- Gene editing has become one of biotech's hottest advances this year.
- The tech carries the promise of curing diseases with one treatment, upending the drug industry.
- Insider toured some of the leading gene-editing biotech labs and spoke with industry leaders.
CAMBRIDGE, Massachusetts — Verve Therapeutics has rocketed to a valuation of more than $2 billion since its stock-market debut in June, but it could be years before investors find out whether the gene-editing upstart is worth a cent.
Verve's stunning rise is the latest example of the rapid ascent of gene editing, which has become one of the hottest parts of biotech over the past year. Excitement has reached new heights with the first glimpses of data from trials in people, which suggest that the approach holds the potential to cure certain genetic diseases with a single treatment.
Verve launched just two years ago, raising a Series A round from investors such as GV and ARCH Venture Partners. Even today, the company has fewer than 100 employees (though it's hiring aggressively) and doesn't plan to start initial human testing until 2022. Yet Verve's valuation suggests that investors are wooed by the promise of tackling heart disease with cutting-edge therapies.
Verve isn't sitting on its IPO cash. In another sign of its ambitions, it's prepping to move offices again next year into a space five times as large as its headquarters right now. The biotech moved into its current facility last summer, and blue tape still frames some of the doors, while TVs have yet to be hooked up in conference rooms.
As more entrepreneurs and investors are storming into gene editing, Verve is focused on differentiating itself by focusing on the world's greatest killer:
"It's an ecosystem that is rapidly expanding, and we see ourselves as the cardiovascular company within that space," Andrew Bellinger, Verve's chief scientific officer, said. "We're building the expertise to own the cardiovascular space."
A 'revolution in medicine'
Noubar Afeyan, a longtime biotech entrepreneur who runs Flagship Pioneering, the venture-creation firm that founded Moderna — the biotech known for its coronavirus vaccine — said technologies such as gene editing are fundamentally different from the drug industry's usual approach.
"Biotech is just beginning," Afeyan said. "In the past, biotech was a little bit of bio and a little bit of tech. I think the amount of it that is bio now in terms of actually understanding has gone up and the amount of technology is incredibly higher. The result is going to be more drugs, more predictably, hopefully with less cost."
Even the most advanced gene-editing programs have provided only preliminary results. But that early data has been enough to drive further enthusiasm, reinforcing the belief that the technology can usher in a new era of drug research.
"We are part of this revolution in medicine to go toward one-time cures," said John Evans, CEO of the gene-editing specialist Beam Therapeutics, which commands a $6.2 billion valuation. "We're just still at the beginning innings of what's going to be possible in this field. The spirit of discovery is very much alive here."
Investors are pouring billions into gene editing
The discovery of the key gene-editing tool Crispr is not even a decade old, and the industry already features a variety of companies with multibillion-dollar valuations, chasing lofty aspirations of upending the drug industry.
One research firm forecasts the gene-editing industry will grow to a $23 billion market by 2030. So far this year, investors have poured $2.6 billion into eight gene-editing biotechs through public and private financing.
The scientists who discovered Crispr were awarded the Nobel Prize last year, and the public got a major introduction to Crispr's story through the biographer Walter Isaacson's latest best-seller.
Still, gene-editing therapies are years away from reality, and therapies that rely on altering our genes have run into trouble before. In 1999, the field of gene therapy suffered a massive setback after the highly publicized death of a young participant in a clinical trial. It wasn't until 2017 that the first gene therapy was approved in the US.
Gene editing's supporters argue it is more precise and powerful than gene therapy. Some leading gene-therapy programs have faced recent setbacks over toxicity and durability concerns. While gene therapy typically uses a virus to replace a faulty gene with a working one, gene editing corrects errors in the genetic code, or DNA itself, similar to fixing a typo in a line of computer programming.
Gene editing brings a new approach to drug research
It's just in the past few years that researchers have assembled all the tools they need to make gene editing a reality.
At the turn of the 21st century, the Human Genome Project completed the first rough draft of the entire genetic sequence of the human body. Since then, knowledge of human genetics has exploded, and the cost of sequencing a genome plummeted to about $1,000 from $300 million.
