New NHP data demonstrate successful functional
delivery of CRISPR/Cas9 and base editing complexes with engineered
ARMMs to multiple cell types
Additional in vivo data demonstrate highly
selective cell targeting and functional delivery of gene editing
complexes using engineered ARMMs cell-specific engagers
Vesigen Therapeutics, Inc., a biotechnology company developing a
novel non-viral delivery platform for gene editors, RNA, and
protein-based therapeutics, recently showcased two data
presentations at the Association for Research in Vision and
Ophthalmology (ARVO) Annual Meeting and ten data presentations at
the American Society of Gene & Cell Therapy (ASGCT) Annual
Meeting. ARVO was held from May 5-9 in Seattle, Washington, while
ASGCT was held from May 7-11, 2024 in Baltimore, Maryland. New data
further supports the potential of Vesigen’s ARRDC1-Mediated
Microvesicles (ARMMs) technology to functionally deliver a variety
of payloads, including genome editors, to a broad range of
disease-relevant cells and tissues.
“We’ve made substantial strides with our ARMMs platform since
last year’s ASGCT Annual Meeting. We are thrilled to share new data
from non-human primates (NHP) studies showing successful gene
editor delivery and demonstrating our ability to target ARMMs
selectively to cell types of interest in vivo,” said Paulash
Mohsen, Chief Executive Officer at Vesigen. “Our data demonstrate
the therapeutic potential of engineered ARMMs for in vivo delivery
of genome editors to a wide range of cell types and the safety
benefits of leveraging a human cell-derived system. We look forward
to continuing to advance our technology while also working toward
moving our lead program into clinical development.”
Key insights from the presentations are summarized below.
Presentation materials are available upon request.
New in vivo and in vitro data, including NHP data,
demonstrate successful functional delivery and biodistribution of
ARMMs to a diverse range of cell types
Multiple studies demonstrated that ARMMs biodistribution
translates across species and payloads can be successfully
delivered to the retina of adult minipigs and NHPs via subretinal
administration (ASGCT #663/ARVO B0291). ARMMs rapidly and robustly
transfect the retinal pigment epithelium (RPE) and the
photoreceptors. Notably, in the NHP eye, ~80% of the cones,
including those in the macular region, were transfected.
Ocular (ASGCT #660/ARVO #A0081)
Administration of ARMMs resulted in the functional delivery of
therapeutic genome editors and achieved up to 80% base editing in
the targeted region of the ABCA4 gene in in vitro and ex vivo
models. This was further supported by in vivo data in both mouse
and NHP retinas following subretinal injection, supporting the use
of ARMMs as a potential treatment for genetically-driven ocular
diseases such as Stargardt disease.
Immune Modulation
After confirming that ARMMs could successfully deliver payloads
to liver sinusoidal endothelial cells (LSECs) and liver Kupffer
cells in mouse and NHP models (ASGCT #1238), data showed that gene
editing payloads could also disrupt inflammatory mediators such as
the NLRP3 inflammasome and IRF5 (ASGCT #1247 and #1736). Disrupted
NLRP3 inflammasome activation was demonstrated to ameliorate
inflammation in a mouse acute liver injury (ALI) model.
Neurology
Another study (ASGCT #635) showed that ARMMs could package and
deliver a genome editor and two different gRNAs to Friedreich
ataxia (FA) patient-derived neurons and primary mouse neurons from
a disease model, successfully excising the pathogenic GAA
trinucleotide repeat expansion.
ARMMs can be engineered to selectively target hard-to-reach
cell types, including T cells
ARMMs can reach many cell types in vivo by leveraging their
natural biodistribution. Furthermore, ARMMS can be selectively
targeted to cell types of interest by surface engineering them to
present cell-type specific engagers, thereby significantly
expanding the therapeutic potential for this technology.
In one study (ASGCT #1248), ARMMs were engineered to display
anti-CD8 antibodies that interact with specific T cell populations.
Selective targeting and functional delivery of gene editing
complexes were demonstrated both in vitro and in vivo in mouse
models.
In another presentation (ASGCT #1249), researchers showed that
engineering ARMMs with several surface engagers enabled directed
delivery of payloads across multiple target cell types. The
modularity of this directed delivery platform was further
demonstrated in ASGCT #635. ARMMs were decorated with engagers
specific to proprioceptive neurons, potentially enabling in vivo
delivery to disease-affected cell types in FA.
Vesigen continues to optimize process development to prepare
for large-scale manufacturing
Two data presentations (ASGCT #1246 and #1746) highlighted
continued development and optimization of scalable approaches to
produce and characterize ARMMs. The presentations provided evidence
supporting production, purification, and characterization processes
that enable GMP manufacturing of engineered ARMMs at scale. The
final products show high purity, consistent size distribution and
payload concentration, as well as functional payload delivery in
both in vitro and in vivo experiments.
Poster Details
Engineering ARMMs with Engagers to Direct Biodistribution to
Specific Neurons as a Therapeutic Strategy for Friedreich Ataxia
(ASGCT #635)
ARMMs as Non-Viral Vehicles for the Delivery of Genome Editors
to Treat Inherited Retinal Diseases (ASGCT #660/ARVO #A0081)
Biodistribution of ARMMs as Non-Viral Vehicles for Therapeutic
Payloads by Subretinal Administration in Minipigs and Non-Human
Primates (ASGCT #663/ARVO #B0291)
ARMMs as Non-Viral Vehicles for the Delivery of Therapeutic
Payloads to Liver Sinusoidal Endothelial Cells (ASGCT #1238)
Fractionation of distinct extracellular vesicle populations by
charge and density to evaluate the heterogeneity and purity of
ARMMs (ASGCT #1246)
ARMMs as a Versatile and Modular Non-Viral Platform for the
Functional Delivery of Genome Editors (ASGCT #1247)
Engineering ARMMs with Modular T Cell-Specific Engagers for
Non-Viral Delivery of Therapeutic Payloads (ASGCT #1248)
Engineering Directed Tropism in the Non-Viral ARMMs Delivery
Platform (ASGCT #1249)
ARMMs as Non-Viral Vehicles that Enable in vivo Functional
Delivery of Cas9 to Disrupt NLRP3 in Kupffer Cells and Ameliorate
Acute Liver Injury (ASGCT #1736)
Suspension Cell-Based Production and Scalable Purification of
Engineered ARMMs as a Platform for Non-Viral Therapeutics (ASGCT
#1746)
About Vesigen Therapeutics
Vesigen Therapeutics is a biotechnology company developing a
novel, non-viral delivery technology for gene editing, RNA, and
protein-based therapeutics. Vesigen’s patented technology, called
ARMMs (ARRDC1 Mediated Microvesicles), can be used to precisely
deliver a wide range of payloads to a unique set of tissue and cell
types. Vesigen has demonstrated highly efficient in vitro and in
vivo functional delivery of a range of payloads across multiple
cell types and is committed to developing transformative medicines
that address current unmet medical needs. ARMMs were discovered and
engineered into a drug delivery system at the Harvard T.H. Chan
School of Public Health.
For additional information visit www.vesigen.com.
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Investor and Media Contact: Adam Bero, Ph.D. Kendall
Investor Relations abero@kendallir.com