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BioCommunique Article

Biocom Member Spotlight: Interview with Keith Murphy, CEO and Co-Founder of Viscient Biosciences

Biocom Member Spotlight: Interview with Keith Murphy, CEO and Co-Founder, Viscient Biosciences

  • 2019-10-22T17:33:00.000+0000
  • San Diego
  • Author: Heather Ramsay

Biocom recently had the pleasure of sitting down with Keith Murphy, CEO and Co-Founder of Viscient Biosciences, a company displacing the use of animal models by building 3-D bio printed liver tissue to use in drug discovery. Biocom representatives Matt D’Angelo, Heather Ramsay, and Harry Chang visited with Keith at his home office to learn more about how Viscient found success in San Diego.

Matt D’Angelo: We’re here in beautiful Los Angeles with our next Biocom Member Spotlight featuring Keith Murphy, CEO of Viscient Biosciences. First question is one that a lot of people are curious about when it comes to CEOs: how do you start your day?

Keith Murphy: I usually wake up pretty early and think about what I can do to get my team ready and successful for the day. I also like to optimize the best time to contact our investors, banks, and other collaborative partners on the east coast. I focus on the team’s short term goals and a few long term goals and make sure I’ve got the day planned out.

MD: Can you tell us a little bit about Viscient’s technology and your company’s objectives?

KM: Viscient is taking advantage of complex 3-D bio-printed tissues and similar types of complex in vitro models and using them to replace animal models in drug discovery. If you think about the traditional drug discovery process, you have an animal model with a disease – usually induced- and you study its biology as a stand-in for human biology.

What we’ve found as an industry is that we can’t properly reproduce many diseases in animals, especially fibrosis, and more specifically, liver fibrosis. No one has been able to tweak the models to make them predictive. As an industry, we’ve taken dozens of drugs into the clinic that looked good in animal models, and they have failed. I think there have been two notable late-stage clinical trial failures in 2019 alone. That’s a problem.

These new 3-D cell cultures can possibly be more predictive because you’re taking actual human cells into the tissue context, whereas cells taken out onto a dish may not perform. If we can keep them in the tissue context, maybe we can see the disease and reproduce it properly. We’ve got nice profiles of fibrosis that look like what you would see in a clinical sample – that becomes our disease model.

Harry Chang: Have there been any drugs approved when animal models were not available?

KM: There have been. Jeff Miner, the co-founder and CSO of Viscient, has previously used animal models that didn’t work, like the Gout program that was built at Ardea Biosciences. They didn’t have an easy 3-D cell culture model to use and they had to do an incredible amount of work to prove to the FDA that the animal models didn’t work.

There have been programs that focus on using 3-D cell cultures. For example, Vertex has a cystic fibrosis franchise and they previously did not have an animal model. Aurora, a San Diego company, connected with Vertex and their cystic fibrosis 3-D lung cell culture that allowed them to see better aspects of the disease. This is an early, stand-alone example. But it also shows that the FDA will approve things with scientific evidence showing why it is predictive and how it could affect humans.

Heather Ramsay: I imagine there are a few reasons for displacing the animal model – including animal rights as well as the models’ lack of predictability. Is this a trend you’re seeing – scientists trying to get away from animal models?

KM: Yes, it’s just a matter of how fast the adoption is. It’s expensive and people aren’t trained in it. As people change over in pharma, there is more openness to it. It’s innovative – but there’s a slow adoption to innovation in our field. That’s okay though – that’s how innovative companies come to be.

MD: How did you decide to focus in non-alcoholic fatty liver disease and NASH? Are they diseases that are hard to detect without a 3-D model?

KM: I think that’s generally right. There are two reasons we’re in NASH in particular: one, because it is well-accepted that animal models are not predictive. Partners are more ready to accept that this new technology is needed. Second, liver is one of the more advanced complex tissues. There are already building blocks that will allow us to take the next step in drug discovery. 3-D liver tissue has shown that tissue can perform like a liver and could also last for weeks. They have revealed more so far, throughout the target identification stage. I think we’re doing very well.

