cancer.”
Therapies that employ the human cell machinery to make protein, as opposed to producing proteins in labs—the core of the synthetic biology—are revolutionizing biotech. They also have the potential to do the same for medical care, asserts Lewis. “One of the lessons I learned while treating people with cancer is the incredible resiliency of the human body,” he says. “It is just beyond anything that anyone can imagine. I think if one can harness that power in the right way, it’s going to be a whole new world.”