Genetic medicines in development for blood disorders include several therapies made by taking a patient’s cells and editing them outside of the body. Novartis is one of the companies testing this approach, but it also sees advantages in treating these diseases with therapies that work inside the patient. The pharmaceutical giant is turning to the technology of Precision BioSciences to achieve such in vivo edits.

The goal of the partnership announced Tuesday is to develop a curative, one-time treatment for inherited blood disorders of hemoglobin, such as sickle cell disease and beta thalassemia. Precision Bio will use its proprietary technology to develop a custom nuclease, or cutting enzyme, capable of inserting a therapeutic gene at a specific location in the genome.

Durham, North Carolina-based Precision Bio is responsible for developing the nuclease up through lab testing. After that, Novartis assumes responsibility for further research, development, manufacturing, and if approved, commercialization of a therapy using this nuclease.

Novartis has agreed to pay its new partner $75 million up front, as well as an unspecified amount of research funding. The therapy would use Precision Bio’s technology to add an anti-sickling gene to hematopoietic stem cells. This edit is expected to prevent mature red blood cells from taking on the sickle shape characteristic of sickle cell disease. If the work results in a commercialized gene-editing therapy, the biotech could receive up to $1.4 billion in milestone payments, plus royalties from sales. Novartis will receive an exclusive license to the nuclease.

Novartis began exploring gene-editing therapies for sickle cell disease through a partnership with Intellia Therapeutics. The research has led to a therapy made by taking a patient’s hematopoietic stem cells and using CRISPR-editing technology perform an ex vivo edit that induces those cells to produce fetal hemoglobin. The edited cells are then infused back into the patient. This research is currently in early-stage clinical testing.

Precision Bio employs a proprietary editing technology called ARCUS. Derived from algae, the Precision Bio technology employs enzymes that are smaller compared to those used in other editing approaches. The company says this smaller size allows for in vivo delivery to tissues and cells, as well as the capability to perform complex edits such as gene insertion.

Novartis is the second big pharma partner for Precision Bio. In 2020, the biotech began an alliance with Eli Lilly focused on developing in vivo gene-editing therapies that employ ARCUS nucleases. The initial disease targets are Duchenne muscular dystrophy, as well as unspecified liver and central nervous system targets. Lilly paid Precision Bio $100 million up front and could pay up to $420 million more in milestone payments for each licensed product. The biotech also partners with startups. Last year, Precision Bio struck up an alliance with Philadelphia-based iECURE, a University of Pennsylvania spinout that has licensed rights to use ARCUS for four liver indications. Precision Bio received an equity stake in iECURE.

One of the goals of Precision Bio’s alliance with Novartis is to make genetic medicines more widely accessible. In a Wednesday investor presentation, the biotech said that more than 300,000 babies are born with sickle cell disease each year. Of the approximately 1,000 children that are born with sickle cell disease every day in Africa, more than half will not reach their fifth birthday. The only curative therapy for the disorder is a bone marrow transplant. However, even when available this procedure comes with risks and not all patients are eligible.

“If successful, an in vivo therapy for [sickle cell disease] might be administered in regions that do not have transplant centers,” the company said.

Precision Bio’s own in vivo gene-editing research is preclinical. The most advanced program targets the liver to potentially treat familial hypercholesterolemia. The company also uses ARCUS for single-gene edits of allogeneic cancer immunotherapies. The most advanced of its ex vivo-edited therapies, PBCAR0191, is a CAR T-therapy in Phase 1/2a testing for lymphomas. Earlier this month, Precision Bio reported early but encouraging data in a small number of patients with aggressive lymphomas that had relapsed following earlier treatment with CAR T.

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