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Beam launches into base editing
CAMBRIDGE, Mass.—In the middle of May, Beam Therapeutics announced its launch and a goal of developing precision genetic medicines that make edits to individual base pairs in the genetic code. Beam’s co-founders say that Beam will be the first company to pursue development of new therapies using CRISPR base editing technology.
Founded by Drs. David R. Liu, Feng Zhang and J. Keith Joung, Beam’s research will focus on multiple DNA base editor platforms developed in Liu’s lab at Harvard University, as well as on the RNA base editor platform developed by Zhang at the Broad Institute of MIT and Harvard. Joung is a leading researcher at Massachusetts General Hospital (MGH) and Harvard Medical School who has developed important technologies for targeted genome editing.
Newly headquartered in Cambridge, Mass., Beam is launching with up to $87 million in cumulative Series A funding for itself and an affiliated entity, led by F-Prime Capital Partners and ARCH Venture Partners. Beam’s board of directors includes CEO John Evans; investors Kristina Burow, Stephen Knight and Robert Nelsen; and independent director Dr. Mark Fishman, professor of stem cell and regenerative biology at Harvard University and formerly the founding president of the Novartis Institutes of BioMedical Research. Evans was most recently senior vice president of corporate development and portfolio leadership at Agios Pharmaceuticals, and is also a venture partner with ARCH. Dr. Giuseppe Ciaramella, most recently chief scientific officer of Moderna Therapeutics’ Infectious Disease division, will lead research as chief scientific officer.
“Our co-founders helped put CRISPR on the map. With Beam, they’re coming together again to push forward an exciting and differentiated approach to genome editing,” said Knight, F-Prime president and managing partner.
DNA is made up of billions of nucleobases, each represented by a single letter (A, G, T, C), which are subsequently encoded in RNA messages for expression by the cell. Base editors are capable of precisely targeting and directly editing just one base out of billions within the genome, without cutting the DNA or RNA. Beam aims to use these technologies to generate a broad pipeline of precision genetic medicines that repair disease-causing point mutations, write in protective genetic variations or modulate the expression or function of disease-causing genes.
“Base editors are capable of making single-base changes with high efficiency and unprecedented control,” noted Evans. “Beam has assembled the key technologies in base editing and is dedicated to establishing base editors as a new therapeutic option for patients with serious diseases.”
Beam’s first licensing agreement is with Harvard University for base editing technologies in the field of human therapeutics. This license covers two base editing platforms developed in Liu’s lab in Harvard’s Department of Chemistry and Chemical Biology. “We developed programmable molecular machines that go to a target site of our choosing in the genomic DNA of a cell and directly convert one base to another base without making a double-stranded break in the DNA,” Liu said.
According to a May 14 Harvard University press release, Liu’s base editors directly convert the target base from the mutated form to the corrected form, and in some cases also enlist an additional protein component to prevent the cell from undoing the correction. Meanwhile, the engineered Cas9 nicks the unedited strand of DNA, prompting the cell to mend that second strand with a base that complements the corrected base. The result is a double swap that permanently changes an entire base pair (such as A-T) to a different base pair (such as G-C).
The first platform is the C base editor, originally published in Nature in 2016, which features Cas9 linked to a cytidine deaminase to deliver programmable C-to-T or G-to-A edits in DNA. The second is the A base editor, published in Nature in 2017, which features Cas9 linked to an evolved form of adenosine deaminase capable of editing DNA to deliver programmable A-to-G or T-to-C edits. Liu’s team has also reported on the development of various base editors in Nature Biotechnology in February 2017, Nature Communications in June 2017, Science Advances in August 2017 and Nature in February 2018.
“Over the past year and a half, we’ve greatly expanded the scope of base editing technologies, broadening their targeting scope, improving their target DNA specificity and creating new classes of base editors that could have a substantial impact on the treatment of genetic diseases,” Liu pointed out. “That’s the ultimate goal: in an unmodified organism, whether it’s a human or a plant or an animal, to be able to change a DNA base to another DNA base at will, cleanly and with high efficiency. If we can get there, I think the potential for societal benefit is high.”
Beam has also been able to acquire RNA base editing technologies from Zhang’s lab. This includes the RNA editor platform (REPAIR), first published in Science in 2017, which features Cas13 linked to an adenosine deaminase to deliver single base A-to-G editing of RNA transcripts, in a second agreement with the Broad Institute. Both licenses provide an initial period of exclusivity for human therapeutic use, after which there is a mechanism to extend a license to others on an individual gene target basis, if the technology is not being actively developed for that target.
Thirdly, Beam has entered into a licensing and option agreement with Editas Medicine for exclusive rights to certain intellectual property licensed to Editas Medicine by Harvard, the Broad Institute and MGH, as well as to certain Editas Medicine technologies. Under this agreement, Beam has received an exclusive sublicense to patent filings by Harvard for base editing technologies developed in the Liu lab and patent filings by MGH for CRISPR technology developed in the Joung Lab, as well as an exclusive option for future sublicensing of additional Cas9 patent families and Cpf1 patent families in the field of base editing. In return, Editas Medicine has received an equity stake in Beam and will be eligible for royalties on medicines utilizing the related intellectual property and technologies.
“With this next-generation gene editing technology, world-class team and significant resources, Beam is uniquely positioned to change how we treat and potentially even prevent diseases,” stated Nelsen, managing director and co-founder of ARCH Venture Partners.