Orlance
Press Release
Orlance Inc. Awarded NIH SBIR Grant for Next Generation Gene-Gun Delivered DNA and RNA Immunotherapeutic Vaccines for Melanoma
For Immediate Release:
July 10, 2024
SEATTLE, WA – July 10, 2024 – 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.
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
Orlance feature courtesy of our University of Washington partners
'Gene gun' aims to make universal flu vaccine possible - December 13, 2023
Orlance
Press Release
Orlance Inc. Awarded NIH SBIR Grant for Next Generation Gene-Gun Delivered DNA and RNA Immunotherapeutic Vaccines for Melanoma
For Immediate Release:
October 11, 2023
SEATTLE, WA – October 11, 2023 – Orlance, Inc., a Seattle biotech developing next-generation DNA and RNA vaccines and therapeutics, has been awarded a National Institutes of Health (NIH) Phase I Small Business Innovation Research (SBIR) grant to use its needle-free MACH-1™ platform for creating a vaccine regimen that induces strong tumor specific immune responses and protection from melanoma.
The MACH-1 platform is a high-performance microparticle ‘gene gun’ technology that efficiently and uniquely delivers DNA or RNA vaccine-coated microparticles directly into cells in the epidermis, the uppermost layer of the skin. The epidermis is rich in immune-stimulating cells. MACH-1 delivery harnesses this environment and the natural machinery of its immune cells to deliver DNA and RNA vaccines or therapeutics; these encode proteins that trigger potent immunity including generation of antibodies to block an infection and activation of T cells that can either eliminate infected cells or kill tumor cells. Unlike current licensed mRNA vaccines, MACH-1-delivered vaccines are stable at room temperature, are painless and needle-free, and can trigger protective levels of immunity or efficacy with much lower doses.
While personalized cancer antigens have been identified from patients tumors, effective methods to deliver these antigens and stimulate specific immune responses are still lacking. MACH-1 stable, painless, targeted, and lose-dose DNA and RNA vaccines show promise for addressing these shortcomings in melanoma treatment, based upon MACH-1 data in other relevant models. Researchers aim to enhance MACH-1’s effectiveness by exploring combinations of genetic enhancers (adjuvants) and DNA or RNA formulations in comparison to other delivery methods in mice.
“Orlance is thrilled that our MACH-1 technology has broad applicability in both infectious disease and oncology. Our preclinical accomplishments in vaccines for viral infections have caught the eye and generated rapid enthusiasm among multiple cancer collaborators, including the National Cancer Institute (NCI) via this SBIR award,” stated Kristyn Aalto, Orlance CEO. “Overall, we’re seeing the field recognize the attributes of targeting the skin itself, rather than deeper tissues, as the ideal immunologic tissue and dosing site for DNA and RNA vaccines. We are confident that MACH-1’s standalone ability to delivery specifically into the epidermis will continue to yield strong results across multiple disease targets. Melanoma is an exciting first crossover into cancer for us due both to unmet need and its perfect skin-targeting opportunity.” This new SBIR grant, led by Orlance’s Dr. Hannah Frizzell, PhD, will enable Orlance to complete proof of concept, formulation, and adjuvant incorporation necessary to advance lead candidates into later-stage preclinical development activities and IND readiness. If successful, program output will be a vaccine candidate shown to induce significantly slower tumor outgrowth in preclinical models that also incorporates all MACH-1 stability, dose-sparing, tissue targeting, and needle-free advantages.
This award brings Orlance’s SBIR funding total to $12.9M to advance next-generation DNA and RNA vaccines and therapeutics. Orlance was founded as a University of Washington spin out company in 2016 to develop the MACH-1 platform based on technology invented by Deborah Fuller, PhD, Professor of Microbiology at the University of Washington School of Medicine. Orlance plans to initiate Phase 1 clinical trials for the company’s lead infectious disease asset in 2025.
