The American Society of Gene and Cell Therapy (ASCGT) annual meeting continues to see companies present promising therapies for multiple disease indications. As the conference enters its fourth day, BioSpace takes a look at some of the presentations.
Based in California Capsida presented its therapeutic approach which the company says will unlock the potential to treat rare and common diseases at all ages.
Capsida shared its first-generation AAV engineering pilot programs, as well as the results of its capsid engineering platform used to screen adeno-associated virus 9 (AAV9)-based vectors for the treatment of central nervous system diseases . In his presentation, Capsida CEO Peter Anastasiou said the data demonstrates better distribution in cortical, subcortical and deep brain regions at low doses by IV administration compared to invasive assay methods for AAV9.
The company also included an oral presentation titled “CAP-001: Systemic AAV Gene Therapy with Next Generation Capsids for MPS II Disease.” CAP-001 is a novel modified capsid containing a human iduronate-2-sulfatase (IDS) transgene. The company noted that CAP-001 had been selected for further characterization as a proof-of-concept to treat mucopolysaccharidosis type II (MPS II), or Hunter syndrome, a lysosomal storage disorder.
When administered intravenously, the results showed that CAP-001 achieved better biodistribution in the brain than AAV9 by other routes of administration. It also provided “significantly more even distribution across all areas of the brain with >50-fold improvement in subcortical and deep brain regions, an area where ICM administration was found to be poorly distributed.” “.
Texas-based Organic Instil showed results of genomic and correlative analyzes in a cohort of patients with metastatic melanoma treated with tumour-infiltrating lymphocytes (TIL). In its presentation this week, Instil showed a correlation between tumor response and clonal expansion of TILs.
Additionally, the company noted in its oral abstract that there is an inverse correlation between tumor response and specific T cell populations. Instil said expression profiling and transcriptional network analysis point to what he calls “master regulatory” genes that can be manipulated during TIL manufacturing to enhance TIL activity.
“We believe that TILs represent more than a potential therapy for patients, as they are also a platform for understanding fundamental T cell biology,” Bronson Crouch, chief executive of Instil Bio, said in a statement. . “We are applying recent advances in analytical technologies to deeply probe the function of TILs and hope to generate insights that could be fundamental for the development of cancer therapies.”
Based in California Adverum presented data which further supports its Phase II development plans for ADVM-022, a therapeutic candidate for wet age-related macular degeneration (wet AMD). The data presented show the results of studies in non-human primates that support the company’s intended 6 X 10^10 vg/eye (6E10) dose for use in its upcoming clinical trial.
Data highlights from the presentation show that the human equivalent dose of 6E10 (3 X 10^10 vg/eye dose in NHP) demonstrated potential therapeutic levels in both aqueous humor and vitreous humor , the company said. Additionally, Adverum stated that administration of the human equivalent dose of 6E10 (3 X 10^10 vg/eye dose in NHP) was well tolerated. No adverse clinical signs were observed during the three-month study, the company added.
“We are very encouraged by the aflibercept expression levels and tolerability of the human equivalent dose of 6×10^10 vg/eye supported by our data in non-human primates,” said Richard Beckman, Chief Medical Officer of ‘Adverum Biotechnologies in a press release. “As we explore doses of 2×10^11 vg/eye and below, we are excited about the potential for improved safety profile while building on the robust response that ADVM-022 has demonstrated to date in wet AMD.”
Based in the Bay Area Metagenomi presented preclinical data on novel gene editing systems that have shown extremely high editing efficiency in human primary immune cells and the ability to integrate at multiple targeted sites. At ASGCT, the company made two presentations.
The first study, “CRISPR-associated gene editing systems discovered in metagenomic samples enable efficient genome engineering in multiple primary immune cell types,” presented the ability of CRISPR-associated gene editing systems to Metagenomi to modify primary human cells with high efficiency, including T cells, natural killer cells, B cells, hematopoietic stem cells and induced pluripotent stem cells. The company says it has achieved over 95% editing efficiency.
The second presentation, “Active CRISPR-Associated Transposases from Natural Environments,” showcased a novel family of proprietary CRISPR-associated transposase (CAST) gene-editing systems. CAST