Interview – Beam heralds new Crispr edit, but patent issues remain

Beam Therapeutics is developing a new method of Crispr genome editing, but it could get caught up in the same old patent problems.

This week's emergence of a new preclinical Crispr company, Beam Therapeutics, must have had deal bankers rubbing their hands with glee. But will patent lawyers acting in this notoriously litigious field be equally pleased at the prospect of gaining a new client?

Beam’s chief executive, John Evans, believes not, telling EP Vantage that the company has cornered the intellectual property for base editing, its flagship technology. But targeting the relevant part of the genome will still require Crispr enzymes, including the infamous Cas9 – which could eventually give Beam a headache.

Mr Evans concedes that Beam is keeping a close eye on the Cas9 patent dispute between the Broad Institute and the University of California, Berkeley. 

Beam me up

For now, Mr Evans does not seem too concerned about patent issues, and is instead celebrating an $87m series A round that should fund Beam for several years – exactly how long depends on how many projects the company develops.

If the group does manage to take its projects to market itself, as the chief exec hopes, it will presumably need a lot more cash, and going public, while off the table for now, could be an option in the future, Mr Evans says.

Raising money does not currently seem to be a problem for Crispr companies, and some might say that the field is overhyped. While Mr Evans agrees that excitement around Crispr is high, he is adamant that Beam has a differentiated technology that could set it apart from the pack.

Mr Evans describes Beam’s base-editing technique as like a pencil, whereas conventional Crispr – or nuclease editing – and other technologies like zinc fingers and Talens are like scissors.

The other methods involve cutting out sections of the genome, which is “not tremendously efficient”, according to the chief exec, and might account for off-target effects that have – controversially – been linked with Crispr.

Meanwhile, Beam says it is able to change chemically a single base in a sequence that makes up DNA or RNA while leaving the remaining genome intact.

The main use for this would be in diseases caused by a single base change, or point mutation. Over half the genetic errors linked with disease are caused by such mutations, according to Beam.

Beam's Crispr licences
Licensor Target Name Crispr enzyme Edit
Harvard University DNA C base editor Cas9 C to T/G to A (on corresponding DNA strands)
Harvard University DNA A base editor Cas9 A to G/T to C (on corresponding DNA strands)
Broad Institute RNA Repair Cas13 A to G
Source: Company release.

Mr Evans adds that base editing could also be used to counteract harmful mutations, or perhaps even in disease prevention. He is not saying what diseases Beam will go after, but disorders involving point mutations include cystic fibrosis and sickle cell anaemia.

The chief exec is also keeping quiet about when the company might take its first projects into human trials, but says that Beam aims to have a “very broad pipeline”. He adds that everything is on the table, including ex vivo approaches – which might include CAR-T therapy – and in vivo approaches through lipid nanoparticle and viral vector delivery.

“We’re already actively working on 10-15 programmes in the research stage,” Mr Evans says.

Cas9 conundrum

While Beam’s editing method is different from that used by other Crispr techniques, the way it homes in on a specific area of the genome is the same. This could set up a legal headache in the future – particularly as Beam’s main DNA-targeting technology, licensed from Harvard University and the Broad Institute, involves Cas9, the enzyme at the centre of the dispute over who invented Crispr.

If Cas9 proves to be a problem Beam is hedging its bets with an exclusive option on an alternative Crispr enzyme, Cpf1, from the public Crispr group Editas Medicine, which now has an undisclosed stake in Beam. The intellectual property for this enzyme is not contentious, according to Mr Evans.

Beam also has an RNA base-editing technology, licensed from the Broad Institute, that uses a different Crispr enzyme, Cas13, which he says is similarly free of IP issues. RNA editing could be useful if reversible or transient genome editing is needed – one example of the latter could be spurring bone formation.

The edits made by Beam’s DNA-targeting technology can address around two thirds of the known point mutations, Mr Evans says, while around half are addressable by the A to G edit carried out by the RNA editor. Beam is working on novel editors to address the remaining mutations, he adds.

IP questions aside, the chief exec is confident that Beam can co-exist with the other Crispr companies. As proof he points to the fact that Editas – which shares co-founders with Beam – chose not to develop base editing itself. “They view this as a very different platform technology and it needed its own focus and depth of research.”

As for the remaining Crispr players, Mr Evans says: “I wouldn’t say we’re competing with them – in a way we feel like we’re all part of a large team.” Judging by the history of Crispr in the courts, others might not agree.

To contact the writer of this story email Madeleine Armstrong in London at [email protected] or follow @ByMadeleineA on Twitter

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