There is no shortage of approaches to slow or reverse the human aging process among biotechnology companies. However, AgeX Therapeutics’ CEO Dr. Michael West says increasing a person’s “healthspan” should also be included in anti-aging research. AgeX Therapeutics, based in Alameda, Calif. (near San Francisco), was founded by Dr. West in 2017 with a mission to apply technology related to cellular immortality and pluripotency to human aging and age-related disease. The company’s technology platform has three facets: Pluripotent stem cell-derived progenitor cell lines representing over 200 types of cells in the body (PureStem technology); HyStem matrices; and induced tissue regeneration (iTR) – the latter being an emerging technology aimed at mimicking the regenerative mechanism of the Mexican Salamander, toward inducing regeneration of tissues.
Before launching AgeX, West served as CEO at BioTime, parent company of AgeX, and a biotech company where he continues to serve as co-CEO. BioTime focuses on degenerative aging diseases. Prior to that, he was president, CEO and CSO of Advanced Cell Technology, which, as Ocata Therapeutics, was acquired by Astellas Pharma of Japan in 2016. In 1990 West also founded Geron (short for Geronology) Corp. While at Geron, he also created the research consortium that led to the first isolation of human embryonic stem cells. West received a B.S. degree from Rensselaer Polytechnic Institute in 1976, an M.S. in Biology from Andrews University in 1982, and a Ph.D. from Baylor College of Medicine in 1989, concentrating on the biology of cellular aging. Having written numerous articles in peer-reviewed scientific journals, he is also the author of “The Immortal Cell: One Scientist’s Quest to Solve the Mystery of Human Aging” (DoubleDay, 2003). He has been featured in a variety of media outlets including The New York Times, The Economist, CNBC, and NBC’s “Meet the Press.”
WuXi AppTec Communications, as part of a new industry series, recently interviewed West about the clinical direction and goals of AgeX’s anti- aging programs and what the future holds for research extending human life as well BioTime’s work in aging diseases.
WuXi: How do you define aging? Is it an illness itself? Is it a specific group of diseases?
Mike West: This is an interesting question, isn’t it? Historically, medical researchers would have answered in the negative, that is, that aging is not a disease. They would have said that it is part of the normal life cycle. However, it is very clear that modern research is beginning to see aging in a new light. The reason for the shift, I believe, is the recognition that some diseases, for instance those that cause premature aging disorders like progeria (Hutchinson-Gilford syndrome), are called diseases. And children with progeria have multiple age-related pathologies similar to normal aging such as atherosclerosis, alopecia, osteoporosis, and stroke; it’s just that they occur earlier in life. Still, we label progeria as a single disease with multiple sequelae. So, in the same way, many researchers, while perhaps not calling aging a disease, are nevertheless treating it like one in that they are performing research to understand the process and devise novel technologies to intervene in it.
WuXi: What is your anti-aging technology and how are you applying it?
Mike West: At AgeX Therapeutics, we are applying the biology of the immortal regenerative potential of the germ-line to human aging and age-related degenerative disease. By this we mean that there are some cells in human biology that don’t age. The human species continues from generation to generation in an unending pattern because some reproductive cells called “germ-line” cells (examples being sperm and egg cells), can escape aging. Babies are, after all, born young. In addition, early in human development, tissues can regenerate if injured. This property is lost with age. Animals that have body cell types that combine these two traits (i.e. can replicate indefinitely and can regenerate endlessly) often show no signs of aging. Using modern molecular technologies, AgeX is translating the biology of immortal regeneration to distinct applications in age-related disease.
WuXi: What is the goal of your technology? Is it improving quality of life for more years or extending the average life span?
Mike West: One of our primary goals at BioTime, where I serve as co-CEO, is to positively impact the lives of others and this can be clearly seen in our lead Ophthalmology program, OpRegen. As a reminder, we are studying OpRegen, a retinal pigmented epithelium (RPE) cell replacement therapy, which is in a Phase I/IIa multicenter trial for the treatment of late-stage, dry age-related macular degeneration (dry-AMD). There are currently no approved therapies for dry-AMD and dry-AMD accounts for approximately 90% of all AMD cases, which is the leading cause of blindness in people over the age of 60. It is further estimated that there are approximately 30 million people worldwide currently living with this debilitating disease that will most likely end with blindness. AMD is a gradual, progressive, painless deterioration of the macula, the small sensitive area in the center of the retina that provides clear central vision. Damage to the macula makes facial recognition, reading and driving difficult or impossible. So back to your initial question, is the goal of our technology to improve quality of life for more years or extending the average life span. I think the answer is pretty clear…If we were able to provide someone with the ability see for many more years. To provide someone with the ability to enjoy the simple everyday tasks many of us take for granted: to read a book, drive a car, see their grandkids playing again, their regained quality of their life would be unquantifiable. For me, for us at BioTime, this is one of our main goals that we are focused on.
From the AgeX perspective, I believe there is a consensus among researchers and patients as well that extending human lifespan without a corresponding extension of healthspan provides no useful purpose. In other words, living longer but in an increasingly decrepit state is undesirable. As a result, the first priority of most aging researchers, and AgeX as well, is to increase first and foremost the human healthspan. But since this extension targets the root causes of aging, we believe science will also be extending the human lifespan as well.
WuXi: What will define success for your anti-aging technology?
