By Richard Soll, SVP of Research Service Division at WuXi AppTec (@richsollwx)

Dream big, think deeply, question the ‘status quo,’ and execute diligently. This leads to new ideas that are groundbreaking in nature. We all have an opportunity to make new inroads. These opportunities are valuable not just for business, but most importantly, they are valuable for people and our society. We have to shift from disease to health, from pathways to systems, and from treating symptoms to cure and prevention.”

Throughout his celebrated career, Dr. Peter Mueller has been finding new ways of pushing scientific and medical frontiers. The seasoned scientist has been a driving force in the life science industry, first leading pharma R&D at Boehringer Ingelheim, then in biotech as the R&D leader at Vertex Pharmaceuticals, where he championed discovery, development and global approvals of the first novel therapies for the treatment of hepatitis C with Incivek and  Kalydeco for cystic fibrosis, both breakthrough medicines that transformed lives of countless people around the globe.

Most recently, Dr.Mueller – whose role models are Albert Einstein and former NASA flight director Gene Kranz – is leading a team of scientists at Cambridge-based start-up Axcella Health to forge an innovative frontier of systems medicines by restoring amino acid homeostasis, a central driver for cell viability and function.  Axcella – named by Forbes as the Hottest Healthcare Startup in 2015 is developing a new class of oral biologics derived from the proteins in the human diet to treat brain, metabolic, muscle, and liver disorders that are linked to imbalances in amino acid homeostasis. Axcella is also credited with providing new insights into the role of amino acids in disease and health, well beyond its known function as the building blocks for proteins. The company is using a systems pharmacology approach to deliver disease-specific amino acid compositions that selectively and simultaneously  improve the function of several disease related biological pathways and regenerate health. This revolutionary new field has the potential to address critical unmet medical needs for the patients of more than 2,000 diseases across all indication areas where amino acids play a central role.

Towards that goal, Axcella, funded by Flagship Ventures, Fidelity Research and Management Group, Gurnet Point Capital and Nestlé Health Science, is developing a portfolio of new compounds with its lead compound PN-107 that has the potential to tackle muscle loss caused by aging, long bed rest, immobilization or gene defects. Through its first human studies, which evaluate the homeostatic effects of several of these “food” proteins with optimal amino acid profiles, the company has demonstrated a statistically significant impact on muscle and metabolic physiology.

I recently caught up with Dr. Mueller, who shared his insights on Axcella’s mission to transform the way we look at medicine, how best to move innovation forward, and why he’s having fun. 

Rich Soll: Axcella Health is a start-up breaking new ground in the area of amino acid homeostasis and biology. What has been your motivation in taking on a leadership role in this company and others in your career?

Peter Mueller: The motivation comes from what I personally believe is important; I grew up in an environment where we basically put the human being and human well-being in the center. Therefore, one of the areas of my interest is to help solve problems, in particular diseases where people have no choice other than poor quality of life. Having said that, I basically took the route of science to understand the complex biology of diseases in the body.

The reason I joined Boehringer Ingelheim, for example, was because it had a reputation for high levels of innovation so it was an opportunity to have people and interdisciplinary teams that were really forward looking at the leading edge of science and trying to figure out ways to make medicines. Although I was a chemist in those days, I learned the importance of an interdisciplinary, integrated environment where many functions came together to create drugs in ways that were different from previous approaches.

At Vertex we raised the stakes in two ways: transformative medicines and new business models.  It was Josh Boger, then CEO who attracted me to work there and to create transformational drugs rather than symptomatic approaches, a thinking that was really new in 2003 during an era where there was a new wave of science that was coming together with genomics and integration between big data machines and algorithms that allowed us to understand more complex systems. In addition, we molded a new business model based on integrated and interactive networks (comprised of pharma and biotech entities, academia, foundations, regulatory authorities, clinical experts, manufacturers and other service providers) where we brought together the best and brightest in global collaborative partnerships to open up innovation and solve problems faster, which at the time was outside of the thinking within pharma.  It was during this time that WuXi was developing a huge global network, creating one of the powerful manufacturing networks.  For Vertex’s Incivek and Kalydeco, access to WuXi and its network translated into manufacturing that resulted in having the drug stocked on the shelf in less than three days after approval, which was significantly faster than the best companies could do at the time.

Rich Soll:  How is Axcella Health pushing the frontiers of science and how is the company different?

Peter Mueller:  In my experiences, Axcella is strongly reconfirming my belief that we need to be very diligent at defining the problem we are going to solve, engaging people to keep them excited, and taking risks to make a difference in patient’s lives. In most of my career our approach was essentially one target or gene, whereas at Axcella, the approach is tackling the next evolutionary step through a systems-wide approach to treating disease as well as advancing preventative medicine. Specifically, at Axcella we view disease as being deviations from a balanced state, impacting not just a function but rather a system (the human) and further, we realize that amino acids are more than the building blocks of proteins.  In fact, amino acid homeostasis, or balance, plays a critical regulatory role in more than 2,000 diseases. Our approach actually affects a paradigm shift from treatment to prevention where we seek to maintain or restore balance. Further, our technology capitalizes on orally digestible, recombinant polypeptides originating from the food proteome that release amino acid compositions of interest into the blood stream, which otherwise would be challenging using monomers. We are not taking 10 amino acids, dissolving them in a beaker and then ingesting them because amino acids are poorly palatable, often poorly soluble and show as a mixture a PK/PD profile not commensurate with practical treatment regimens. What we are doing is big. We are able to leverage what nature gave us – digestible amino acid prodrugs found in food.

