The Amnion Foundation is non-profit organization with the mission to build a genetically diverse public cell bank that can provide an immunological match to the majority of the population. Amniotic stem cells, which can be sourced from the amniotic fluid or the placenta after a live, healthy birth, possess a unique blend of multipotency and lack of tumorigenicity. In an extension of the cord blood banking model, these cells may improve outcomes where long-term cell survival and functionality is important.
Recently, I had the honor of interview Dr. Todd McAllister, Executive Director at Amnion Foundation. In this interview, we discuss the foundation’s vision, research and clinical approach, scale-out strategy, and interest in joint partnerships. It is captivating to get an insider look at the Amnion Foundation, a niche player within the large cord blood and tissue banking market.
Interview with Dr. Todd McAllister of Amnion Foundation
Cade Hildreth: What’s your background and how did you get involved with the Amnion Foundation?
Dr. Todd McAllister: I have a PhD in biomedical engineering. Straight out of graduate school I started a company called Cytograft, which was focused on tissue-engineered vascular grafts and then later a suite of tissue bulking and reinforcement biomaterials, all of which were grown from cells and contained no synthetic scaffolds or exogenous biomaterials. With this background, my expertise leverages a cell biology approach, rather than an engineering or a synthetic materials approach.
About a year ago, I got a call from Dr. Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine (WFIRM) and Chairman of the Board of the Amnion Foundation. He gave me a succinct pitch that really resonated with me. The basis for that pitch was that for a lot of different applications, the cell therapy community should perhaps be seeking functional repair, rather than paracrine effects that are anti-inflammatory or immunomodulatory. That is, for many conditions like heart failure and diabetes, we might need to increase the emphasis on cellular engraftment to impart some sort of long-term repair.
Dr. Atala felt that the concept of using a traditional autologous cell or a non-immunologically matched allogeneic cell might be fundamentally flawed, or at least not the ideal solution for these specific applications. While he was a Harvard affiliate, he developed a technology to extract placental-derived stem cells from birth tissues that would otherwise be thrown away. It is an extension of the cord blood banking model, and as we’ve seen in cord blood banking, you can create a bank of immunologically matched cells at a relatively low cost.
With the amniotic or placenta derived cells, however, he demonstrated that these cells are essentially pluripotent. This suggests that you can apply similar approaches to what is being done now with cord blood, but targeting a broader range of therapeutic targets. Simply put, we might have the ideal cell solution by having young, healthy cells that are immunologically matched.
Cade Hildreth: That is an inspiring vision.
Dr. Todd McAllister: Yes, that was a career- changing pitch in the span of just a few minutes. When I heard it I thought, “That is a plausible solution to what I consider to be the most enduring topic in cell therapy (cell sourcing), and if that works, it could completely transforms medicine. Literally over the span of a few weeks, I packed up the family and moved from San Francisco to North Carolina to transform the concept from an academic technology into something that,although operating under a non-profit umbrella, is, scalable, and able to move forward into clinical trials. That is what I have been doing for the last year.
Cade Hildreth: How many amniotic samples have been stored to date by the Amnion Foundation?
Dr. Todd McAllister: As you can imagine, the hurdles to building an FDA and GMP compliant facility are not trivial. Even though those capabilities exist across the street from where I’m sitting at Wake Forest, to rebuild and translate those out of the academic setting and into a standalone bank is not trivial. So over the last 6 months we have completed our infrastructure, and focusing mostly on training, engineering and validation runs.
We are just now turning the corner to being able to bank tissues suitable for human clinical use, but we are not focused on scaling out that effort yet. Instead, we are focused on making sure that all of our quality systems are in place, and we won’t “flip the switch” to aggressive banking for probably another two or three months. Then, our first objective will be to build a pilot bank of about 3,000 samples.
We need a large enough bank that we can start enrolling patients into some of the clinical studies that we want to do, but not so large that we invest all of our funding into a stem cell bank that may not work. Because we are philanthropically supported, we want to be cost-effective and prudent in our approach.
Cade Hildreth: Of course.
Dr. Todd McAllister: It is obviously cheaper to screen more patients than to bank more cell lines, but it is also important for us to begin to build out a diverse bank of cells.. So it is a bit of a balancing act to identify where to get the most cost-effective outcome, but that study is ultimately what drove us to pur initial target of somewhere between 2500 to 5000 individual samples for our first run in clinical trials.
