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ATHENS, GA & SAN JOSE, CA, USA I November 25, 2024 I Blue Lake Biotechnology, Inc., a clinical-stage intranasal vaccine company developing parainfluenza virus 5 (PIV5)-vectored vaccines that harness the full breadth of the immune system to protect against serious infectious diseases, and its affiliate CyanVac LLC, today reported data from a 227-participant Phase 2a clinical trial demonstrating the safety, tolerability, immunogenicity, and efficacy of CVXGA, the company’s intranasal vaccine candidate against COVID-19. In this study, which was the first double-blind, placebo-controlled trial of a PIV5-vectored vaccine, there was no significant difference in the number of adverse reactions observed in CVXGA-vaccinated versus placebo-vaccinated participants, providing evidence that PIV5-vectored intranasal vaccines can be safe and well-tolerated. Clinical trial participants vaccinated with CVXGA had S-protein specific serum antibody titers at 29 days after vaccination which were 1.9-fold greater than titers in participants who received placebo, a level greater than has been previously reported for other intranasal vaccines in adults. CVXGA induced S-protein specific serum antibody responses in both younger adults (18-64 years old, p=0.002) and older adults (65 years and older, p=0.032), an important consideration given the latter group’s greater risk for severe illness after infection. Participants who received a single dose of CVXGA had a 78% lower risk of developing symptomatic COVID-19 infection compared to the placebo group in the first month after vaccine administration. “The 78% protection compares quite favorably with the efficacy of approved COVID vaccines, which has been reported to be 52% at four weeks after vaccination,” said Biao He, Ph.D., CEO of Blue Lake and CyanVac. “Most reassuring are the results showing how well tolerated our intranasal COVID vaccine is, in contrast to currently approved COVID vaccines which are commonly associated with injection site reactions, fever, fatigue, and headache. The safety and efficacy data from this trial are highly encouraging, and we look forward to the dosing of more volunteers in the next clinical study of CVXGA.” The Phase 2a study was a double-blind, placebo-controlled study that enrolled 227 participants who were randomized 1:1 to receive either CVXGA (targeting the S-protein of the omicron XBB.1.5 variant strain of SARS-CoV-2) or placebo. Primary endpoints included assessments of safety, tolerability, and immunogenicity, and exploratory endpoints included assessment of the proportion of participants diagnosed with symptomatic SARS-CoV-2 infection. “COVID-19 continues to be a public health threat. A more effective, better tolerated, and easily administered vaccine should increase the vaccination rate and reduce the hospitalizations and deaths that continue to occur with COVID-19,” added Dr. He. About CVXGA CVXGA is a clinical-stage COVID-19 vaccine candidate based on a proprietary parainfluenza virus 5 (PIV5) vector that encodes the spike (S) protein of SARS-CoV-2. The PIV5 vector was developed at the University of Georgia and is based on a respiratory virus that is not known to cause disease in humans which has been commonly administered to dogs as part of combination distemper/kennel cough vaccines for decades. CyanVac and its affiliate, Blue Lake Biotechnology, are developing CVXGA as a single-dose, intranasal vaccine to prevent SARS-CoV-2 infection and serious complications associated with COVID-19. Preclinical studies have demonstrated that CVXGA is immunogenic and protective and prevents transmission of SARS-CoV-2. Phase 1 and Phase 2a clinical studies have shown that subjects dosed with CVXGA showed robust mucosal, cellular and humoral immune responses with limited or no reactogenicity and no serious events assessed as related to the vaccine. About CyanVac and Blue Lake Biotechnology CyanVac LLC and its affiliate, Blue Lake Biotechnology, Inc., are developing intranasal vaccines that harness the full breadth of the immune system to keep people healthy, prevent serious infectious diseases, and protect the health of vulnerable populations. Our platform uses a proprietary parainfluenza virus 5 vector into which a foreign gene from a targeted pathogen is inserted. We have generated a robust clinical-stage pipeline of best-in-class vaccines designed to overcome the limitations of existing vaccine technologies. Our lead product candidates have demonstrated potential for efficacy following a single intranasal dose with few vaccine-related side effects. Learn more at CyanVac and Blue Lake Biotechnology. SOURCE: CyanVac