Rich Soll: During your career have you seen a fundamental shift in the way the pharma industry operates?

Peter Mueller: I saw how big organizations grow into less productive environments; too big and too much bureaucracy. This change is caused by a shift of culture in big pharma over a span of the last 20 years from an originally research and science-driven environment to a more commercially-driven environment, resulting in stifled innovation, growing risk averseness and ’me too‘ strategies. That led me to look for other opportunities because I fundamentally believe curing diseases is a very hard problem – harder than flying to the moon- that needs innovation, walking on the science and development edge, risk taking and courage, and a patient centric mindset. I think this is one of the reasons I started to work with medium-sized pharmas and start-ups in order to push further the frontier of medical science.

Rich Soll: What do you like about being in a start-up environment today?

Peter Mueller: What attracted me to the start-up environment is very simple – you have people who are highly innovative, especially in the Boston area, where you are surrounded by more than 600 biotech companies as well as first class medical and academic institutions. There’s talent and the willingness to go the extra mile. There’s an incredible spirit and passion to make a difference in people’s lives. At the end of the day, what we have is this dynamic energy, medical science and knowledge to make patient’s lives better. Thirty years ago there was no real start-up environment; there were only big companies. There were not a lot of experienced people in biotech.  That has changed dramatically. Now, a lot of people with experience who partly were with big companies make the start-up environment a lot more effective and a lot more successful. So I thought I could share a little bit of my own experience.

Rich Soll: What inspires you most about being involved with Axcella?

Peter Mueller: What’s inspiring to me is the company culture, the clear focus and willingness to make a difference in patients, and the courage to open a new page in the book of medicine by integrating internally and externally the brightest minds in the field.  We bring everybody to the table in a meaningful way to solve those major problems on the planet. Diseases are not driven and stopped by borders; diseases are global, and mankind is global. Therefore, I personally believe that this has to be reflective of how you do business and how we leverage each other’s knowledge for the betterment of mankind. That’s one of the most exciting things about the scientists and the people here at Axcella.

Rich Soll: That is very inspirational. What kind of technologies do you have to bring to the table for this all to come together?

Peter Mueller: You can do proteomics and genomics and all sorts of other biology’s, but all of these basically have one common denominator:  an endless amount of data that needs to be handled, curated and interpreted. You have to develop algorithms to understand the complexities of the systems. In terms of other technologies that go along with it, there are things like single cell technologies that enable a look at one cell and study almost everything that works in that cell. There are all these new, super sensitive methodologies that shed more light on different problems in an organ or in the entire body. There are people who have these technologies that can be integrated into our platform to basically solve particular problems. This is an example of this network approach where you augment in-house core competencies with external technologies; you have to leverage the smartest people and the best technology.

Rich Soll: Are you able to target the root cause of disease simply by re-balancing?

Peter Mueller: Great question. You are bringing up an interesting point. I think at the end of the day, what we are doing, is restoring function wherever possible, which does not mean you have to always correct the underlying (e.g. genetic) root cause. Look at cystic fibrosis (CF) and Kalydeco.  Now, with the right drugs, those people basically have almost no symptoms anymore (but still carry the G551D mutation). They have a substantially increased life expectancy. And that is actually an important component of our amino acid homeostasis approach. You can re-install functionality and overcome the root cause problem in many of the cases.

Rich Soll: I also noticed that Axcella has a very diverse staff, including experts in informatics and nutrition. What have you learned so far in bringing all those different disciplines together?

Peter Mueller: You have to find a mix of people that have good ideas and that can translate them into action. And they have to be one team. They have to like each other and talk to each other. It has to do with a deep emphasis on culture and the people you hire.  I think the challenge in a start-up is you have to hire fast, but you have to hire right. The good news is, in our case, because we are in the Boston area, there is a huge talent pool. We also do global searches and hire people from all over the globe. We have people from North, Middle and South America, parts of Europe, Middle East, and Asia, including India. It is about a global network, and it is a good thing to have diversity; people from different backgrounds have different ways of solving problems. I truly enjoy nothing more than going in the morning to the coffee corner and hearing six different dialects and accents talking to each other all driven by the same goal.

Rich Soll: Do you find that this dynamic mix of disciplines is leading to different sets of questions that are being asked, how people are approaching different kinds of experiments, and how people are thinking about problems?

Peter Mueller: The short answer is yes. As soon as you bring multi-function to the table, have people who openly speak their mind, and creatively provide ideas and solutions, you come to a new level of thinking. Nobody knows everything, but everybody knows something. And that something, at the end of the day, could be a solution to bigger problems. If I don’t have people in-house I’m also inviting people from outside from other industries. They look at different things from a very different angle. Everybody is part of an entire chain – you have the person who makes the drug, one that uses the drug, one that invents the drug, and the patient, the physician, the regulator – and if you have everybody at the table, you come to unprecedented and impactful solution for complex problems.