Hi everyone, welcome to episode 107 of Cell and Gene, the podcast. I'm your host, Erin Harris. Today's episode dives deep into a topic that's front and center for many gene therapy developers: how we're using large animal models, particularly non-human primates or NHPs, in preclinical testing. My guest is Ralph Schmid, PhD, associate director of preclinical research at Novartis. I think you'll glean from this episode that Ralph has a strong track record across the full drug and therapy development life cycle, from early stage discovery to clinical implementation. He specializes in the ideation and development of genetic and biologic therapeutics, with a particular focus on cutting-edge genetic therapies for CNS disorders. Ralph and I talk about everything from the challenges of sourcing NHPs to the growing interest in alternatives such as pigs and sheep, to what the future might hold for preclinical testing in gene therapy. Plus, Ralph gives us a preview of the Next Generation Gene Therapy Vector Summit coming up later this month, and many more exciting innovations on the horizon. So, stick around. This is a timely and thought-provoking conversation with Novartis' Ralph Schmid. Enjoy.
Hi, Ralph. Welcome to the Cell and Gene podcast. Thanks for being here.
Hi, Erin. Nice to be here. Thanks for inviting me.
Absolutely. So, okay, a couple of things. First, tell us a little bit about your professional background and the upcoming Next Generation Gene Therapy Summit conference coming up.
Yes. I'm right now associate director for preclinical research with Novartis Biomedical Research in Cambridge, Massachusetts, where I lead several of the gene therapy programs. I lead the teams to really push those gene therapy programs hopefully to the clinic soon. We have some exciting programs in the neuroscience space. Before I joined Novartis, I worked for several years with Jim Wilson at the Gene Therapy Program at the University of Pennsylvania, where Jim laid a lot of the groundwork for gene therapies, the gene therapies we're seeing coming towards the clinic right now. And I really learned the basics there, which I'm trying to apply now in industry. And thanks for asking about the conference. It's an important part still. I think it should be an important part of every researcher's life to go to conferences and exchange ideas and hear new ideas. So I will be attending and participating in a panel discussion at the fifth Next Generation Gene Therapy Vector Summit, put together by Hanson Wade, at the end of July. So that's July 29th through 31st in Boston. It's a great conference to learn about cutting-edge new gene therapy vectors, how key stakeholders in the industry think about moving programs into the clinic, safety considerations, biomarkers, and things like that. If you want to find out more, the website is very easy. It's nextgengenetherapyvectors.com, and you can find out more information there.
Wonderful. Thank you so much. And yes, listeners, be sure to visit that website to learn more about the conference. We'll be talking about it a little bit here and there throughout our conversation, but definitely check that one out. It's going to be a great event. So Ralph, talk to us a little bit about what recent news or innovations in gene therapy that you're most excited about.
Well, I think most of us have been really excited about the next-gen AAV capsids being developed by several small companies, but also by academia. And so recently there have been several announcements that companies are either finishing up their preclinical package or even have an open IND. And so I'm really excited to see some of those companies entering the clinic, because the expectation really is that this is an absolute game-changer for neuroscience in terms of biodistribution of the gene therapy payload in the brain.
Good. Okay. Going back to our conference that we talked about a little bit, how will your role and the role of the 25 other speakers at the conference enable these innovations that we're referring to perhaps progress even further?
Well, we had actually not that long ago a more specialized conference, and I think that will be put on again in the fall, looking at those next-generation capsids, the different ones which are out there. So what this conference is more focusing on: okay, now you have something really cool, you have something which has great clinical promise, now what? So how do you really implement that? So how would you, you know, what are your best options? What are the opportunities for small animal studies, large animal studies? You know, what would you need to file to file your IND? What are your safety considerations? What are your regulatory considerations? It's really, I think this conference will help people to better understand what the framework is, even if you're already working on this. So you might learn something new, make some new connections with other attendees to hopefully drive your work forward.
Great. Okay. We talk a lot about non-human primates on Cell and Gene, and so I would love to get your perspective on that particular topic. And so my question for you is, what are the biggest scientific or logistical hurdles you've encountered when relying on non-human primates, or of course NHPs, for preclinical safety and efficacy work in gene therapy vectors?
Yeah. First of all, non-human primates have a very dominating role as a large animal model, and I think most of the genetic medicine modalities, including gene therapy, because you know the size and the evolutionary distance is closest to the human. So the thinking is still, you know, this is best to study both the biodistribution or the expected efficacy of your gene therapy, but also safety aspects. And I think the field has kind of narrowed in on those models, and you know there's a lot of specialized CROs out there which can help you with the work. But now on the flip side, that has really increased the demand for NHPs dramatically. I mean, like 10 years ago there was very little demand, and then it suddenly increased a lot. And since the pandemic, it has become a huge problem to source enough of those NHPs, because the sourcing environment has dramatically changed since the pandemic, where several countries are not allowing exports anymore in Asia, where they normally came from, and demand has increased at the same time. So that had negative effects on price, and also from the more practical research side is that you never know what you get. So if you want to do your studies, you have to, you know, we're relying on CROs, and they're trying to source as best as they can. But what we had to find, it makes a difference from which part of the world those NHPs come from, in terms of both size and, you know, physical health, but also how they react to gene therapy. And that's a little bit unfortunate that studies are a lot more complicated these days with NHPs.
Fair. Okay. Talk to us a little bit about the timeline impacts of NHP studies compared with alternative large animal models. What does that timeline look like, excuse me, and then how do those pressures influence project, you know, do we do it, do we not type of thing, decisions inside big pharma?
