George Vlasuk knows more than a thing or two about building leading biotech platforms from their earliest stages through commercialization. His career spans 30 years at both small startups and large pharmaceutical companies. With past leadership roles at Sirtris Pharmaceuticals where he served as CEO as well as Wyeth, Corvas (acquired by Dendreon), Merck and California Biotechnology (Scios, acquired by J&J), George took the helm as President and CEO of Polaris-backed Navitor Pharmaceuticals in October 2013. Here he is driving a team poised to develop the chemical compounds that will change the way cells respond to nutrients, thus, potentially impacting a myriad of important diseases. Read on to understand how they plan to achieve their goals – and why patience in the face of chaos is so vitally important.
Can you explain in layman’s terms what Navitor does and how you think it could change the world?
Put in the simplest form, we are trying to exploit the biology of how human cells and tissues sense and respond to the ever-changing availability of nutrients that, in turn, is critical to maintaining health, but also is the basis of many diseases. Specifically, we are developing compounds that modulate cellular pathways that are regulated by nutrients to impact a broad array of diseases.
For example, in diseases characterized by metabolic dysfunction like obesity and associated Type 2 diabetes, the body’s response to increased availability of nutrients is one of the critical factors that lead to the development of these syndromes. If we can modulate the body’s response to nutrient availability, we can intervene and thereby rebalance the processes that lead to disease. This is true not only in metabolic diseases, but also those characterized by neurodegeneration such as Alzheimer’s, Parkinson’s and Huntington’s diseases. In these devastating diseases, the same cellular pathways that regulate the response to nutrients also are critical in controlling the way cells deal with abnormal proteins which are a hallmark of all neurodegenerative diseases. By modulating these nutrient responsive pathways with specific compounds we can turn up the cell’s ability to clear these abnormal proteins with the hope of effectively treating these diseases in a way that has not been attempted before. These are but two examples of how our focus on developing new therapeutics based on the modulation of cellular nutrient sensing pathways may have wide-ranging impacts on many unmet medical needs in diseases that affect millions of people.
How do you prioritize which disease to attack first?
First, we need to identify the chemical compounds that can specifically impact the molecular targets controlling the cellular response to nutrients. Then we need to look at how these compounds affect animal models of disease to determine which types of compounds have the most promise. The importance of cellular response to nutrients in Type 2 diabetes has been studied in significant detail thus, this is area we may be targeting to demonstrate the effectiveness of our approach. Other areas included immune regulation, neurodegeneration and several rare diseases characterized by an aberrant cellular nutrient response.
What are the biggest challenges you face in moving the company forward and how will you address them?
The real challenge is to understand the biology of cellular nutrient sensing and response in sufficient detail and feel confident that the chemical compounds will work in the way we designed them to and have the desired pharmacological effect in disease settings. This challenge is always number one for cutting-edge, early stage biology-driven companies. It is really important that we understand the biology in sufficient detail so we aren’t surprised down the road. This is particularly relevant to the biology we are targeting which is highly complex and composed of many molecular players and signaling pathway networks. The unknown and surprises which are a hallmark of new biology – those are situations we hope to avoid.
From a timeline point of view, our exclusive and close relationship with our scientific founder David Sabatini at the Whitehead Institute of MIT has given us unique insight into this complex biology based on his defining leadership in this area of science over the last several decades. Based on this relationship with David, we feel confident that we are targeting the most validated aspects of the cellular nutrient sensing pathway. However, it does take time to develop chemical compounds that can specifically and predictably modulate the biology we are targeting so that we can then advance into human trials. This process takes about 2-3 years, but that is not unusual for a company at our stage of development and with our strong investor group led by Polaris, we are in a good position to achieve this goal.
What are the key factors of success for Navitor during this phase of the company?
It is important to hit our key milestones to ensure we are making progress. Most of these are based on 1) identifying the specific chemical matter that has the impact on the biology we are targeting and 2) demonstrating that these compounds can positively impact the diseases associated with aberrant cellular nutrient signaling. This is a huge factor in staying on the right path and showing the necessary proof of concept to advance the program and justify further investment.
You’ve built a number of biotech companies. Are you able to learn from past experience?
Every experience is different. And the biotechnology field has changed dramatically since I went into the industry after my postdoctoral training in the early 1980s. I joined California Biotechnology when the business of biotechnology was nascent and wide open to almost anyone pitching the wonders of recombinant DNA. Joining Merck in the mid-80’s where I had my own lab and small group was amazing since it was a time when pharmaceutical companies still did a lot of basic research to identify biological mechanisms to target disease. Merck, in particular, was at the pinnacle of the industry.
Going back to a start-up company called Corvas in the early 90’s, where I was privileged to serve as Chief Scientific Officer and a member of the Board of Directors, allowed me to learn how to translate basic scientific discoveries to the clinic where we advanced two novel proteins discovered at Corvas into patients. At Wyeth and Sirtris, different challenges posed by the consolidation of the pharma industry and the targeting of unvalidated biology, respectively, allowed me to develop a different set of “coping” skills.
But drug discovery programs aren’t like putting together cars. It really is never the same twice and with the constant changes in the industry in terms balancing risk with investment, it requires one to not only deal with increasingly difficult science, but also how to effectively bring value to investors and effective, safe therapies to patients.
Who inspires you? Are there other CEOs or industry leaders you look up to for their leadership qualities?
There are a number of people in my career who have been inspiring. My doctoral advisor Frederick Walz instilled in me the basic foundations of scientific research and asking the right questions. Ed Scolnick who was the head of research at Merck when I was there inspired me to look at drug discovery as a passion. He also showed me what a tough and scientifically rigorous leader in the industry should be. Paul Friedman, who was my direct boss during my last years at Merck was also pivotal as an example of how a leader manages a scientific business and makes decisions which he demonstrated with great success as CEO of Incyte.
In terms of contemporaries, John Maraganore who is CEO of Alnylam is a fantastic, dynamic leader and scientist who has weathered adversity in a developing what could be a transformational technology. I’ve seen John develop from a competitor back in the day when we were both trying to advocate for our particular new anticoagulant strategy (his got approved!) to a respected and innovative leader in the industry.
What is your favorite part about your job?
I love the fact that every day is different. We have objectives, budgets, and targets to meet, but science is constantly changing. It’s incredibly dynamic. Each day I go through the literature to see what else has come out and how it impacts our company. Change has always been a constant – from day to day and sometimes from hour to hour. I love it.
I also love seeing results. Often we are seeing things for the very first time. That is, no one has viewed such discoveries before. Even though we are not doing basic research per se, the applied effects we are trying to achieve are new.
If you could give one piece of advice to a startup CEO, what would it be?
My advice is short and sweet: You must have patience in the face of chaos. At a startup company you will face many ups and downs. It is never a straight line. I am not the most patient person in the world, but I realize that I have to look at the long term and keep a steady hand. Patience is something you can learn, and by default you find yourself reacting in such a manner. If you try to address all the changes at once, it will not be fun.