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

CAMBRIDGE, Mass., May 13, 2024 /Business Wire/ — 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.

Investor and Media Contact:

Adam Bero, Ph.D.
Kendall Investor Relations
abero@kendallir.com

CAMBRIDGE, Mass., April 22, 2024 /Business Wire/ — Vesigen Therapeutics, Inc., a biotechnology company developing a novel non-viral delivery platform for gene editors, RNA, and protein-based therapeutics, today announced that the Company will be presenting 10 posters sharing new preclinical data from its engineered ARMMs platform at the upcoming American Society of Gene & Cell Therapy (ASGCT) Annual Meeting. The conference will be held from May 7-11 in Baltimore, Maryland.

Vesigen’s delivery technology has been shown to be non-immunogenic and is re-dosable. ARMMs can be targeted to cell types of interest. Vesigen will be presenting new preclinical data demonstrating successful biodistribution of its ARMMs in non-human primates (NHPs). The team will also be sharing data on its new targeted ARMMs technology, demonstrating the ability to deliver to otherwise hard-to-reach cell types.

Details of the poster presentations are listed below. All posters will be presented in the poster hall of the Baltimore Convention Center at 12 PM EST.

May 8 Poster Presentations

Engineering ARMMs with Engagers to Direct Biodistribution to Specific Neurons as a Therapeutic Strategy for Friedreich Ataxia

• Presenting Author: Wendy Zhao, Ph.D.
• Abstract Number: 635

ARMMs as Non-Viral Vehicles for the Delivery of Genome Editors to Treat Inherited Retinal Diseases

• Presenting Author: Qin Yu, Ph.D.
• Abstract Number: 660

Biodistribution of ARMMs as Non-Viral Vehicles for Therapeutic Payloads by Subretinal Administration in Minipigs and Non-Human Primates

• Presenting Author: Joseph Nabhan, Ph.D.
• Abstract Number: 663

 May 9 Poster Presentations

ARMMs as Non-Viral Vehicles for the Delivery of Therapeutic Payloads to Liver Sinusoidal Endothelial Cells

• Presenting Author: Ryan von Kleeck, Ph.D.
• Abstract Number: 1238

Fractionation of distinct extracellular vesicle populations by charge and density to evaluate the heterogeneity and purity of ARMMs

• Presenting Author: Kristin Luther, Ph.D.
• Abstract Number: 1246

ARMMs as a Versatile and Modular Non-Viral Platform for the Functional Delivery of Genome Editors

• Presenting Author: Qiyu Wang, Ph.D.
• Abstract Number: 1247

Engineering ARMMs with Modular T Cell-Specific Engagers for Non-Viral Delivery of Therapeutic Payloads

• Presenting Author: Wendy Zhao, Ph.D.
• Abstract Number: 1248

Engineering Directed Tropism in the Non-Viral ARMMs Delivery Platform

• Presenting Author: Silvia Piccinotti, Ph.D.
• Abstract Number: 1249

 May 10 Poster Presentations

ARMMs as Non-Viral Vehicles that Enable in vivo Functional Delivery of Cas9 to Disrupt NLRP3 in Kupffer Cells and Ameliorate Acute Liver Injury

• Presenting Author: Mike Thomas, Ph.D.
• Abstract Number: 1736

Suspension Cell-Based Production and Scalable Purification of Engineered ARMMs as a Platform for Non-Viral Therapeutics

• Presenting Author: Steven Greenway
• Abstract Number: 1746

For more information about the ASGCT Annual Meeting, including registration details, please visit https://annualmeeting.asgct.org/.

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.

Investor and Media Contact:

Adam Bero, Ph.D.
Kendall Investor Relations
abero@kendallir.com

Vesigen proposal selected as a “Winning Solution” for programmable delivery systems for gene editing

Proposal builds on recent data demonstrating cell type-specific targeting of Company’s non-viral delivery platform

CAMBRIDGE, Mass., December 19, 2023 /Business Wire/ — Vesigen Therapeutics, Inc., a biotechnology company developing a novel non-viral delivery platform for gene editors, RNA, and protein-based therapeutics, was selected as a Phase 1 winner of the National Institutes of Health TARGETED (Targeted Genome Editor Delivery) Challenge. The Company’s proposal, “Engineered ARMMs: Promising Human-Derived Vectors for Cell Type-Specific Delivery of Genome Editors”, builds on recent data demonstrating directed tropism of the Company’s non-viral ARMM (ARrestin-domain 1 Mediated Microvesicles) delivery platform and was among five proposals selected as “Winning Solutions” for programmable delivery systems for gene editing.