ATHENS, Ga. & SAN JOSE, Calif.--( BUSINESS WIRE )--Blue Lake Biotechnology, Inc., a clinical-stage intranasal vaccine company developing parainfluenza virus 5 (PIV5)-vectored vaccines that harness the full breadth of the immune system to protect against serious infectious diseases, and its affiliate CyanVac LLC, today reported data from a 227-participant Phase 2a clinical trial demonstrating the safety, tolerability, immunogenicity, and efficacy of CVXGA, the company’s intranasal vaccine candidate against COVID-19. In this study, which was the first double-blind, placebo-controlled trial of a PIV5-vectored vaccine, there was no significant difference in the number of adverse reactions observed in CVXGA-vaccinated versus placebo-vaccinated participants, providing evidence that PIV5-vectored intranasal vaccines can be safe and well-tolerated. Clinical trial participants vaccinated with CVXGA had S-protein specific serum antibody titers at 29 days after vaccination which were 1.9-fold greater than titers in participants who received placebo, a level greater than has been previously reported for other intranasal vaccines in adults. CVXGA induced S-protein specific serum antibody responses in both younger adults (18-64 years old, p=0.002) and older adults (65 years and older, p=0.032), an important consideration given the latter group’s greater risk for severe illness after infection. Participants who received a single dose of CVXGA had a 78% lower risk of developing symptomatic COVID-19 infection compared to the placebo group in the first month after vaccine administration. “The 78% protection compares quite favorably with the efficacy of approved COVID vaccines, which has been reported to be 52% at four weeks after vaccination,” said Biao He, Ph.D., CEO of Blue Lake and CyanVac. “Most reassuring are the results showing how well tolerated our intranasal COVID vaccine is, in contrast to currently approved COVID vaccines which are commonly associated with injection site reactions, fever, fatigue, and headache. The safety and efficacy data from this trial are highly encouraging, and we look forward to the dosing of more volunteers in the next clinical study of CVXGA.” The Phase 2a study was a double-blind, placebo-controlled study that enrolled 227 participants who were randomized 1:1 to receive either CVXGA (targeting the S-protein of the omicron XBB.1.5 variant strain of SARS-CoV-2) or placebo. Primary endpoints included assessments of safety, tolerability, and immunogenicity, and exploratory endpoints included assessment of the proportion of participants diagnosed with symptomatic SARS-CoV-2 infection. “COVID-19 continues to be a public health threat. A more effective, better tolerated, and easily administered vaccine should increase the vaccination rate and reduce the hospitalizations and deaths that continue to occur with COVID-19,” added Dr. He. About CVXGA CVXGA is a clinical-stage COVID-19 vaccine candidate based on a proprietary parainfluenza virus 5 (PIV5) vector that encodes the spike (S) protein of SARS-CoV-2. The PIV5 vector was developed at the University of Georgia and is based on a respiratory virus that is not known to cause disease in humans which has been commonly administered to dogs as part of combination distemper/kennel cough vaccines for decades. CyanVac and its affiliate, Blue Lake Biotechnology, are developing CVXGA as a single-dose, intranasal vaccine to prevent SARS-CoV-2 infection and serious complications associated with COVID-19. Preclinical studies have demonstrated that CVXGA is immunogenic and protective and prevents transmission of SARS-CoV-2. Phase 1 and Phase 2a clinical studies have shown that subjects dosed with CVXGA showed robust mucosal, cellular and humoral immune responses with limited or no reactogenicity and no serious events assessed as related to the vaccine. About CyanVac and Blue Lake Biotechnology CyanVac LLC and its affiliate, Blue Lake Biotechnology, Inc., are developing intranasal vaccines that harness the full breadth of the immune system to keep people healthy, prevent serious infectious diseases, and protect the health of vulnerable populations. Our platform uses a proprietary parainfluenza virus 5 vector into which a foreign gene from a targeted pathogen is inserted. We have generated a robust clinical-stage pipeline of best-in-class vaccines designed to overcome the limitations of existing vaccine technologies. Our lead product candidates have demonstrated potential for efficacy following a single intranasal dose with few vaccine-related side effects. Learn more at CyanVac and Blue Lake Biotechnology.

