Episode 44: Max Darnell- CEO & Co-Founder at Modulus Therapeutics

Max Darnell, CEO and co-founder of Modulus Therapeutics, takes us through his thrilling journey from bioengineering and systems biology to launching a biotech startup. Max unveils how his team's curiosity and motivation, along with their high throughput discovery platform, are revolutionizing cell and cell therapy component designs. Hear how Modulus is making strides in the autoimmune space and harnessing the power of DNA barcoding and sequencing to transform traditional assays into high throughput screens.

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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Chapters

• 0:06 Revolutionizing Cell Therapy Design
• 9:27 Advancements in Cell Therapy Design

Transcript

Speaker 1: 0:06

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 connect with Max Darnell, ceo and co-founder at Modulus Therapeutics. Stay tuned to explore the groundbreaking world of cell therapy design and its promising future.

Speaker 2: 0:44

Hi, I'm Rich McCormick, executive Vice President of Clinical Strategy, here at Vile. Today I have the pleasure of welcoming Max Darnell, ceo and co-founder of Modulus Therapeutics, to our First In Human podcast. Hi Max, would you mind telling us a little bit about yourself?

Speaker 3: 1:01

Sure thing, thanks for having me Rich, pleasure to be here. I'm the CEO and co-founder of Modulus Therapeutics. My background is in bioengineering and systems biology. I did my PhD at Harvard, working in Dave Mooney's lab, and came out to the West Coast, to Seattle, to do a postdoc at University of Washington in single cell and functional genomics methods development, had the chance to join the Allen Institute for Artificial Intelligence and a startup incubator that they run there, where I met my co-founder, bryce Danes, and that was where we ended up spinning out Modulus from. So excited to tell you a little bit more about the story today.

Speaker 2: 1:38

That's a great segue. Why don't you let us know what inspired you and Bryce to start Modulus and then the Allen Institute of Artificial Intelligence, and how that played a role in your vision?

Speaker 3: 1:48

So AI2, which is what it's referred to, as we had a mandate to broadly explore ideas that were at the intersection of high throughput biology and computation.

Speaker 3: 2:00

So that incubator provided an environment to do that exploration and provide a little bit of structure for that being.

Speaker 3: 2:07

In Seattle, which is a cell therapy hotbed, the cell therapy application space was just staring us right in the face and we started to dig into the ways that cell therapies were being conceptualized and designed, and we realized that we were in a pretty interesting spot in the cell therapy industry evolution.

Speaker 3: 2:27

At this point this was late 2020, we had a handful of CAR T cell therapies that had been approved in oncology and we also had just an ever-growing list of cell engineering tools at our disposal. But we realized there was a key gap in information of how to best deploy those tools. So, say, you have new fancy gene editing which genes do you edit? You have new protein engineering methods what signaling pathways do you need to drive in order to get some increased function out of your therapeutic? And so the founding thesis of the company was that if we could build a high throughput discovery system for cell therapies, we would be able to dramatically open the aperture of functionality that we could get into these therapeutics moving forward and ultimately hopefully be able to bring cell therapies forward to the clinic faster as well.

Speaker 2: 3:22

Yeah, it's really interesting. So Modula started in about 2020. What key milestones or achievements stand out for you over the last three years? What do you envision for future growth? I?

Speaker 3: 3:34

mean I have to start with our team. So I'm extremely excited and proud of the team we've built. We are bringing in folks from the cell therapy industry veterans, as well as people from cutting-edge molecular biology labs and computational backgrounds for which this is their first cell therapy for a. But overall this is a team that is curious, is driven, is motivated to do things differently, and it's just been a pleasure to work with all these folks thus far, so that's definitely number one.

Speaker 3: 4:03

On the technical side, in the past two or three years we've definitely been successful in building this high throughput discovery platform. We've been able to discover various designs for cells and cell therapy components that would be very difficult, or if not impossible, to discover in other ways, and so that's been really satisfying. But we're at a pivotal moment in the company's lifecycle right now because we are starting to translate this discovery platform into our own internal therapeutics programs. So we've recently kicked off our first program in the autoimmune space, hoping to be in the development candidate stage early next year, and that, hopefully, is really paving the way for us to do a lot more development in the future.

Speaker 2: 4:50

It's great to be able to describe a team as curious, especially in this space. I think that's a great characteristic for a team to have. So, max, can you explain how your convergent design platform works and how it's revolutionizing the field of cell therapy?

Speaker 3: 5:04

Absolutely. When we think about how we want to design therapies, we start with the objective first. So typically that's what is the function that we want to dial up or dial down to improve the efficacy or safety of one of these cell therapies, and the bedrock of that are the functional assays that we have at our disposal. And so in the cell therapy industry there are a handful of these gold standard assays that folks use to characterize function. This could be how well does your cell therapy kill target cells? How well does your cell therapy persist in harsh conditions? These sorts of questions. But typically these assays are run one or two or several designs at a time, and so what we've done is we've used techniques like DNA barcoding and DNA sequencing to convert those gold standard assays into high throughput screens. So instead of looking at a handful of candidates at once across different wells, we can look at tens of thousands of candidate cell therapy designs just in a single well, all in parallel, measuring that functional information.

Speaker 3: 6:15

So just to give you a quick example to make that a little bit more real in T cell or natural killer cell therapies, exhaustion is one of these key criteria that people think about a lot. So if you expose your cell to target cells over and over, and over and, over and over again, your cells become exhausted and can't kill the target cells after some point. So we had a hypothesis that we could design chimeric antigen receptors, cars. This is the CAR in CAR-T that could increase that time to exhaustion. So we took a gold standard functional assay that measures and characterizes exhaustion, did a high throughput screen of several thousand CAR designs and were able to identify a handful of CARs that actually doubled the time to exhaustion in these NK cell therapies is what we were looking at. So that's a more concrete example for you about how the platform works.

