EG 427 presented groundbreaking advances in its non-replicative HSV-1 (nrHSV-1) vector technology at the 28th Annual Meeting of the American Society of Cell and Gene Therapy (ASGCT) in New Orleans on May 13, 2025. The company showcased two significant developments that highlight its leadership position in neurological gene therapy applications.
Revolutionary Dual-Transgene Vector System
The first major advancement involves a novel vector containing two different transgenes under the control of independent regulatory elements positioned in different epigenetic regions of the HSV-1 genome. Both in vitro and in vivo studies demonstrated that this unique configuration allows the two transgenes to express with distinct duration patterns.
"This innovative dual-payload nrHSV-1 vector, which enables the delivery of multiple transgenes with distinct expression dynamics within the same cell, provides a completely new approach for genetic medicines of the future," said Teddy Jégu, Ph.D., VP of Research at EG 427.
The transgene inserted outside the latency region displayed short-term expression, while the transgene placed within the latency region maintained stable expression throughout the study period. This capability represents a significant technological leap compared to current gene therapy vectors, particularly AAV vectors, which often require multiple constructs to deliver a single therapeutic gene.
Dr. Jégu emphasized the potential clinical applications: "Our vision is to be able to develop a single vector with, for example, the ability to delete genes in vivo, through a transient expression of gene editing proteins, and to replace with a corrected gene with the capacity to deliver long-term expression to treat autosomal dominant disease."
Enhanced Neuronal Targeting and Expression
The second poster presented at ASGCT highlighted a nrHSV-1 vector derived from EG 427's HERMES platform that demonstrates remarkable neuronal targeting capabilities. When stereotactically injected into the striatum of mice, this vector—expressing the mGreenLantern reporter gene under the control of the CAG promoter—showed high-level transgene expression in layer V cortical neurons.
This result contrasts sharply with previous academic experiments that showed poor transgene expression with highly defective HSV-1 vectors. Importantly, cells expressing the transgene in the cortex were exclusively neurons, and stable expression was maintained for at least six weeks post-administration.
These findings suggest the potential for targeted biodistribution of therapeutic proteins within the brain, opening new avenues for treating a broad range of neurodegenerative diseases.
Clinical Progress and Future Directions
EG 427 has already begun translating its technological advances into clinical applications. Earlier this year, the company treated the first patient in a clinical study of EG110A for urinary bladder dysfunction in spinal cord patients.
"We have made great progress in advancing our novel non-replicative HSV-1 vector platform, which is not only seen in the data presented at ASGCT but also in the significant milestone announced early this year when we treated the first patient in our clinical study of EG110A," said Philippe Chambon, M.D., Ph.D., founder and CEO of EG 427.
Dr. Chambon added that these advances provide "strong, early evidence that our genetic medicines could offer safe, targeted and cost-effective ways to treat some of the large medical needs of patients suffering of chronic neurological diseases."
Technical Advantages of the HERMES Platform
The company's proprietary HERMES platform delivers precise neurotherapeutics to treat prevalent diseases of both the peripheral and central nervous systems. The platform's vectors achieve focal transduction in specific regions and selective expression of transgenes in targeted neuronal subsets through sophisticated regulatory elements.
Key advantages of the nrHSV-1 vector technology include:
- High transduction rate of neurons in the CNS even at very low doses
- Efficient distribution to connected brain regions via retrograde transfer
- Large payload capacity allowing for versatile DNA delivery
- Demonstrated clinical safety with potential for repeated dosing
- Ability to host multiple transgenes with independent expression profiles
Poster Presentations at ASGCT
EG 427's findings were presented on May 13 at the ASGCT meeting in New Orleans through two posters:
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"New gene therapy vehicle for the expression of multiple transgenes with distinct kinetics of expression" (Poster #873), presented by Senior Scientist Justine Basset
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"Long-term expression of transgene in targeted cortical neurons following inoculation in the mouse striatum of a non-replicative HSV-1 vector" (Poster #537), presented by Preclinical Manager Julien Ratelade
Implications for Neurological Disease Treatment
The advances presented by EG 427 have significant implications for treating neurological disorders. The ability to deliver multiple transgenes with distinct expression patterns could revolutionize approaches to complex genetic conditions, particularly autosomal dominant diseases where both gene silencing and replacement may be necessary.
Additionally, the targeted neuronal expression capabilities demonstrated in the second poster suggest potential applications in neurodegenerative conditions such as Parkinson's disease, Alzheimer's disease, and other disorders affecting specific brain regions.
The company's lead candidate, EG110A, is being developed to address multiple severe bladder diseases, including overactive bladder (OAB). EG 427 believes this approach has the potential to significantly improve upon existing therapies, resulting in better patient care and reduced healthcare costs.
As the first human study using this type of vector targeting sensory neuron-based diseases, the ongoing clinical trial of EG110A represents an important milestone in translating the company's innovative technology from bench to bedside.
