RARE Daily

Precision BioSciences and Novartis Enter In Vivo Gene Editing Collaboration Targeting Rare Blood Disorders

June 22, 2022

Precision BioSciences entered into an exclusive worldwide in vivo gene editing research and development collaboration and license agreement with Novartis Pharma in which it will develop a custom ARCUS nuclease that will be designed to insert, in vivo, a therapeutic transgene at a “safe harbor” location in the genome as a potential one-time transformative treatment option for diseases including certain hemoglobinopathies such as sickle cell disease and beta thalassemia.

Photo: Michael Amoroso, CEO at Precision BioSciences

“This collaboration will build on the unique gene insertion capabilities of ARCUS and illustrates its utility as a premium genome editing platform for potential in vivo drug development,” said Michael Amoroso, CEO at Precision BioSciences. “With this agreement, Precision, either alone or with world-class partners, will have active in vivo gene editing programs for targeted gene insertion and gene deletions in hematopoietic stem cells, liver, muscle, and the central nervous system showcasing the distinctive versatility of ARCUS.”

Under the terms of the agreement, Precision will develop an ARCUS nuclease and conduct in vitro characterization, with Novartis then assuming responsibility for all subsequent research, development, manufacturing, and commercialization activities. Novartis will receive an exclusive license to the custom ARCUS nuclease developed by Precision for Novartis to further develop as a potential in vivo treatment option for sickle cell disease and beta thalassemia.

Precision will receive an upfront payment of $75 million and is eligible to receive up to an aggregate amount of approximately $1.4 billion in additional payments for future milestones. Precision is also eligible to receive certain research funding and, should Novartis successfully commercialize a therapy from the collaboration, tiered royalties ranging from the mid-single digits to low-double digits on product sales.

“We identify here a collaborative opportunity to imagine a unique therapeutic option for patients with hemoglobinopathies, such as sickle cell disease and beta thalassemia—a potential one-time treatment administered directly to the patient that would overcome many of the hurdles present today with other therapeutic technologies,” said Jay Bradner, president of the Novartis Institutes for Biomedical Research.

Sickle cell disease is a complex genetic disorder that affects the structure and function of hemoglobin, reduces the ability of red blood cells to transport oxygen efficiently and, early on, progresses to a chronic vascular disease that can lead to acute episodes of pain known as sickle cell pain crises, or vaso-occlusive crises, as well as life-threatening complications.

Beta thalassemia is also an inherited blood disorder characterized by reduced levels of functional hemoglobin. The condition has three main forms – minor, intermedia and major, which indicate the severity of the disease. While the symptoms and severity of beta thalassemia varies greatly from one person to another, a beta thalassemia major diagnosis is usually made during the first two years of life and individuals require regular blood transfusions and lifelong medical care to survive. Though the disorder is relatively rare in the United States, it is one of the most common autosomal recessive disorders in the world.

Precision’s proprietary genome editing technology ARCUS uses sequence-specific DNA-cutting enzymes, or nucleases, which are designed to either insert (knock-in), remove (knock-out), or repair DNA of living cells and organisms. It is based on a naturally occurring genome editing enzyme, I-CreI, that evolved in the algae Chlamydomonas reinhardtii to make highly specific cuts in cellular DNA. The company can use an ARCUS nuclease to add a healthy copy of a gene to a person’s genome. The healthy copy of the gene can be inserted at its usual site within the genome, replacing the mutated, disease-causing copy. Alternatively, an ARCUS nuclease can be used to insert a healthy copy of the gene at another site within the genome called a “safe harbor” that enables production of the healthy gene product without otherwise affecting the patient’s DNA of gene expression patterns.

“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, chief scientific officer and co-founder of Precision BioSciences. “Perhaps most importantly, it could open the door to treating patients in geographies where stem cell transplant is not a realistic option. We believe that the unique characteristics of the ARCUS platform, particularly its ability to target gene insertion with high efficiency, make it the ideal choice for this project, and we look forward to working with our partners at Novartis to bring this novel therapy to patients.”

Upon completion of the transaction, Precision expects that existing cash and cash equivalents, expected operational receipts, and available credit will be sufficient to fund its operating expenses and capital expenditure requirements into the second quarter of 2024.

Author: Rare Daily Staff

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