Abstract
BGTC said it will develop a standard set of analytic tests to apply to the manufacture of viral vectors made by consortium researchers. A clinical component of BGTC-funded research will support between four and six clinical trials, each focused on a different rare disease. The trials will employ different types of adeno-associated virus vectors that have been used before in clinical trials. For these trials, the BGTC will aim to shorten the path from studies in animal models of disease to human clinical trials.
BGTC also plans to explore methods to streamline regulatory requirements and processes for the FDA approval of safe and effective gene therapies, including developing standardized approaches to pre-clinical testing.
NIH and private partners will contribute ∼$76 million for 5 years to support BGTC-funded projects—including ∼$39.5 million from participating NIH institutes and centers, pending availability of funds.
“There are now significant opportunities to improve the complex development process for gene therapies that would accelerate scientific progress and, most importantly, provide benefit to patients by increasing the number of effective gene therapies,” said NIH Director Francis S. Collins, MD, PhD. 1
Private partners include Biogen, Janssen Research & Development, Novartis Institutes for BioMedical Research, Pfizer, REGENXBIO, Spark Therapeutics, Takeda Pharmaceutical, Taysha Gene Therapies, Thermo Fisher Scientific, and Ultragenyx Pharmaceutical. Several nonprofit partners are also involved in BGTC, including the Alliance for Regenerative Medicine, the American Society of Gene and Cell Therapy, CureDuchenne, National Organization for Rare Disorders, and The National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL).
AETNA NETWORK TO COVER THREE GENE THERAPIES
Beginning January 1, 2022, GCIT will cover Spark Therapeutics' Luxturna (voretigene neparvovec-rzyl), Biogen's Spinraza (nusinersen), and Novartis' Zolgensma® (onasemnogene abeparvovec-xioi) for the treatment of inherited retinal disease and spinal muscular atrophy. The GCIT network is included as a standard medical benefit in all Aetna fully insured plans and is also available to self-insured plans.
Aetna's national GCIT network includes access to >75 designated GCIT service providers that according to the insurer have demonstrated quality and value in the delivery of GCIT services. Providers in the GCIT network must meet manufacturer-specific guidelines and Aetna cost and credentialing standards.
“We're creating a differentiated provider network that our customers can experience as being caring, connected and convenient,” said Richard Gentleman, Executive Director, National Partner Strategy for Aetna. “Our multi-pronged approach encompasses safety, member access to cutting-edge therapies, and cost management to support the medical and economic needs of our members and customers. It also paves the way for future FDA-approved gene therapies to be added quickly and cost-effectively so that we can help more people achieve their best health.” 2
VERTEX, MAMMOTH PARTNER ON CRISPR GENE EDITING
The companies are not disclosing which diseases they will target.
“We are focused on developing in vivo gene-editing therapies in two indications for specific serious and/or life-threatening diseases with the Vertex team,” said Peter Nell, Mammoth's Chief Business Officer and Head of Therapeutics Strategy. 3
Mammoth and Vertex did say, however, that they will apply Mammoth's CRISPR platform consisting of a proprietary toolbox of novel Cas enzymes—what the company calls the largest toolbox of CRISPR proteins on earth.
These include Cas12, which targets double-stranded DNA; Cas13, which targets and recognizes single-stranded RNA; Cas14, which targets single-stranded DNA; and Casɸ, which is encoded exclusively in the genomes of huge bacteriophages.
Mammoth has exclusively licensed foundational IP around novel CRISPR Cas12, Cas13, Cas14, and Casɸ systems from the University of California, Berkeley, where they were discovered in the laboratory of Nobel laureate and Berkeley-based researcher Jennifer Doudna, PhD.
Doudna is a cofounder of Mammoth Biosciences along with CEO Trevor Martin, PhD; Janice Chen, PhD, the company's CTO; Lucas Harrington, Mammoth's CSO; and Ashley Tehranchi, PhD, who served as CTO until May 2019.
Cas14 and Casɸ are the smallest known CRISPR systems. Their sizes—530 amino acids for Cas14a and 757 amino acids for Casɸ-2—are less than half those of commonly used variants of Cas9 (1368 amino acids for SpCas9) and Cas12 (1,300 amino acids for FnCas12), offering numerous potential advantages for the therapies Mammoth plans to develop, Martin said in September.
CATALENT PLANS $230M EXPANSION OF HARMANS, MD GENE THERAPY CAMPUS
The Harmans campus, located near Baltimore Washington International Airport, includes a fully operational FDA- and European Medicines Agency-approved facility consisting of 10 commercial-scale manufacturing suites.
