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Founder Spotlight #49: Wyatt McDonnell @ Infinimmune

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Published in
18 min readMar 28, 2023

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Infinimmune is a biotechnology company pioneering a novel approach to antibody drug discovery and development. Founded by a world-class, multidisciplinary team of scientists and technologists, Infinimmune is reinventing antibody discovery with an end-to-end platform to deliver antibody drugs derived directly from the human immune system. These truly human antibodies are designed to drug new targets with improved safety and efficacy. Infinimmune will deploy its holistic approach to build its own pipeline of drug candidates and partner with pharmaceutical companies to advance their antibody programs, fill their pipelines, and reach new patients and new indications. To learn more, visit infinimmune.com and engage with us on LinkedIn and Twitter.

Wyatt McDonnell is Co-Founder, CEO, & Chairman of the Board of Directors @ Infinimmune, a biotechnology company utilizing natural immunity to transform natural antibodies into safer and more effective drugs for complex diseases. Previously, Wyatt developed 10x Genomics’ first therapeutic antibodies and core immunology intellectual property behind three commercial products to interrogate the immune repertoire. He has co-authored 31 peer-reviewed papers in journals including Nature, Cell, and Nature Medicine, and 19 published patents in relation to immunobiology, genomics, and disease. He has been invited to speak at conferences including PEGS, the Keystone Symposia, the World Vaccine Congress, and PMWC.

Personal Spark

What prompted you to pursue a career in Life Sciences? Was there a specific moment in time or influence you can remember?

I grew up in a rural town in northern Michigan where there wasn’t a lot to do but there was an excellent public library, nature all around, and a good public school system. My folks didn’t really let us watch TV or movies, but would let us read almost anything we could find, went out of their way to take us to museums and made sure we went on every school field trip, and spent a lot of time encouraging us to think about and engage with anything that piqued curiosity. The first photo of me in a lab is from when I was 5 or 6 years old and a family friend showed me how to turn a copper penny silver by redox reactions — I remember that being absolutely magical.

Most of my early interest in science was closer to natural history — my mom and dad picked up a cheap used microscope and slide set of various tissues that I wore out. That microscope set was a good example of how I would obsess over a science/nature-related thing for a number of months and then land on a new interest. Unsurprisingly, I wound up collecting rocks, seashells, ladybugs (family Coccinellidae), butterflies, encyclopedias (fish, birds, mammals, dinosaurs), and most recently antique medical and immunology textbooks and correspondence.

It was easy to keep up my interests because I was lucky and had many excellent science and humanities teachers from elementary school through college. I also benefited from being able to do increasingly formal research from about 12 years old onwards — I started with calculating bullet velocities and comparing to manufacturer specifications in middle school, public health surveys in high school, and zapping drug-resistant S. aureus bacteria with blue light and heme precursors in college. I landed on immunology in grad school because it’s a fast-moving and complex field and because immunology is at the center of many of history’s most impactful drugs. Working in biotech is immensely satisfying because it’s difficult to get bored, the problems you solve require fun and brilliant interdisciplinary teams, and the end products you work on can create a different world for patients, providers, and scientists.

How did you get your training to be able to build your company?

I did 3 years of research in college and was able to take focused and deep coursework in virology, immunology, molecular biology, and cellular biology with small class sizes, journal clubs, and dedicated labs. I went to grad school thinking I was going to work on bacterial immunology, and fell in love with adaptive immunity instead. I was fortunate enough to be mentored by clinician-scientist Simon Mallal and his research teams at Vanderbilt University and the Institute for Immunology and Infectious Diseases at Murdoch University in Australia, and by Ivelin Georgiev, a computational biologist starting his professorial career out of a deep structural and computational antibody background at the NIH’s Vaccine Research Center. Along the way, I gained exposure to automated robotics, a few programming languages, a lot of molecular biology and human immunology, and a very healthy dose of reality (research is time-consuming, hard to do well, and mostly you need to listen and learn constantly). My PhD committee included basic and translational scientists and clinicians, who were very supportive of letting me wander through projects and help other groups with their research.

I got a ton of early exposure to single cell sequencing with the 10x Genomics Chromium platform, which was a fascinating and hackable piece of biotechnology, and my experience with that platform led to a job at 10x Genomics directly out of my PhD. I spent a few years at 10x working on their existing immune repertoire products and shipping a new one, BEAM, and gained exposure to business development, industry IP development, and how to model from scratch how you invest in building a new product. Learning how to think about and solve problems during my PhD and then putting those skills to work in industry is a common and useful combination of experience for myself and many others in industry.

Can you tell us a little bit about your background & career thus far? What were you doing before you started running a high potential venture backed startup?

