I'm really excited to host this panel, particularly because of the panelists that we have joining us today. We're going to be talking about gene and cell therapy translation opportunities, both the challenges as well as the successes. To help us do that, I'm joined by three panelists from different venture funds that really represent an incredibly broad swath of investments, modalities, strategies, and thinking. So I think it's just going to be a terrific discussion. First, Bob Nelsen, who's Managing Director and Co-founder of ARCH Ventures. Chris Parmar, who is also Managing Director at 5AM Ventures. And Dave Berry, who is a Managing Partner at Flagship Pioneering, as well as Co-founder and CEO of Valo Health. Looking forward to engaging with all three of you on this really exciting topic. So Bob, I'm actually going to throw it over to you first, and I'm going to do that sort of in two ways. First, one of the things as we're thinking about the translation of these types of therapies is we've seen great success in some ways in the approvals both in cell and gene therapies and FDA, as well as some challenges as we're finding more money coming into the marketplace, more opportunities and programs coming into the clinic, and then really having to translate that. So I wanted to go over to you first because you've done something incredibly interesting at ARCH with Resilience, which has both an enormous amount of capital and a grand vision. I'd like to ask you to speak to what was the driver behind that in your thinking and what are you looking to accomplish with that, including unmet needs and what you want to solve for using that entity initially.
It was just a response to the kind of slowness, or at least my perceived slowness and frustration, with the supply chains in the pandemic. But I think what we discovered, which I think is an obvious thing and we just all have to look around in gene and cell therapy to see it, is that we're kind of living in a show of CMC variability: delays, failures, every process being a one-off. It's because manufacturing is an afterthought, not a forethought. You get data and then you figure out how to make it. An academic institution tries to pass it to a biotech or pharma, and they spend another two or three years trying to figure it out. The existing vendors will make a recipe if you give it to them, but we wanted to rethink the way the system works by anticipating the problems in advance. So that was the general goal. We're thinking about that both in creating resilience to pandemics by creating a more decentralized digital system, and also the same problems of the pandemic are the problems of gene therapy and cell therapy. When you think about viral vectors or mRNA or delivery, or figuring out how to rapidly prototype a process that can work in a regulatory framework, that's the general thought of the company: to rethink the way we make these things, invest in advance of the problem in new modalities and automation and systems that can make these technologies not just more systematizable but much, much cheaper, orders of magnitude cheaper. If you think about what the semiconductor industry did, biotech has not done that. It's been a reactive system, not a proactive system. So really what Resilience wants to be is a proactive investor. We're going to invest a huge amount in technological innovation with universities, with biotech companies, and with pharma.
Terrific. Thanks. So Chris, maybe I'd ask you to pick up a little bit on that. I think you at 5AM just personally have built a really interesting portfolio in the cell and gene therapy space. Your work in Vor and in Soma and Akouos really spans the gamut of the different technologies that can be utilized as these new modalities emerge, as well as thinking about either very specific administration, for instance Akouos is in the ear, or systemic administration for some of these other companies. How have you guys been thinking both about some of the challenges that Bob surfaced and their thinking around Resilience, either on a company by company basis or across the portfolio as you guys continue to invest in this space?
Yeah, thanks Meredith. Thank you for having me here as well. To add to Bob's comments, I do think that we have a structural challenge currently in cell and gene therapy through the lens of entrepreneurship and company building. The parameters that we have to work with are: go build it yourself, because there's no way you're going to be able to rely reliably on service providers to bring what's going to be central to your success, central to your value, and central to your risk and opportunity. In building any of these companies, it is massively important and critical. So it was really about time for some major structural change. I commend you, Bob, for going at it head on. The portfolio that you just mentioned of companies that I'm actively involved in—and I'll say some past companies that I have been involved in in gene and cell therapy prior to those—there's been a lot of learnings. I'm not alone in this. We stand at a really interesting juncture in the history of where venture is in cell and gene therapy. It's a bit of the renaissance in this past decade, always standing on the shoulders of the giants before us. The very first investors and venture community members entering gene and cell therapy are really off of decades of work within academia, starting to translate those initially. Where we stand today, there are so many learnings. Bob just listed one of them. These are learnings that have come about just in the past number of years after a lot of investment in cell and gene therapy. Now we have not just anecdotal evidence of the clinical challenges, but we're seeing some of the commercial challenges and also the opportunities. So I think one has a really well-informed, better-informed venture community that understands the fact that you can have dramatic clinical benefits for patients. Let's make that scalable, to Bob's point, and that's the challenge we have to address. In other areas where things have not gone so well, that's presenting and clarifying the problem sets that we need to be developing solutions around. I think that's a whole other generation of companies. Those companies you mentioned, Akouos, coming very much out of here and Mass General with Luke's foundational technology, I think is an example of taking a foundational technology that seems to be working in other places but really bringing a mission-centered focus with people who are deeply committed to the inner ear and very knowledgeable there, and bringing the right things together. At a later point I'd love to touch on that because I think the basis and DNA of these companies for the future are going to be less and less single widget technologies. It's really an amalgamation of multiple tool sets. I think us as the venture community need to be thinking a lot more about not taking a widget and making everything, or a hammer and making everything a nail, but really being creative in how small-to-small collaborations can happen, because that's where I think the greatest opportunities will come out.
