If biopharma had a Sputnik program, it would have to be stem cells. Research has been intensely competitive, and international. What has been missing, though, is clinical evidence of stem cell therapies’ efficacy and practicality.
Last month, some of the world’s leading stem cell researchers, as well as interested pharma company experts, met at the ninth Annual World Stem Cells Regenerative Medicine Congress in London, to discuss the state of the science, and what they’re doing.
Pluristem Theapeutics, an Israeli/U.S. company, is moving quickly to establish itself in this market, working with partners in the U.S., Europe and Korea, and taking an evidence-based approach to proving the efficacy of its PLX (placental expanded cells).
So far, PLXs have shown great promise in Phase I and II clinical trials. For example, in tests involving hip replacement patients with damaged muscle tissue, injections of PLX were shown to lead to a 500% increase in muscle force, and 315% increase in muscle volume after six months. In clinical trials on patients with critical limb ischemia, cell injections were found to reduce the risk of amputation or death by 59%. Pluristem plans to start a clinical trial to evaluate the cells for treating pre-eclampsia in pregnant women.
The company had started up eleven years ago to license and sell 3-D bioreactor technology that it had acquired from Technion University and The Weizman Institute, to companies that would use it to make stem cells.
Aberman, a mechanical engineer by training, decided to change the company’s direction radically, and to shift from equipment and devices to therapeutics, and use the bioreactor to culture stem cells instead. Pluristem uses placentas, which are readily available as medical waste, as a source for the cells. This eliminates ethical problems, as well as some of the incompatibility issues and delivery limitations that can be seen with injected donor cells. Pluristem has also customized the 3-D reactor to recreate an environment that, Aberman says, closely simulates the natural one.
The company is working on a variety of new clinical trials, and is also supplying its cells for a research project with the U.S. National Institute of Allergic and Infectious Diseases (NIAD) that is being funded by the US Department of Homeland Security. Its goal would be a simple intermuscular injection that anyone could use to prevent destruction of bone marrow after exposure to nuclear radiation (say, after a nuclear bomb explodes). Aberman says it is the only stem cell supplier to have an FDA and EMA-approved cGMP facility in place to generate clinical volumes of cells.
Before travelling to London to speak at the World Congress, Aberman talked about the company’s history and current strategy.
Contract Pharma: Please tell us about your history at Pluristem.
Zami Aberman: When I joined Pluristem nine years ago, I decided that we should change from being a device company to a therapeutic company. I had the idea to use placenta afterbirth as a source for stem cells, and combined that with the idea of using the 3-D bioreactor to harvest the cells. Today we have an approved cGMP facility in Israel, and branches in the U.S. and Israel. We are a US/Israeli company with 165 employees, including 17 Ph.D’s and three M.D.’s.
CP: We’ve all been in awe of the videos of crippled mice walking after stem cell injections, and have heard of global stem cell research projects for quite a while now. What is needed to push the technology to the next level?
AZ: I truly believe that cell therapy will be the next generation of biopharma development. But to prove that, you must first show that it is real and can actually help patients. Right now there is a lot of very interesting work going on around the world, but what is missing is any demonstration of significant outcome in clinical studies, and clear improvement in patient. Twenty years ago, this same situation existed with antibodies, and there were few clinical studies. Contrast that with today’s picture.
Cell therapy is clearly the future of the industry. There are already a handful of players in this business today, such as Mesoblast in Australia, and Athersys in the U.S., specializing in allogeneic cells.
CP: What partners are you working with to develop the technology?
AZ: We have approval to conduct clinical trials in the U.S., Europe, Israel, Australia and South Korea. We’ve outlicensed the use of PLX-PAD for PAH to United Therapeutics in the U.S. They do all the clinical development for us. We lead the other clinical studies. We also work with CHA Bio and Diostech Co., Ltd., of South Korea, which conducts clinical studies in Korea. In R&D we supply cells to NIAD, which is financing research that is testing the use of stem cells to treat radiation symptoms up to 48 hours after exposure. The project is for the U.S. Department of Homeland Security, and two stages have been successful so far. We also work with Texas A&M’s Health Science Center, on pre-eclampsia and with Duke University and Mount Sinai on other studies. In Europe, we work with Charite in Berlin and in Israel with Technion, among others.
CP: How does the bioreactor work?
AZ: The 3-D bioreactor makes the microenvironment a bit more like the natural environment in which stem cells are found. That way, when we harvest cells, we inject cells that have been cultured in an environment that simulates real conditions.
CP: Why are you focusing on South Korea, and do you have plans to move into the Japanese market? Are they changing their restrictive position on clinical trials?
AZ: South Korea is advanced in its regulatory approach to approving cell therapies. For orphan drugs, you can market there after a successful Phase II, as long as you continue safety and efficacy studies, so you can finance that activity by selling product. This situation is unique to Korea.None of the global regulatory agencies have approved this approach, although Japan seems to be moving in that direction, and a formal announcement is expected this November that could open the market to advanced therapies. The U.S. has different paths to approval. Nobody knows what the final regulatory approval process will look like. But we do know that our cells address a real unmet medical need, and that we can generate positive outcomes in the clinic.
CP: Why did you decide to use placental cells?
AZ: With this approach, you take cells from the borderline between mother and baby, two separate individuals. It turns out that this approach allows for greater flexibility in administration mode. The cells can be injected subcutaneously, via IV, or directly into the muscle.
Nine years ago, it was common dogma that the Mode of Action (MOA )of stem cells was replacing injured tissue. We didn’t think about things in an allogeneic way, or foresee problems in matching between patient and donors. At the end of the day, cells secrete a cocktail of proteins, so the cells become a sort of sophisticated drug delivery system.
Another benefit is the fact that it is easy to get supply, since placenta is medical waste and materials are donated. We can start processing four hours after birth and no ethical issues are involved. One placenta can, in theory, supply enough material to provide cells to treat 10,000 patients.