HR: Timing seems to be everything in this industry. At what point were you confident enough to dive into this venture?

KM: Yeah, you want to be on the cutting edge but sometimes it can hurt. Everything started to add up around 2015. The liver tissue started building from 2015-2017 and 2017 is when Jeff and I began. At that point, the tissue was ready.

I think we’re still on that cutting edge and timing is good. It is well understood that it is a huge commercial opportunity [for NASH]. Pharma is very interested but has had trouble cracking the code. Drugs will get approval in the next 2-3 years. There are some decent drugs, but they may only benefit 25 percent of patients, and with a 12.5 percent placebo effect. The problem isn’t solved. We will be coming with additional solutions and a better understanding of the biology.

MD: What excites you most about what Viscient is doing?

KM: The challenges.

For example, once we had the equivalent of an animal model, then we also needed the equivalent of a screening model. We’ve had to invest in that over time. We’ve had to invest in something that allows us to get 3D cell culture in plates with more wells.

Additionally, there has been a lot of investment in understanding the biology and cutting-edge bioinformatics. With these tissues we’ve built, we look at the gene expression and see what’s active and examine each individual cell’s profile. Technologically, it is quite difficult. We’ve got a world-class platform, but that took a lot of time, investment and failure.

The biggest challenge lies in the number of cells that you must extract material from. There are four different cell types that all act differently – you have to come up with a solution that can be used for all at once, and then handle the large amount of data gathered. It is very complex. We’re basically like a biotech pharma ourselves. We’re a therapeutic company building a drug discovery platform with target opportunities. We will discover and develop multiple drugs, and having worked out the challenges to establish this liver platform, it will become easier to expand into other tissues, moving into kidney, lung, and other areas. We have the path laid out now.

MD: We’d love to learn more about what led you to where you are today…

KM: My training was in chemical engineering as an undergrad at MIT. I got into biotech because of Robert Langer’s work, who is a well-known professor of chemical and bioengineering at MIT. I had some classes with him and did work with him. He was inspirational because he was studying so many things. His lab is now about 150 grad students on any given year – it’s massive. He’s had a huge impact in several areas of bioengineering, especially things like the long-acting release form of drugs using biopolymers. That caught my interest, so when I left school, I knew I wanted to work in that field.

I got a job in Boston at a company that used his technology. It involved building the process that made the drug for a sustained release 30-day version of HGH, which was in partnership with Genentech.

MD: Are there any other mentors like Robert that led you to where you are today?

KM: I follow a lot of case studies. I treat everything I read as a case study to learn from. I don’t necessarily focus on the individual, but I think a lot about how different businesses evolved. Every business story out there that I have been exposed to has informed how I think about things.

HR: How did you make the leap from Massachusetts to California?

KM: I was recruited by Amgen after working for five years at a company called Alkermes, mostly on sustained release of protein-based drugs. Amgen was interested in doing similar things after the success at Alkermes. It’s interesting how these things work throughout your career – that was a big inflection point for me.

While I was full-time at Amgen, I went to UCLA Anderson Business School, and eventually transitioned to more of the business / product strategy side and became Global Operations Leader for a major drug in Amgen’s pipeline at the time.

When we formed Organovo, I felt like I had a unique insight into the tissue engineering. A lot of Langer’s work was based on the polymers we’ve used to encapsulate proteins. Those were the same polymers Langer used in a tissue setting. There were a lot of challenges when using them in the proteins. The polymer’s breakdown often had a negative effect on the proteins. I surmised this to be a problem in tissue engineering.

I eventually connected with a professor of biophysics at University of Missouri at Columbia, Gabor Forgacs, who became the scientific founder of Organovo and my cofounder. Through his technology, we were able to build up a tissue without the polymers. We found ourselves at a “Eureka” moment.

MD: What do you think makes Southern California such a good life science community?

