Abstract
The first patient was dosed at Oregon Health and Science University Casey Eye Institute, the home institution of the trial's principal investigator Mark Pennesi, MD, PhD, an Associate Professor of Ophthalmology, Kenneth C. Swan, Endowed Professor, and Division Chief, Paul H. Casey, Ophthalmic Genetics Institute.
AGN-151587 is being evaluated as a potential treatment for LCA10 caused by a homozygous or compound heterozygous mutation involving c.2991 + 1655A>G in intron 26 of the CEP290 gene (LCA10-IVS26).
Up to five cohorts of patients across three dose levels will be enrolled in the open-label, multicenter clinical trial. Both adults and children aged 3–17 with a range of baseline visual acuity assessments are eligible for enrollment. Patients will receive a single administration of AGN-151587 directly to photoreceptor cells via subretinal injection in one eye. The trial's estimated primary completion date is March 22, 2024.
“This dosing is a truly historic event—for science, for medicine, and most importantly for people living with this eye disease,” stated Cynthia Collins, President and CEO, Editas Medicine. 1,2
$2.7B Gene Regulation Collaboration
The collaboration includes ST-501 for tauopathies including Alzheimer's disease and ST-502 for synucleinopathies including Parkinson's disease, a third treatment targeting an undisclosed neuromuscular disease target, and additional treatments for up to nine additional undisclosed neurological disease targets over a selection period of 5 years.
Biogen and Sangamo agreed to apply Sangamo's proprietary zinc finger protein technology, which is delivered via adeno-associated virus (AAV) and designed to modulate the expression of key genes involved in neurological diseases by functioning at the DNA level to repress or activate the expression of specific genes selectively in order to achieve a desired therapeutic effect.
According to the companies, highly specific, potent, and tunable repression of tau and alpha synuclein has been shown in preclinical studies using AAV vectors to deliver tau-targeted (ST-501) and alpha synuclein-targeted (ST-502) zinc finger protein transcription factors.
Biogen agreed to pay Sangamo $350 million, consisting of a $125 million “license fee” and $225 million from the sale of approximately 24 million shares of new Sangamo stock at $9.21 per share. Sangamo could also receive from Biogen up to $2.37 billion tied to achieving development, regulatory, and commercial milestones, including up to $925 million in pre-approval milestone payments and up to $1,445 million in first commercial sale and other sales-based milestone payments.
Sangamo will also be eligible to receive tiered high single-digit to sub-teen double-digit royalties from Biogen on potential net commercial sales of products developed through the collaboration. 3
Amicus' R&D Ribbon Cutting
The 75,000 ft 2 Center is located on the top three floors of the new building at 3675 Market Street. The Center will ultimately house approximately 200 researchers and drug developers focused exclusively on gene therapies, Amicus said.
Amicus marked the Center's opening with a ribbon-cutting ceremony attended by guests that included James M. Wilson, MD, PhD, Director of Penn's Gene Therapy Program, company executives, government officials, and patients and their families who are living with rare diseases.
In 2019, Amicus and the University of Pennsylvania launched a major expansion of a gene therapy collaboration launched the previous year. The partners expanded their rare genetic disease programs from three to six, adding programs in Pompe disease, Fabry disease, CDKL5 deficiency disorder, Niemann–Pick type C, mucopolysaccharidosis type IIIB, as well as a next-generation program in mucopolysaccharidosis type IIIA, both also known as part of Sanfillipo syndrome.
Amicus also obtained exclusive rights to collaborate with Dr. Wilson on developing new gene therapy platform technologies and programs for most lysosomal disorders and 12 additional rare diseases, including Rett syndrome, Angelman syndrome, myotonic dystrophy, and select other muscular dystrophies.
“With exclusive global rights to 50 rare diseases in collaboration with Dr. Wilson's team, we hope to be able to alleviate an enormous amount of human suffering with the great science work that will be done in this new facility,” Amicus Chairman and CEO John F. Crowley said. 4
Rocket-Fueled Collaboration with Forty Seven
Under their collaboration, whose value was not disclosed, the companies will initially evaluate their treatment regimen in Fanconi anemia. RP-L102 involves treatment with patients' own gene-corrected hematopoietic stem cells, while Forty Seven's all-antibody based conditioning regimen is designed to address limitations of current pretreatment conditioning therapies linked to serious side effects, including severe infection, cognitive impairment, infertility, endocrine dysfunction, secondary malignancies, and organ damage.
Preliminary data have shown that RP-L102 may confer efficacy without pretreatment conditioning, while the combination of RP-L102 with Forty Seven's all-antibody conditioning regimen may provide patients an alternate treatment option in situations where conditioning may be advantageous, the companies said. A first-in-human healthy volunteer study of FSI-174 is set to be launched in the first quarter, Forty Seven said. 5
Fujifilm Diosynth's Texas Expansion
The expansion will include the addition of cell culture and high throughput manufacturing suites. The expanded facility will house multiple 500 L and 2,000 L bioreactors to support the production of gene therapy products that have high production demands. The expansion is part of a previously announced capital investment of approximately ¥13 billion (approximately $120 million) in gene therapy by FDB parent FUJIFILM Corp.
FDB said it expects to complete its expansion of the Flexible Biomanufacturing Facility by the fall of 2020. The Facility is designed to complement the development and early phase manufacturing capabilities provided by the company from its National Centre for Therapeutic Manufacture, also located in College Station.
FDB announced the expansion a week before disclosing the retirement of CEO Steve Bagshaw effective April 1, 2020. He is being succeeded by Martin Meeson, FDB's President and COO.
“These investments are part of FUJIFILM Corporation's long term strategy to provide leading, future proofed end-to-end gene therapy solutions, from pre-clinical to commercial launch,” Meeson said. 6,7
Gene Therapy “One-Stop Shop”
Two years after GlaxoSmithKline consolidated global R&D operations in part by selling its Upper Merion West R&D campus in suburban Philadelphia,
Earlier this year, The Discovery Labs partnered with health-care investment management firm
Work has begun toward constructing of a total 86 suites for plasmid manufacturing, viral vector production, universal cell processing, current Good Manufacturing Practice testing, process development, and cell banking, as well as on reserving capacity for the new facilities now for use starting later this year.
The Center has signed a long-term lease for 40% of the space (680,000 ft 2 ) at The Discovery Labs King of Prussia. The 280-acre, 1.6 million ft 2 campus combines the 1 million ft 2 former GSK campus in Upper Merion Township, Pennsylvania, with the adjacent Innovation Renaissance campus. 8