James Peyer: Where are stem cell therapies headed?

Someday soon we may be able to replace tissues or entire organs with those grown from a patients’ own stem cells… but just how soon? What challenges do stem cell therapies face on the path of development, as they progress from the lab to the commercial world? James Peyer, investor and former stem cell biologist, answers below (find the transcript underneath, and the full interview here):

TEGAN: So your academic career focused on stem cell biology–can you talk about where you see stem cell therapies going?

JAMES: I think that stem cell biology has two roles to play, one outside of geroscience, and one within geroscience. Outside of geroscience, I think what we’re seeing already from companies working on CRISPR and chimeric antigen T cell receptors and similar things is that the bone marrow transplants generally (and genetic engineering even more broadly) are incredible tools to change our genes in specifically designed and engineered ways to fight specific diseases. So that can cover diseases we inherit, or diseases we acquire like cancer. And the ability to modify the way our cells work, since our cells are such powerful tools, and especially in the case of the blood system, our immune cells–that’s a huge role that stem cell biology is already playing in medicine. In the geroscience context, we have a number of other stem cell approaches that are coming into their own, and these are mostly organ-specific stem cells–so like bladder, colon, skin, blood, even neural stem cells–and this idea of being able to grow and replace pieces or whole cloth entire damaged organs is such a powerful idea. And it seems like we’re especially able to do it for certain simpler organs like bladder and trachea, which have shown excellent results in the clinic so far. Initially this will be for people with very severe conditions, not just for people who are getting old and think, “Well, I’ve been using my trachea for 80 years, I should get a new trachea now.” I think that this trend is going to be extremely relevant for geroscience, but it’s kind of a “next wave” sort of relevance, because stem cell biology is incredibly challenging, and these tissue engineering approaches are so tough that we’re going to see them developed bit by bit, the way that they’ve been making progress so far. It’s amazing progress, and they’ve been moving quite fast, but quite fast still means many years as we perfect the technology and make it broadly safe and applicable to lots of people. So I see geroscience using these stem cell therapies after the general healthcare system switches over to the idea of replacing tissues and treating diseases before they start breaking the body down. And for that we have to have very safe, routine, effective organ rejuvenation therapies, whether that’s replacing organs whole cloth with tissue engineering approaches, or reprogramming cells inside the body, which has yet to be seen, but I also think those therapies may have a role to play in this. That in my mind is the second wave of geroscience approaches, but is among the first wave of things that seem to be ready to jump from lab bench to clinic, which groups in the investing world like Apollo are fascinated by right now.

TEGAN: What are some of the barriers, besides regulation and insurance structures not being a good fit for stem cell and reprogramming therapies?

JAMES: So I think that stem cell therapies are worth discussing slightly separately from a regulatory standpoint, because there is still a big regulatory hurdle that some–but not all–stem cell therapies have made. If you’re a regulator, how do you deal with the fact that every individual cell you take out of a person, grow in a lab, and then put back into the person really behaves like a different drug? It’s not like you’re manufacturing the same lot of pills in a factory and then giving the same pill to each person. You’re taking their own cells, growing them, and putting them back into that person. So one of the big issues that the stem cell world is grappling with right now is the “autologous versus allogeneic” debate, autologous meaning, “How do we regulate stem cells that come from a person and are modified outside the body, then put back into that person?” which has specific regulatory challenges; versus the allogeneic approach, which is where we have a single line of cells that’s quite uniform, and can be looked at and regulated like a drug, so it has less regulatory problems. But when you try to play a catch-all solution in cellular biology and put those cells into multiple people, then you have all sorts of scientific problems, like immune responses and so on. So there’s this scientific and regulatory push-pull on how to ensure the highest quality for therapies and ensure that what we’re doing actually works for patients, and then on the other hand how to build something that is really going to have the effect we want. So this jumps to the next problem, which is how to measure efficacy for the stem cell therapies. I think that the field is a bit tainted, because in a lot of the early human clinical trials in what they called “the stem cell field” back then, people did this in very much the wrong way, where clinical trials were designed without scientific thresholds substantial enough to show true efficacy. Which, don’t get me wrong, is an incredibly complicated question when you’re modifying entire organ systems and not just individual pathways. But because of these very challenging clinical trials that were set up and then showed middling results, it has kind of polluted the water for follow-on stem cell therapies. So I think that the strategy piece of this–how to design and execute something that will go after a much needed target, that will help patients in a quantifiable way, that makes sense to regulators–is not at all a straightforward problem. The only other piece I would mention in terms of major therapies in stem cell biology is that, compared to manufacturing aspirin and sending the pills out to pharmacies, the cost of stem cell therapies is astronomically high. It’s so much work for each individual patient, and so many more things can go wrong when you’re dealing with biology as opposed to chemistry, that the companies that are really trying to move this to a mega scale and industrialize the delivery of stem cell therapies have enormous cost challenges that they have to deal with. Because they want to keep the cost of the therapies as low as possible, while still making enough money to pay for the years of R&D and clinical trials that came before launching the drug, and also to fund their work on the next version of the drug, while still giving some kind of financial return to their investors, who bore 20 years of patience and risk while that drug was developed. So that cost piece is a very big challenge, and we’ve seen some innovative therapies, especially on the gene therapy side, struggle with this already, where the initial price tags have been so high that it’s caused some backlash.

TEGAN: Are these problems specific to tissue engineering approaches? Would reprogramming strategies be able to dodge them?

JAMES: I think think that with reprogramming it depends on how you approach it, it really depends on the therapeutic actor. You get around some of the problems no matter what, because no matter whether you use a virus, or a small molecule, or a cocktail of small molecules to do your reprogramming, lipid nanoparticles with a plasmid inside to modify the DNA, those sorts of things are all cheaper than trying to grow new organs whole cloth for implementation. So you end up with fewer cost problems there, but as we’ve seen from the gene therapy space, there are still major issues on the cost side. In the reprogramming world you’re definitely going to run into this, because there’s a very serious concern about the creation of teratomas within tissues. So the bar for safety on a reprogramming therapy is going to have to be set incredibly high, and we’ll have to just be very careful and thorough in assessing any putative reprogramming agent as we move to clinical trials in humans.