Episode 42: Dr. Timothy Miller - Co-Founder, President, & CEO at Forge Biologics

Ever wonder how the complexities of gene therapies are addressed from bench to bedside? The creative solutions lie within the innovative approaches of seasoned professionals like Dr. Timothy Miller, Co-Founder, President, & CEO at Forge Biologics. With a fascinating career that interlaces academia, biotech, and entrepreneurship, Dr. Miller brings a wealth of knowledge to the realm of gene and cell therapy. Join us as we delve into the intricate machinery of Forge - from their pioneering cell line to their clinical-stage program.

First In Human is a biotech-focused podcast that interviews industry leaders and investors to learn about their journey to in-human clinical trials. Presented by Vial, a tech-enabled CRO, hosted by Simon Burns, CEO & Co-Founder. Episodes launch weekly on Tuesdays. To view the full transcript of this episode, click here.

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Transcript

Speaker 1: 0:07

You are listening to First in Human, where we interview industry leaders and investors to learn about their journey to in-human clinical trials presented by Vile, a tech-enabled CRO hosted by Simon Burns, ceo and co-founder. Featuring special guest host Rich McCormick, evp of Clinical Strategy and Head of Oncology. In this episode, we delve into the challenges of managing clinical trials effectively. Join us as we explore the importance of striking the right balance between collecting every data point and ensuring efficiency in the study process.

Speaker 2: 0:46

Hi, I'm Rich McCormick, executive Vice President of Clinical Strategy, here at Vile. Today I have the pleasure of welcoming Dr Timothy Miller to our First in Human podcast. Hey, dr Miller, would you like to give us a brief intro? Hey, rich, sure, thanks for having me on today, looking forward to having a great discussion around forage and gene therapy and how we're helping improve patient lives.

Speaker 2: 1:08

For myself, I've been in the biotech and gene and cell therapy industry for about 25 years, going back into the early 1990s where I was doing some research on cystic fibrosis and worked in academia for a couple of years and in some biotech doing gene therapy for CF. Then I finished my PhD and jumped into biotech company after biotech company where I did clinical trial operations. I ran regulatory and worked with the FDA. A lot of business development and fundraising helped build teams and have helped build a lot of manufacturing facilities. What you can get with me is a CEO, both private and public, who's been an entrepreneur and started and ran through a number of companies, some of which have been successful and some of which have not been. It kind of held on the spectrum. Awesome, quite an impressive background. What inspired you to co-found forage and work in the gene therapy space. When we think about the phases of gene therapy over the past 20 years, we've watched technology really improve Over the past 15 years. One of the new forms of gene therapy is all about delivery. You'd have lots of different ways to go about it, but the idea is to try to get to the target problem. Gene therapy you'll hear us talk a lot about it's all about delivery Over the past 15 years, as some of the new viral vectors that have come out and really been developed. When you start to see some of the data that comes out of that in a lot of the animal models and the impact that that might be able to have on patient lives, it really helps us bridge the science, the clinical translation, to improve patient lives. That's really part of the foundation around why FORGE was started to help provide that access and address a number of the challenges in gene and cell therapy, which is manufacturing. We'll talk a little bit more about that, but that's really some of the basis of FORGE trying to solve those problems of manufacturing for large patient populations around the world. Great Thanks, dr Millett.

Speaker 2: 3:05

So transitioning these gene therapies from bench to application is quite complex. Can you maybe talk us through how your team at Forge navigates the challenges of preclinical to phase three and that gene therapy space. We have a really amazing leadership team here at Forge with the combined leadership team of about 13 people has over 200 years of hands-on gene and cell therapy experience. It's very rare to find that much focused gene and cell therapy experience in one company. We work with over 35 clients right now working in over 60 different programs around the world and what we try to do with a lot of these groups is help them bridge their preclinical work that they often bring out of an academic institution into IND enabling or toxicology studies to help. The FDA has really said, hey, you really need to do this work and this type of manufacturing method to get into a clinical trial and then you need to make clinical trial drug materials. A certain way we help our clients with a deep understanding of the manufacturing, the regulatory and the preclinical studies needed to help accelerate and go clinical trial. Every program is bespoke when it comes in here but you try to help bridge them through manufacturing methods that the FDA and EMA and Europe are going to accept and understand as they move into a clinical trial. So that's one of the ways that we help transition genes therapies from bench to bedside or concept to clinic, whichever way you want to think about it. That's where FORGE serves part of the key model, and you asked about really transitioning from preclinical all the way to phase three, and there are two ways that you can do that. You can scale out okay, which is just build more and more really laborious, intensive process, or you can scale up, which is make it process but bigger. So, and we do that by providing big bioreactors, some of the biggest in the world, and we can talk more about that too. Definitely, yeah, it's a great self.

Speaker 2: 5:00

The FORGE website mentions that your heart facility is the foundation of the company. Excellent video fly by drone activity. I would recommend it to any of our listeners. Can you explain how this state of the art facility contributes to the gene therapy manufacturing process? The hearth is a 200,000 square foot state of the art facility and we love the fly through of the drone footage. But right now we have 20 GNP Swedes with the ability to expand to probably upwards close to 40. What's important about them is they are at all scales okay, from in working through preclinical to clinical up to commercial, so you can work in really, really small volumes the size of like a Red Bull container, or you can work in something besides an aquarium or you know, a fish tank, or you want to even build even bigger, and we all think about micro group facilities. If you were able to make the gene therapy that could treat hundreds to thousands of patients in these big 5000 liter bioreactors, there's no one else in the world that can do that to this scale. Today FORGE is leading the charge, you know, with those types of bioreactors and that's awesome. So AAV production is sort of a quarter soda of your platform.