Before I started Infinimmune, I was working at 10x Genomics, where my role was interdisciplinary and involved doing core R&D, inventing and protecting IP, providing one of many opinions on future business opportunities, and serving as a customer-facing expert and “internal consultant” on immunology-related opportunities. This kind of role is hard to find and you have to get lucky in finding a great company and managerial team who will enable and support you in your work, and this experience remains useful to me on a daily basis. It was also where I bumped into my future co-founders and gained a deep appreciation not just for the many types of expertise that are required to solve hard problems but also for how rare impactful life science tools companies are. At Infinimmune we decided from day one that we weren’t going to build and sell tools because we could have a bigger impact applying the incredible tools that already exist to meaningful problems instead of trying to sell yet another tool.

Anything else you’d like to share about your life, academic trajectory, etc.?

Several “early” life experiences continue to push me into working on problems that can reduce suffering. Our immediate and extended family has had experience with aggressive pediatric lymphoma, Huntington’s disease, rheumatoid arthritis, and comorbidities from chronic viral infections. Many people like me who have watched these events happen in their family, sat at deathbeds, and listened to patients end up being motivated to build better drugs or drugs that don’t yet exist. We traveled a lot when I was younger, which also drove home that there’s a lot of beauty all over the world and there’s also a lot of suffering that’s hard to appreciate without leaving the ZIP code you grew up in.

Company Overview

Quite simply, what does your company do?

Infinimmune is working on building safer, better antibody drugs for multiple diseases by developing drug candidates from safe and effective antibodies produced by the human immune system. The success and impact of antibody drugs in the past two decades have been impossible to ignore — conversely, the tools to directly screen and identify antibodies in human immune systems are extremely new and human antibody responses are poorly understood. Many acute and chronic diseases have immune-mediated components, but immunotherapies are not available for most of these diseases. In a world where antibodies and biologics are taking over and effectively treating many diseases, we build antibodies which nature has already validated for their safety and efficacy in the human body.

Now in more depth, what are the specifics of what your company does?

Infinimmune screens the human immune system for antibodies that are impossible to identify from any other process, by sequencing antibodies of single B cells, engineering these antibodies to help large populations of patients, and identifying novel antibody biology and targets.

How did you become motivated to tackle this particular problem?

Infinimmune is working on building safer, better antibody drugs for multiple diseases by developing drug candidates from safe and effective antibodies produced by the human immune system. The success and impact of antibody drugs in the past two decades have been impossible to ignore — conversely, the tools to directly screen and identify antibodies in human immune systems are extremely new and human antibody responses are poorly understood. Many acute and chronic diseases have immune-mediated components, but immunotherapies are not available for most of these diseases. In a world where antibodies and biologics are taking over and effectively treating many diseases, we build antibodies which nature has already validated for their safety and efficacy in the human body.

Why does your solution matter for the world when you get it right?

When we get this right, we will be able to deliver antibody drugs for humans, from humans — this will mean fewer side effects, more affordable medicines because of increased potency, and an improved understanding of how the human immune system deploys autoimmunity to protect us.

Genesis

Tell us about the founding of your company — how did everything come together?

All of Infinimmune’s founders had decided they wanted to move on from tackling life science product commercialization to tackling new problems in human health at various times between 2021 and 2022. I sat down to grab a beer with our co-founders in July 2022, sketched out a few ideas, incorporated, started fundraising and doing proof-of-concept work, which culminated in a $12M seed round in the fall of 2022. The tools that are best positioned to understand and learn about the adaptive immune system have been underadopted and underapplied, and our founding team couldn’t stop thinking about the prospect of building better drugs while learning about the actual targets of the human adaptive immune system.

How did you meet your co-founders?

Infinimmune’s co-founders all worked at 10x Genomics previously, mostly indirectly and in very different roles, and depending on which pair of founders you pick have known each other for 2–7 years. Funnily enough, when I was hired by 10x, David Jaffe, one of our computational co-founders, was one of my interviewers. I ended up sending him a note after the interview with some more thoughts/reading material in response to a very interesting question he asked me. Unsurprisingly, David and I ended up working closely together for most of my time at 10x across multiple projects.

Was there a specific moment when you knew you should pursue this business idea? If so, what was it?

We’d all seen a series of small but meaningful step changes in biotechnology, some of which we’d contributed to at 10x Genomics, set against a backdrop of the world finally paying attention to antibodies full-time during the COVID-19 pandemic, and validated by several direct-from-human drugs reaching the clinic and even FDA approval. Several pieces of data analysis that we completed led us to realize that we could build some core technical functionalities that were unlikely to be built by or even tractable for life science tools companies. A recent paper in Nature from two of Infinimmune’s co-founders about a new property of antibodies light chain coherence strengthened our resolve that screening human immune repertoires in antigen-specific and antigen-agnostic fashion wasn’t a fool’s errand, and our investors shared our enthusiasm!