Orlance
Press Release
Orlance Inc. Awarded Pivotal $3M NIH SBIR Grant for Advancing MACH-1TM Needle-Free, Powdered Influenza Vaccine and Delivery Platform to Clinic
For Immediate Release:
September 19, 2023
SEATTLE, WA–September 19, 2023–Orlance, Inc., a Seattle biotech advancing low-dose, needle-free vaccines and therapeutics, has been awarded a three-year $3M National Institutes of Health (NIH) Phase II Small Business Innovation Research (SBIR) grant titled ‘Clinic-Ready Gene Gun for delivery of a universal influenza DNA vaccine.’ This funding allows Orlance to move its MACH-1 powdered vaccine and therapeutics formulation and delivery platform toward Phase 1 clinical trials of its lead MACH-1 asset, a universal influenza vaccine. The project addresses the need for a low-dose, rapidly produced and easily distributed vaccine that can protect from annual influenza strains and the emergence of new variants that could cause future pandemics. This award brings Orlance’s SBIR funding total to $12.5M to advance next generation vaccines and therapeutics.
The MACH-1 platform is designed to deliver DNA or RNA-coated gold microparticles directly into the uppermost live layer of the skin, the epidermis, using high pressure gas. MACH-1 is a powder mediated epidermal delivery (PMED) technology, a subset of ‘gene gun’ technologies used in various life science research applications, that delivers small genetic sequences into cells to code for intended proteins, in this case immunogens. It is pain free, needle-free, requires substantially lower doses of DNA or RNA to achieve efficacy than other DNA or RNA vaccine formulation and delivery methods, and eliminates cold chain distribution requirements. DNA and RNA vaccines require significantly shorter manufacturing times than other vaccine types, enabling rapid response to seasonal and pandemic needs and greater production capacity. Orlance can uniquely target the shallow, highly immunogenic epidermis of the skin due to its novel, highly-localized, and efficient delivery technology that eliminates wasted vaccine, additional components required for injection, and safety concerns associated with injectable formulations. The company’s lead asset, a universal influenza vaccine, is designed to induce systemic and mucosal immune responses that can prevent transmission and minimize disease from currently circulating and emerging strains. The MACH-1 universal influenza vaccine accomplishes this by inducing broad antibody and cellular immune responses that target conserved viral sequences common across all influenza subtypes.
“We are very excited about what Orlance MACH-1 vaccines are positioned to offer the healthcare industry and overall health landscape,” stated Kristyn Aalto, Orlance CEO. “As an example, while many groups are working toward universal influenza vaccine candidates that reduce seasonal vaccine-to-strain mismatch and can reach underserved markets, they face limitations posed by standard injectable technologies that favor antibody over cellular immune responses, don’t really target our most immunogenic tissue compartments, can cause side effects due to dose size and formulation components, and inherently have stability and supply chain challenges. MACH-1 DNA vaccines create both antibody and longer-lived cellular immune responses, use epidermal delivery methods demonstrated to create both systemic and mucosal immunity including within essential lung mucosa, and have the stability and longevity to reach global markets currently without sufficient access to seasonal vaccines.”
This new SBIR grant enables Orlance to complete the formulation, design and preclinical validation activities necessary to prepare the MACH-1 system for Phase 1 clinical trials. If successful, this program will provide a high-performance clinic ready platform to deliver a universal influenza vaccine that could reduce the burden of influenza diseases worldwide and potentially prevent the next influenza pandemic. This program will also result in MACH-1 systems ready for partnering opportunities to address other vaccine and therapeutic indications.
Under previous SBIR funding, Orlance demonstrated that its MACH-1-delivered universal influenza DNA vaccine induced broadly specific universal antibody and T cell responses and protection from diverse influenza challenges in multiple preclinical models. Orlance was founded as a University of Washington spinout company in 2016 to develop the PMED technology invented by Deborah Fuller, PhD, Professor of Microbiology at UW, that became the MACH-1 platform. The company plans to initiate Phase 1 clinical trials in 2025.