Xanadu Bio Obtains Licenses and Options to Novel Platform Technologies from Yale University to Develop an Intranasal SARS CoV-2 mRNA Vaccine Booster Aimed at Inducing Local Mucosal Immunity to Prevent SARS CoV-2 Infection and Virus Transmission

~ Company licenses PACE, a next generation polymeric nanoparticle delivery platform, and options intranasal PACE/Spike mRNA and Spike recombinant protein vaccine boosters for the treatment of aerosolized viruses; initially targeting SARS CoV-2 ~

~ Technologies developed in the laboratories of Yale University Professors Mark Saltzman and Akiko Iwasaki ~

~ Preclinical data demonstrates intranasal PACE/Spike mRNA and Spike recombinant protein boosters induce robust mucosal immunity in the nasosinus and upper respiratory tract and protect against lethal doses of SARS-CoV-2 variants when administered after systemic immunization with Pfizer’s mRNA COVID-19 vaccine ~

NEW HAVEN, Conn., Feb. 08, 2022 (GLOBE NEWSWIRE) -- Xanadu Bio, a privately held company focusing on next generation delivery of mRNA and other nucleic acids, today announced a broad exclusive license agreement from Yale University for a next generation polymeric nanoparticle delivery platform known as PACE. Additionally, the company has executed options with Yale University for the intranasal delivery of PACE/Spike mRNA and Spike recombinant proteins for the development of mucosal immunity in the nasosinus.

Xanadu is developing an intranasal SARS-CoV-2 vaccine booster, after systemic vaccination, to protect against infection in the nasosinus/upper airways, thus potentially reducing SARS-CoV-2 transmission in the community. Spread by asymptomatic infected patients in both vaccinated and unvaccinated populations has proven challenging because although current intramuscular vaccines against SARS-CoV-2 are often effective in preventing death and hospitalization, they do not prevent local infection in the nasosinus and associated transmission.

“Eliciting respiratory tract mucosal immunity through nasal vaccines could be used to fight SARS-Cov-2 and other aerosolized viruses, such as influenza and RSV,” said Bruce C. Turner, M.D., Ph.D., chief executive officer and chair of the board of Xanadu Bio. “This is why we found the work of Dr. Iwasaki, a world authority on mucosal immunity who has published extensively in this field, so profoundly interesting.”

Akiko Iwasaki, Ph.D., is a Waldemar Von Zedtwitz Professor of Immunobiology and Molecular, Cellular, and Developmental Biology, Professor of Epidemiology, Yale University, and Howard Hughes Medical Institute Investigator. She proposed the novel vaccination strategy of “Prime and Pull” which has recently been applied to COVID.

“Prime and Spike” and “Prime and PACE” (with Spike mRNA), are novel intranasal vaccine booster strategies, which are covered under Xanadu’s agreement with Yale University. “Prime” refers to existing immunity generated by primary intramuscular mRNA vaccination and PACE/Spike refers to a later, local antigenic challenge with a booster that leverages existing immunity to elicit mucosal immune memory (the “Pull”) within the nasal and respiratory tract. This strategy was used to evaluate the intranasal delivery of both SARS-CoV-2 spike protein and PACE/Spike mRNA in transgenic mice that express the human ACE2 receptor, thus susceptible to infection by SARS-CoV-2. The results demonstrate that PACE/Spike mRNA booster elicits broad and sustained immune responses when administered intranasally. Vaccinating with intranasal PACE/Spike mRNA after intramuscular priming with Pfizer’s mRNA COVID-19 vaccine yields high levels of tissue-resident, Spike-specific T and B memory cells and Spike-specific mucosal IgA-secreting B cells. Mouse outcome data following delivery of intranasal PACE/spike mRNA after Prime with Pfizer’s mRNA COVID-19 vaccine demonstrate statistically significant survival protection following lethal challenge with SARS-CoV-2 in the context of waning systemic immunity. These results have been submitted for peer-review and potential publication, and can be accessed by the public at https://www.biorxiv.org/content/10.1101/2022.01.24.477597v1.

“It is very satisfying to see the PACE technology that I have spent the past decade developing and improving, now being used in a novel mRNA booster against SAR2-CoV-2 that induces local mucosal immunity in the nose at the site of entry of the virus, potentially helping to end this awful pandemic,” said Mark Saltzman, Goizueta Foundation Professor of Chemical and Biomedical Engineering; Professor of Cellular & Molecular Physiology; Head, Jonathan Edwards College, Faculty Co-Director, Center for Biomedical Innovation and Technology, Yale University. “PACE technology can be optimized to deliver nucleic acids payloads, including mRNA, to major organs including the bone marrow, lungs, gastrointestinal tract and pancreas, and can also be modified to allow for cell specific delivery, potentially enabling highly targeted genomic intervention.”

Xanadu Bio was co-founded in 2021 by Mark Saltzman, Ph.D., Akiko Iwasaki, Ph.D., Marie Egan, M.D., Matthew Simon, Ph.D. Alexandra Piotrowski-Daspit, Ph.D., Todd Wider, M.D., and Bruce C. Turner, M.D., Ph.D. Dr. Turner, chief executive officer of Xanadu, is a life sciences industry veteran who previously served as a senior pharmaceutical executive at F. Hoffmann-La Roche AG responsible for nucleic acid drug development, managing director at Tavistock Group/Boxer Capital and co-founded Gennao Bio.

“We believe that by combining the foundational technologies developed by distinguished Yale Professors Saltzman and Iwasaki, we can develop intranasal vaccine boosters against SARS-CoV-2 to kill Covid-19 virus in the nasosinus before it spreads deeper into the respiratory tract endangering the patient. By killing the virus in the nose, transmission to others in the community may also be prevented,” said Dr. Turner. “We plan to enter the clinic in the near-term with a nasally delivered vaccine booster against SARS-CoV-2 using mRNA technology which has been proven safe and effective, and has a unique profile that includes inducing mucosal immunity at the site of entry, hopefully killing the virus before both symptoms develop and the virus has spread to others.”

About Xanadu Bio

Xanadu Bio is a privately held, next generation nanoparticle delivery company focusing on the delivery of mRNA and other nucleic acids that utilizes PACE platform technology. PACE technology is a next-generation polymeric nanoparticle that consists of three monomers that are fully biodegradable, and allows for efficient delivery of and protection from nuclease degradation for different types of nucleic acids, including mRNA. PACE is easily manufactured, cost effective, scalable and can be functionalized to allow both organ and cell specific delivery of its nucleic acid payload. PACE is formulated and optimized to allow safe delivery either systemically or intranasally. Leveraging PACE, Xanadu is initially focused on developing nasal vaccine boosters for the prevention and treatment of SARS CoV-2 infection and for other indications.