In early 2016, Anthony Philippakis found a brave new idea.

A former cardiologist at Brigham and Women's Hospital and adviser to the American Heart Association, Anthony has dedicated his career to helping patients and their families manage heart disease. Cardiovascular disease is the leading cause of death in the world, and in the United States, one person dies every 36 seconds from the affliction.

GV Venture Partner and Verve Co-Founder Anthony Philippakis GV Venture Partner and Verve Co-Founder Anthony Philippakis

Anthony is also a venture partner at GV, where we have worked on several fantastic companies together over the years, including Foundation Medicine and Flatiron Health. Anthony is constantly on the go given his many roles — one day, he walked into our shared office with his ever-present leather brown bag slung over his shoulder, ready to rush off. He was holding a ten-page proposal for a research grant. He was about to stuff it in his bag when he stopped and said, "Hey, can I tell you about this thing I've been working on?"

We sat down and started talking about it. Anthony was excited by the proposal's radical idea: a "vaccine for heart disease" using gene editing. I didn't understand at first, but as he walked through the paper, the concept took hold in my mind as well. I couldn't believe the proposal had just been rejected in a research competition, but I could immediately see this would be an amazing company.

Spearheaded by Dr. Sekar Kathiresan, a world-renowned physician-geneticist, the idea was to use CRISPR-Cas9 to edit the human genome and introduce mutations known to be protective against heart disease. CRISPR-Cas9 had been harnessed in the human genome only three years prior, in 2013.

The Superstar Cardiologist: Dr. Sekar Kathiresan The Superstar Cardiologist: Dr. Sekar Kathiresan

Anthony also serves as Chief Data Officer at the Broad Institute of MIT and Harvard and has spent his life's work at the intersection of genome sequencing, data science, and clinical medicine. He felt this was a moment unlike any other, and he wanted to see this idea happen. Anthony, Sek, and GV Venture Partner Issi Rozen knew they needed the best minds in human genetic analysis and gene editing to push their idea forward. Issi was the logistical mastermind behind forming new companies, so they got to work.

GV Venture Partner and Verve Co-Founder Issi Rozen GV Venture Partner and Verve Co-Founder Issi Rozen

The group started meeting in a conference room at GV's Cambridge offices. It seemed like every time I walked by, I saw Anthony, Issi, and Sek in there. It wasn't that small group for long; Sek is a human magnet for other great people. He's the kindest, most thoughtful, hardest working executive you may meet, and beloved in academic and medical circles (STAT once called him a "superstar cardiologist"). The Sek effect, amplified by Anthony and Issi, soon became clear. More people kept showing up.

First, drug developer Burt Adelman. Then leading genome editor Keith Joung. And Barry Ticho, Kiran Musunuru, Eugene Braunwald, Andrew Ashe, and John Evans. Our office hallway turned into a veritable runway for major names in genetics, epigenetics, gene editing, drug development, and cardiology. The roadmap was set, and the conviction was clear — this was something we should try.

In 2018, this group formed Endcadia Inc., whose name was (thankfully) changed to Verve Therapeutics, and they set out to tackle the number one disease killer in the world. The idea was bold, unproven, and many people were skeptical. GV led the $58.5M Series A.

The Verve team The Verve team

While simple medications like cholesterol-lowering statins can dramatically reduce the risk of heart disease, a significant percentage of people who have severe heart attacks do not take the medication prescribed to them. In GV's payor/provider practice, we have looked at many ways to try and incentivize, remind, and cajole people into taking their medications. But over time, we realized that we simply need a new therapeutic approach.

Verve's aim is a single-course treatment for cardiovascular disease that targets specific genes in the human body, found in the liver, that are well-validated to increase cardiovascular risk: PCSK9 and ANGPTL3. Verve's gene editing programs are designed to permanently lower cholesterol in the liver and eliminate the problem of adherence to lifestyle modifications and lifelong medication administration.

Staying true to its synergetic roots, Verve set up a unique collaboration and license agreement with GV portfolio company Beam Therapeutics to target a single letter in a genetic sequence using base editing. The company also secured license agreements with the Broad Institute of MIT and Harvard and Harvard University for foundational CRISPR patents.

Verve's approach Verve's approach (Source: Verve Therapeutics)

Early tests of Verve's therapeutics on non-human primates are extremely promising, and the data speaks for itself. GV doubled down on our initial investment and participated in a Series B led by Wellington Management and Casdin Capital. Last month, the team published new findings in Nature, revealing that "We observed a near-complete knockdown of PCSK9 in the liver after a single infusion of lipid nanoparticles." As far as scientific papers go, they had to be modest. But it was one of the most beautiful data sets I had ever seen. The company remains heads down as it continues marching toward human clinical trials in 2022.

Figure 3 Figure 3 from Verve's Nature article. One of the more striking early datasets!

Today we're standing on the cusp of one of the most astounding scientific breakthroughs of the 21st century: a single-course treatment to combat the number one disease killer among humankind. But we stand on the shoulders of giants. None of this would be possible without advances in CRISPR, base editing, and gene editing.

I firmly believe that we're entering a new era of biology, and some of these modalities should start to look like software. The biology equivalent of the first Motorola bag phone has been built, and now we are seeing rapid progress. We haven't quite seen the iPhone and Android biology equivalents appear yet, but I believe we will see major shifts in how broadly and easily gene editing is used in the coming years. Verve is among the first to plant a seed for what I hope are more new efforts into major disease areas.

The incubation of Verve only worked because of the people involved. You wouldn't have Flatiron Health without Nat Turner and Zach Weinberg or ROME Therapeutics without Rosana Kapeller. Successfully incubating a company with a game-changing idea starts with exceptional people asking exceptional questions. As the ideas coalesce into a perspective about how the world should be, our job is to find a way to help those founders and scientists make that thing happen — and then get out of their way.

Today, Verve's story enters its next important phase, and now with the resources it needs to get there. On behalf of everyone at GV, congratulations to Sek Kathiresan, Anthony Philippakis, Issi Rozen, and the tireless, talented, and brilliant Verve team on today's IPO. Verve on!