Abstract
CapsidMap—a delivery platform developed in Church's laboratory at Harvard Medical School—uses artificial intelligence (AI) to design novel capsids that confer improved functional properties to AAV vectors. At the core of CapsidMap, according to Dyno, are advanced search algorithms applying machine learning and the company's large quantities of experimental data.
“Dyno's CapsidMap platform is powered by machine learning models trained on our own experimental data, meaning it has the potential to produce optimized AAV capsids for any target tissue or cell type,” Eric Kelsic, PhD, Dyno Therapeutics CEO and cofounder, told GEN. “The Dyno capsids from this collaboration will be designed for improved skeletal muscle and heart targeting relative to existing AAV vectors, along with de-targeting of other organs.” 1
Kelsic added that the collaboration's focus on skeletal and cardiac muscle was driven primarily by the Astellas strategic focus and existing expertise.
Muscle disease and gene therapy are two of Astellas' 10 areas of therapeutic interest. The other eight are oncology, urology, nephrology, immunology, neuroscience, muscle diseases, ophthalmology, and vaccines. Astellas is also interested in digital health and other health care businesses it calls “Rx+®.”
The research collaboration is designed to combine Dyno's artificial intelligence-based AAV vector engineering capabilities with Astellas' global presence in AAV-based gene therapy.
“Through our efforts in gene therapy and the Astellas Gene Therapies Center of Excellence, Astellas strives to identify, develop, and deliver transformative gene-based therapies for patients with genetic diseases who currently have few or no effective treatment options. Our principal focus is on developing adeno-associated virus delivered therapies for the treatment of well-defined serious diseases,” said Naoki Okamura, chief strategy officer and chief financial officer, chief business officer at Astellas. 2
Fujifilm Diosynth to Expand U.K. Biomanufacturing Facility
The new multimodal campus will include a viral gene therapy good manufacturing practice (GMP) facility, as well as a GMP mammalian cell culture facility. The facilities are part of a ¥90 billion ($780 million) global capital investment package initially outlined by FUJIFILM Diosynth Biotechnologies' parent company FUJIFILM Corp. in June 2021.
FUJIFILM Diosynth Biotechnologies said its new campus will allow it to expand the viral vector and gene therapy services it offers from the United Kingdom with dedicated process development capabilities and a commercial-scale viral gene therapy GMP facility, both located on the Billingham campus. The expansion is designed to deliver a 10-fold increase in U.K. gene therapy production capabilities, cement its leadership in the viral vector market, and complement its existing global footprint, which includes sites in College Station, TX, and Watertown, MA, both in the United States.
The new cell culture facility will triple existing cell culture capacity capabilities at Billingham with the addition of four 2,000 L and two 500 L single use bioreactor production capabilities for the manufacture of both monoclonal and novel antibody treatments. The investment will also facilitate the expansion of existing capabilities in vaccine manufacturing, along with new capabilities that include mRNA production.
“With a strong growing demand for microbial, cell culture and viral gene therapy services, we are adding the capacity and latest technologies within one campus to offer a range of modalities to build an offering that will deliver novel promising treatments to patients for years to come,” FUJIFILM Diosynth Biotechnologies CEO Martin Meeson said. 3
Aviadobio Emerges from Stealth with $80M Series a Financing
New Enterprise Associates and Monograph Capital led the financing, which attracted participating investors that included LSP, seed investors Advent Life Sciences, the United Kingdom's Dementia Discovery Fund, F-Prime Capital, Johnson & Johnson Innovation–JJDC, and medical research charity LifeArc.
Based in London, AviadoBio was launched with $16.5 million in seed financing in 2019. The company's technology was developed in the laboratory of Christopher Shaw, a professor at Kings College London. Shaw and colleagues have developed a gene therapy platform designed to produce AAV vector therapies that are engineered to target neurological disorders such as FTD and ALS, neither of which now have viable therapies available.
“Whilst neurodegenerative conditions are focal at onset, the pathology eventually spreads throughout the nervous system. We have seen that modifying gene expression can be curative, but achieving widespread distribution is the greatest challenge. We have shown that precision micro dosing to neural networks will deliver broad central nervous system expression, providing safe and effective treatments,” said Shaw, who is also cofounder and chief scientific officer of AviadoBio. 4
AviadoBio's most advanced therapy candidate is AVB-PGRN, a treatment for FTD that is based on the company's gene supplementation platform. Proceeds from the financing are also intended to fund a first in human clinical trial of AVB-PGRN, which has an intrathalamic delivery route into the brain and will target progranulin, a glycoprotein encoded by the GRN gene. The therapy will deliver copies of the unmutated GRN gene to neurons to raise progranulin levels and reduce symptoms in those affected.
AviadoBio also plans to invest in developing its other preclinical programs, targeting ALS and other forms of FTD through gene inactivation, and bring them closer to the clinic. The company is led by CEO Lisa Deschamps, an industry veteran who has spent 25 years working at Novartis, and has two scientific cofounders, Youn Bok Lee, PhD, and Do Young Lee, PhD, both of Kings College London.
Pfizer Opens Durham, NC, Facility for Gene Therapy Manufacturing
The 85,500-square-foot (7,943-square-meter) Durham facility is expected to create >50 new jobs in coming years, in addition to the ∼40 employees who will relocate from Pfizer's Chapel Hill, NC, site. Pfizer employs >3,600 employees in North Carolina.
