The next hurdles for gene-editing medicines are therapies that do their work inside the patient. But so far, biotechs have had a hard time developing such in vivo therapies that target anything other than the liver. Beam Therapeutics has acquired a startup whose technology could deliver the biotech’s genetic medicines to more tissues in the body, broadening the potential to address more diseases.

Beam said Tuesday that it paid $120 million up front to acquire Guide Therapeutics in an all-stock deal.

The gene-editing technologies that have reached the clinic—CRISPR, zinc finger nucleases, and TALENs—make their edits by snipping DNA at the target site. Cambridge, Massachusetts-based Beam aims to make more precise edits with genetic medicines that employ base-editing. Instead of snipping the genome, base editing allows for edits of individual letters in a genetic sequence.

Beam employs three approaches to deliver its genetic medicines to cells. Electroporation, a technique that involves running an electric current to make the cell membrane more permeable, is used for ex vivo delivery of therapies to blood and immune cells. The company’s in vivo therapies reach the eye and central nervous system via adeno-associated viruses, while its liver therapies employ lipid nanoparticles (LNPs).

GuideTx will help Beam develop LNP-based medicines. The startup spun out of Georgia Tech in 2018 and is based on the research of James Dahlman, a professor in the university’s department of biomedical engineering and school of medicine. The GuideTx technology screens for lipid nanoparticles inside the body that can be used to deliver RNA to cells throughout the body. On its website, GuideTx says the Dahlman lab’s research demonstrated that in vivo screening for nanoparticles is better than in vitro, or lab screening, because lab screens are not predictive of the delivery of a genomic medicine inside the body.

GuideTx finds LNPs by employing “DNA barcodes,” which are molecular tags for specific nanoparticles. The company says this approach enables the company to screen hundreds of nanoparticles simultaneously, speeding up the generation of in vivo drug delivery data. In its announcement of the deal, Beam said it believes that the GuideTx capability to sequence in vivo drug delivery data in a broad range of tissue types will enable the company to identify the LNPs best suited to deliver its genomic medicines to targets other than the liver. The Beam pipeline so far includes three LNP-delivered medicines, all of them for rare liver diseases.

Both Beam and GuideTx emphasize that the Georgia company is focused on nonviral drug delivery of genetic medicines. AAV-delivered therapies can trigger a dangerous immune response. Lentiviral vectors offer an alternative, but these viruses pose a cancer risk. For example, though bluebird bio engineered its lentiviral vector to avoid the cancer risk, the Cambridge-based biotech last week suspended clinical trials of its sickle cell disease gene therapy after two patients in the studies were diagnosed with cancer. The company’s inquiry into the cancer cases is expected to take several weeks.

Preclinical Beam is still a young company. It emerged from stealth in 2018, unveiling a base-editing approach backed by $87 million in financing. The biotech went public a little more than a year ago, raising $180 million. It priced the stock offering at $17 per share. On Monday, the last trading day before the GuideTx acquisition was announced, Beam’s stock price closed at $110.41 per share.

Beam’s shares rose sharply in December during the annual meeting of the American Society of Hematology, where the biotech reported preclinical and laboratory data showing its technology made precise base edits in the gene that causes sickle cell disease. Furthermore, no off-target edits were observed. The company said the data would support its plans to seek FDA permission to begin clinical testing of its sickle-cell therapy, BASE-101, in the second half of 2021.

Late last month, Beam announced it had raised $260 million from a syndicate of institutional investors. The company said at the time that the cash would fund clinical trials and strategic partnerships. But Beam opted not to finance its GuideTx deal with cash. Instead, the company took advantage of its soaring stock price, which gives the biotech a market capitalization of nearly $6 billion, and structured an all-stock acquisition.

If Beam achieves certain goals with therapies developed from the GuideTx technology, the Georgia company’s shareholders could earn up to $320 million more—$100 million for technology milestones and $220 million pegged to product success milestones. Like the upfront payment, those milestones will also be paid in Beam stock.

Image: Getty Images, 4X-image



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