KM: I always think there need to be three things to get a business up and going, and San Diego has all of those: you need the people, you need the funding, and you need the space. Sometimes people forget how hard it is to work in our field without the right space. It can be a real challenge.

Our first lab started in January 2009 and we subleased a space in San Diego that someone was leaving. We walked into wet lab space and a clean room, which was important to us for the tissue culture side. That was really imperative to get us going quickly. Things have only improved since then.

The talent in San Diego is tremendous because you have the industry and the academic research institutes there – that makes the cluster sing. There’s a great environment there and it’s geographically tightly packed, which allows for networking, support, and collaboration. Viscient looks globally for partners, but we end up finding them in San Diego.

HR: What do you look for in terms of team culture when building your team?

KM: I think that comes easily because there is a great culture that already generally exists in San Diego. There are a lot of commonalities in the culture at Organovo, Viscient, and the other companies we work with. There are a lot of people who like what they do. We certainly do hire for culture. We have a “team first” mentality, and we don’t want someone who takes away from that.

MD: We’ve found the same to be true across all of the regions Biocom serves in California – couldn’t agree more. Have you found the Biocom network to be helpful in Viscient’s development so far?

KM: It’s been great. It has been very helpful for us to have the easy connections to the people you need to get your lab going, and get the support from the perspective of not having the cash burn be as high in areas where you don’t have the ability to negotiate yourself.

MD: What excites you most about the future of Viscient?

KM: I think it’s this opportunity to continue to do this and to stretch into new tissue areas. Animal models have been tremendously beneficial in finding drugs that save people’s lives, but there’s this new opportunity to go beyond that. The really cool thing about them is that it’s not an animal model – it takes individual cells and builds a tissue out of it – which really creates a lot more connectivity to clinical studies.

For example, we can understand the doses needed in the clinical setting much better because when you dose these tissues, you’re actually doing something that’s going to be relevant to the final dose for humans. You still need to figure out the pharmacokinetics from the gut to the bloodstream, but that’s an easier challenge to nail down with the dosing information you’ll have. You’re not trying to make a mathematical leap from a rat to a human. You actually know what you want in the final tissue, which is a really exciting aspect.

Also, you can do what starts to become like personalized medicine. It’s not quite there yet, but you can certainly direct drug development and your studies to a specific group of patients. Let’s say you launch a drug, like a drug for NASH, and it’s only effective in 50 percent of patients. What’s going on in the other 50 percent? We can take those people that it didn’t work on and get cells to build a model. We can narrowly build a drug that works just for them. You can enable the development of drugs that would have never come to fruition because you can make the development cheaper and thus you can do it for populations you wouldn’t have otherwise.

HR: Are you impacted by a lot of legislation, like what’s going on with FDA approvals? Do you have to get ahead of new regulations coming out?

KM: We focus on regulatory aspects on how to develop drugs for NASH. We watch from the FDA perspective as well. From a drug pricing perspective – the legislative side – we’re very thoughtful.

Personally, I try to be somewhat active in that arena. I think it’s compelling for Congress to hear an innovative side of the story. It’s good to have big pharma there, but it’s useful for them to see another side represented specifically to talk rhetoric about paying for the truly innovative drugs, while stopping groups from squeezing value out of the system in non-value added ways. If we don’t pay for truly innovative drugs, we won’t have them.

If we have a lot of rhetoric about price capping, price controls, price referencing to other countries, then I’m not going to be able to raise money next year to take these drugs to the clinic. You lose the ability to have innovative drugs.

HR: Do you have any advice for companies going out on their own?

KM: I always tell people that you need a personal financial plan to survive. If you are at an early stage in your career and you can afford to live on ramen, that’s fine. But if you’re in the middle of your career and you have a house – you have to think about that. It’s really important for entrepreneurs to not put themselves in the position of being in dire personal financial need. You would have done all this work and you’ll give it up for a song because you were so desperate. I was always careful to have a plan with Organovo, which included spending my entire 401K, but it worked. Usually you’re taking risks, that’s why you’re an entrepreneur, but you need to think everything through.