Cell therapy weekly: IND clearance for bispecific CAR-T therapy for MS
This week: The US Food and Drug Administration (FDA; MD, USA) cleared an Investigational New Drug (IND) application for a bispecific CAR-T therapy for multiple sclerosis (MS) and granted Rare Pediatric Disease (RPD) designation to a gene therapy for Leber congenital amaurosis. Plus, Genentech (CA, USA) used Mission Bio‘s (CA, USA) Tapestri single-cell multiomic assay to enhance the characterization of gene-edited CD8+ T-cell therapies.
The news highlights:
- IND clearance for bispecific CAR-T therapy for MS
- Ocular gene therapy receives RPD designation
- Tapestri enhances T-cell therapy characterization
IND clearance for bispecific CAR-T therapy for MS
The US FDA has cleared an IND application for ImmPACT Bio’s (CA, USA) CD19/CD20 bispecific CAR-T therapy for MS, IMPT-514.
Chief Medical Officer, Jonathan Benjamin, stated: “The dual-targeting nature of IMPT-514 offers a unique opportunity to potentially ablate autoreactive B cells and the likely pathogenic CD20-expressing T cells. Moreover, the ability of CAR T-cells to cross the blood–brain barrier could potentially overcome the limitations of current disease-modifying therapies such as anti-CD20 antibodies that are not effective at crossing the [blood–brain barrier], where potentially pathogenic cells reside.”
In preclinical studies, IMPT-514 was successfully manufactured from heavily immunosuppressed patients, demonstrated potent elimination of autologous B cells and exhibited a moderate cytokine profile. ImmPACT plans to launch a Phase I dose escalation trial in the first half of 2025. The trial will focus on patients with inadequate disease control, even after receiving high-efficacy disease-modifying therapies.
Ocular gene therapy receives RPD designation
Opus Genetics (NC, USA) has received a RPD designation from the US FDA for its ocular gene therapy OPGx-LCA5, which is designed to treat Leber congenital amaurosis resulting from biallelic mutations in the LCA5 gene. OPGx-LCA5 utilizes an adeno-associated virus 8 vector to deliver a functional LCA5 gene to the outer retina and its safety and preliminary efficacy is currently being investigated in a Phase I/II dose-escalation study at the University of Pennsylvania (USA).
“We are thrilled to receive [RPD designation] from the FDA for our OPGx-LCA5 gene therapy. This important milestone brings us closer to delivering a potential treatment for patients with LCA5,” said Ben Yerxa, CEO of Opus. “At Opus, we’re committed to advancing therapies that help treat patients with inherited retinal diseases, and this designation further validates the potential impact of our innovative ocular gene therapy approach. We look forward to providing updates on the Phase 1/2 clinical trial evaluating OPGx-LCA5 soon.”
Tapestri enhances T-cell therapy characterization
Mission Bio has announced the release of data demonstrating the successful use of its Tapestri platform by Genentech’s Analytical Development Group to enhance the characterization of gene-edited CD8+ T-cell therapies. Published in Frontiers of Bioengineering and Biotechnology, the study highlights how Mission Bio’s DNA and protein multiomic assay revealed heterogeneity in on-target and off-target edits within individual cells, as well as the correlation to cell subtype. This advancement offers cell therapy developers a new level of resolution for identifying critical quality attributes crucial for chemistry, manufacturing and controls processes.
Maryam Moshref, co-author of the study stated: “By leveraging single-cell DNA sequencing, we uncovered diverse editing outcomes, including variations in zygosity and the presence of off-target edits and translocations. Additionally, by integrating immunophenotypic information, we concluded that these editing events are evenly distributed across CD8+ T cell subpopulations. This comprehensive characterization, which surpasses the capabilities of bulk analysis, is crucial for truly understanding the outcomes of edited cell products.”
