Beam Therapeutics Inc. CEO John Evans told BioWorld that the company's $135 million series B influx – following sooner than some expected the $87 million series A raise last May – is meant to "make sure that resources aren't the limiting factor" in pushing along the company's next-generation CRISPR technologies, expanding the pipeline of base editing programs, and adding to the firm's scientific and technical leadership.

Deploying on base editing technology developed in the Harvard lab of David Liu and others, Cambridge, Mass.-based Beam can tinker with the genome at the level of a single letter – A, G, C, T – without cutting the DNA or RNA strands. "At almost every step, Beam has gone faster than I expected," Evans said. "It's a different kind of edit than anyone else can do. The [series] A was really about launching the company. [We said,] 'Let's get this into a company, give it enough resources to go deep into the technology and science, and make sure we can find a place where it can work.' The great update in the last year is that we've had our labs open and, sure enough, not only does it work, it works very broadly."

Beam has "about 10 programs active across a wide range" of disease areas, Evans said. "In most of those we now have editing levels in cells that would be therapeutic if we could move that into a patient," and the series B provides "enough capital to pivot toward the clinic, even as we continue to go deep into the technology and the platform that we've built."

Gene editing is "an exploding field with a lot of complexity, for sure," he said, but Beam is plainly distinct from the first wave of research that involved nucleases programmed to go to a certain spot in the DNA and make a double-stranded break a la scissors. Evans mentioned Crispr Therapeutics AG, of Zug, Switzerland; Richmond, Calif.-based Sangamo Therapeutics Inc., with its zinc finger technology; Cellectis SA, of Paris, with its TALEN platform; and Precision Biosciences Inc., of Durham, N.C., with ARCUS genome editing. "All of them have, relative to each other, different pros and cons and technical advantages and disadvantages, which I am not an expert in, but at the end of the day, the kind of edit that they make is still fairly similar," he said. "We're not cutting the genome. We're using CRISPR but only to land at a certain site. The edit is made by a second component that we've got tethered to it called a deaminase, [which] makes a chemical edit to the DNA which converts a base, a letter, at that site from one to the other, and then lets go and never made a cut to the genome."

Evans declined to specify the disease areas under investigation. "We're not giving that information yet, but out of those 10 programs we have many that are beginning to move quickly toward later-stage research studies" to enable INDs, he said. "Our goal ultimately is not only to move a single thing into clinical trials but actually to try to generate a wave of INDs across a diverse range of disease types so that we can create a pipeline that has a lot of different options and diversified risk. We'll start to publish more science over the course of the next year, and it will become a little clearer."

'Still growing fast'

In general, though, the Beam approach has upside in certain areas, Evans noted. "An obvious one is looking for point mutations, a disease where it's caused by a single letter misspelling in your gene," he said. "A bunch of things in our pipeline have that flavor." The technology should be able to turn off genes and change their expression. "There's lots of other territory we're thinking about," he said. "Delivery, of course, is still really important for us. It's not easy to get these things to the right cell where they can make the edit," and Beam will probe "all of the known delivery modalities which are clinically validated for genetic medicines, and do that in parallel," including ex vivo, in vivo and viral vector strategies. "I'm sure there will be" particular areas of concentration, he said. "We want to follow the science. We've got a whole lot of things rolling, and we're going to be data driven."

Since the series A, Beam has expanded significantly. "We were probably 20 people or so in the spring of last year, and now we're about 70, and we've got labs in Central Square, Cambridge, a 36,000-square-foot facility that we moved into in the fall," Evans said. "Certainly [we're] still growing fast."

Participants in the series B included new investors Redmile Group LLC, Cormorant Asset Management, GV, Altitude Life Science Ventures and additional undisclosed investors. Existing backers who also lent their support include F-Prime Capital, Arch Venture Partners, Eight Roads Ventures and Omega Funds.

CRISPR continues to make news. At the start of the year, Johnson & Johnson's Janssen Pharmaceuticals Inc. agreed to pay Locus Biosciences Inc. $20 million up front and up to $798 million in potential milestones plus royalties for exclusive rights to develop, manufacture and commercialize CRISPR/Cas3-enhanced bacteriophage products. The preclinical programs target two key bacterial pathogens for the treatment of respiratory tract and other infections. Called crPhage, the platform uses the type I CRISPR/Cas3 system, which is designed to shred the DNA of target bacteria cells while leaving the many other species of good bacteria unaffected. Unlike CRISPR/Cas9, which makes clean cuts in DNA that can be repaired by the cell, CRISPR/Cas3 shreds it beyond repair. The company's founding scientific team developed the approach at North Carolina State University and Duke University. (See BioWorld, Jan. 4, 2019.)