Speaker 2: 6:11

Can you explain how FORGE has differentiated itself from other companies in the space? When you come to FORGE, one of the things that you get access to is our cell line, and the cell line is what grows in these bioreactors, and we take things and we put them into these cells that the clients want. Then the cells grow up and expand and then we boil this all down and purify things out of the cells and make it very, very pure and that's what ends up getting delivered to patients. So, from our perspective, when clients come, they get to work with over 350 team members to help expand their program and take it through this preclinical translation and into clinical trials. That's really interesting.

Speaker 2: 6:54

Would you mind maybe providing a little bit of insight into your FORGE pipeline of these disease modifying AAV based therapies, one of the things that differentiates FORGE, as you asked, we do actually have our own clinical stage program. Very few contract developing manufacturing organizations have that FORGE does and it really allows us to help experience the same type of challenges that many of our clients do. It's the FORGE gets it. It's what we hear from a lot of our clients because we do have our own clinical program that uses our own clinical material made here. So we get to go to our clients and say, hey, here's what we're hearing from the FDA, you've got a similar type of program using a similar type of AAV and you're going in through a same route of injection. Here's what we can tell you. The FDA has said to us in the past six to 12 months. You might want to consider this. Our own program. We thought of FBX 101. It's for patients with Crab A disease and its clinical state even rolled a number of patients and the data that's coming back is really remarkable and we can chat more about that, but it's the only program like it in the world right now.

Speaker 2: 7:57

So your forged journey started about three years ago, so it would be great if you could share a pivotal lesson or an experience from your time leading forged that you believe would maybe benefit other entrepreneurs in the field. Yeah, you know, it's always an interesting talking about the founding story, because I left the last company that I founded and ran for a number of years and in January of 2020, I would not have anticipated what was to come, which was a pandemic and having to do a series A and a series B financing. I think the best piece of advice that you know I'd have for entrepreneurs, particularly in the biotech or pharma spaces surround yourself with good, trusting team members that have direct experience in what you're trying to do. You have to have a mission and a vision and good investors, but bringing on the team is really what differentiates a lot of companies from success or failure. Collaboration is a real common path in terms of biotech breakthroughs. So can you elaborate on how forge approaches, partnerships and alliances?

Speaker 2: 9:01

When we think about the biotech ecosystem in gene and cell therapy, it's a network of many different stakeholders, right From investors to contract research organizations, to manufacturers, to academic facilities to the researchers doing a lot of this work. Many of us in this industry know each other that have been working in and around the space for 20 years, so we look for collaborations across all areas. One of the ones that we talk a lot about in Ohio is working with Ohio Life Sciences and how we think about the workforce development initiatives. You're trying to build an ecosystem. We talk about when people come and join the company. It's, you know, hey, you might be here for two or three years, maybe it's longer, but how does this job prepare you for the next one? And hopefully that's your at forge right. But what we're really trying to do is continue to build that ecosystem so that people come in and they move up the ranks and move in through experience. But as people move out of the company you can go elsewhere. You want them to stick around and continue to build within this space through collaborations, and so we work with Case Western Reserve University, you know, and a number of other, you know, academic centers to try to do these workforce development initiatives. We work with many of the investment banks to help get our story out and to get our client's story out. So lots of different ways to build relationships and collaborations in the industry. So, looking ahead, what excites you the most about the potential impact of gene therapies on healthcare? And then, how do you envision forge biologics contributing to the future state of gene therapies when we look out over the next eight to 10 years?

Speaker 2: 10:36

One of the main strategies that's gotten the most focus is using things like AAV to deliver what's called a gene replacement strategy. Right, that's the hey. There's been a gene that's been identified. We know that it's not working right in a patient. Can we deliver the correct, functioning copy of that gene back? And that's been tremendously successful in this industry. And remember, what we talked about earlier is that gene therapy is all about delivery right.

Speaker 2: 11:00

Well, one of the newer technologies that's really been getting a lot of focus and a number of different companies are using it is called gene editing technology, and that's the technology to be able to go in and say well, we're not going to just give you the whole gene back, we're going to go into yourselves, get with this very specific pair of scissors, cut out the thing that makes it not work and put the right piece back in. That technology has the potential to transform many diseases that are not amenable to a gene replacement strategy to just to give it back. So when you're asking me, what gets me really excited is thinking about new advances in the gene editing technology that can be melded with the current technology for delivery. So, historically, what's happens? That the gene editing technologies are too big, it's difficult to get them to the areas where they need to be effective. Newer advances in that are shrinking the signs and allowing them to be packaged in these AAVs. So combining AAV delivery technology with the gene editing technology, that's gene therapy for the next five to 10 years.

Speaker 2: 12:02

So, dr Miller, it's been a pleasure meeting with you today. The team here at Vial wish you and Port Biologics nothing but success. Thanks for joining us today. Well, thanks for the opportunity and congratulations for everything at Vial.

Speaker 1: 12:23

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