1. Why stem cells? Of all the biotech areas you could have worked on, what inspired you to work on stem cells? Was there a defining moment, for example, in school or during your experience in a lab, when you first heard about them that inspired you?
GVB: Actually, we didn’t start out with a focus on stem cells or regenerative medicine. In fact, in the beginning we were more interested in the concept of non-viral gene therapy as a novel approach to treating disease. The team of us that started Athersys were all interested in building a company committed to developing innovative products and technologies that could help us address areas of unmet medical need, and to doing great science. We believed that by focusing on innovative and cost effective solutions to address big challenges, we could make a difference, and also be in the best position to build a great company and create value for our shareholders. Initially, we were committed to be the first group to create a human artificial chromosome, essentially a synthetic and miniaturized version of a normal chromosome. We envisioned this platform could be useful as a non-viral vector for gene therapy, and would enable us to address a range of genetic disorders. When we published our work, demonstrating we had established the ability to make synthetic microchoromosomes, it got a lot of scientific and media attention internationally. That work also shaped our thinking several years later when we became aware of an important new discovery in the field of stem cell biology. The defining moment for me, related to stem cells and the concept of regenerative medicine, really was meeting Catherine and doing a deep dive with our team looking at her work. It became pretty clear to me that her team’s discovery had potentially enormous ramifications. Namely, if one could produce a stem cell therapy in a scalable and consistent manner, that could safely be administered like type-O blood, and that could promote healing and tissue repair in multiple ways, it could transform medicine as we know it in a range of areas.
2. How’s Athersys doing?
GVB: Despite the challenging economic environment of the past several years, I think we’re doing great. We’ve survived a lot of storms, our pipeline continues to grow and mature, and investors are beginning to recognize and appreciate the value creation potential from our portfolio of programs. Now it’s largely about executing well, and making sure we have the resources to do what we need to do. If we stay focused and achieve what we are capable of, I’m confident that one day we’ll be widely recognized as a global leader in the industry.
3. I was recently looking at clinicaltrials.gov and saw 5 Athersys trials listed*. Can you briefly fill us in on how these are going?
GVB: Right now we have 5 clinical stage programs – this includes three in the inflammatory and immune disease area (an ongoing Phase 2 trial to treat patients with Ulcerative Colitis, part of our partnership with Pfizer; a proposed Phase 2/3 trial for preventing GVHD in patients with leukemia or related conditions that is currently under review at the FDA, and a third program in the liver transplant support area). We also have an ongoing Phase 2 trial in the neurological area (to treat patients that have suffered a stroke), and a Phase 2 trial authorized by the FDA for treating patients that have suffered an acute myocardial infarction (heart attack). We’re very excited about the stroke and IBD trials that are ongoing and actively enrolling patients. The trial with Pfizer is essentially a step on the way to evaluating MultiStem as a treatment for Crohn’s disease, which is where I expect the longer term focus to be in IBD. But the stroke trial could be a game changer, in a lot of ways. Unless you’ve had a family member or loved one that has suffered a serious stroke, it’s difficult to understand just how big an area of need it is. There are roughly 2 million people a year that suffer a stroke in the U.S., Europe and Japan, and very few patients actually get treated with tPA, the clot dissolving agent that has to be administered within 3 – 4 hours after the stroke. That time frame is just too tight, and most patients don’t get to the doctor in time. We and our collaborators have published work from preclinical studies that suggests that we can give MultiStem in more practical time frame following a stroke, perhaps several days. If it helps patients recover, it could change stroke clinical care, and it’s also an enormous commercial opportunity – which is something that gets our shareholders very excited. In addition to these programs, we have done a lot of exciting work in other disease and injury areas, especially in inflammatory & immune, neurological, and cardiopulmonary indications. So we’re actually well positioned to advance quite a few other programs into proof of concept clinical trials when we have the resources to support all that activity. We don’t expect everything to work, but if we are successful in even a few of these areas, it will be a big deal.
4. MultiStem seems like a “Renaissance” product that can do many things. Is there one particular application that it does best? Is there anything it can’t do?
GVB: The interesting thing about stem cells as therapies is that they can do more than just one thing. Early on, everyone as thinking about cells simply as a replacement therapy. However, our experience with MultiStem shows that these cells actually home to sites of tissue damage, inflammation and injury, by responding to certain cues in the body. We also know they dynamically interact with other cell types and organs in the body, and can promote healing and repair in a variety of ways – primarily by producing multiple factors that enhance repair. That represents a huge potential advantage over traditional therapeutic approaches, such as pharmaceuticals or biologics that typically only do one very specific thing. We and our international network of collaborators have seen that MultiStem can reduce inflammatory damage, promote healing and repair through immunomodulatory mechanisms, protect “at risk” cells and tissue through cytoprotective, neurotrophic or other effects, as well as promote formation of new blood vessels in regions of ischemic injury. That is a really powerful combination of effects. I think it’s too early to say where the best clinical fit or biggest impact might be – clearly something like stroke could be one of them. Working with a broad international network of collaborators, we’ve seen promising results in quite a few disease areas, but not everything we have tried has worked the way we hoped. It is fair to say we’re incredibly excited about the potential across a range of areas. Ultimately, however, we have to determine where our best opportunities are by running rigorously designed clinical trials, that are properly controlled and adequately powered. These types of trials are the best way to determine whether we are seeing a robust therapeutic effect, as well as consistent safety. We’ve seen very good safety so far, and some promising signs of efficacy, but we can’t take that for granted.
