Precision Bio climbs on near-$1.5bn sickle cell pact with Novartis

Novartis has shouldered its way into the in vivo gene editing category via a deal with US biotech Precision BioSciences, focused on a therapy for sickle cell disease (SCD).

The Swiss pharma group is paying $75 million upfronting cash and equity to get the ball rolling on the collaboration, with another $1.4 billion in potential milestones if the project advances through development and onto the market.

The deal comes a year after Intellia and partner Regeneron reported promising results from the first clinical trial of a drug used to edit the genomes of cells within the body, in patients with rare disease ATTR amyloidosis.

Previously, all therapeutic applications of gene-editing techniques like CRISPR/Cas9 and zinc finger nucleases have involved the modification of cells outside the body – ex vivo – which are then reinfused into the patient.

That can be a lengthy, expensive and hazardous process, as it generally involves a stem cell transplant that carries a significant risk of serious complications, mainly from the preconditioning treatment used to wipe out the bone marrow and prepare it for the new cells.

Systemic administration of gene-editing drugs would avoid that process with an "off-the-shelf" option for a one-shot, potentially curative treatment for diseases associated with genetic mutations.

It is a challenging proposition, however, as delivery of the therapeutic gene sequences to cells can be difficult and raises the risk of insertion mutations that can lead to side effects, including cancer.

Precision Bio aims to address those challenges using its proprietary ARCUS nuclease platform, which is designed to insert a transgene with high accuracy into the genome.

The technology aims to introduce the sequence into a "safe harbour" region – in other words, part of the genome that is unlikely to disrupt other molecular pathways.

The biotech will develop an ARCUS nuclease for Novartis that will be used to target the gene sequence that codes for the mutated haemoglobin in SCD as well as beta thalassaemia.

Other companies – notably Vertex Pharma/CRISPR Therapeutics and bluebird bio – are taking an ex vivo approach to SCD and thalassaemia and are much closer to market.

Precision Bio will take the ARCUS candidate through early-stage discovery, with Novartis taking over for the research, development, manufacturing and commercial stages.

It is also working with Eli Lilly on in vivo gene-editing drugs against three targets, including one in Duchenne muscular dystrophy, under the terms of a $1.4 billion agreement that started in 2020.

"The in vivo gene editing approach that we are pursuing for sickle cell disease could have a number of significant advantages over other ex vivo gene therapies currently in development," said Derek Jantz, the company's chief scientific officer and co-founder.

"Perhaps most importantly, it could open the door to treating patients in geographies where stem cell transplant is not a realistic option," he added.

The deal will bolster Precision Bio's cash reserves, allowing it to continue operations into the second quarter of 2024 without raising further financing.

Nonetheless, the biotech has just announced a $50 million offering of common stock, the proceeds of which will be used to fund its in-house R&D, including trials of its ex vivo CAR-Ts PBCAR0191 and PBCAR19B, in trials for B-cell malignancies, and PBCAR269A for multiple myeloma.