Last summer, Mikael Dolsten, head of research and development at Pfizer and the company's top scientist, was thinking of new uses for the messenger RNA technology the pharmaceutical giant had developed so effectively for its coronavirus vaccine.
The drugmaker already envisioned messenger RNA, or mRNA as it's commonly known, as a foundation for improved vaccines for influenza and other infectious diseases, but saw broader potential. At the top of Pfizer's list was base editing, a more precise form of gene editing that can be carried out inside the body using mRNA as an intermediary.
On Monday, Pfizer took a major step toward that vision, announcing a four-year research partnership with Beam Therapeutics, a high-profile biotech company that specializes in base editing and the mRNA components used to deliver such treatments into the body.
Pfizer will pay Beam $300 million upfront. In return, Beam will conduct research on three undisclosed base editing targets in the liver, muscle and central nervous system. Should that research produce a drug candidate, Pfizer will have an option to pick up global rights, after which it would lead clinical development. All told, Beam could receive as much as $1 billion more in conditional payments across the three programs.
"We saw a lot of synergy working with them on these kinds of products," said John Evans, Beam's CEO, in an interview. "It's all stuff that we aren't doing currently, so it expands the playing field for us and I think these targets would be great in Pfizer's hands."
Early outreach to Beam came from Dolsten and from there, Evans said, the deal came together very quickly, with discussions taking place over video conferences between the Pfizer and Beam teams.
The deal's announcement Monday coincides with the first day of the J.P. Morgan Healthcare conference, typically a forum for major licensing or acquisition agreements in the biotech and pharma industries. The meeting is being held virtually due to COVID-19.
Beam was formed five years ago around research from the laboratory of Harvard University's David Liu that showed a way to edit genes more precisely. Unlike the first generation of CRISPR-based gene editing, which cuts both strands of DNA, base editing is designed to change a single DNA "letter" into another without that double-stranded break.
Its potential, like CRISPR's, is vast. The technology could be used to correct disease-causing mutations, to silence genes or activate them, and in theory carries lower risk of causing unwanted genetic changes. Beam, which recently began the first clinical trial involving base editing, plans to develop treatments for blood diseases like sickle cell and beta thalassemia as well as for rare diseases of the liver and eye.
One of the steepest challenges facing Beam, along with other gene editing developers, is developing reliable ways to get the nucleic acid and proteins that make up its editors into cells. For editing inside the body, Beam encodes the editing machinery in mRNA, which is then wrapped inside a fatty shell known as a lipid nanoparticle.
Those two components — an mRNA sequence and a lipid nanoparticle — are the core of mRNA vaccines like the one developed by Pfizer and its partner BioNTech for COVID-19.
"I think Pfizer was looking at the capabilities they had built in lipid nanoparticles and mRNA and saying, 'Well, what are we going to do with these capabilities now that we've built them?'" said Evans.
Beam is well positioned to explore how lipid nanoparticles could be engineered to reach tissues, such as the muscle and the central nervous system, that are harder to reach than the liver, where infused medicines often end up. An acquisition last February, for example, gave Beam access to technology that can tag lipid nanoparticles with a DNA "barcode," enabling researchers to determine which formulation reaches a target tissue most effectively.
"That gives you a lead," said Giuseppe Ciaramella, Beam's chief scientific officer. "You still have to confirm what you've done, but it's given you a head start very rapidly to [determine] exactly what are the features that are meaningful."
The Beam partnership is Pfizer's most substantive foray into gene editing. Until now, the pharma company has invested more heavily in gene replacement therapy, and now has two treatments for hemophilia and Duchenne muscular dystrophy in late-stage clinical trials.
And by choosing Beam, Pfizer is skipping over first-generation CRISPR editing in favor of base editing, as well as focusing on inside-the-body treatment rather than on therapies made up of cells modified in the lab. Clinical development of the latter type of therapy, such as one from CRISPR Therapeutics and Vertex, is more advanced, but they are logistically more complex and come with other risks.
For Beam, meanwhile, the deal will swell its cash holdings to about $1.2 billion and, according to Evans, allow the company to accelerate investment in its research.
Beam also retains an option, for a fee, to co-develop and co-commercialize any one of the three programs developed with Pfizer, following early studies. The companies would then share costs and any profits, with 35% going to Beam and 65% to Pfizer.