After many years of research, Sir Peter Donnelly made the leap from academia to founding his own company, to lead the charge in having a truly tangible impact with everything we are learning about genetics. His venture, Genomics PLC, has acquired funding from top-tier investors like F-Prime Capital, Oxford Sciences Innovation, Foresite Capital, and Lansdowne Partners.
In this episode, you will learn:
- Learning to love the journey and learning itself
- His outlook on COVID and other pandemics
- The great progress being made in genetics for combating serious diseases
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About Sir Peter Donnelly:
Peter Donnelly is Director of the Wellcome Trust Centre for Human Genetics and Professor of Statistical Science at the University of Oxford, and a founder and director of Genomics plc, a fast-growing company in the genome analytics space.
He has played a leading role in many of the major projects and developments at the interface between genetics, healthcare, and clinical medicine, including the HapMap project, the Wellcome Trust Case Control consortia, and WGS500, one of the studies pioneering whole-genome sequencing in clinical medicine.
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Read the Full Transcription of the Interview:
Alejandro: Alrighty. Hello everyone, and welcome to the DealMakers show. Today we have quite an interesting guest going from academia to being an operator and doing something that is remarkable. I think that you are going to find it really unbelievable. But without further ado, let’s welcome our guest today. Sir Peter Donnelly, welcome to the show.
Sir Peter Donnelly: Hi and thank you very much.
Alejandro: Peter, tell us a little bit about your upbringing. Everything started for you in Australia, so how was life growing up there?
Sir Peter Donnelly: That’s right. I’m Australian by birth, and I’m Australian still. I grew up in Brisbane in Queensland, Australia. I went to school there, a fantastic school, which I really enjoyed as in the case of Australia, involved lots of things outside of schoolwork, lots of sports. I love playing cricket and rugby. I sailed a bit. I enjoyed schoolwork and met fantastic friends who have remained good friends for the rest of my life.
Alejandro: Tell us about public speaking because that was something that you found quite useful over the years, but something that you actually developed very early on there.
Sir Peter Donnelly: I did. In Australia, at the time, and actually, still, in some parts of the world, debating was a formal competitive thing. There was a structure, and there were teams, and I debated for my school and was lucky enough to be chosen to represent the state team when I was at school’s level, and then in my university’s career in Australia, I was elected captain of the adult state team. That early experience of public speaking, and arguing, and so on has been incredibly helpful throughout my career. There are so many aspects of our lives being about communication, and I was lucky enough to have that kind of grounding early on in my career.
Alejandro: That’s amazing. In your case, certain things led one thing to another, and you ended up in the UK, so what happened there? Ultimately, it was your Ph.D., but that’s quite a transition, so tell us about that.
Sir Peter Donnelly: Yes. I grew up and went to school in Australia, and then I did my first degree. I did a science degree at the University of Queensland, majoring in mathematics. Then at the end of that process, I was keen to go on to further research to do a Doctorate. I was lucky enough to be awarded a Rhodes Scholarship, which sends people to Oxford. I moved from Brisbane to Oxford as a Ph.D. student at Oxford; doctorates are called D-fields, and I had three incredible years as a student at Oxford. It was good academically, but fantastic in terms of experience, a chance to understand and learn a different culture. It’s a very international university, so I had friends from all over the world, including many friends who were UK-based. Oxford is a place I fell in love with. Within my first term, I had fallen in love with Oxford: the beauty, the history, the sense of scholarship, and an amazingly interesting and vibrant community of friends and fellow students. It’s college-based, which says they are a bunch of people you get to know really well and play sports with them and so on, but across the colleges, through the Rhodes connection, and then many other ways. It was a fantastic three years of my life.
Alejandro: Why, out of all things, academia? Why did you decide that academia was your path?
Sir Peter Donnelly: Great question. I loved doing research. My job was about research and mathematics. I was developing mathematical models for real-world phenomena that involved randomness, so actually, academics, which is timely these days, but also genetics and the ways in which populations develop. I loved doing that work. I was reasonably good at it. Actually, in my time at Oxford, I spent a lot of time doing things other than my academic work but somehow managed to finish the doctorate and was keen to try and pursue an academic career. I enjoyed the teaching side but the opportunity to keep doing research. It’s an extraordinary privilege as an academic to be able to focus on pushing research forward in your chosen area.