“Today represents the next step in strengthening Pfizer's in-house gene therapy capabilities and underscores the unique ability, expertise, and resources we have to guide gene therapy through the entire development and manufacturing process and deliver this potentially life-changing technology to patients,” said Paul Mensah, vice president, BioTherapeutics Pharmaceutical Sciences at Pfizer. 5
The facility is one of three scalable gene therapy manufacturing facilities totaling 300,000 square feet (27,871 square meters) that Pfizer has spent $800 million over the past 6 years to build. The facilities intended to support gene therapy research, development, and manufacturing, and thus demonstrate the company's commitment to gene therapies and the rare disease patients expected to benefit from them.
The Durham facility joins Pfizer's worldwide R&D network, which includes locations in La Jolla, CA; Boulder, CO; St Louis, MO; Pearl River, NY; Groton, CT; Cambridge, MA; and Andover, MA.
Bluebird Bio Reports Updated Positive Phase I/II Data in SCD
In addition to continued complete resolution of severe VOEs, the 35-patient pivotal cohort Group C achieved near normal levels of key hemolysis markers and experienced sustained improvements in patient-reported quality of life after treatment. After engraftment, median total hemoglobin increased from 8.5 g/dL at baseline to ≥11 g/dL from 6 through up to 36 months postinfusion in all patients. Sickle hemoglobin (HbS) in all patients was <60% of total hemoglobin, and gene therapy-derived antisickling hemoglobin, HbAT87Q, contributed at least 40% of total hemoglobin, according to the company.
All 25 evaluable patients continued to experience complete resolution of severe VOEs through up to 36 months of follow-up, compared with a median of 3.5 per year in the 24 months before enrollment. The number of severe VOEs in those patients ranged from 2.0 to 13.5 per year.
From 6 months postinfusion through the last visit, several indicators of the health of red blood cells suggest that treatment with lovo-cel improved biological markers for SCD to near-normal levels, Bluebird added.
HGB-206 consisted of Groups A (7 patients), B (2 patients), and C (35 patients), reflecting progressive adaptations to the treatment and manufacturing processes.
The updated data were presented at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition, held in Atlanta and virtually in December 11–14, 2021, with select data from the Group C cohort of HGB-206 simultaneously published in The New England Journal of Medicine.
“The remarkable depth and breadth of data presented at ASH and published in The New England Journal of Medicine distinctively demonstrates the impact of lovo-cel on biologic and clinical outcomes, as well as to patient-reported outcomes that indicate a meaningful difference in the daily lives of people with sickle cell disease,” said Richard Colvin, MD, PhD, Bluebird's Chief Medical Officer. 6
Tataa Biocenter Opens Qc Analytics Laboratory
The new laboratory offers novel methods for quality control of gene and cell therapeutics based on quantitative PCR (qPCR), digital PCR, and next-generation sequencing, according to Mikael Kubista, PhD, CEO, and founder of the TATAA Biocenter.
“We're offering innovative methods for quality control of gene and cell therapeutics, and these are based on qPCR, digital PCR and next-generation sequencing. We're the first lab with this focus, which is our core competence since 20 years,” Kubista said. 7
TATAA said the new facility will be among the first in the world to specialize in QC analytics for nucleic acid-based therapies, to address unmet needs within nucleic acid-based drugs, especially within gene and cell therapies. The new 2,000-square-meter (21,528-square-foot) facility is designed to minimize contamination and optimize laboratory workflow. TATAA said the new laboratory will differentiate itself from traditional contract research organizations and established laboratories through new methods intended to meet the sensitivity requirements necessary for robust molecular analyses for its projects.
Intellia Doses First Patient in Trial of Second Candidate
NTLA-2002 is Intellia's second CRISPR therapeutic candidate to be administered systemically, by intravenous infusion, to edit disease-causing genes inside the human body with a single dose.
The Phase I/II study (NCT05120830) will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of NTLA-2002 in adults with Type I or Type II HAE, including the measurement of kallikrein protein levels and activity as determined by HAE attack rate measures. The Phase I portion of the study is an open-label single-ascending dose design used to identify up to two dose levels of NTLA-2002 that will be further evaluated in the randomized placebo-controlled Phase II portion of the study. The study will identify the dose of NTLA-2002 that will be used in future studies.
“Currently available chronic therapies have a high treatment burden,” said Intellia President and CEO John Leonard, MD. “With the progress of our first-in-human clinical study evaluating NTLA-2002 for people living with HAE, we look forward to beginning clinical testing as we aim to develop a single-dose treatment for these patients.” 8
Spark Reports Durable Expression of FVIII in Hemophilia a Patients
The data were published in the New England Journal of Medicine (NEJM).
The updated analysis of all 18 study participants, which had a data cutoff of May 3, 2021, followed the presentation of initial data at the International Society of Thrombosis and Hemostasis (ISTH) 2021 Virtual Congress in July, showing a 91.5% reduction in annualized bleed rate and a 96.4% reduction in annualized number of FVIII infusions.
In the safety analysis, 33 treatment-related adverse events (AEs) occurred in 8 participants of which 17 were vector related, including 1 serious AE, and 16 were glucocorticoid related. Two participants lost all FVIII expression due to an anti-AAV capsid cellular immune response, unresponsive to immunosuppression. The remaining 16 participants maintained FVIII expression, of whom 12 were followed for >2 years, and showed no apparent decrease in one-stage FVIII activity over time.
“This Phase 1/2 study for SPK-8011 demonstrates our commitment to following the science to develop gene therapies for hemophilia A that demonstrate safety, predictability, efficacy and durability at the lowest effective dose and with an optimal immunomodulatory regimen,” said Gallia Levy, MD, PhD, chief medical officer, Spark Therapeutics. 9