In 2012, the discovery of Crispr as a gene-editing tool allowed researchers to imagine the possibilities of easily manipulating that genetic code. Suddenly, scientists had a tool that could fix the genetic mutations responsible for certain diseases. In the past few years, researchers have developed more precise iterations called base editing and prime editing.
Less glamorous research into tiny blobs of fat has also led to a better delivery tool to get Crispr into human cells. So-called lipid nanoparticles have gained widespread use in Moderna's and Pfizer-BioNTech's coronavirus vaccine. Now, several gene-editing companies are delivering their potent medicines enclosed in these tiny fat bubbles.
Even with these advances, Beam's Evans compared gene editing's status to the computer industry in the early '80s.
"We've got the first laptop, we've got the first mainframe, we've got the early internet," he said. "But you think about where we're going to be in 20 years from now, as each of those technologies does its own improvements and they start to augment each other, it's easy to see we're at the very beginning stages of this."
Despite promise, the field is still in early days with challenges and scientific uncertainty ahead
The space is still in its early days, company leaders readily acknowledge.
The early data from Intellia and Crispr Therapeutics is from fewer than 30 patients in total. Testing more patients and following them for longer could show more variability or raise other unforeseen concerns, said Ali Behbahani, a venture capitalist at New Enterprise Associates who sits on Crispr Therapeutics' board.
Additionally, the first gene-editing medicines are targeting the low-hanging fruit: diseases driven by a single genetic mutation. Fixing that single mistake could be the difference between being healthy and being sick.
But the biggest disease of today — cancer,
, Alzheimer's — are more complex and not nearly as easy to treat.
"The real question is, can you translate it outside of the low-hanging fruit to bigger diseases, and I think that's where it's tricky," Behbahani said. "Verve and Beam are interesting stories, but they're still early. You just have to be cognizant that not everything is going to work despite Intellia and Crispr showing intriguing data."
Companies barrel ahead, as encouraging first results instill confidence
Nevertheless, the industry is moving with blazing speed. Six gene-editing leaders — Editas Medicine, Intellia Therapeutics, Crispr Therapeutics, Beam, Verve, Graphite Bio — have gone public since 2016.
A decade ago, none of these businesses existed. They command a combined market value of about $34 billion — up from a total of $6 billion at the time of their respective IPOs.
More are on their way. Prime Medicine officially launched on July 13 with $315 million. The Cambridge biotech (the vast majority are based in Cambridge) is developing a technology, first described in 2019, called "prime editing" that's similar to Crispr but doesn't require fully breaking the DNA to perform edits.
Early data is stoking excitement
The first glimpses of clinical data have stoked further excitement.
Crispr Therapeutics announced the first gene-editing results in humans in November 2019, publishing data from the first two patients treated for genetic blood disorders. The latest update, given in June, found all 22 participants responded to the treatment, and support the hope that these one-time treatments could work as cures for sickle-cell disease and beta thalassemia.
Then, Intellia published landmark results last month describing the first six patients treated with its gene-editing medicine. Crispr Therapeutics' approach relies on an arduous process of extracting stem cells from patients, editing those cells in a lab, and reinfusing them back into patients.
Intellia's approach is much simpler. Intellia is using mRNA inside a lipid nanoparticle (the technology shared with coronavirus shots) to edit genes directly in the body.
The early data show few and mild side effects, with the one-time treatment dramatically slashing levels of a disease-causing protein in patients with a genetic nerve disorder.
Geulah Livshits, a biotech analyst at Chardan specializing in genetic medicine, said Intellia's results are a boon for gene editing overall.
"This moves the field into more of an engineering stage than a guess-and-check strategy," Livshits said, emphasizing the consistency of gene-editing data from animals to humans. Often, treatments that work when first tested in mice or rats can fail to actually help people.
Traditionally, pharma companies have relied on screening compounds to discover new drugs, hunting through chemicals in a somewhat random manner at times. The search for each drug can be an entirely new hunt.
In contrast, gene-editing platforms aspire to build something programmable and modular. The hope is that with an approach like Intellia's, to target a new disease you simply enter a new stretch of genetic code that you want to target.
Intellia CEO John Leonard said, "We're going right to the problem in the first place, not with a chemical crutch — and I don't mean that in a disparaging way — but directly to the biologic solution."