Alejandro: What were some of those projects that you were involved with, as well, because you were a sought-after individual for your expertise? What were some of those projects that, over the course of time, you were involved with either at a national level or international level that perhaps my listeners are going to really get a good impact from listening? What were some of those as examples?
Sir Peter Donnelly: Yeah. I was involved in various things across my career. I was lucky in my career to work for most of the time at universities in the UK, but some of the time at universities in the USA. I visited Michigan for a while and the University of Chicago. One area I worked in the early 1990s was DNA evidence, so the way in which that should be quantified in courts. That was quite interesting. When I was growing up, I had been a bit undecided about whether to become a lawyer or to do mathematics. It brought those two things back together, so thinking about evidence and how to present evidence, and I was involved as an expert witness in various court cases; that was one interesting area. My research had been in mathematics, but I moved it 20-25 years ago. It evolved more and more into genetics, and I went from being someone who found the inherent mathematics interesting to getting to a position where I learned about the science. What I was really driven by was solving the scientific problems. I was very fortunate. The last 20 years have been an extraordinary time in our knowledge and understanding of genetics and its involvement in common diseases. I was fortunate to be involved in the leadership role in the project, which followed on from the human genome project called the HapMap Project, which characterized patterns of genetic variation in different parts of the world. I led, in the UK, some of the very large national and then international studies that changed our knowledge of the genetic basis of common human diseases. In around 2005, for the common human diseases, we knew a handful of examples of bits of DNA changes, which affect people’s susceptibility of developing those diseases. Then over a number of years from them, because of the particular type of studies, called a Genome-wide Association Study that we were able to do, that knowledge just exploded. Whereas, 15 years ago, there were a handful of these examples; there are over hundreds of thousands of them now, and I was very lucky to be leading many of the large studies that disease by disease helped unravel the genetic components of disease susceptibility.
Alejandro: I’d like to ask, as well, about what you’re up to now, which is your baby, your company. But before we go into that, which is quite timely for your expertise, what we’ve experienced with COVID has been pretty crazy, the type of diseases that we get to experience as human beings once every 100 years or so, but it seems that from what experts are saying, they think that this could be something that we’re going to be seeing more often than what we were used to before. What are your thoughts on this? Do you think COVID-type of situations are going to be happening more often than what we were exposed to before, or what are your thoughts on that?
Sir Peter Donnelly: I should say I don’t really have any particular expertise in this, but broadly, I think that’s the case. The level of movement in the world now makes transmissions of new infectious viruses and bacteria much easier than it was even 100 years ago, and we’ve seen that with COVID, and we’re still seeing it with COVID, new variants that rise in one part of the world, and within months, they are dominant in countries, literally, on the other side of the world. I think that’s a factor. One would hope that in terms of pandemics if there are more pandemics in the future, and there will be—I think the question is when—we’ll be a bit more prepared. We’ll learn the lessons from this time around. I think as different societies, we’ve had variable success in learning lessons, and it’s a tough game. But I think you’re right that we need to be aware that these sorts of issues will be a part of our future much more than they’ve been a part of our past.
Alejandro: Let’s switch gears here because, after 25 years of being involved with Oxford as a professor there, the opportunity of becoming an entrepreneur came knocking at your door. So tell us how the whole experience of genomics came about and tell us about the launching of this project and you going from academia to you being an operator and an entrepreneur yourself.
