As we start a new year, we continue our series of conversations with our board members to hear their reflections on Dewpoint’s journey so far and their aspirations for our next five years. Today we spoke with the chair of our Board of Directors, Amir Nashat, who in addition to being the first investor, was Dewpoint’s initial CEO from 2018 until 2020.
Amir has created and invested in a breadth of category-defining biotechnology companies during his 22-year tenure with Polaris Partners. He also serves on the Partners Innovation Fund, the Investment Advisory Committee for The Engine at MIT and helped launch the MIT Sandbox Innovation Fund as its active president. He previously served on the board of the New England Venture Capital Association. He has been named to the Forbes Midas List of “Top 100 Venture Capitalists”.
You were Dewpoint’s initial investor, what was it that made Dewpoint stand out to you as an opportunity?
I’m an engineer by training, I studied chemical engineering at MIT, and so I am used to thinking about systems as a series of chemical reactions happening across space and time. But when I started in biotech, it surprised me that the way people looked at cells was so simplified. Rather than seeing how things constantly moved and changed, the scientific consensus was really to study cells in almost a steady state. Even as a student, I was mystified. We learnt that there were enzymes that could “turn on” a reaction and ones that could “turn off” the same reaction, and I would ask, how does the “on” switch work if the “off” switch is right next to it? If there was one kid that turned the light on sitting next to a kid that turned it off, how would the light ever be on? And I never really got an answer that felt very satisfying.
One evening I found myself In Florida with my friends Rick Young and Phil Sharp, and we started discussing Rick’s new experimental work which modeled how reactions occur outside of an equilibrium. He showed me evidence of how reactions weren’t just governed by the contents of a cell but by the way molecules moved around within them. He introduced me to the idea of condensates, transient, membrane free organelles which form and dissolve dynamically, compartmentalizing and concentrating molecules to enable biochemical processes. This was the piece of the puzzle I’d been missing; the condensates temporarily separated the kid turning the light on from the one who wanted to turn it off, allowing the lights to stay on for just the right amount of time. It was Phil Sharp who said, if you ever want to start a company in this space, the person you need is Tony Hyman, who’s been working on this at the Max Plank institute in Germany for a decade.
About a year later, I got a call from Rick out of the blue, to say he had Tony Hyman sitting in his office and could I come? I was so intrigued that I left the meeting I was in, and drove straight to Cambridge where the three of us spent the afternoon looking at Tony’s latest research on the potential to drug condensates. Right away I knew we were onto something exciting, so we pulled together investors and started recruiting, mainly chemists directly from the pharma industry. I remember when we interviewed those first 10 or 20 people: each time we described the principles of condensates it was like a eureka moment. For me, condensates really are the most exciting new biology and today, five years in, I’m still so excited by their potential.
What is Dewpoint doing differently from other condensate-focused companies?
In my first conversation with Tony Hyman, he told me that people would see condensates and try to take a typical drug maker approach of trying to quickly find molecules to target specific regions or proteins, looking for a single pathway to act on. But Tony believed there was a bigger opportunity, that through condensate modification we had the potential to change the entire course of many different diseases. So I think this is really Dewpoint’s biggest difference. We have taken the time to fully understand the biology, why proteins move the way they do and how they collaborate to cause diseases. As well as going deep into the science, we’ve also gone broad, today we are researching diseases from cancer to neurology which is only possible because of these strong foundations, and the support of our investors who believed in us enough to commit to this 10-year runway.
How important have partnerships been to Dewpoint’s progress so far?
We knew from the start that to fully understand condensates we needed to go deep in our research, and to do this we needed investors who had the vision to support us through the first 10 years. Getting investment for something so different can be a challenge, but the science combined with our founders Tony, Rick and Phil is just such a strong combination! Investment does remain a challenge though, for us as with most biotechs. The market has shifted, interest rates are high, and we need to work to keep bringing in capital to maintain innovation in parallel with now running clinical trials.
We’ve also been lucky to have built really strong partnerships with the pharma industry, which have allowed us to extend the breadth of the pipeline and move much faster than we could have done alone. Our earliest, with Bayer was a very natural fit. They are experts in small molecules, and they saw the potential of our work to bring a new way of using small molecules for new applications. They brought tangible experience in cardiology, nephrology and pulmonology which has allowed us to really push forward, and will help us to get drugs to patients suffering from these diseases much faster.
What challenges did you face early on?
At the very beginning, the team did something which our competitors didn’t, they compared what you got when you drugged a condensate in a test tube vs. a condensate in a cell. In the test tube, we got many false positive and negative results — the translation to cells just wasn’t good enough. The condensate is so complex, with up to 50 different proteins at play, and things shifting all the time, that so you can’t recreate reactions by pulling out 1 or 2 things, you have to study them in their native habitat. On top of that, we found we needed to look at the entirety of reactions, so we collected data in video, tracking how 50 or 60 things moved simultaneously. This meant that our first challenge was not one of biology, but one of data, and how to process such a staggering amount.
To solve this, we had to really invest in tech, in data processing and in machine learning. We had to invent a lot of technology and go outside of our normal sphere, even buying an advanced graphics company. Technology is still a major theme for Dewpoint and just recently we announced a new partnership with Chemify, a chemistry AI and automation technology platform that will support us in extending and speeding up our development process.
What is the next hurdle that Dewpoint will need to overcome?
Our early data in animal models has shown that we can create drugs that solve challenges no one has been able to overcome before. We’re looking at drugs for diseases like cancers and ALS, which could transform diseases outcomes. But it’s still early, and our challenge now is to prove that the drugs work in humans. Moving into human trials comes with lots of challenges, some of these will be unique to condensates, but some are just part of the process. People forget that half of all drugs that go into phase 3 fail because of the process and manufacturing part of their submission. So, we can have the best science and the best drugs, but we need to make sure we also have the specialists to deal with all the technical aspects that are required to get our drugs to market.
But these are problems for every platform biotech – typical growing pains – and something which I believe our CEO, Ameet Nathwani, has the vision and experience to overcome.