“We are honored that the potential to engineer our non-viral ARMMs platform for cell type-specific delivery of gene editing payloads has been recognized by the NIH,” said Joseph Nabhan, Ph.D., Chief Scientific Officer at Vesigen. “The data we have generated demonstrate that ARMMs enable functional delivery of gene editing payloads across a broad range of cell types in vitro and in vivo, and that they can potentially be tailored to selectively target cell types of interest in vivo. We look forward to advancing our platform toward the clinic and unlocking the full potential of genetic medicines.”

The NIH launched the TARGETED Challenge to advance genome editing technology by sourcing innovative solutions for delivering genome editing components safely and effectively. The three-phase challenge supports the NIH’s Somatic Cell Genome Editing (SCGE) commitment to developing targeted delivery systems for delivering genome editors to somatic cells in the body.

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.

Investor and Media Contact:

Adam Bero, Ph.D.
Kendall Investor Relations
abero@kendallir.com

Robust uptake observed in photoreceptors and retinal pigment epithelium (RPE) of mice, minipigs, and non-human primates

Additional data demonstrate rescue of acute liver injury disease model by delivery of a gene editor to Kupffer cells

CAMBRIDGE, Mass., October 19, 2023 /Business Wire/ — Vesigen Therapeutics, Inc., a biotechnology company developing a novel non-viral delivery platform for gene editors, RNA, and protein-based therapeutics, presented data further highlighting the potential of the Company’s non-viral ARMM (ARrestin-domain 1 Mediated Microvesicles) technology to deliver novel therapeutic payloads to cell and tissue types relevant to multiple therapeutic areas with high unmet need. Specifically, the Company presented new data demonstrating retinal biodistribution of engineered ARMMs across multiple species – including non-human primates – and data demonstrating successful in vivo functional delivery of a Cas9/guide RNA gene editing complex. The data were presented at the Cracking the Code: The Dawn of Nucleic Acid Medicines meeting, taking place October 17-19, 2023, in Worcester, MA.

“These data further demonstrate the potential of our non-viral ARMM technology to deliver challenging therapeutic payloads, including gene editing complexes, to multiple cell and tissue types impacted in disease,” said Paulash Mohsen, Chief Executive Officer at Vesigen. “We have shown that our ARMM technology can successfully deliver functionally active gene editing complexes to Kupffer cells and ameliorate disease in an acute liver injury model. Additional data in mice, minipigs, and non-human primates demonstrated the efficient delivery of subretinally administered ARMMs to the RPE and photoreceptors, cell types associated with multiple retinal diseases. Together, these data sets underscore the transformative capacity of our technology to overcome fundamental delivery challenges that limit the potential of promising new genetic medicines.”

Details of the poster presentations are as follows.

Wednesday, October 18

Biodistribution of ARMMs as Non-Viral Vehicles for Therapeutic Payloads by Sub-Retinal Administration in Minipigs and NHP

• Engineered ARMMs were administered to adult minipigs and non-human primates (NHPs) by subretinal injection
• In both minipigs and NHPs, robust ARMMs uptake was observed in rod and cone photoreceptors as well as the retinal pigment epithelium
• Histopathological evaluation showed no evidence of immune cell infiltration, cytotoxicity, or cell death following ARMMs administration

ARMMs Enable In Vivo Functional Delivery of Cas9 to Disrupt NLRP3 in Kupffer Cells and Ameliorate Acute Liver Injury

• ARMMs loaded with Cas9 and a guide RNA targeting NLRP3 – a central regulator of liver disease pathogenesis – were administered intravenously in a mouse model of acute liver injury
• Mice treated with ARMMs loaded with Cas9/NLRP3 gRNA complexes exhibited ~60% on-target gene editing efficiency in liver Kupffer cells, significant reduction in circulating liver enzymes, and improved liver cell viability compared to vehicle-treated mice

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.

Investor and Media Contact:

Adam Bero, Ph.D.
Kendall Investor Relations
abero@kendallir.com

CAMBRIDGE, Mass., September 7, 2023 /Business Wire/ — Vesigen Therapeutics, Inc., a biotechnology company developing a novel non-viral delivery platform for gene editors, RNA, and protein-based therapeutics, today showcased new data at the Exosome Based Therapeutic Development Summit 5^th Annual Meeting held September 5-7, 2023 in Boston. The presentation highlighted new data on the company’s proprietary ARMM (ARrestin-domain 1 Mediated Microvesicles) delivery technology, including therapeutic in vivo gene editing in a preclinical model of acute liver injury, and summarized biodistribution translation evidence generated across species, including non-human primates.

Details of the oral presentation are as follows:

• Engineered ARMMs for Delivery of Therapeutic Payloads. Joseph Nabhan, Ph.D., Chief Scientific Officer, Vesigen Therapeutics. Thursday, September, 7, 2023, 11:30 AM ET.

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.

Investor and Media Contact:

Adam Bero, Ph.D.

Kendall Investor Relations

abero@kendallir.com