Dyne, NeuBase, Graphite and More Present Programs at ASGCT

Gene Therapy

The American Society of Gene and Cell Therapy's (ASGCT) 25th Annual Meeting is happening Monday through Thursday in Washington, D.C., featuring the latest scientific research in genetics and cellular therapies. BioSpace pulled some of the top highlights so far. 

CANbridge/UMass SMA Collab Yields Preclinical Fruit 

CANBridge Pharmaceuticals, in collaboration with the Horae Gene Therapy Center at the UMass Chan Medical School, presented initial data from its gene therapy research agreement targeting spinal muscular atrophy (SMA), a genetic disorder that causes atrophy in skeletal muscles through the loss of motor neurons.

The novel second-generation scAAV9 gene therapy, which expresses co-hSMN1 from an endogenous hSMN1 promoter, demonstrated superior efficacy and safety in mice models of SMA compared to a benchmark vector similar to the vector used in current gene therapies for SMA. The gene therapy produced an extended lifespan, restored muscle function and better neuromuscular innervation. Treated mice also showed higher SMN1 expression, the gene that promotes motor neurons' survival.

The collaborators plan to develop the therapy for use in humans.

Dyne Therapeutics Myotonic Dystrophy Type I Data Shows Potential

Dyne Therapeutics presented new in vivo data for its therapeutic DYNE-101, which is intended to treat myotonic dystrophy type 1 (DM1), an inherited multisystemic disorder that causes progressive muscle weakness.

In mice models of DM1 and non-human primates, monthly dosing of DYNE-101 led to a substantial knockdown of DMPK RNA, the toxic gene product which promotes altered splicing in cells causing muscular damage. DYNE-101 has previously shown that it can correct splicing malfunction as well, and the company believes it has the potential to be a disease-modifying therapy with low, infrequent dosing. 

Additionally, the therapeutic was found to be well-tolerated in a 13-week toxicology study with no changes being observed in kidney and liver functioning as well as endpoints in cardiac, respiratory, neurologic or ophthalmic endpoints.

NeuBase Presents Preclinical Data for DM1 Treatment

NeuBase Therapeutics presented preclinical data supporting the development of its lead candidate NT-0231.F. The therapeutic is designed as a whole-body treatment solution for DM1.

NT-0231.F targets mutant DMPK pre-mRNA with a novel peptide-nucleic acid and is designed to selectively engage with toxic RNA structures to release and restore splicing proteins. A single intravenous injection of the therapeutic showed rapid and wide distribution into tibialis anterior muscle, heart muscle, and brain tissues in mice. Each tissue evaluated displayed an extended elimination phase with measurable tissue concentrations for at least four weeks following treatment.

These results demonstrate the therapeutic's potential to be a whole-body treatment solution for DM1 by being deliverable to various major tissues. NeuBase believes that the drug could potentially treat myotonia, muscle weakness, cardiac effects and cognitive impairments seen in those with the disease.

Graphite Bio Targets Beta-thalassemia

Graphite Bio presented preclinical data for GPH102, the company‚Äôs differentiated gene replacement program for beta-thalassemia, an inherited blood disorder, which replaces a mutated beta-globin gene with a functional gene. Current results have shown that GPH102 can restore the expression of these genes, showing a path forward for further development. GPH102 aims to restore the expression of adult hemoglobin to levels similar to those who do not have the disease.

Graphite also presented an encore of the trial-in-progress poster for its gene replacement program, GPH101, an investigational therapy designed to directly correct the genetic mutation responsible for Sickle Cell Disease. SCD is an inherited blood disorder that affects the shape of red blood cells, which can block blood flow.

Graphite is presently testing GPH101 in Phase I/II trials titled Cedar. The trial is dosing approximately 15 patients with severe SCD. Primary endpoints include safety, transplant-related mortality, overall survival and frequency and severity of adverse events. Secondary endpoints include efficacy, including levels of globin expression, gene correction rates and clinical manifestations of SCD. 

Cellectis Debuts Novel Immune-Evasive Universal CAR T-cell

Cellectis presented its first research data on its development of a universal CAR T-cell with immune-evasive properties. Universal CAR T-cells with immune-evasive properties can revolutionize oncological treatments by killing target tumor cells, avoiding depletion by the immune system and proliferating without attacking host tissues.

Cellectis showed that its therapy was able to overcome alloresponsive T-cell and natural killer cell attacks from the immune system and showed similar efficacy towards natural killer cells in healthy donors as well as acute myeloid leukemia and acute lymphocytic leukemia patients. Additionally, the CAR T-cells exhibited prolonged antitumor activity in the presence of cytotoxic levels of natural killer cells.

The therapy was developed using Cellectis' TALEN-mediated gene editing and AAV dependent gene insertion. 

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