Forbes - Innovation

This Gene Editing Startup Raised $315 Million For A Next Generation Crispr Tool To Cure Rare Diseases

The gene editing technology Crispr may have been Nobel Prize-worthy, but Andrew Anzalone was convinced he could make it even better. Often likened to a pair of molecular scissors, it enables scientists to cut DNA and rewrite the code of life, such as turning off disease-causing genes. But the technology has some drawbacks—it breaks the DNA double stranded helix, which can lead to unwanted changes in other sections of the code. As a postdoctoral researcher in the Broad Institute lab of David Liu, Anzalone set out to build the equivalent of a Crispr Swiss Army knife—a multifunctional gene editing technology that can correct entire sequences of code all without breaking the double helix. “The idea was to really try to broaden the scope of what we can do with gene editing,” Anzalone says of the invention called “prime editing.”  

The human genome is made up of 6 billion combinations of the four letters known as bases: A, T, G, and C. The bases make up segments called genes, which include the instructions for certain hereditary information. Crispr-Cas9 allows researchers to hone in on a specific location within a gene and make a cut and add or delete genetic material. It is particularly good for inactivating or “knocking out” genes. But one of the downsides is unwanted insertions and deletions of random bits of code due to breaking the DNA double helix, which can cause unintended mutations in other parts of the genome. Other diseases, such as sickle cell disease, are caused by an error in a single base pair. That’s where base editing, which can swap out individual bases, comes into play, though currently base editors can only perform 4 different swaps. 

This is where prime editing comes in. This technology can perform all of these functions—insertions, deletions and the 12 different mismatches of bases—and could potentially correct up to 89% of the known mutations that can cause genetic disease. It’s being developed by Cambridge, Massachusetts-based biotech startup Prime Medicine. The company announced $315 million in combined Series A and B funding on Tuesday for the technology, which it describes using terms associated with word processing software. “We like to use the analogy of search and replace, because the beauty of the Crispr system is you can tell it where to go exactly in the genome. Our [prime editing] system also tells it exactly how to fix it, and that’s really what makes it unique,” says Anzalone, the co-scientific founder and head of the prime editing platform. The funding values the less than 2-year-old company at $1.2 billion, according to PitchBook. Prime declined to comment on the valuation. 

While $315 million may seem like a hefty sum for a company that really only started operations in July 2020 when it hired former Merck and Rhythm Pharmaceuticals executive Keith Gottesdiener, the majority of investors are repeat funders of Prime’s co-scientific founder David Liu. While Liu isn’t involved in the day-to-day operations of Prime, he has spun several companies out of research conducted in his Broad Institute lab. F-Prime, Arch Venture Partners, GV (formerly known as Google Ventures), Cormorant Asset Management, and Redmile Group were all investors in Beam Therapeutics, the base editing company Liu cofounded that went public in early 2020. Casdin Capital, GV, and T. Rowe Price Associates were investors in Editas Medicine, a gene editing company where Liu is a co-scientific founder that went public in 2016. Other investors in Prime include Newpath Partners, Moore Strategic Ventures, Public Sector Pension Investment Board and Samsara BioCapital. 

The investor excitement around Prime is driven by the sheer scope of the prime editing technology and the promise it could theoretically be more powerful and more precise than other Crispr-based tools leading to more personalized treatments and cures, especially for rare diseases with very few patients. “It had the potential of being what I might call a universal editor, meaning that you could read and write and fix multiple mutations,” says Stephen Knight, president and managing partner at F-Prime. “And that seemed to be both attractive intellectually but also groundbreaking.” An early investor in Beam Therapeutics, Knight once again jumped at the chance to fund commercializing research coming out of Liu’s lab. 

“It won’t be many years before we’re actually trying this out in patients and hopefully making an extraordinary difference.”

Keith Gottesdiener, Prime Medicine

Early on, Prime and Beam entered into a licensing agreement where Beam has the rights to commercialize prime editing applications for sickle cell, so as not to cannibalize its existing pipeline. The agreement also includes commercializing the technology for other, undisclosed conditions. Both companies also agreed to share research and expertise, including manufacturing and delivery mechanisms, to get prime editing in human trials as soon as possible, says Prime’s CEO Gottesdiener. As someone with extensive experience bringing therapeutics to market, the speed of the advancements in gene editing is unparalleled, he says. “It’s not this long term goal, where we’re thinking about how our grandchildren are going to carry it forward,” he says. “It won’t be many years before we’re actually trying this out in patients and hopefully making an extraordinary difference.”

As far as Prime’s own pipeline goes, the choice of more than 75,000 genetic mutations to go after and correct also makes it more challenging to prioritize. Gottesdiener declined to name specific diseases but provided broad categories that Prime is going after, including drug discovery programs targeted at the liver, eye, and neuro-muscular indications, as well as hematopoietic stem cells outside the body. A look at the 2019 Nature paper published by Anzalone, Liu and team, offers some potential clues for specific prime editing applications, including Sickle Cell disease, the rare nerve disease Tay-Sachs and resistance to neuro-muscular prion-related diseases. The true holy grail—and one of Prime’s future aspirations—would be to use one prime editor to fix multiple mutations. “One of our hopes is that we can literally march up a chromosome—move from spot on a chromosome to spot—and we can correct for every mutation in that particular gene in a very efficient way,” says Gottesdiener.

Gottesdiener would not provide specific milestones or timing, but Prime has already raised more money than Beam did before it went public. Positive data on studies in mice and monkeys have caused Beam’s market cap to grow from around $1 billion in mid-2020 to around $6.2 billion today. When Cambridge, Massachusetts-based Intellia Therapeutics released data last month that it had successfully gotten its Crispr-based treatment for a rare disease into six human patients, the stock soared over 80% in the course of a week from $88 to $171 a share. 

Despite the technology’s potential, prime editing still needs to be demonstrated to work in people. So far, the highest level model organism prime editing has been tested in is mice, and there is a ways to go before it will reach human trials, but the future potential is palpable. “Our goal really is to cure, halt or prevent genetic diseases,” says Gottesdiener. “It’s not always clear that by changing the genetics you can go back and fix things that already were broken, so we can’t always promise that every change we’re going to make is a cure for an individual patient.” But, at a minimum, the diseases will not progress, he says, “and maybe someday we’ll get to those diseases early enough before any damage actually occurs.”

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