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Nick Goldner is a treatment resistance scientist, investor, and entrepreneur. He is the Co-Founder & CEO @ resistanceBio, which focuses on developing therapies for treatment-resistant cancer. He received his Ph.D. from Washington University in St. Louis, where he focused on understanding and overcoming treatment resistance mechanisms. Beyond resistanceBio, Nick is a venture partner for Pioneer Fund and focuses on investing in the broader biotech, diagnostic, and digital healthcare space.
resistanceBio enables the development of novel treatments for patients with treatment-resistant cancer. We’ve developed the ResCu (resistance culturing) system, a proprietary, pre-clinical, cell culture-based, ML enhanced discovery system that accurately identifies and overcomes clinical treatment resistance across cancer types in months, not years. ResCu enables the discovery of clinically relevant novel druggable targets and biomarkers before dosing the first patient.
What prompted you to pursue a career in Life Sciences?
I’ve always been interested in biology. As a kid, I remember going on long walks with my mother, who is an artist, learning to appreciate nature as she sketched it. My dad owns a small business, so entrepreneurship has always been ingrained in what I wanted to do. The pivotal moment for my interest in healthcare came in high school when I was diagnosed with Crohn’s disease. I was an athlete in highschool and lost 30 lbs over a few months before I was accurately diagnosed. It was frightening, and I realized that there had to be a better way.
How did you get your training if any to be able to build your company?
I’ve been extremely deliberate in my training, but at the same time I’ve been incredibly lucky. I come from a family of entrepreneurs, and am an Eagle Scout. So when I got to college I used my skills and interests to start the iGEM program at my university, a small liberal arts school. In our second year competing, we got the same medal as MIT, a big deal. It was the first proof point our school administration needed to keep the team going strong 7 years after I left. That program got me more interested in research, and I went on to get my PhD from Washington University in St. Louis.
I knew I was interested in research and business, so I wanted to use grad school as an opportunity to explore that intersection. It seemed like the logical next step to lend me the freedom to build a team and start a company. I met my co-founder Chris in grad school; we joined the same lab simultaneously. We meshed well, and through our collaborations, we were able to graduate together with Ph.D.’s in less than four years right before entering YC. We actually had back to back thesis defenses on the same day. These opportunities add to how much luck was involved in my entrepreneurial journey and our company’s founding. I feel incredibly grateful.
What problem is your resistanceBio solving?
Treatment resistance is a massive problem in many diseases, and in cancer especially, it is a leading cause of relapse. We are discovering cancer therapeutics that solve the problem of treatment resistance. Traditionally, modeling clinically relevant treatment resistance in cancer cells is very difficult and often untranslatable because the process of creating a resistant cell line is variable. We built and validated the ResCu (resistance culturing) system to consistently create accurate treatment resistant cell populations which model how the tumor will evolve and adapt over time. We identify novel treatment resistance-related targets by characterizing and prioritizing the broad biological differences in cancer cell populations (genomics, transcriptomics, etc.) before and after treatment adaptation. We then design therapeutics that take advantage of these insights.
How did you become motivated to solve this problem?
Treatment resistance is in everything. I’ve had Crohn’s Disease for quite awhile and as a result have had all sorts of manifestations of treatment resistance. I was on one drug for seven years before it stopped working, and even then, before it stopped working I was taking a quadruple dose of it. I had a MRSA infection in my arm and was on multiple antibiotics to try and quell it, but ended up getting a C. Diff infection. My mentor, the person who gave me the first opportunity to be a scientist, passed away from treatment resistant breast cancer. Unfortunately, the luck I’ve had to get to this point has all been unified by treatment resistance in some form. I’ve seen how common it is and how helpless you become, so I’m incredibly motivated to tackle it head on.
Why does your solution matter for the world when you get it right?
Most people look at treatment resistance as a barrier. Treatment resistance is the block that prevents us from moving forward in treating a specific disease. But we’re finding that cancer cells can’t protect themselves against everything. In becoming resistant to one thing, they have to become susceptible to another. So we’re trying to characterize the residual cancer and discover novel resistance associated druggable targets that enhance the sensitivity of the cancer to treatment. As a result, we get closer to long-term, durable treatments for cancer patients.
What is your company’s founding story?
Chris and I met in Gautam Dantas’ lab. We were both fascinated with the idea of understanding how therapies can be circumvented by an organism and what cellular and population level systems changes occur as a result of treatment. Chris was working on a population level resistance dynamic and I was looking at mechanisms. Chris was computationally focused, and I was focused on more physical wet lab work, which worked out really well. We were a part of writing 5–6 grants the first year we were in the lab, and it crystallized our decision to become entrepreneurs. We knew that the scale and speed of research and development that we wanted to perform wasn’t possible in academia and required us to build a company and become entrepreneurs; which we fully embraced.
How did everything come together?
resistanceBio started from Chris and I doing Y-Combinator. We did a podcast episode for Learning with Lowell, which ended up getting posted on a subReddit that had a huge YC community of partners looking for new ideas. Adora Cheung reached out to us and connected us with Diego Rey, the YC Bio partner at the time and were encouraged to apply from that. Our initial company, Viosera, was focused on antibiotics but I’ve always been interested in how treatment resistance can be applied to disease such as cancer. The first person who joined our team, sadly passed away from treatment resistant cancer this past year. Long before then, we realized that cancer resistance was primarily being thought of and treated from a genomics context and so resistanceBio was born to explore the entirety of both genomic and non-genomic resistance mechanisms. His passing reaffirmed our decision to focus on cancer.
What are some of the notable milestones your resistanceBio has achieved thus far?
I’m most proud of our team and what we’ve been able to accomplish as a result of our collective talents. We created a cell culture system in less than 18 months that can recapitulate human disease. This is a technology that didn’t exist before and will be instrumental to our impact. We also found a candidate for non-small cell lung carcinoma that so far has been superior to potent synthetic lethal combinations. This is for patients who have non-targeted Ras mutant NSC lung cancer who don’t have other options for treatments.
What are some of the biggest hurdles ahead? How do these create points of value inflection?
We are looking forward to partnering with larger pharmaceutical companies that can help us translate the pre-clinical work to potentially better patient outcomes in the clinic. Ultimately clinical validation is key to any new therapy and along the way we’ve identified ways to validate these discoveries in patient samples through partnerships.
Pay It Forward
For folks coming out of academia, what advice would you share?
You can’t think like an academic in a startup. In many ways, academia is the antithesis of what industry is like. You have to be able to put things in action quicker and keep moving things forward. There is a difference between being in lab and doing lab work and that mindset change needs to happen for those transitioning into entrepreneurship. Execution is key in industry.
The other thing is that industry is like a professional team sport and requires frequent collaboration and communication, whereas academia is often isolating. Industry is very much about “how we can attract the right people to get this thing done as quickly as possible,” whereas in academia it is easy to fall into the trap of “how can I do this with the least amount of help.” That mindset needs to flip to be successful as a team and is something I had to get over in becoming a leader.
Can you demystify the process of what it was like to raise VC funding? Any advice or words of wisdom for future founders?
It’s about finding the right fit. More often than not, investors don’t pass because you have a terrible idea. Investors will pass because they are not a great fit for you or vice versa. Do your research beforehand because some passes are always going to be passes, so try not to let it become demoralizing and instead learn from each interaction.
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