5. I’m very interested in your work with ARM as Chair as well. What has that experience been like?
GVB: Serving as Chairman of the Alliance for Regenerative Medicine for 2 1/2 years was an extremely challenging and rewarding experience. When the leadership of the Alliance first asked me to consider it, I was of course, honored. I also had to think about it, because I knew it would be a lot of work, and I probably wouldn’t see much of my family for a couple of years. I realized, however, that this was a rare opportunity to really help shape an emerging field that has truly transformational potential. I was very happy to see the kind of growth we experienced, and the progress on multiple fronts, and I’m confident that will continue with the new leadership team. When you think about the challenges we face as a society, in terms of areas of significant unmet medical need, an aging population that will require much more in terms of health care resources in the years ahead, and the financial pressures created by the growing demands on Medicare and Medicaid, it becomes pretty obvious that we need to do something. Otherwise, we’re left with a world of healthcare rationing, which nobody really wants. In my view, technological innovation provides the ultimate solutions to the challenges we face, and in the health care area, I think regenerative medicine has more potential than anything else. That’s why we need a national strategy, and why I think it makes sense to establish a national or even international initiative in regenerative medicine, that is tantamount to the human genome project. It’s a strategic investment that could pay huge dividends for all of us.
6. I recently did a post arguing that stem cells are not a zero sum game. In other words, what is good for one type of stem cell (iPSC, adult, embryonic, and now we can add SCNT embryonic) is not necessarily bad for others, and vice versa. In fact, I see the knowledge and advances related to the different kinds of stem cells as being in certain cases additive and even synergistic. Do you buy my argument? Why or why not?
GVB: I absolutely agree. I think this logic applies on multiple levels, including understanding basic biology, as well as development of technology related to cell therapy manufacturing and other areas. It’s a bit naïve to think that only one approach will work, or adequately address all the areas of unmet need. I believe that allogeneic, autologous, and a range of other approaches have tremendous potential. I also think that science has proven that it can help us overcome areas where society has concerns, or reservations about important issues. A good example of this is the development of iPSC and related technologies, and the emergence of new technologies in the tissue engineering space. All of these things are positive advancements, and can help us get to where we want to be as a society, and do so in a way where people are comfortable. I see it as a “rising tide” phenomenon. As we experience more and more success in various areas, it will generate more and more confidence and excitement.
7. Besides Athersys, can you give us one or two other stem cell-related biotechs that get you excited and why?
GVB: Wow. I could give you a long list of things I’m excited about. I’m excited by products that are already on the market and helping people, and the many things I see coming. I think the next 50 years are going to be filled with exciting innovation in the cell therapy and tissue engineering space. It would be very hard to pick just one or two. The notion of being able to really help someone with a serious neurological condition like stroke, Alzheimer’s or Parkinson’s, heart disease or critical limb ischemia, traumatic brain injury, spinal cord injury, diabetes, or many other conditions where traditional medicine doesn’t have an answer is pretty exciting. It’s a long list of challenges and opportunities – and some will clearly be more difficult than others – but we don’t need to be successful in all of them in order to have a meaningful impact.
8. What is your perspective on the non-compliant operations out there? How seriously (or not) should we be concerned about them?
GVB: This is an area I worry about a lot. The biggest thing I worry about is when a desperate family or individual buys into hype around an unproven treatment, and they then spend their life savings on a procedure based on the belief that they are going to be “cured” – when in fact there is no legitimate data to support that hope. We have to be extremely vigilant about these types of activities.
9. What’s your view of compassionate use of stem cell-based therapies?
GVB:I very much believe that therapies that have a demonstrated record of safety can be appropriately advanced into compassionate use programs, provided there is appropriate regulatory oversight, and the patient or the family member or guardian making the decision on behalf of the individual provides informed consent. Honestly, in many instances, that may the best way, if not the only way to effectively determine whether a therapy that has demonstrated safety can help someone that is desperately in need, and who may have no other option. This is especially true in indications where running a traditional clinical trial may be very challenging, or even impossible.
10. What potential changes do you envision in the regulatory arena in coming years? Is there reason for hope for streamlining clinical development, particularly for treatment of patients with unmet needs? How do we balance innovation with safety?
GVB: I think there are several reasons to be very optimistic, and multiple things are already happening. Last year the Biotechnology Industry Organization (BIO) led the charge to work with the FDA to implement some important legislation, FDASIA (the FDA Safety and Innovation Act), which included a renewal of PDUFA (the Prescription Drug User Fee Act) and some important new regulatory reforms that will soon go into effect. A lot of groups, like ARM supported this effort. These reforms include things like a broadening of the Accelerated Approval pathway, the creation of a “Breakthrough Therapies” paradigm, and other initiatives that will meaningfully shorten development times in areas of unmet medical need. Those are all really positive steps for the field of regenerative medicine. Ultimately, however, we all have to remember that the FDA is committed to ensuring patient safety, and I believe we have to not only acknowledge and respect that, we should share that commitment. But it’s also clear that given the magnitude of the need and the challenges we face, the FDA is now willing to think about things a bit more creatively, and we can work together in a collaborative way to make these new technologies a medical reality faster. That’s a big step in the right direction.
*there are technically 6 trials listed, but one has been withdrawn.
More on Dr. Van Bokkelen. From 2010 through 2102 Dr. Van Bokkelen served as Chairman of the Alliance for Regenerative Medicine (ARM), the leading policy and advocacy voice for the field of stem cells and regenerative medicine. He is also the Chairman of the Board of Governors for the National Center for Regenerative Medicine, and serves on a number of other boards, including the Biotechnology Industry Organization’s ECS board of directors (from 2001 to 2004, and from 2008 to present), the McGowan Institute for Regenerative Medicine and the Regenerative Medicine Foundation. He received his Ph.D. in Genetics from Stanford University School of Medicine, his B.A. in Economics from the University of California at Berkeley, and his B.A. in Molecular Biology from the University of California at Berkeley.