Eight Lessons from John Maraganore (Alnylam)
Life sciences reflections
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John Maraganore is the CEO of Alnylam, the leader in RNAi medicines. Before Alnylam, Maraganore was an SVP at Millennium Pharmaceuticals leading their protein drug development work, and a director at Biogen where he led the work to develop Hirulog, which was ultimately approved for patients with percutaneous transluminal coronary angioplasty (PTCA).
1.“We were always going to focus on therapeutics. We believed that RNAi was much more than a research tool. If you could design molecules to be administered to humans to silence genes that are involved in the cause or pathway of human disease, you could have a new class of medicines just like antibodies, just like recombinant DNA and just like small molecules. I can show you our five year plan that was developed within the first three months of my joining the company. It has not changed. We are adjusting things here and there, in part since we’ve been somewhat more successful than we expected, but we are executing on that plan”
Since joining Alnylam in 2002, Maraganore stuck with the vision to develop new drugs based on RNA interference (RNAi) and executed on his plan over the last ~18 years.
2. “I value judgment, not hyper-analysis. When people are afraid to make decisions, they often rely on hyper-analysis. I don’t believe in that. We are brutally honest about the science, and we get a bunch of people around the table with gray hairs and wrinkles to talk about what the science is telling us.”
Maraganore leads with science - models (i.e. NPV) and various forms of analysis could be useful to some cases, but a deep understanding of a drug candidate’s advantages and limitations is more effective to decide which indications to focus on and candidates to move forward.
3.“This is an industry that 30 years ago now addressed HIV and, within a reasonable short period of time, was able to find treatments for HIV and convert HIV from a death sentence to a disease that people can live with for the rest of their lives. That was an amazing period. This is 10 times what I saw back then.
I was at Biogen as a young scientist during the HIV crisis and we were working on medicines for HIV. We used to go to the AIDS conferences every year. There was a lot of cooperation between companies at that time and between public health officials, but this is an order of magnitude beyond what I saw in the 1980s around HIV. We have an enormous amount of science and innovation coming from this industry, working together, sharing information, sharing approaches, and sharing data. It is a totally different world.”
Biotechnology really came through in an important way during the COVID-19 pandemic and similarly with HIV/AIDs; Maraganore is building a company to speed up the process of going from a disease to a treatment/cure.
4.“Part of it is really understanding and articulating the value. The fair price ought to be consistent with a value proposition. Let’s put it this way. What’s the price of not having drugs for Alzheimer’s? What’s the price of not addressing hepatitis B infection?”
On drug pricing, Maraganore is focused on value rather than sticker price. Drug companies need to do a better job at justifying their price with science and patient impact.
5.“Yeah, I mean, again, it’s probably one of the beauties of our technology. The fact that we can use genomic information. We can use the gene sequence as a way to design our drugs.
That is something which we’ve had in our technology from the beginning. And it does allow us, as soon as those gene sequences become known, it does allow us to rapidly deploy our technology to basically develop a new medicine. And so, but, you know, from an internal perspective, what it obviously takes is you rally your group of scientists together, and you look at the need to adjust things within your plans, and you stop some things that you were doing before so that people can shift and focus and work on this new thing coming out. But when you have a public health crisis, that’s what you do.”
RNAi medicines have the advantage that once the backbone and chemistry of the modality is figured out, then pursuing different targets and diseases could be as simple as swapping which sequences to target.
6. “At Biogen, I managed a group as large as thirty people and I felt I was having an impact on setting strategy and corporate goals after being in business development for some time. Being able to manage something larger seemed attractive. I was also absolutely convinced that genomics was going to make a very big difference in medicine. And it has. That idea started back in 1989 when Wally Gilbert made a presentation at a Biogen SAB meeting. People were skeptical about being able to make money on genomics but, frankly, I was a bit frustrated that Biogen was not more active in this area.
At Millennium, we all had a healthy naiveté about how long it would take to advance drugs from genomics. The whole process of finding novel structures that are exciting based on the way they look, and rapidly figuring out how they can be used from a clinical standpoint, turned out to be much harder than anyone ever expected. Yet, it was clear that we had the ability to use genomics with all the sequencing work that we were doing. But to be honest, it was almost a side project for Millennium given that the company’s main focus was small molecule discovery. My job, at Millennium Biotherapeutics was to use genomics to take on Human Genome Sciences in the realm of protein-based therapeutics.”
Maraganore’s leadership experiences at Biogen and Millennium set him up to bring new medicines to patients while building more scalable business models.
7.“We have to rely on the science. We can’t make decisions on how to develop important new medicines based on a calculation of net present value. For quite some time, Big Pharma has put forecasting from the marketing group ahead of the judgment of their R&D group. To think you can fool yourself into a number, and that is going to make it into a real thing, it’s insanity.”
8. “We have had options in our history to make a quick buck. We have built the foundation to do that but are not taking that route. Look at the value of Biogen, Genzyme, Genentech, and Gilead, among others. To me, it is a far better outcome for shareholders if you can stick it out like they have. Millennium was also a success, although I think they might have forced a profitability profile too soon. They were struggling with earnings growth and pipeline investment. They had a “pig in the python” challenge that only a big brother like Takada could come in and take care of. I think Alnylam can get to that profitability horizon, which is still some years out, and be there with the right pipeline. I have seen the Biogen and Millennium models succeed but also have challenges. The scars they have provided me have given me a lot of insight to think about what we have to do here.”
Maraganore has the vision to build Alnylam into one of the largest biotechnology companies in the world.