Cade Hildreth: If everything went well, what would be your five year vision?
Dr. Todd McAllister: I usually like to under promise and over deliver, so I’ll say that we will be well into the clinical trials timeline for at least three different indications: heart failure, neurodegenerative diseases, and stroke. In the background, we will also be working on diabetes, but we still have basic research on cell differentiation and survival to do for that disease indication. Of course the optimist in me would like to say that we will have shown an improvement in efficacy relative to current approaches.
Cade Hildreth: How did you choose those indications?
Dr. Todd McAllister: A combination of rationale. First, we want to be treating a patient population where first in-man studies make sense. For example, while cerebral palsy is clearly an important target, we don’t want to target a pediatric population for first in-human use for our cells. By contrast, for patients with heart failure, which are generally older, sicker patients with essentially no option, the ethical considerations are completely different.
The second rationale is from a practical perspective, we wanted to take on indications where there has been a lot of work done and clear protocols worked out. If you take heart failure and stroke together, there has been some staggering work that has been published over the last two years.
While these studies may not have been able to demonstrate full clinical efficacy that would support FDA approval, the trends are very encouraging. Therefore, our strategy is to partner with some of the investigators that have worked out these protocols. We want to come in and say, “Let’s see if this immunological matching strategy gives you that final 5% or 10% push that you need.” We will clearly do much of our clinical work using the infrastructure that Dr. Atala has built at WFIRM, but a partnering strategy will likely accelerate our transition to high quality clinical trials,
To clearly answer your question as to what we want to do in five years, our goal is to work collaboratively with leaders in the field, because it dramatically shortens developmental timelines. We would like to leverage the experiences of leaders in the field, like Texas Heart Institute and Emerson Perin and James Willerson. Our goal would be to piggyback on their clinical and regulatory experience to accelerate the pathway forward into clinical studies.
We want to be deeply into clinical trials within five years for the aforementioned indications, allowing us to get a clear understanding of whether or not the placental stem cell banking model is going to work. Most of our budgeting and business model is predicated around a five-year time horizon, so we aim to use this period to get a clear answer as to whether the approach is transformational. Given where the field is today, it is reasonable to say that we have the capacity to be into Phase II or III clinical trials within five years.
Obviously if I did not think that these things had a high probability of working, I wouldn’t have quit my job and moved across the country to pursue it. I think I’m one of the few realists in that field, but even from a conservative perspective, I believe this approach has the potential to be transformational.
Cade Hildreth: Is the long-term model to stay philanthropic or to bring in outside investors?
Dr. Todd McAllister: That is a great question and it is a complicated answer, which is both yes and no. The mission of the Amnion Foundation is to build the bank, support clinical research, and to support patient education. Let’s say we are successful at building a bank of tens of thousands to maybe at the most 100,000 samples, and low and behold, we show a pathway to a cure for diabetes. It is likely beyond the scope of a philanthropically supported organization to try to commercialize that or to scale-up manufacturing to initiate sales and distribution. I’m not sure that falls under a philanthropic business model or a philanthropic strategy.
It does however dovetail in a sustainability plan, which is a big part of what we want to promise our philanthropists.
Ultimately, if we are sitting on an asset that is of value as a therapeutic product, we will partner with private industry, for example, a Boston Scientific or Medtronic or Novo Nordisk or a similar company. In this case, we would essentially be an OEM manufacturer of a component of their end product, but they would package it, sell it, and deliver it. Remember also that it would be a massive task to build large scale cell lines out of every banked tissue sample. Again, this is beyond the scope of a philanthropically supported organization. So the bottom line is that our goal is to show clinical success, and if we are successful, we will partner with private industry and allow that financial backing to broaden our scope and to support other clinical studies and applications.
Cade Hildreth: Excellent. What potential does placental stem cell banking have to impact the larger cord blood and cord tissue banking market?
Dr. Todd McAllister: While the cord blood and tissue market has been experiencing slow growth, and some might even say negative growth over the last few years, I think we’re going to see a massive resurgence of that field and not necessarily one that is limited to the classic blood cancer applications. Things as simple as wound care or orthopedic are relatively inexpensive products, relatively efficacious products. I think these relatively new applications and products will drive significant growth in the field.
