Beam Therapeutics made a splash last year when it launched with $87 million to develop medicines that use a more precise form of CRISPR editing. Beam’s promise of CRISPR-based therapeutics that swap out specific bases or “letters” in the genome—something the current generation of CRISPR-based drugs can’t do—has been so enticing to investors that they have put in $135 million in a Series B investment less than a year after the first funding round.
CRISPR-Cas9 gene editing, which just last month entered clinical trials in the U.S. for the first time, can cut DNA at specific locations to take out or add a piece of DNA. But thousands of diseases are caused by much smaller single-letter mutations. To edit these point mutations, a new kind of CRISPR technology is needed: base editing, which was developed by one of Beam’s scientific founders, David Liu (pictured left) of the Broad Institute, and his team. Base editors consist of two key enzymes: a CRISPR enzyme that’s programmed to home in on a specific location along the genome, and an editing one that changes a base, for example, from an “A” to a “G”.
John Evans, Beam’s CEO, says his company has 10 programs underway. Although he wouldn’t say which diseases or targets those programs focus on, he did say they cover all the different methods that are being used to deliver CRISPR to target tissues in the body: so-called ex vivo approaches, which involves editing cells, such as immune and blood cells, outside of the body before introducing them into patients; lipid nanoparticles, which target the liver, and AAV, which are viruses that deliver genes and other molecules to tissues like the liver, eye, muscle and central nervous system.
Evans adds that in most of Beam’s programs, his team has been able to edit disease-causing mutations in human cells “at a therapeutic level” and will soon start testing the base editors in lab animals. He says that his company this year is moving beyond just cell-based studies of base editors “to making these things into medicines.”
That means looking at manufacturing, regulatory, and safety issues, including possible unintended edits made by CRISPR base editors beyond the targeted DNA site. Researchers showed the possibility of these “off-target edits” in two papers published last week in Science. One of the studies showed that one type of base editor—known as the cytosine (C) base editor, which converts C to T—made about 150 wrong edits in the mouse genome. The adenine (A) base editor, which switches A to G, made few off-target edits.
Evans says the papers were largely good news, because about half of all the single-letter mutations linked to disease can be addressed by the adenine base editor, which made almost no off-target edits and is a big part of Beam’s pipeline. Evans says the cytosine base editor would be useful for only about 17 percent of those mutations, and the new findings gives his team clues on how to improve this base editor.
With the new funding, Evans says Beam will use new tools to look for off-target edits, improve existing base editors, develop new ones, and move the programs toward clinical testing. He declined to say when Beam, which now has 70 employees, will reach the clinic, but says he hopes to share more data and other details about the programs in the next year.
The latest funding for Beam comes from earlier investors F-Prime Capital, ARCH Venture Partners, Eight Roads Ventures, and Omega Funds. Several new investors joined the round: Redmile Group, LLC; Cormorant Asset Management; GV; Altitude Life Science Ventures, and other undisclosed investors.