SEATTLE, July 10, 2024 /PRNewswire/ -- Seattle-based biotech Orlance, Inc. has been awarded a Phase I Small Business Innovation Research (SBIR) grant from the National Institutes of Health (NIH) to develop and optimize RNA vaccine formulations using its needle-free MACH-1 platform. This technology aims to enhance the safety, stability, and efficacy of RNA vaccines for infectious diseases, including influenza and Covid-19, along with cancer immunotherapy applications.

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The Orlance MACH-1 gene gun platform technology represents a potentially significant advancement in RNA vaccine delivery. Unlike traditional lipid nanoparticle (LNP) RNA vaccine formulations, which require ultra-cold storage and have been associated with rare adverse events like myocarditis, the MACH-1 platform utilizes dry, stable RNA-coated gold microparticles. This method enables direct delivery into the epidermis, the skin's highly immunocompetent layer, leading to robust immune responses at much lower doses. Importantly, MACH-1 results in all vaccine staying within the target skin tissue and cells, eliminating the movement to non-target tissues that can result in adverse events potentially attributable to either a vaccine's active immunogens or the liquid LNP vehicle fluid carrying the vaccine.  Orlance can deliver all subtypes of RNA vaccines currently in commercial use and under development such as mRNA and self-amplifying RNA technologies.

The MACH-1 platform works by propelling RNA-coated gold microparticles directly into the epidermis using a burst of pressurized gas. Once these microparticles penetrate the outermost layer of the skin, they are taken up by the immune cells that reside there. Moreover, this needle-free and painless delivery system ensures better stability at ambient temperatures, providing significant supply chain advantages in both developed and low-resource settings. Finally, MACH-1 vaccines can significantly improve patient comfort and compliance associated with discomfort and fear of needle-based injections.

The SBIR-funded project, titled "Gene Gun-delivered RNA vaccines," will be led by Orlance Principal Investigators Hannah Frizzell, PhD and Kenneth Bagley, PhD. It aims to optimize RNA formulations for MACH-1 gene gun delivery that maximize loading, maintain functional integrity, and ensure stability and immunogenicity. The team will compare the effectiveness of MACH-1 delivered RNA vaccines against traditional LNP/RNA vaccines in inducing systemic and mucosal immune responses in preclinical models. Preliminary studies have shown that MACH-1 delivered RNA vaccines can achieve comparable immunogenicity to LNP/RNA vaccines with significantly lower doses.

Kristyn Aalto, Orlance co-founder and CEO, explains "While the breakthrough of mRNA vaccines in recent years has established the enormous potential of genetic (RNA and DNA) vaccines as a class, we still have significant work to do to improve utility and overall global health impact.  We are very grateful for NIH's continued support and are rapidly accomplishing MACH-1 platform goals that could truly enhance the clinical reach and impact of genetic vaccines."

The 2 year NIH SBIR grant of $300,000 per year will enable Orlance to conduct crucial preclinical studies to optimize RNA formulations for gene gun delivery. This work is expected to pave the way for subsequent phases of development, ultimately leading to clinical trials.  Ms. Aalto continues, "Orlance already has a well-developed MACH-1 DNA vaccine candidate portfolio, and offering both DNA and RNA vaccine options allows us to leverage the attributes of both platforms to provide ideal solutions tuned to the immunogenicity, protection, and durability profiles sought for specific indications."

Founded in 2016 as a spin-out from the University of Washington (UW) and gene gun vaccine innovator Deborah Fuller, PhD, Professor of Microbiology at UW, Orlance is focused on developing next-generation MACH-1 vaccines and cancer immunotherapies. With $13M in SBIR funding awarded to date, the company has advanced MACH-1 toward readiness for initial regulatory filings in 2024. Orlance plans to initiate Phase I clinical trials for its lead infectious disease asset in 2025 and is actively partnering with other vaccine developers to develop MACH-1 vaccine and immunotherapy candidates across multiple indications.

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