Perhaps more exciting is the work that we are starting to see out of Joanne Kurtzberg’s lab. While it is perhaps a little too early to celebrate, her work is extremely encouraging, and robust. While few of us would have predicted the types of clinical successes that she is seeing in C-P and autism, it is hard not to be excited right now. Again, this expanded use for cord blood could have dramatic implications for both private and public cord blood banking.
Cade Hildreth: What role does patient education have for the Amnion Foundation?
Dr. Todd McAllister: One of the things that the Amnion Foundation has recognized is that patients often find themselves in a complex situation where they are desperate, because they have no realistic treatment options that involve traditional drugs or devices or small molecule therapeutics. This leaves them ripe then for exploitation and desperately seeking alternative therapies. In these situations, we would like to weigh in as an objective source of information.
Imagine the power of a non-profit entity that could be a source of education, using an approach that could be as simple as publishing ten whitepapers. For example, everyone is excited about the work that Joanne Kurtzberg is doing in autism or cerebral palsy. I’m excited about it as well. If I was a parent with a child with one of those conditions, I would be clamoring to get into one of her clinical trials. Unfortunately, she enrolls maybe 100 or 200 patients a year, but more than 8,000 babies and infants are diagnosed with the condition each year, as well as another 1,500 preschoolers. Additionally, over 500,000 children and adults in the U.S. show signs of cerebral palsy. With autism, the numbers are even higher, with an estimated on in 68 children affected by it. Getting into one of those clinical studies is like winning the lottery.
As a result, you see literally dozens if not hundreds of stem cell clinics springing up around the world. These clinics get painted by the FDA and the broader stem cell community with a broad brush. They’re all good or they’re all bad. Again, imagine the impact of an objective agency that could come in and say, “Here is the level of evidence that we have that these treatments are efficacious. Here is the spectrum of treatment centers that are offering these treatments. Here is how these treatment centers are different than Joanne Kurtzberg’s at Duke University.”
Our goal would be to give patients tools to understand and evaluate objectively what their risk-benefit ratio is.
They may still elect to go out to a GIOSTAR in India or another stem cell tourism locations, but at least they go into the experience understanding what their potential benefit are from the therapeutic, what the potential risks are to their health, and perhaps most importantly, it would give them the tools to ask the right questions.
We would like to empower patients to understand key questions, for example: What does the treatment process involve? How do they minimize the risk of sepsis or stroke? How do they track patients? How do they track efficacy? What evidence of efficacy do they have? Is it delivered by a specialist or a general practitioner? What’s their IRB approval? Who is that IRB? Who is on their data safety monitoring board?
These might be basic questions to you and I with expertise in field, but the vast majority of patients have no grasp of how to address questions like this.
Cade Hildreth: I’m happy to hear that, because there is such a void of information and so many patients seeking it. That could be a great contribution and to have that information come from an unbiased non-profit would be profound.
Dr. Todd McAllister: Right, well again, that is exactly our thinking. I’m glad to hear you say that. While the Amnion Foundation may not have the bandwidth to pursue this, another worthy mission would be to establish an accreditation process.
For example, you fly to a stem cell clinic in Bangkok or India or Costa Rica and you do a simple audit by asking: Who’s doing the procedures? What’s the IRB approval? Who’s on your data safety monitoring board? Are these people really independent? What sort of patient follow up do you have? What sort of data collection do you have? Show me the facility. Let’s look at the training documents. Let’s look at when the last time you certified your equipment.
In one day, I guarantee you, you could go into any lab on the planet doing any cell-based procedure and categorize them into three or four groups, ranging from “do not ever contemplate coming here” to “this is legitimate clinical research and at least you’re not going to die of sepsis.” The goal would not be to choose one clinic over another, but to review bullet points on an inspection check list and categorize clinics according to relative safety.
If you look at some of the real debacles over the last few years, like the three patients that were blinded by an ocular procedure performed in Florida, U.S. Stem Cell treated both eyes in the patients at the same time. Irrespective of what they were approved to do, an accreditation review would rate that type of procedure as high-risk. This type of assessment would help patients to better understand standard protocols versus more high-risk protocols.
To do this education piece, I don’t think it will requires 50% of Amnion’s efforts. It could probably utilize 0.5% of our effort and still have a really meaningful impact. Education is a critical objective at the Amnion Foundation and one that complements our research and clinical work.
Cade Hildreth: Very true. How can people learn more about the Amnion Foundation?
Cade Hildreth: Fantastic, thank you for your time and for sharing your insights on the Amnion Foundation with our audience.