Sir Peter Donnelly: Let me take both parts of that question separately. I’ve been fortunate to be right at the center of what some people call the genetic revolution, the transformation and knowledge of how genetics play into common human diseases. Throughout all of that, the pace of the science was extraordinary. Over 10-15 years, the pace of discoveries was amazing. Every year, with every talk we gave and every paper we wrote and with every grant we wrote, we’d say somewhere, usually at the beginning and the end, these advances are going to have a big impact on patients. Yet, it dawned on me over time that we kept saying that admin and people on the academic side mean well, but they weren’t actually having much impact on patients. On reflection, there are a number of reasons for that. It’s partly to do with the incentive in the academic world, but it’s also because going from a scientific breakthrough to something which matters in this case, most actually in healthcare, is a lot of work, and there’s as much or more of a gap to bridge there as there is in doing the science in the first place. With some colleagues seven or eight years ago, I was, at the time, director of a very large genetics research center in Oxford called the Wellcome Centre for Human Genetics. One of my senior colleagues, Gil McVean, was Head of Oxford’s Big Data Institute. With two other colleagues, we founded Genomics PLC wanting to do two things. The first piece was to keep doing what we felt, and I hope others would still feel what is still world-leading science. But the second piece was to build on the other aspects that we needed to get that science into healthcare. That’s the vision behind the company. We organized a group of the best and brightest in our fields as a startup, and Genomics was formed, and we’ve had an interesting journey. I think we’ve made good progress, but there’s lots and lots still to do in terms of transforming the power of genetics and the power of genomics to make a real difference in healthcare.
Alejandro: Tell us about the business model of Genomics, and what do you guys have in mind to make money with it?
Sir Peter Donnelly: We do that in two different ways, and they’re complementary. I’ll explain them both. One part is in drug discovery. Many listeners will be aware that at the moment, in spite of hundreds of billions of dollars spent a year by pharma and Vitech on R&D and incredibly smart people. Most drug targets fail when they get into clinical trials, and only 10% or fewer of them actually succeed. There are many reasons for that, but one of the main reasons is the choice of target, the protein, or the piece of biology that the drug is targeting turns out not to be very relevant for the disease in question. We only learned that very late on. We have to develop molecules, target that protein, and then we have to try them in humans. That process is incredibly expensive, and it takes many years. Then over 90% of drugs fail when they get to clinical trials. The very simple idea of how genetics can help there, and now growing amounts of data which show imperially that it does. But informally, when we think about giving someone a drug, we’re trying to change some little piece of their biology. We’re trying to stop a protein from working, for example. At the moment, to know whether that works, we have to develop a way of making that change, a molecule that interacts with a protein, and then we have to try. It’s a simple idea that all depends on the genetic approach, which is if drugs are trying to change things about human biology, we know genetic variants that we carry also change the human biology. So if you want to know what happens if I modify this protein, we build up an unparalleled data resource and algorithm, but we can look in that data to individuals who happen to carry genetic change, which affects the same protein. It’s almost as if, and some people have called it Nature’s Clinical Trial, their genetic change is mimicking the drug that you’re thinking of developing. Then, instead of making the drug, we can just look in the data to see what happens to those people. That’s the high-level idea about using genetics to find better drug targets. That’s one part of our business. At Genomics, we have a big partnership with Vertex Pharmaceuticals, which is very successful in large Vitech small pharma companies where we find drug targets of interest for diseases that Vertex is focused on. Then we have some internal on-discovery programs as well. That’s one part of the business around drug discovery. The other part is understanding individual risk in healthcare, and it’s about powering what I think will be a fundamental change in the way we do healthcare. Everyone knows, and it’s true in most developed countries, particularly true in the U.S., that healthcare systems are probably unsustainable, and they can’t format because the expenditure goes up and up and up. Everyone says one way of tackling that is to move from trying to fix people when they get really sick to trying to stop them getting sick in the first place. A key to making health systems sustainable is the idea of getting much better at preventing disease rather than letting it happen and then trying to fix it. Again, genetics is critical there. We’ve known for many years that for all of the common diseases: heart disease, diabetes, breast cancer, prostate cancer, and so on, for all of those common diseases, genetics is a key part of the risk that individuals have. It’s why some people are more likely to develop one disease, and others are more likely to develop others. We’ve known