Wyatt McDonnell wears many hats — immunologist, founder, inventor (of 43 patents), author (of 31 peer-reviewed papers). These days, he’s creating drugs for human use, starting with human antibodies. As CEO and co-founder of biotechnology company Infinimmune, he’s pioneering a new approach to antibody drug discovery and development that’s derived directly from the human immune system.
In this conversation, McDonnell dives into how better antibody drugs can improve patient care, why he made the transition from academia to the startup world, and his vision for the future of biotech.
What’s the role of human antibodies in drug development? How can they improve patient outcomes?
Truly human antibodies are designed to drug new targets, safely and effectively. They’re less likely to provoke immune reactions in patients because the body recognizes them as “self.” They’re also more precise in what they interact with, and stick strongly to their intended targets. That makes them uniquely suited for targeting complex biological systems — specifically, diseases that have been considered “undruggable” or “partially druggable” in the past. Ultimately, better antibodies lead to more treatment options and potentially improved patient outcomes.
What’s your vision for Infinimmune?
Infinimmune will be the single source of a safer and better generation of antibody therapeutics: drugs that target specific molecules to treat diseases, derived entirely from completely human antibodies. Our technology — built and tested internally for many years — gives us a deep understanding of the antibodies these diseases need, and the autoantigen targets of human immune systems. We’re now building our own pipeline of drug candidates, and partnering with pharmaceutical companies to advance antibody programs together.
We’re focused on autoimmune diseases. The focus of our lead program is atopic dermatitis, which has the potential to expand to chronic obstructive pulmonary disease (COPD), oncology, and ankylosing spondylitis, a chronic type of arthritis. The second program is in ulcerative colitis, Crohn’s, and allergic airway disease. A third is in chronic kidney disease and B-cell autoantibody depletion. What ties these together is the current lack of any sort of biologic therapy, which is a type of highly effective treatment that uses the body’s own immune system to fight diseases.
What will one of these programs look like in action?
Imagine you have to go into a doctor’s office multiple times a month to get an infusion or a painful injection. What if you could easily inject yourself at home every three, possibly six or 12 months instead? That’s what we’re building: molecules that will work better for everyone involved. They’ll be easier for patients to take and tolerate and simpler for doctors to check and make changes to if needed. And it will be much clearer for payers to see if they’re worth the cost and actually helping people get better.
Playground is your lead investor. What appealed to you about working together?
Playground is unique as an early VC because it believes in scientific diligence, and has an in-depth diligence process. When I first met partners Jory Bell and Benjamin Kim, our 30-minute meeting turned into a three-hour whiteboard conversation. Then Ben and our team spent a month generating an approximately 100-page diligence document. If you don’t have that type of collaboration from your investor, you should wonder how your investor is going to help you. Playground took the time to think and pay attention, which is unusual in our distracted digital age. Playground invests in technology that’s physically connected to the real world, and not just the digital world.
I was also impressed that Playground was one of the earliest correct voices on the importance of RNA therapeutics, five to seven years ahead of the curve.
You’re a rare hybrid founder, fluent in gene sequencing, coding, and software engineering. But your professional story begins in academia, right?
In 2015 I started my PhD at Vanderbilt University in Tennessee, where I got a baptism-by-fire experience being mentored by a T-cell clinician and immunologist and a B-cell structural biologist and computer scientist. I realized that very few peers in my immunology cohort were coding, so I learned how. At the time, Vanderbilt was one of three universities in the world where researchers could access all of the first generation of single cell technologies including controllers from 10x Genomics (Chromium), BioRad (ddSEQ), and Fluidigm (C1). I had a courtside seat to watch people line up to use those instruments. The Chromium controller had the longest customer line, and most customers didn’t know what to do with that sequencing data — which was a great opportunity for me to learn some new skills, explore new areas of science, and collaborate with experts in many disciplines.
How and why did you transition out of academia?
After my Master’s and PhD, I joined the Vanderbilt faculty. Eventually, 10x Genomics lured me away to build products. I was one of three immunologists at the company when I joined. I cut my teeth learning how bad I was at software engineering, and figured out instead that I’m pretty good at creating intellectual property, and getting people in wet labs (where the experiments that involve handling liquids and chemicals happen) and dry labs (where research happens, but without any physical materials or substances) to communicate and solve problems. But eventually it became clear to me that biopharma is slow to adopt really compelling technologies. So I left and started Infinimmune with four other co-founders I’d met along the way, who are brilliant scientists and problem-solvers in their own rights.
What’s the future of biotech?
The stuff that’s going to make the biggest difference will be in spaces you and I will never physically see, touch, or interact with. Real-time changes are being made in hardware and manufacturing components in life sciences, and AI is doing the same in the manufacturing of medical devices and biologics. But they’re not appreciated by the public — and are missed by a lot of investors.
A second shift is a move away from synthetic biology. I think you’ll stop seeing so much focus on lab meat, for example. Instead, you’ll see renewed focus on making drugs that are more stable in supply chain delivery — drugs that you can actually formulate in different ways so that patients in many different environments can receive them easily, whether intramuscular injections or injections they can administer themselves. That’s where good investments, placed strategically, will make a big difference.
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Pullquote:
“We’re building molecules that will work better for everyone involved. They’ll be easier for patients to take and tolerate and simpler for doctors to check and make changes to if needed.”