To start off, will you please walk us through the circumstances that brought Verve Therapeutics to life?
Prior to founding Verve, I was a Harvard Medical School professor studying the genetics of heart attacks. I spent about ten years trying to figure out why some people have heart attacks while others do not, and I discovered a group of people who had very low levels of blood cholesterol and were remarkably protected from this risk. We discovered that the reason for this protection was that a gene was turned off - in a sense, these people won the genetic lottery and had life-long low cholesterol levels. This observation sparked the idea of creating a one-time medicine to mimic this natural occurrence.
In 2016, the American Heart Association had a competition, looking for the best ideas to cure heart attack - we put forward our idea of a one-time therapy that would turn off a cholesterol raising gene for good. While we did not end up winning, we decided to go ahead and do it anyway - we raised the funding, assembled the right team and started Verve in 2018. Over the last five years we were able to take it from concept to showing its efficacy in monkeys, and treating our first patient in 2022.
Gene editing has been gaining traction in recent years; why did you choose to take this route and what makes your solution unique?
Heart attacks are the leading cause of death in the world and a very expensive disease. Human genetics taught us that the solution is to get LDL cholesterol as low as possible, for as long a time as possible.
We have options right now to lower cholesterol but they all take the form of the chronic care model, meaning daily treatment. This is, however, a broken model - even after a heart attack, people's cholesterol levels are not adequately controlled and demand strict adherence to medicine, regular access to healthcare, and extensive infrastructure — all of which are in short supply.
By substituting chronic care with a one-time medication that significantly and permanently lowers blood cholesterol, we hope to dramatically alter the way this condition is treated. The CRISPR technology allows us to permanently change a disease-causing gene, much like correcting a spelling error. The medicine itself is mRNA packaged in a lipid nano-particle and delivered as a one-time intravenous infusion. Our testing showed that the LDL cholesterol in the blood of monkeys decreased by around 70% two weeks after this one-time therapy, and it remained at that level about 2 and 1/2 years later.
What are the next milestones in sight, and what is an optimistic prediction of when this therapy can be made widely available?
Over the last five years we managed to develop this first in class medicine, essentially an entire new modality of treatment called in vivo base editing. We collected data in pre-clinical models using mice and monkeys, submitted it to regulatory agencies for clearance, and then we were able to treat our first patients. We are in Phase 1 trial right now, to understand the safety of the medicine. From there we will move to Phase 2 and 3, to document the full safety and efficacy profile of the medicine. It takes roughly 10 years to develop a new medicine from concept to a doctor being able to write a prescription - we started in 2018, so if we have a treatment that patients can get by 2028, we will be in good shape.
What has been most challenging in this journey so far?
The main challenge is that there is no playbook to outline the steps we need to take along the way. We are doing everything for the first time and tackling adaptive problems that have no prior proven solutions and require the generation of new knowledge. Our focus was to build a robust team and enable them to creatively problem solve. We have a group of 200 people in the company right now that is working hard on every aspect of our drug development.
This type of research requires massive capital and markets have been fairly challenging in the past couple of years. What has worked best for you when it comes to financing your efforts?
So far, we have raised about USD 800 million in capital, across three private rounds and two public financings (we are a publicly traded company on Nasdaq). Since inception we have spent about USD 250 million so we have a significant amount (about USD 550 million) still left at our disposal to continue the development of this medicine. The next inflection point for us will be to complete studies and prove the efficacy and safety of the medicine in human patients. That data will be a key catalyst to raise additional capital to continue the journey, and ultimately have a commercial product.
Did the global pandemic leave a mark on the life sciences sector, particularly on its innovative side?
The pandemic had a big impact on us. We had been using mRNA as our drug format since 2018 and the fact that the COVID vaccines developed in 2020 were using the same methodology was a fortuitous thing. There is now a much better understanding of this technology and we know this kind of drug can be produced cost-effectively at scale. This gives us a nice line of sight to our ultimate goal, which is applying this advanced technology to a very broad and common problem. So far, gene editing has been applied mainly to cancer and rare disease and we are trying to apply it to the most common cause of death in the world. To be able to do that, we need access to cost-effective solutions. The similarities between our product and the COVID vaccine is really helping that.
What are you most excited about for the next couple of years?
The potential to help millions of patients suffering from cardio-vascular disease and fundamentally change the way that this disease is cared for is incredibly exciting. Over the past century, chronic disease has been treated with chronic care - what we have in sight is a one-time therapy that provides dramatic protection. We are still in the early stages and there are still a lot of challenges ahead; but the ability to show how with a very precise DNA "spelling" change you can dramatically improve someone's health for good is a truly stunning thing.