Speaker 2: 7:10

That's really interesting. That's nice for elaborating there. Would you mind talking through how modular design is utilized to create customized DNA cassettes for human cells and what are some of the real-world applications for this?

Speaker 3: 7:24

approach Cassette is the operative word you really said there and we really view the cassette as the DNA operating instructions for the cell. Each of these cells that we're working with in cell therapy have some interesting native functionality that we're using as the basis for the therapeutic. Then we're doing some engineering on top of that to enhance that functionality or redirect it. The cassette is the set of instructions that's encoding the secret sauce of how to enhance that baseline function in interesting ways. The way it works is that we perform these high-throughput discovery experiments such as the ones I just described. Then eventually the interesting things coming off of the platform get mixed and matched into these sets of components that can all be expressed simultaneously inside your cells.

Speaker 3: 8:18

We leverage that architecture in two different ways. The first is by working with partners to enhance their own cell therapy designs. We have a lot of discovery capabilities. There's absolutely the potential to work with partners to drive different functions that they might be interested in In. The second is to use these cassettes as the basis for our own internal therapeutics programs. Of course, in a cell therapy you have the cell manufacturing process and then you have your operating instructions for what you want that cell to do beyond baseline. Something we're excited about is the very modular nature of some of these cell therapies, where we can use a common manufacturing process across programs, a common DNA cassette architecture across programs. Then, from program to program, what we're doing is we're just swapping out different components. This is why we think that, in the long run, despite the fact that cell therapy right now is not the most scalable modality, if designed correctly, cell therapy can actually be very scalable. That's interesting.

Speaker 2: 9:26

Some access. You continue to pioneer the field of cell therapy design. What are some of the more promising developments or breakthroughs that you see coming in the near future? What trends are you currently following?

Speaker 3: 9:39

In the last decade or so, this CAR T paradigm has really dominated the cell therapy space. When you think about CAR T, you think about mounting a dramatic inflammatory response against a large number of cells. You're targeting cancer, right. There's a lot of cells there to kill. You need a large therapeutic response to make a dent.

Speaker 3: 10:01

But what we're starting to see now is, through different types of engineering, through different cell types that are being the basis for these therapies beyond T cells and new indication spaces like autoimmunity, where cell therapies are starting to be at least partially de-risk, I think there's going to be an opportunity for one or more new paradigms.

Speaker 3: 10:24

So to give you an example of something worth thinking about a lot inside modulus, as we have kicked off a program in the autoimmune space, the situation is very different than in oncology. The patient is already sensitive to inflammation and the number of target cells to actually kill is significantly less than in the oncology setting. So there perhaps you want a cell therapy that acts a little bit more like a traditional drug where you could administer it. It has very controlled kinetics. It goes in, does its thing and a week later it's completely gone. Clinician very in control of that process, and so that would be a really interesting paradigm that would open up new application spaces and, we think, one that could also broaden the accessibility of cell therapy. So that's one of the things I'm looking out for.

Speaker 2: 11:14

So success can be defined in a lot of ways. What's your personal definition of success as a leader at a biotech company? And then, what advice would you have for aspiring entrepreneurs and scientists looking to make an impact in this space?

Speaker 3: 11:29

One in the industry is motivated by patient impact, whether you are doing late stage clinical trials or early stage discovery.

Speaker 3: 11:37

That's kind of the North Star for everybody, and we are very much included in that. I think something else that really motivates our team, beyond any deal we might sign or any particular therapeutic program we might try to advance is just this notion that this is an interesting space. It's an exciting space, but there are paradigms that need reinvention and evolution and the fact that we're contributing to that and doing something new is something that very much motivates the team on a day to day basis. Even if we never get a drug into the clinic, the fact that we have injected new thinking and hopefully, fresh energy into the system is something that gets our team at a bed every morning. And in terms of advice for folks, I would say not only peg yourself to that North Star of patient impact, but figure out how you can motivate yourself via the process as well. Enjoy the process and get motivated by those little things you're doing every day to march towards that North Star.

Speaker 2: 12:43

Great answer. I'm sure you've put in countless hours since starting Modulus. How do you maintain a balance between professional commitments and your personal well-being when it comes to managing the pressure that comes along with being a CEO of a biotech company?

Speaker 3: 12:58

Well, you unfortunately can't have it all. I think there's a saying, I've heard, that you can only do two or three things at any time in your life. Well, and that is definitely, I think, held true for me. So I've learned, though, that there are definitely enough hours in the day if you are just honest with yourself about what those priorities are, and you cut out a lot of the rest, and so for me, obviously, with Modulus, that is super important. Also, I have a family, two young girls, and I really prioritize physical fitness, because that allows you to do the rest, and so, unless other activities are aligning with any of those three, they tend to be pretty low priority, but you can make it all work.

Speaker 2: 13:42

Yeah, that's awesome, great answer. So, max, it's been a pleasure meeting with you today and thank you for being a guest on the first in-human podcast. The team here at Bio wishes you and the team at Modulus, their pudics, nothing but future success.

Speaker 3: 13:55

Well, thanks a bunch for it. Great questions, really enjoyed it. Good luck to you guys as well, thank you, thanks for listening.

Speaker 1: 14:08

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