There were two cool early moments when we had a pretty good idea that things were going to move forward. The first was when what was supposed to be a 1-hour-walk-and-talk with Josh Elkington (one of our earliest supporters) turned into a 4-hour-hike-most-of-Berkeley. The second was when my first meeting with Jory Bell and Ben Kim from Playground turned from a half hour meet-and-greet into a 3-hour whiteboard session.

Timing is everything — how did you know the timing was right?

Each of us had watched some incredible tools start to change the face of biological research and clinical medicine — DNA sequencing, single cell sequencing, biomanufacturing, and a long-running streak of blockbuster antibody drugs. We also watched many great biotech companies get beat up in the public market and figured that now was as good a time as any to start a new company, recruit incredible talent, and take advantage of technological innovations that still haven’t deeply penetrated life sciences.

Accomplishments

What are some of the notable milestones your company has achieved thus far?

  • We recently closed a $12 million series seed round, led by Playground Global with participation from Pear VC, Civilization Ventures, Axial VC, and angel investors Ron Alfa, Paul Conley, and Joshua Meier.
  • It took just 3 months for Infinimmune to close its seed round beginning in mid-July 2022 when we incorporated.
  • We’ve hired our first two team members and are hiring more talented folks to work end-to-end on new therapeutic antibodies (including BD)! Please get in touch via careers@infinimmune.com or founders@infinimmune.com if you’d like to bring your skills to bear on the problems we’re solving!

What are some of the biggest hurdles ahead? How do these create points of value inflection?

Infinimmune’s long-term strategic hurdles fall into two categories: hurdles that affect all companies building antibody drugs, and asset-specific hurdles related to the biology of antibody drugs built at Infinimmune. Fortunately for us we get to benefit from decades of excellent legacy work in assessing, protecting, and testing antibody drug candidates. We spend more time thinking about how antibodies from humans could behave in unexpected ways in preferred models of specific diseases, require additional engineering for manufacture in industry-standard CHO cell lines, and how lead optimization and selection for human antibodies might differ from antibody candidates derived from other discovery workflows. In the meantime, we’re also focused on meeting strategic milestones in advance of future fundraising.

Pay It Forward

Throughout the journey, what have been some of your biggest takeaways thus far? What advice/words of wisdom would you share from your story for other founders?

For me personally, having multiple co-founders that I trust and respect deeply at Infinimmune has been unbelievably empowering. I have deep respect for the insanity and vision found in solo founders. Being able to start a company with a team whose advice and feedback you can listen to has made all the difference for us — and that applies to our investors too! You want to build a team within and around your company who you can listen to when they have feedback to share.

Beyond finding and listening to people you can trust, learning how to start, fund, and operate a company for me has boiled down to two sources: speaking to other founders, and reading-thinking-doing-repeating. There’s a ton of advice on how to do this that you’ll be able to find, though you may not be able to take advantage of all of it, and some of it you may not want to take at all. You’ll learn more about how to start a company by getting going and starting than you will by reading about it, and that’s why you should try to connect “doing/testing” to advice you read. Experiments don’t just happen in the lab!

Lastly, patience and focus are required. It will take you time for you to figure out what you actually want to do, what you will do, and how you’ll bring new team members and investors or funders alongside to make it happen. There will be a million things you can do with your time. Focus on getting just one high priority thing done at a time, find a mental model or tool that works for you such as the urgency-importance matrix, and stick to it. Nobody will identify your critical path for you, so it’ll be on you and your team to figure out the order of events and what does and doesn’t matter. Speaking to people who have done this before will help you find strategies that you can try out and will remind you that this process is as exhilarating as it is exhausting!

What are some of the must-haves for an early stage Life Sciences startup in your eyes? (Key critical components like team, academic papers, industry know-how, etc.)

I think the exact critical components are highly dependent on what you’re trying to do, what your background as a founder is, and how you want to grow the company. If you’re trying to build a tools company, you’re going to need advice and hands-on help with engineering, productization, commercialization, and builders for software/hardware/kits/etc. If your company will be built around a drug for a specific disease, you’ll need to focus on how you’re going to find candidates (or why your candidate is better than what’s out there), get detailed early-on about clinical trial details, bring in experts in the indication you’re targeting, and focus on finding investors who are comfortable with high-risk-high-reward asset investing. If you’re an academic spinning out a company, you’ll want to read resources like 50 Years’ Spinout Playbook and focus on getting your tech transfer knocked out and deciding who will help you operate your company and if you’re going to also come out of academia to run your company. In almost all cases, you will be well-served by finding people who have worked in industry for a number of years because the pace of work in industry and in startups is much different than academia, and if you’re coming from industry, you don’t want to drop that pace. Above all else, hire to cover your blind spots and spend time figuring out what you don’t know and are missing — assuming that you’ll be able to single-handedly learn everything you need to do to succeed is a huge mistake.