that for a long time, but until recently, we haven’t had a very good way of measuring it. It’s only in the last couple of years that we’ve worked out how to capture that genetic component of risk for each disease, and we can do that using the idea of something called a polygenic risk score. It turns out for any of those diseases, there are literally hundreds of thousands of positions in our DNA, individual positions that affect your risk of, say, heart disease, and there are a different hundred of thousand positions that affect your risk of diabetes. We now can identify those, and we can measure them. And those individually have a small effect on risk. We can add them up across those hundred thousand positions. That allows us, for the first time, to understand the genetic part of risk, and here’s how you might make sense of that. Instead of worrying about people when they’re sick, think about people when they’re healthy, and measure those genetics in people, say, initially and most naturally, in middle-age. Then, we can use the genetic part of risk, in some cases, other factors like heart disease with combined blood pressure and cholesterol levels, and so on, and we can identify the people who turn out to be at high risk of heart disease. Some of those people will be currently invisible to the system because a lot of that risk is genetic, which we haven’t had a way of measuring. So we can identify people who are at very high risk of disease and then work out what to do to prevent disease. In the case of heart disease, the natural thing is lifestyle changes and statins. If we find out that a woman is at high risk for breast cancer, and there are women who have high values of these polygenic risk scores, the top 3-4% of the population would have something like a 30-35% lifetime risk of breast cancer. If we identify those risks—and again, they’re currently invisible. We don’t know who they are, but if we can measure them, then they should be screened earlier; they should have mammograms probably earlier in life and more often or MRIs, and so on. The idea of this new approach, and it’s been called Genomic Prevention, is we develop sophisticated tools for understanding people’s risks when they’re healthy, and then we work out individuals who are at high risk for each of a different set of diseases. Then the health system can do what it needs to do to reduce that risk, whether it’s statins or screening for some of the cancers, and so on. The result of that is instead of waiting until people get sicker, fixing them, we can catch disease early by screening, or in some cases, prevent it altogether. It will empower a potential shift in healthcare. That’s the high-level idea. Then to answer your question, “How do you make a living out of that if you’re a company?” We put a lot of effort into developing those methods. We’ve got the most powerful methods available, and we’re at the stage of doing implementation studies. We’re doing a study in heart disease and cardiovascular disease with primary care physicians in the UK with the NHS. We’re doing a similar study with colleagues at Stanford in the Stanford Hospital systems, and we’re talking to healthcare systems in the U.S., and the UK, and other countries about doing this at a much larger scale.
Alejandro: That’s amazing. By the way, that’s a shift and a transformation that is very much needed in healthcare because it just doesn’t make any sense that doctors are trained to cure versus being trained to prevent, which I think makes more sense. So, really amazing! In terms of financing, I’m sure that really caring and ramping this up cost quite a bit of money, so how much capital have you guys raised to date?
Sir Peter Donnelly: We’ve raised a bit under $100 million.
Alejandro: Got it. In terms of the team and the size or scope of the operation, is there anything that you can share with us, maybe in the number of employees or whatever that may be?
Sir Peter Donnelly: Genomics currently has a bit over 100 employees. I would normally say we’ve got offices in Oxford and Cambridge in the UK and Cambridge in Massachusetts. Actually, we do have the offices, but no one is in them at the moment because of COVID, but 100 employees split between those three bases for the work we’re doing in the UK and in the U.S.
Alejandro: One question that comes to mind that I think is going to be very interesting to hear your thoughts is, imagine if you go to sleep tonight, Peter, and you wake up in a world where the vision of Genomics is fully realized, what does that world look like?
Sir Peter Donnelly: First of all, it’s a world where there are a whole lot of people alive who would not be alive if it doesn’t happen, because, for those people, we’ve been able to identify their risks earlier and take the precautions or get them screened earlier. What does the world look like? It’s a world where healthcare is much smarter about understanding risk. You or I probably aren’t at high risk for heart disease, and we’re probably not at very high risk for prostate cancer, but we’re each at high risk for something. So from an individual’s point of view, it’s about helping us understand what our particular risks are as we move forward in life, and from the healthcare system’s point of view, it’s about understanding for each disease who are the people we want to pay attention to and get into our prevention programs or our screening programs. It’s about much smarter risk prediction, and it’s about taking clinically actionable steps by existing on new pathways for those high-risk individuals to either stop the disease developing or to catch it early.
