5 Questions with Jimmy Blair, Ph.D.

Jimmy is the scientific co-founder and VP of Chemical Biology at Totus Medicines, where he pioneered the Totus hit generation engine and leads the discovery chemistry and platform innovation teams. His research is steeped in covalency, including the development of novel covalent molecules for protein kinases and the synthesis of covalent inhibitors for neglected diseases. Prior to Totus, Jimmy contributed to chemical biology and metabolomics efforts at Jnana Therapeutics, and he was a faculty member at Williams College, where he led an undergraduate team in the pursuit of novel antibiotics. Jimmy was formally trained as a chemical biologist at the University of California, Berkeley (Ph.D.), and as a microbiologist at Stanford University (NIH postdoctoral fellow).

We spoke with Jimmy recently to learn more about his background, his early days at Totus and his advice for anyone interested in entering this field.

Tell me about your job and how you got started in this field.

At Totus, I oversee all the early discovery chemistry activities and contribute to platform innovation. It’s safe to say that I've always wanted to know how things work - machines, computers, nature - and this curiosity eventually led me to chemistry. In graduate school, I asked a lot of questions about how we could use chemistry to answer biological questions, and through that I found my calling in the field of chemical biology in Kevan Shokat's lab at UCSF. There, I studied drug design and how to develop small molecules that can probe how well enzymes work in cells. I've continued my career at the intersection of chemistry and biology, which led me to biotech and my co-founding of Totus Medicines.

You were there at the beginning: Describe the early days of Totus.

In January 2020, Neil and I started out at the LabCentral incubator in Cambridge, Massachusetts. We were just two guys renting a bench, developing experiments to help answer key questions in how our covalent small molecules worked. Many of those experiments still echo their way through Totus’ research platform today. Back then, we'd meet early in the morning, chat for a few minutes, and get to work. It was an exciting time, and working adjacent to other scientists at other startups at LabCentral was a fun and collegial environment. Then the Pandemic hit. Like everyone else worldwide, the breadth of our work was curtailed by the lockdowns and supply chain issues, and because of our off-set schedules, Neil and I were not able to meet face-to-face for long stretches of time. But what this did offer us was extreme focus. Knowing we had limited scope, we chose to focus exclusively on what became TOS-358, our PI3Ka inhibitor, and our research platform. I have fond memories of our exciting breakthroughs that year: the day our novel platform assay worked, running our first cell-based screen for new chemical matter, and for our first proof-of-concept data on TOS-358 in mice.

Now that you are 30+-strong and based in the Bay Area, what do you like best about working at Totus?

I love the people I’m working with because we’re a diverse, passionate group of bright, hardworking, and curious people. We’re all laser focused on our mission of making a difference, and we collaboratively move swiftly toward this goal. A key aspect is the wide spectrum of experience from very seasoned to green, which offers us a dynamic learning and growth environment - each day I’m teaching and learning from them all, because we all have something to contribute. I also like working on hard problems: it’s invigorating to have a dogged pursuit to solve. And finally, most importantly, tacos are so much better on the West Coast!?

What goal are you most passionate about achieving at Totus and what unique/niche skill do you bring to the table to achieve/support the achievement of that goal?

I left academia as an educator with a desire and a passion to leave things better than I found them, reach a much bigger audience, and change peoples’ lives. I felt I could best do that by bringing a molecule like TOS-358 off the whiteboard and to market, something that will literally save lives. At Totus, we’re a lean, agile team where each of us has an ability that contributes to our success, and the role I play is bridging the gaps across functional areas. Drug discovery is a team sport and with such a small but mighty team, we need folks like me who can switch hit on both the chemistry and biology side.?

What advice would you give someone seeking to enter your field?

I’ve taken an nontraditional route to co-founding Totus but with the common themes that I’ve focused on the science, stayed curious, and worked tirelessly throughout. My advice for anyone seeking to enter my field is if you can continue to follow those themes, so many opportunities will remain open to you. Go to college, get a degree in a specific field, and grind on it; or you can prepare yourself in a variety of ways and take the road less traveled. Either path works; I happen to have taken the latter route. Also, having a desire to be a team player and care for the people around you goes a long way, because even if you pivot from one science area to another, the opportunities will continue to be open to you, like how I bumped into Neil for the first time at a conference in 2019! Serendipity and connections can sometimes be transformative for your career, so being focused and curious about what’s meaningful to you will help you stay on a course that keeps you in your passion areas.