Editing genomes, one letter at a time
CEO: John Evans
Based: Cambridge, Massachusetts
Clinical focus: Genetic diseases caused by point mutations
The scoop: Drugs based on gene editing are still in the earliest stages of development, but that’s not stopping new players looking at refining and improving the technology. Beam Therapeutics—co-founded by a trio of top-flight CRISPR researchers—is focusing on a technique known as base editing that ups the ante on CRISPR’s precision by making it possible to find, remove and replace a single nucleotide base, or “letter,” without affecting those surrounding it.
The company sees base editing as complementary to other approaches such as CRISPR/Cas9, TALEN, zinc fingers—all of which cut DNA and attempt to insert or remove larger stretches of DNA—but much more suitable for correcting single-point mutations. That’s a group that accounts for more than half of all genetic changes linked to human diseases.
What makes Beam fierce: “It’s not often that you get the opportunity to work on a completely new therapeutic modality,” said CEO John Evans, who told us in May that while CRISPR is likened to a pair of scissors, base editing “is more like a pencil. When it reaches its target, it finds a letter, erases it and rewrites it as a different letter without disrupting the sequence of other letters around it.”
Evans believes that, for many diseases, that precision will make base editing the best tool for the job. Some 33,000 point mutations have already been linked to genetic diseases, and base editing would allow those single disease-causing genes to be transformed into healthy ones without causing other effects to the genome.
Beam’s founders are three of the world’s leading CRISPR experts. David Liu, Ph.D., of Harvard University is the inventor of base editing and a co-founder of one of the world’s first CRISPR companies, Editas Medicine. Keith Joung, M.D., Ph.D., a gene editing researcher at Massachusetts General Hospital and Harvard Medical School, is also an Editas co-founder. Rounding out the trio is Feng Zhang, Ph.D., of the Broad Institute of MIT and Harvard, one of the inventors of CRISPR gene editing.
While the company is still holding its cards close to its chest when it comes to specific disease targets, Evans notes that it has eight to 10 projects on the go across “multiple genetic targets.” They're looking at applying base editing outside the body (ex vivo) to cells that could act as therapeutic candidates, as well as in vivo, using delivery technologies such as lipid nanoparticles or adeno-associated virus vectors that could correct genes in tissues such as the eye, muscle, skin and liver.
“The cool thing about this technology is that once we get into clinical trials, in every case we will know at an early stage who we are treating and the outcomes we are hoping to achieve,” said Evans. “I think that means that, compared to other technologies, we should be able to progress more quickly and have a higher chance of success.”
Work on the core platform is continuing, for example with the optimization of its current base editors and the discovery of new ones.
CRISPR has become something of a battleground when it comes to intellectual property, but Beam has tried to avoid that by signing three licensing agreements—with Harvard, the Broad Institute and Editas—that he believes have shored up Beam's position in single-base editing. Given the fierce fighting going on between players in CRISPR/Cas9, “we wanted to stay under the radar while we put together our IP position,” said Evans.
For now, Beam has 25 staffers—many of whom have transferred from the labs of its founders—but Evans expects that number to rise sharply in the coming months as the biotech closes in on its lead indications. Some hires will go to building the base-editing platform, while others will flesh out its therapeutic area teams and build additional expertise in areas such as delivery technologies.
It’s already raised $87 million in a series A that should give it a two- to three-year runway to develop its pipeline.
Investors: ARCH Venture Partners, F-Prime Capital Partners, Inevitable Ventures