That's terrific, and that's actually a great segue over to Dave. Flagship, I think, now Flagship Pioneering is a terrific name for the work that you guys have done in creating companies that are in some ways looking to even skip over some things and really bring new modalities in. I'd point out actually from my perspective, Seres, which you could argue is a cell as a cell therapy and really being at the forefront of thinking about a bug as drug and that cell as a new modality, to Rubius, which I think really is potentially transformative in the way that they're thinking about the cell as a delivery mechanism. And now your work at Valo, which maybe picks up on some of what Kush was talking about, which is that integration of things and thinking broadly across networks. For you guys, how are you thinking about these next generations and what's next? Are you worried about some of the concerns and the hiccups that we're hitting along the way, or are you guys still full charge, thinking not about what's near but what's next?
Well, thanks Meredith. It's great to be here today. I really appreciate the opportunity to speak to everyone. As we think about things in the context of Flagship, we're constantly thinking about how do we bring forth transformation, how do we think about where that next frontier is, how do we think about that next generation. It's really this question of where can we bring disruptive, powerful science that can bring in a whole new frontier of therapeutics—not a single drug, not a single opportunity, but a platform that can reproducibly and reliably deliver. This means a whole set of different things. There are sets of the arena of biotechnology that have systematically been art, not science. Trying to bring that science, if not engineering, as a framework by which we can reliably and reproducibly bring forth therapeutics that opens up doors. Even if we just think about it in the narrowest context of gene therapy focused on double knockout diseases, there are about 3,000 of them. The community at large has brought forth treatments for about 35 of them over the 20-odd year history of the area. If we want to be able to cure them all, we need to change the scale, the scope, and the efficiency by which we bring this forward. That's where pioneering really comes into play, but it also involves systematically changing the scope, speed, and reliability of drug discovery and development. That's where companies like Valo come into play, where we've been able to use things like human-centric data at each and every step of the drug discovery and development paradigm to rethink how we do it, to make it more human-centric, not built around cells and mice, to make it much more of a parallel process, not a long serial process that has risk pushed all the way off to the end. By doing that, we can start uncovering, for example, new targets much more efficiently. These are the sorts of targets that are like the next PCSK9. In history, they would have required finding that rare family that had that knockout and then trying to convert that into a drug. By getting the right scale of data, we can start understanding them systematically at scale with efficiency and then directly converting them into therapeutics, not just of one modality but many different modalities—the best modality that's fit for purpose. Then bring them forth into an aligned, connected clinical trial that's designed to be fit for the patients that are most likely to benefit. When we start thinking about these systems transformations, we have the opportunity not just to bring forth better drugs, more relevant drugs, more drugs, but to deliver on the promise that I think we all got into this industry for: to bring these treatments and cures to patients as broadly and quickly as possible.
Terrific. I just wanted to see if Bob, Kush, you guys had any comments. Otherwise I'd love to move to a next round of questions on what's been brought up.
Just real quickly, that point is a great point. What's happening is that there's this massive amount of parallelization happening, this innovation wave. So things like Valo and others, and even within pharma, the innovation wave is hitting a scalability problem. That's both if you look at gene cell therapy, it's physical scalability—how do we actually make these things? But it's also a regulatory scalability. In other words, you can't have a system that has a thousand products or three thousand products where every single one has a one-off manufacturing process. It won't happen. FDA will go crazy and we'll have all the kind of variability that we have now. So you need some systematization, some miniaturization, and some kind of digitization of the process so that the regulators can actually pre-approve processes that then you can slot these new innovations in. If that doesn't happen, we're going to be sitting around with a bunch of cool innovations in gene and cell therapy that hit this wall.
Kush, any comments from you on that?
No, I absolutely agree. I think the initial challenges are informed by the evidence that we're seeing. A few years ago it was really a bit of clinical evidence, translational experimental medicine evidence. Now what we're seeing are more robust clinical data sets about what's actually working, what's not working—the immunological barriers, the technological barriers, the delivery barriers—and now these questions of scale, reach, and access. We're living those challenges right now. There have been some great successes as well, no doubt, but they're becoming much more real. As that informs us as the early stage innovation community, it is our responsibility, I think, to be thinking about and maybe laughing at it and being frustrated with the discrepancy between what is possible and where things should be. I think what's being highlighted by Dave and Bob is exactly that: the fact that there's a major mismatch between what is possible right now and where things should be. It calls for new business models and definitely some change. It can't be just companies. Regulatory frameworks and a number of other stakeholders need to be part of this and party to this.