What are some of the traits that make a good founder? What type of risk profile/archetype does someone need to have to be a founder in your opinion?

As a first-time founder, I don’t think I’m well-qualified to answer this question convincingly — I can probably speak more accurately to “what types of traits do you see in founders” than “what distinguishes great founders from not-as-great founders”. My intuition is that folks who are very risk-averse will be very uncomfortable starting a company or even joining a new or early startup. You’ll need to be comfortable being flexible, dropping and picking up ideas rapidly, and you’ll need to be good at starting and continuing conversations when somebody says “no, not now”, “I don’t understand”, “that doesn’t make sense to me”, “can you say more?”. If explaining things without getting frustrated doesn’t come easily to you and you’re still hellbent on starting a company, find a co-founder whose strength fills that gap. I would assume that some level of passionate, deeply held belief or vision that your work will lead to a different and better world is also necessary, and an ability to articulate that to many different people. My last assumption is that great founders are capable of “executing” (which is an overused and abused word in this space) rapidly and not letting things fall through the cracks. That last bit probably requires some degree of obsessive or compulsive tendency, or maybe none at all and I’m just projecting. Ashamed to say I don’t remember where I read this, but another combination of traits that might make sense is “not hesitant to disagree but also open-minded” (I think the original version was “disagreeable but open-minded”).

For folks coming out of academia, what advice would you share?

Get connected with other founders and folks with industry experience immediately. In my opinion you should do this before speaking with your tech transfer office so that you’re getting high-quality external advice from operators and not university employees who aren’t really invested in your short- or long-term vision.

Not everyone knows everything. Often founders have to learn either the science or the business side better. What advice would you give for someone picking up a new skill set such as this?

Try to figure out if you’re going to be any good at it early. If you’re not making rapid progress and improving, quit, and find help! If it’s going well, do an inventory of which skills you’re going to end up failing to maintain, and make sure you’re finding help to cover the things that you’ll do less of if this becomes a focus area for you.

Can you demystify the process of what it takes to raise VC funding? What were the highlights & lowlights? Any advice or words of wisdom for future founders?

Raising VC funding is probably a pretty unique experience both for individuals and specific companies that they start. You need to start getting to know people months in advance of “running the process” — investors need to learn about you, what motivates you, how you interact with people, and see how your vision of your company changes over time. We took on no convertible debt or convertible notes, self-funded (no friends or family) while doing proof of concept, and made our first fundraise a priced round, which helped us select some extremely helpful and high-quality investors. Some of our first conversations were great practice even though we weren’t a fit for some of those investors — and that’s totally okay, very common for all companies, and worth doing! We were able to use the time in the summer to get work done prior to Labor Day, and then ran our fundraising process immediately after, which also worked well for us. Along the way we had a great back-and-forth with our investors throughout the process that improved the quality of our thinking about Infinimmune and the quality of our fundraise, so I’d also encourage new founders to embrace the collaborative aspect of fundraising as much if not more than the adversarial aspect. Don’t underestimate the power of a few smart and well-connected angel investors or “one-person shops” either.

What advice for managing and hiring a great team can you share?

Management styles don’t necessarily generalize — I’d recommend taking some time to reflect on what you’ve seen work well for leaders you’ve worked for and admire. We ask prospective employees at Infinimmune what some of their favorite and least favorite attributes of their past managers and mentors are, for starters. We also ask them what would have happened if they were to leave Infinimmune in just 1–2 years — this gives candidates an opportunity to talk about why they’re looking for new employment if they’re comfortable talking about it, but also some context for how they want to grow and what they’re looking for in leaders. Asking people you admire for concrete examples of managers and leaders they admire and have worked for is also helpful. Some things are very common across disciplines (“they delegate well”, “they listen well and then take action”) and others are very specific (“in addition to being a respectable human this person also has technical and hands-on experience that makes them qualified to run their team and identify other brilliant people to hire”).

Everybody will tell you to be careful with hiring, and they’re right! We prefer hiring slowly and deliberately so that we bring somebody on when there’s not just a specific role for them but a long-term career. Specific things we have found useful at Infinimmune include phone/video screens with >1 person, “small group” sessions during interviews, and using a non-standard set of largely behavioral questions. If this is your first time hiring, you can learn how to do this by reading (I personally recommend Talent by Tyler Cowen and Daniel Gross, taken with several grains of salt), working with a recruiter so that you can see a volume of resumes and understand how people present themselves (though you may not end up using a recruiter at all), and most importantly taking some time to think about whether questions you’re planning to ask in an interview will actually teach you something about the person you’re interviewing and provide them with an opportunity to shine.

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