Faculty Feature: Dr. Ross levine

For this newsletter’s Faculty Feature, Yanyang Chen, Francis He, and Nick Bartelo had the opportunity to sit down with Dr. Ross Levine, MD. Dr. Levine received his MD from Johns Hopkins School of Medicine. He is a Leukemia Specialist & Physician-Scientist, Laurence Joseph Dineen Chair in Leukemia Research, and Senior Vice President of Memorial Hospital Translational Research. He also serves on the advisory board of multiple scientific companies. Dr. Levine is founder of Ajax Therapeutics, a therapeutics company targeting myeloproliferative neoplasms (MPNs) with greater precision by applying state-of-the-art computational chemistry and structural biology. Dr. Levine is revolutionizing the cancer therapeutic industry by developing a new generation of Type II JAK2 inhibitors.

SVG: Ajax Therapeutic was founded in 2019 and it has grown significantly since its inception. Can you tell us more about what led to this start up as well as the current state of the company?
 
Dr. Levine: Targeting mutated JAK2 has been an area of interest for treating myeloproliferative neoplasms for more than 18 years. However, there are significant limitations to current JAK inhibitor therapy both with respect to efficacy and toxicity. My group published the proof of concept paper back in 2014, showing the improved efficacy of type II JAK inhibitors by inhibiting JAK2 in the inactive conformation, instead of JAK2 active conformation (type I JAK inhibitors).

Although Novartis also came up with the initial molecule targeting JAK2 inactive conformation, the non-specificity of this proof of concept compound and toxicity issues hindered them from pursuing the strategy further. With a group of close scientific founders, friends, and colleagues in the biotech and pharma world we decided to start a company to develop type II JAK inhibitors. I was able to get a lot of advice as we began the journey. Ajax formed a medicinal chemistry partnership with Schrödinger and came up with new structures targeting inactive conformation of JAK2. The company was formed in 2019 and we are planning to file an IND next week.

SVG: There have been a few approved JAK inhibitors and the JAK2 inhibitor Ajax is developing focuses on the inactive conformation of the kinase domain of JAK2 to help overcome the resistance to common JAK inhibitors. This language is very scientific. How was your experience talking to other scientists and investors about the science and how did you convince investors that your approach is different from currently approved JAK inhibitors?

Dr. Levine: With respect to finding co-founders in science, we are a collective group of experts highly interested in solving this problem. We have people with expertise in structural biology and chemistry so we weren’t starting from zero, such that Ajax had a “running start”. As for investors, I knew investors in companies where I had been a scientific advisor. When I was thinking about Ajax, I reached out to a few VCs and a couple of them thought this approach had potential value. I also knew a philanthropist in the MPN space who had supported me and other groups, and he introduced me to additional investors. So we did not have the experience of going to 20 groups and pitching the idea. In the end, we went with the offer that also introduced us to Schrodinger, which is a computational chemistry company. We leveraged their expertise on chemistry and achieved our milestones much faster. 

SVG: Some academics that start a company transition to fully work at the startup while you have stayed in academia and continued practicing medicine. How do you balance serving on the board of Ajax Therapeutic with academia & clinical practice?

Dr. Levine: There are amazing synergies between different roles. My expertise and knowledge in academia and medicine helps the startup, and my ability to see how drugs are made gives me a much greater perspective in the field of research. Beyond all the synergies, time is the most limiting reagent. Earlier in my career, I served on several advisory boards. Once I got involved in Ajax, I reduced my involvement advising other companies and focused my outside efforts primarily on Ajax. My feeling is if you commit to being a founder, you have a commitment to the company, the investors, and the project you believe in.

SVG: What advice do you have for graduate students and postdocs who are interested in creating a company?

Dr. Levine: It is very important to pick a few trustworthy mentors and advisors that have created or served on the boards of companies previously. The entrepreneurial ecosystem is complex and it is necessary to get help from those who have experience on which choices to make. For investors, the most important thing is to find those who share both your belief in the idea and long-term vision for the company. Numbers on the sheet are less valuable than surrounding yourself with people you enjoy working with and who share your vision.