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.

Rich McCormick Jr.: Hi, I’m Rich McCormick, Executive Vice President of Clinical Strategy here at Vial. Today, I have the pleasure of welcoming Dr. Timothy Miller to our First in Human Podcast. Hey, Dr. Miller, would you mind giving us a brief intro?

Timothy Miller: Hey, Rich. Thanks for having me out today. I’m looking forward to having a great discussion around Forge, gene therapy, and how we’re helping improve patient lives. 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.

I worked in academia for a couple of years in biotech, doing gene therapy for CF. 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 build a lot of manufacturing facilities.

What you get with me is a CEO, both private and public, who has been an entrepreneur who has started and ran through a number of companies. Some of which have been successful, and some of which have not been. All sorts on the spectrum.

Rich McCormick Jr.: Quite an impressive background. What inspired you you to co found Forge and work in the gene therapy space?

Timothy Miller: 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 (gene therapy is all about delivery, right?) You have a lot of different ways to go about it. But, the idea is to try to get to the target problem.

Over the past 15 years, as some of the new viral vectors have been developed, you start to see some of data coming out in a lot of the animal models, the impact that might be able to have on patient lives, it helps us bridge the science, the clinical translation to improving patient lives. That’s part of the foundation around why Forge was started. To help provide that access, and address a number of the challenges gene and cell therapy, which is manufacturing.

Rich McCormick Jr.: Thanks, Dr. Miller. Transitioning these gene therapies from bench to application is quite complex. Talk us through how your team at Forge navigates the challenges of pre-clinical to phase three in that gene therapy space?

Timothy Miller: At Forge, we have an amazing leadership team of about 13 people with 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 on over 60 different programs, around the world.

What we try to do with a lot of these groups is them bridge their pre-clinical work they often bring out of an academic institution into IND-Enabling or, toxicology studies to help when the FDA has said, “You need to do this work and this type of manufacturing method to get into a clinical trial. Then, you need to made clinical trial drug material a certain way.”

We help our clients with a deep understanding of the manufacturing, regulatory, and pre-clinical studies needed to help accelerate a clinical trial. Every program is bespoke when it comes in here, but we try to help bridge them through manufacturing methods that the FDA and EMA in Europe are going to accept and understand they move into a clinical trial.

That’s one of the ways we help transition these therapies from bench to bedside or concept to clinic. That’s where the Forge serves part of the key model. You asked about transitioning from pre-clinical all the way through phase three. There are two ways that you can do that. You can scale out, build more and more a laborious, intensive process. Or, you can scale up, which is make it process, but bigger. We do that by providing big bioreactors. Some of the biggest in the world. And we can talk more about that too.

Rich McCormick Jr.: The Forge website mentioned that your Hearth 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 gene therapy manufacturing process?

Timothy Miller: The Hearth is a 200,000 square foot state-of-the-art facility. We love the fly through of the drone footage. Right now, we have 20 GMP suites with the ability to expand to probably upwards close to 40. What’s important about them is that they are at all scales. From, and working through pre-clinical to clinical up to commercial. You can work in small volumes, the size of a Red Bull container. Or, you can work in something the size of a fish tank.

Or, if you want to go even bigger? We think about microgroove facilities. If you are able to make a gene therapy that could treat hundreds to thousands of patients in these big 5,000 liter bioreactors. There’s no one else in the world that can do that to this scale today. Forge is leading the charge with those types of bioreactors.

Rich McCormick Jr.: AAV production is a cornerstone of your platform. Can you explain how Forge has differentiated itself from other companies the space?

Timothy Miller: When you come to Forge, one of the things that you get access to is our cell line. The cell line is what grows in these bioreactors. We take things and put them into these cells the clients want. The cells grow up and expand. We boil this all down and purify things out of the cells. That’s what ends getting delivered to patients. 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 into clinical trials.

Rich McCormick Jr.: Very interesting. Would you mind maybe providing a little bit of insight into your Forge pipeline of these disease modifying AAV-based therapies?

Timothy Miller: One of the things that differentiates Forge is we do actually have our own clinical staged program. Very few contract developing manufacturing organizations have that. Forge does. It allows us to help experience the same type of challenges many of our clients do.

 “Forge gets it.” Is 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. We get to go to our clients and say, “Hey, here’s what we’re hearing 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 said to us in the past six to 12 months. You might want to consider this.”

Our own program is called FBX-101. It’s for patients with Krabbe Disease. In its clinical stage we’ve enrolled a number of patients. The data coming back is really remarkable. It’s the only program like it in the world, right now.

Rich McCormick Jr.: Your forge journey started about three years ago. It would be great if you could share a pivotal lesson or an experience from your time leading Forge you believe would maybe benefit other entrepreneurs in the field.

Timothy Miller: It’s always interesting talking about the founding story. I left the last company I founded and ran for a number of years 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.

The best piece of advice I’d have for entrepreneurs, particularly in the biotech or pharma spaces is to surround yourself with good, trusting members with 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 what differentiates a lot of companies from success or failure.

Rich McCormick Jr.: Collaboration is a real common path, in terms of biotech breakthroughs. Can you elaborate on how Forge approaches partnerships and alliances?

Timothy Miller: When we think about the biotech ecosystem and gene and cell therapy, it’s a network of many different stakeholders. From investors, to contract research organizations, manufacturers, academic facilities, and the researchers doing a lot of this work. Many of us in this industry know each other having worked around the space 20 years. We look for collaborations across all areas.

One we talk a lot about is working with Ohio Life Sciences and how we think about the work force development initiatives. You’re trying to build an an ecosystem, we talk about when people come and join the it’s, “Hey, you might be here for or three years. Maybe it’s longer. But how does this job prepare you for the next one?”

Hopefully that’s here at Forge. What we’re trying to do is continue to build that ecosystem so people come in and they move up the ranks. They move in through experience. But, as people move out of the company and go elsewhere, you want them to stick around and continue to build up in this space through collaborations.

We work with Case Western Reserve University. And, a number of other academic centers to do these workforce development initiatives. We work with many of the investment banks to help get ours and our client’s story out. There are of ways to build relationships and collaborations in the industry.

Rich McCormick Jr.: Looking ahead, what you the most about the potential impact of gene therapies on healthcare? How do you envision Forge Biologics contributing to the future state of gene therapies?

Timothy Miller: When we look out over the next eight to ten years, one of the main strategies getting the most focus is using things like AAV to deliver what’s called a gene replacement strategy. That’s when a client asks, “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?”

That’s been tremendously successful in this industry. Remember what we talked about earlier is gene therapy is all about delivery. One of the newer technologies that’s been getting a lot of focus a number of different companies are using it is called gene editing technology. The technology to be able to go in and say we’re not going to just give you the whole gene back. We’re going to go into your cells with a very specific pair of scissors, cut out 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 give it back. When you ask me what gets me really excited is thinking about new advances in the gene editing technology that could be melded with the current technology for delivery.

Historically, what’s happened is 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 are shrinking the size and allowing them to be packaged in these AAVs. So combing the AAV delivery technology with the gene editing technology, that’s gene therapy for the next five to ten years.

Rich McCormick Jr.: Dr. Miller, it’s a pleasure meeting with you today. The team here at Vial wish you, and Forge Biologics, nothing but success. Thanks for joining us today.

Timothy Miller: Thanks for the opportunity. Congratulations for everything at Vial.