Precision BioSciences Announces In Vivo Gene Editing Collaboration With Novartis

Precision BioSciences, Inc. recently announced it has entered into an exclusive worldwide in vivo gene editing research and development collaboration and license agreement with Novartis Pharma AG . As part of the Agreement, Precision 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.

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 are excited to collaborate with Novartis to bring together the precision and versatility of ARCUS genome editing with Novartis’ gene therapy expertise and commitment to developing one-time, potentially transformative treatment for hard-to-treat inherited blood disorders,” said Michael Amoroso, Chief Executive Officer 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. 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.”

“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 (NIBR), the Novartis innovation engine. “We look forward to working with Precision and leveraging the ARCUS technology platform, which could bring a differentiated approach to the treatment of patients with hemoglobinopathies.”

“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, Ph.D., 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.”

ARCUS is a proprietary genome editing technology discovered and developed by scientists at Precision BioSciences. It uses sequence-specific DNA-cutting enzymes, or nucleases, that are designed to either insert (knock-in), remove (knock-out), or repair DNA of living cells and organisms. ARCUS 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. Precision’s platform and products are protected by a comprehensive portfolio including nearly 100 patents to date.

Precision can use an ARCUS nuclease to add a healthy copy of a gene (or “payload”) 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.

Sickle cell disease (SCD) 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. The disease can lead to acute episodes of pain known as sickle cell pain crises, or vaso-occlusive crises, as well as life-threatening complications. The condition affects 20 million people worldwide. Approximately 80% of individuals with SCD globally live in sub-Saharan Africa and it is estimated that approximately 1,000 children in Africa are born with SCD every day and more than half will die before they reach five. SCD is also a multisystem disorder and the most common genetic disease in the US, affecting 1 in 500 African Americans. About 1 in 12 African Americans carry the autosomal recessive mutation, and approximately 300,000 infants are born with sickle cell anemia annually. Even with today’s best available care, SCD continues to drive premature deaths and disability as this lifelong illness often takes an extreme emotional, physical, and financial toll on patients and their families.

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. The incidence of symptomatic cases is estimated to be approximately 1 in 100,000 individuals in the general population. The frequency of beta-thalassemia mutations varies by regions of the world with the highest prevalence in the Mediterranean, the Middle-East, and Southeast and Central Asia. Approximately 68,000 children are born with beta-thalassemia.

Precision BioSciences, Inc. is a clinical stage biotechnology company dedicated to improving life (DTIL) with its novel and proprietary ARCUS genome editing platform. ARCUS is a highly precise and versatile genome editing platform that was designed with therapeutic safety, delivery, and control in mind. Using ARCUS, the company’s pipeline consists of multiple ex vivo “off-the-shelf” CAR T immunotherapy clinical candidates and several in vivo gene editing candidates designed to cure genetic and infectious diseases where no adequate treatments exist. For more information, visit www.precisionbiosciences.com.