Alejandro: That’s amazing. As an Australian there in the UK, I know that you had quite a surreal trip to Buckingham Palace, so tell us about that.
Sir Peter Donnelly: Yeah. As I said, I’m a proud Australian. I’m also a British now and as proud of that. I was very fortunate a couple of years ago to be awarded a Knighthood by the queen. Each year, to celebrate her birthday, she bestows a number of these honors. One part of that process is that you get invited to Buckingham Palace for the formal ceremony. I learned an interesting thing about the English language. You literally do the thing that one sees in movies. You kneel down, and a member of the royal family puts a sword on each shoulder. I learned a thing about the English language. That ceremony is called The Accolade. Nowadays, we use the word accolade to mean something which bestows honor or recognition on someone. It used to mean exactly that ceremony, the ceremony where someone is made a knight by having the sword put on both of their shoulders. I was lucky enough, just before the pandemic started in February of last year, to visit Buckingham Palace, and Prince Charles put the sword on my shoulders and presented me with a medal in honor of my knighthood. As you say, for an Australian, for a boy who grew up in Brisbane, that trip to Buckingham Palace was an extraordinary experience and an amazing thing for me and for me to be able to share with my kids.
Alejandro: I can imagine. Now you’ve been at it with the company for a little bit, and you’ve learned a lot. If you had the opportunity of going back in time to that moment where you were thinking about bringing this to life, and you had the chance of having a chat with your younger self and giving yourself one piece of advice before launching the business, what would that be and why based on what you know now?
Sir Peter Donnelly: I’ll cheat and give two sets of advice. One of them is a much younger version of myself if I could go back. The learning I would share with a much younger version of myself is a rather general one but relevant to this. That is that life is a process that we live in chapters. At least when I was young, I used to plan out my whole career doing what I was currently doing, but I’ve learned you do something for a while, and then you do something slightly different. That would be one learning. In terms of the company, it’s a big leap from the academic world into a company. There’s huge potential to draw on the experience of people who have complementary knowledge and complementary skills. I was incredibly lucky with Genomics that we have a chairman who is a serial entrepreneur. He has created lots of companies. He was brilliant for advice and guidance. And more recently, I have gotten colleagues who have, ironically, Genomics is the first company I’ve ever worked in, so I’ve got colleagues that have a lot more experience in that, as well. I think there’s a piece about combining the best things from what I had learned from my academic career with complementary sorts of things about running a commercial organization. One of the things about my career is I’ve loved learning new things. I’ve really enjoyed this, but it’s a journey, and it’s a journey I’m enjoying, and I’d like to think I’m still improving.
Alejandro: Your academia years have given you an edge because when you’re an entrepreneur and an operator, especially trying to bring something new to life, it’s also trying to make sure that you’re able to share that canvas with the callers that you’re envisioning to a certain degree, and I’m sure that being able to explain and teach others over the course of years maybe came in handy to be able to share and explain what you were trying to accomplish with Genomics so that you were able to get that storytelling side of it and share it with investors and with employees and even customers. What kind of an edge would you think that has given you?
Sir Peter Donnelly: I think you’re absolutely right, but you’ll know from your experience, I’m sure, almost all the entrepreneurs you speak to would have something similar. That ability to construct the story and to tell the story and to bring people on the journey with you to give them a sense not just of the factual piece, but the opportunity and the hope in our case and in many others, a real excitement. That’s absolutely critical, and I think I have been lucky through academic work in learning about that and in learning how to share and develop that. I think the other advantage I have as an academic in my current role is many of the people I would like to deal with in senior roles and in Pharma companies or healthcare systems are people I know a little bit about from my academic career, or they would know about me from my academic career, and that’s quite helpful.
Alejandro: I can totally get that. Peter, for the people that are listening, what is the best way for them to reach out and say hi?
Sir Peter Donnelly: Email or the Genomic PLC website will have a way of contacting people. We’re very excited about what we’re doing and see huge potential. I’m happy to connect with people if they see that potential as well.
Alejandro: Amazing. Peter, thank you so much for being on the DealMakers show today.
Sir Peter Donnelly: It’s been a huge pleasure. Thank you very much.
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