After an initial $130 million investment in 2020, Catalent is constructing a facility with five new manufacturing suites that are expected to be operational mid-2022. The additional facility will include the construction of three additional multiroom commercial suites, as well as expanding the site's storage capabilities for just-in-time inventory space, ultralow temperature freezers, and its water-for-injection infrastructure.
When completed at the end of 2022, the campus will house a total of 18 commercial good manufacturing practice viral vector manufacturing suites, each designed to accommodate multiple bioreactors up to 2,000-L scale and enable the execution of commercial manufacturing from cell bank to purified drug substance.
Other facilities, including multistory parking and an onsite cafeteria, are planned for the campus to support the significant anticipated growth in number of employees. The expansion will see the creation of >700 new technical, scientific, and operational employment positions over the next 6 years.
“By applying the expertise we have gained from the last three years of operating our flagship gene therapy commercial facility, we are able to continue to expand our campus with a design layout that is innovative, efficient, and provides ultimate flexibility for our customers,” said Manja Boerman, PhD, President, Catalent Cell & Gene Therapy. 4
ARBOR BIOTECHNOLOGIES RAISES $215M SERIES B FINANCING
A developer of gene-edited precision therapies cofounded by CRISPR pioneer Feng Zhang, PhD, has more than doubled its total capitalization after completing a $215 million Series B financing.
Arbor also plans to use part of the financing proceeds to further develop its gene-editing technology platform, which applies a toolbox of CRISPR-based genomic editors as well as diverse technologies that include artificial intelligence, genome sequencing, gene synthesis, and high-throughput screening, the aim of which is identifying impactful peptides, proteins, and enzymes.
“By leveraging our proprietary discovery engine—which applies machine learning and AI to mine our protein database containing billions of proteins—we have successfully built the most extensive toolbox of wholly owned CRISPR genomic editors in the industry,” Arbor CEO Devyn Smith, PhD, said. “While our primary focus has been on developing our bespoke CRISPR nucleases, we are also looking to progress our other precision editing innovations, such as CRISPR transposases.” 5
JAGUAR GENE THERAPY TO BUILD COMMERCIAL MANUFACTURING SITE
The 174,000-square-foot (16,165-square-meter) facility—located ∼20 miles (∼32 kilometers) northwest of Jaguar's existing Process Sciences Laboratory in Cary, NC—is designed to support future clinical and commercial production of the company's initial programs, including treatments for galactosemia, type 1 diabetes, and a specific genetic cause of autism.
Jaguar's new manufacturing facility is owned and operated by Alexandria Real Estate Equities.
“This strategic investment will leverage the team's proven CMC (Chemistry, Manufacturing and Controls) expertise and may enable Jaguar to potentially accelerate development timelines and bring our therapies to patients and families as safely and as rapidly as possible,” said Jaguar CEO Joe Nolan. 6
Jaguar said it will continue existing contract development manufacturing organization partnerships and consider adding to their third-party network as needed to ensure dual sourcing and uninterrupted supply.
Jaguar will receive >$7 million in state and local economic development incentives toward the new facility, including a Job Development Investment Grant of >$2 million for 12 years. The state-funded North Carolina Biotechnology Center will provide a $100,000 partnership development grant, awarded for 3 years based on job creation. Jaguar will also receive ∼$5 million in incentives from additional state and local organizations.
SANOFI INVESTS UP TO $60M IN GYROSCOPE THERAPEUTICS
Sanofi agreed to invest $40 million in Gyroscope initially, at a premium to Gyroscope's prior Series C financing, as well as $20 million to be invested based on a future qualifying investment round and subject to the satisfaction of certain closing conditions.
“We are thrilled to welcome Sanofi onboard as an investor in Gyroscope. Their investment is a testament to the promise of our science and gene therapy programmes to make a difference for people with serious eye diseases,” Gyroscope CEO Khurem Farooq said. 7
Gyroscope's pipeline is led by GT005, which is being developed as the first gene therapy for geographic atrophy (GA). On September 30 during the Retina Society's 54th Annual Scientific Meeting, Gyroscope reported positive Phase I/II biomarker data from 13 patients in its ongoing Phase I/II FOCUS clinical trial (NCT03846193), showing sustained increases in vitreous complement factor I (CFI) levels compared with baseline in the majority of patients, as well as sustained decreases in downstream proteins associated with complement system activation.
Gyroscope said it plans to use proceeds from the Sanofi investment to support funding of ongoing clinical trials of GT005 in GA. GT005 has been granted fast track designation by the FDA and is being evaluated in Phase II clinical trials.