Abstract
Precision BioSciences has agreed to develop for Novartis a single custom ARCUS sequence-specific DNA-cutting enzyme, or nuclease, designed to insert in vivo a therapeutic transgene at an undisclosed “safe harbor” location in the genome where a new gene can be added without otherwise affecting the patient's DNA of gene expression patterns. Precision BioSciences has agreed to issue an exclusive license for the custom ARCUS nuclease to Novartis for further development.
“We identify here a collaborative opportunity to imagine a unique therapeutic option for patients with hemoglobinopathies, such as sickle-cell disease and β-thalassemia—a potential one-time treatment administered directly to the patient that would overcome many of the hurdles present today with other therapeutic technologies,” Jay Bradner, president of the Novartis Institutes for Biomedical Research, said in a statement. 1
ARCUS uses nucleases designed to insert (“knock in”) or remove (“knock out”) or repair DNA of living cells. Precision BioSciences can use an ARCUS nuclease to insert or add its payload—typically a healthy version of a gene—at a designated site within the genome to enable healthy gene expression. The healthy copy overcomes the negative effects of the mutated copy.
In the collaboration with Novartis, an ARCUS nuclease will be used to insert a healthy copy of the gene at the safe harbor site, a location in the genome other than where the gene is found—and a location that can be used to insert a healthy copy of the gene replacing the mutated or disease-causing copy, to enable production of the healthy gene product without otherwise affecting the patient's DNA of gene expression patterns.
Novartis is Precision BioSciences' seventh collaboration partner, and the second biopharma giant applying ARCUS to develop treatments; the first is Eli Lilly. “People have started to understand why it is why we believe that ARCUS is the best in vivo gene editing platform in the world,” Amoroso said. 2
GENE THERAPY GROWTH DRIVES PENN's PLANNED PHILADELPHIA EXPANSION
The University of Pennsylvania has selected Longfellow Real Estate Partners to plan and develop a 455,000-square-foot (42,271-square-meter) life sciences facility within Penn's 23-acre Pennovation Works “innovation incubator” campus in Philadelphia.
The facility will consist of 387,000 square feet (35,954 square meters) of R&D space and 68,000 square feet (6,317 square meters) of biomanufacturing space, within two adjoining six-story buildings that are scheduled to open in the fourth quarter of 2025.
The facility will have rooftop terraces with views of Philadelphia's skyline and access to amenities of Pennovation Works, located near Penn's campus within Philadelphia's University City section.
Penn and Longfellow cited growing demand for laboratory space due to increased development of gene therapies and cell therapies within the Greater Philadelphia region, by university spinouts and other companies and institutions.
“As the region continues to be a leader in cell and gene therapy, Longfellow looks forward to delivering the infrastructure the life science industry needs to thrive,” said Jessica Brock, partner real estate operations with Longfellow. 3
Regional employment at gene and cell therapy companies—as well as contract manufacturing organizations, biopharma companies, research organizations, and research hospitals in the gene and cell therapy field—has more than doubled since 2019, rising from ∼4,900 employees to ∼10,500, according to a report issued in June by the chamber of commerce for Greater Philadelphia's CEO Council for Growth and the University City Science Center.
Within cell and gene therapy companies alone, the workforce has jumped 127%, from 939 in 2019 to 2,127 this year. The number of cell and gene therapy companies expanded from 30 to 50 since 2019, the report added. 4
ASTELLAS GENE THERAPIES AND MOGRIFY LAUNCH HEARING LOSS COLLABORATION
The value of the collaboration was not disclosed.
Astellas Gene Therapies agreed to cover the research cost of the work as well as contributing its expertise in adeno-associated virus (AAV)-based genetic medicine and translational capabilities to complete experiments in preclinical models. Mogrify agreed to contribute and exploit its bioinformatic platform, screening, and validation process to characterize potential therapeutic factors.
“We will look to combine the unique delivery attributes of AAV-based gene therapy, with our deep translational capabilities in otology developed through our ‘Targeted Therapeutics for Auditory Regeneration’, and ‘Direct Reprogramming (Transdifferentiation)’ initiatives,” said Mathew Pletcher, PhD, senior VP, Division Head of Gene Therapy Research & Technical Operations at Astellas Gene Therapies. 5
The companies plan to identify novel combinations of transcription factors involved in cell differentiation to generate new cochlear hair cells.
EUROPEAN PANEL RECOMMENDS APPROVAL OF BIOMARIN'S ROCTAVIAN
The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for its gene therapy candidate Roctavian™ (valoctocogene roxaparvovec or “val rox”) for hemophilia A in adults—the first gene therapy to be recommended for approval in Europe for the disorder.
The one-time infusion is indicated as a treatment for severe hemophilia A (congenital factor VIII deficiency) in adult patients without a history of factor VIII inhibitors and without detectable antibodies to AAV5. Roctavian is the first gene therapy to be recommended for approval in Europe for hemophilia A.
The CHMP based its positive opinion on data from the val rox clinical development program, including 2-year outcomes from the global GENEr8-1 Phase III study, supported by 5 years of follow-up from the 6e13 vg/kg dose cohort, and 4 years from the 4e13 vg/kg cohort in an ongoing Phase I/II dose escalation study.
A final approval decision is expected from the European Commission in the third quarter of this year, BioMarin said.
“We are grateful to the patients, investigators and community who have been an integral part in reaching this important milestone that brings us one step closer to delivering on the promise and ingenuity of gene therapy,” said Hank Fuchs, MD, BioMarin's President of Worldwide Research and Development. 6
CARBON BIOSCIENCES, CODE BIOTHERAPEUTICS LAUNCH WITH SERIES A FINANCINGS
Two startups focused on genetic medicines have recently launched with Series A financings.
Carbon is harnessing novel parvovirus vectors that are designed to deliver larger gene therapy payloads with enhanced tissue specificity and with minimal neutralizing immunity. The company says its lead program is the first gene therapy program demonstrating tissue tropism to the lung with the capacity to deliver the full length CFTR gene and an appropriate promotor.
Agent Capital led the Series A financing, joined by Longwood Fund, Astellas Venture Management LLC, the Cystic Fibrosis Foundation, Solasta Ventures, University of Tokyo Innovation Platform, and Camford Capital.
“Carbon's platform has the potential to expand the role of gene therapy in treating some of the world's most devastating and difficult to treat diseases,” said Joel Schneider, PhD, president and CEO of Carbon Biosciences. 7
Also raising Series A capital was Code Biotherapeutics, which launched with a $75 million financing intended to enable the company to advance its two lead programs in Duchenne Muscular Dystrophy and type 1 diabetes (T1D) toward Investigational New Drug-enabling studies, expand its pipeline and platform applications, and expand its manufacturing and operations.
Code Bio's 3DNA® platform is designed to deliver genetic medicines to multiple cell types in a tissuetargeted redosable manner. That enables its use across a broad range of genetic disorders and overcomes key limitations of other delivery approaches, the company said.
Northpond Ventures led Code Bio's financing round, with participation from Amgen Ventures, Hatteras Venture Partners, and UCB Ventures alongside existing investors New Enterprise Associates, 4BIO Capital, CureDuchenne Ventures, the JDRF T1D Fund, UPMC Enterprises, and Takeda Ventures.
“We're energized by the confidence these high-caliber, top-tier investors are demonstrating through their support as we drive our discovery programs forward and strive to rapidly deliver on the promise our proprietary synthetic DNA-based, non-viral genetic medicines delivery platform holds,” said Brian P. McVeigh, Code Bio cofounder, chairman, and CEO. 8