Mike West: My answer may surprise you. Success is not about product approvals or generating billions in sales. Here at BioTime, success is about the difference you make in other people’s lives. That’s, in part, why we are focused in the therapeutics areas we are: aesthetics and ophthalmology. Our lead aesthetics product is called Renevia and it met its primary endpoint in a European pivotal trial in patients with HIV-associated lipoatrophy. HIV-associated lipoatrophy is a severe form of lipoatrophy characterized by the pathological loss of body fat tissue from under the skin. The resulting facial wasting ages the individual’s appearance prematurely and can impact their self-esteem and quality of life to the point where these individuals dread being seen in public because of the negative stigma they can receive from others. While we met the primary endpoint in this pivotal trial, the satisfaction we feel knowing we can help these individuals means much more to us here at BioTime. Switching to our lead ophthalmology program – OpRegen, which is in a clinical trial for the treatment of dry age related macular degeneration or dry-AMD. There are currently no approved therapies for dry-AMD and dry-AMD accounts for approximately 90% of all age related macular degeneration cases, which is the leading cause of blindness in people over the age of 60. Given there are currently no approved therapies, the first company to successfully combat this debilitating disease would reap the financial rewards of a market that is estimated to be well in excess of $40 billion worldwide. For us here at BioTime, there is obviously the potential financial gain, which would be substantial, but I am not quite sure you could quantify the real value in having someone regain their vision who lost their ability to drive, see their grandkids playing, etc.
WuXi: How does your approach differ from other companies in this field?
Mike West: BioTime’s overall approach differs in many ways to other companies in our space and if I had the time, I would be happy to debate the differences. But in the interest of time, here is just one example that I think exemplifies our unique approach and one that we believe will ultimately be successful. If you look at the many different ways diseases are typically treated, most of them try to reduce the effects of the disease, whereas what we at BioTime are trying to achieve is something that we view as more of a cure, rather than focusing on alleviating/targeting symptoms. One of BioTime’s primary approaches utilizes pluripotent cells, which have the ability to become any type of cell in the human body. We have an abundance of technology and multiple methods that we can differentiate human cells. BioTime can make almost any cell in the human body and we have made about 200 types of cells. One of the most fascinating derived cells that BioTime has identified potentially addresses dry-Age-Related Macular Degeneration or dry-AMD. At BioTime, we have taken a unique approach to dry-AMD. Our cell transplant therapy, replaces the missing and/or damaged RPE cells through a sub-retinal injection into the eye. In a similar fashion to that of organ transplants, like the liver or kidney. Circling back to my initial comments, instead of focusing on the disease pathway, which has resulted in no approved therapies to date, we are focused on replacing the layer of damaged and/or missing RPE cells with the hope that we can potentially address this debilitating disease.
Thinking about this from the point of view of AgeX, like most complex diseases, aging has “upstream” and “downstream” events that can be targeted with therapeutics. Think, for example, of heart failure. Some researchers target downstream events in this age-related disorder with drugs designed to increase the force of muscle contraction in the remaining muscle cells. Such strategies are beneficial, but perhaps not optimizing benefit to patients and not necessarily providing the most economical solution because the disease will not resolve on its own, but instead will progressively worsen with time. As an alternative, inasmuch as the heart failure is due to ischemia, one could rebuild the vascular support of the heart with young vascular cells. AgeX is taking this upstream approach to age-related ischemic disease with its product in development called AGEX-VASC1, which include young vascular cells produced using pluripotent stem cell technology.
WuXi: Do you need a different business model than a traditional biotech or pharma company? If so, what are the differences?
Mike West: In many respects, the AgeX technology platform using master cell banks of pluripotent stem cells to manufacture young cells of various kinds is like other biotechnology companies manufacturing biologics. Our strategy is to make allogeneic, off-the-shelf products that can be manufactured in centralized facilities from existing immortal master cell banks. Then the product can be shipped in a frozen form to the point-of-care for transplantation.
WuXi: What kinds of global partnerships do you have or plan to pursue?
Mike West: The AgeX technology platform is very broad. Using pluripotent stem cells it is possible to manufacture young human cells of any kind for use in regenerative applications for a very large number of diseases. In addition, our emerging platform called induced Tissue Regeneration (iTR) is intended to unlock the regenerative potential of human tissues normally present early in human development but lost with age. As such, it has a large number of potential applications in degenerative disease and even cancer. As a result, AgeX plans an aggressive campaign of partnering to develop applications outside of the company’s core focus. These partnerships may include simple licensing of technology as well as collaborations to manufacture or market product.
WuXi: How will your anti-aging technology change medical care?
Mike West: Once the full potential of regenerative medicine becomes clear to clinicians on a daily basis, when they see for instance, technologies available to them to regenerate heart muscle in aged patients, or to regenerate midbrain function in Parkinson’s disease, we believe medical researchers will be asked to make similar products for the scarless regeneration of virtually every tissue in the body. Some leading researchers believe this technology will impact virtually every aspect of medicine.
WuXi: Will cell-based regenerative therapies challenge the current small molecule drug industry?
Mike West: I believe that one day cell therapy will be a larger industry than that of small molecule drugs. There are several reasons for this conclusion. First, clearly the largest demographic trend of our time is the aging of the populations of most major industrialized countries. The vast majority of these countries’ health care costs are associated with chronic degenerative diseases that can in many cases potentially be addressed with regenerative therapy. In addition, the use of pluripotent stem cell-based product manufacturing has the advantage that it is unlikely that biosimilars can be manufactured and used in place of them. This gives this product category a longer potential asset life, which should be a very attractive feature to the pharmaceutical industry.