Unprecedented comprehension of the interaction between Spike and the Human Estrogen Receptor Alfa provides insights for a new generation of anti SARS-CoV-2 and pan-Coronavirus vaccines Italian and US researchers have revealed how the SARS-CoV-2 Spike protein interacts with human Estrogen Receptor-α (ERα) leading to severe coagulopathy observed in COVID-19 patients. The new data - published in Nature’s Signal Transduction and Targeted Therapy - shows that point mutations in the sequence of SARS-CoV-2 Spike (S)-protein eliminate its pro-coagulation effect without compromising immunogenicity. The findings provide actionable insights for designing vaccines lacking of estrogen-receptor mediated side effects for all coronavirus strains and other viral infections. MILAN & SAN MATEO, Calif.--(BUSINESS WIRE)-- Dompé farmaceutici announced today new peer-reviewed data demonstrating that small changes in the SARS-CoV-2 Spike (S)-protein sequence can eliminate its effect in inducing coagulation1. The tendency for the Spike protein to stimulate inflammatory and coagulation has been implicated in coagulopathy observed in the lungs, heart and kidneys of COVID-19 patients with a similar and extremely rare effects observed in a minority of patients who received COVID-19 vaccines. This press release features multimedia. View the full release here: Framework Dompé farmaceutici Biotech production (Photo: Business Wire) Data stemmed from the EXSCALATE supercomputing calculation predicted a potential function of Spike (S) as a co-factor for human ERα nuclear signalling. This interaction is mediated by a nuclear receptor co-regulator (NRC) LXD-like motif present on the viral protein S2 subunit, and the activation function 2 (AF-2) region on ERα2. This work builds on other recent studies3,4 showing that coagulopathy is clearly associated with the interaction of the SARS-CoV-2 Spike (S) protein with the human Erα. While circulating estrogens play a protective role by regulating the immune response to infection, modulation of ERα signalling in SARS-CoV-2-infected lung tissue stimulates proinflammatory signals leading to hypertrophy, vasoconstriction, and vessel obstruction. In the new article the scientists of the italo-american collaboration (encompassing Centro Cardiologico Monzino in Italy and the National Institute on Drug Abuse and the Johns Hopkins School of Medicine in the US) demonstrated that the interaction between the Spike protein and ERα leads to an increase in tissue factor (TF) and the overall pro-coagulation activity in two human endothelial cell lines. The results were further validated by overexpressing S-protein in mice. This pro-coagulative function of Spike in vitro and in vivo, was abolished or strongly reduced by the variants of the Spike proteins carrying mutations in the interaction domain with ERα (as predicted by EXSCALATE). “The value and benefits of vaccines in countering the COVID-19 pandemic remain unquestionable and overwhelming compared to the risks associated with infection from SARS-CoV-2” underscores Maurizio Pesce, a research Group Leader at the Monzino Cardiology Center in Milan, Italy, and initiator of the study in 2021 together with the leading Silvia Barbieri, another research Group Leader at Monzino, “We hope that our findings will be considered in the development of the next generation of vaccines reducing the residual side effects and risks. Our data also unravel a new function of the viral protein in direct regulation of thrombosis associated factors. This has general implications not only for COVID-19, but for other viral infections altering the coagulation pro patients”. “This continuing research is critical to understand the pathogenetic mechanisms associated with SARS-CoV2 infection and causal mechanisms of some rare COVID-19 vaccine side effects,” says Dompé farmaceutici Chief Scientific Officer Marcello Allegretti “Ongoing expanding data is revealing a well-conserved region with the same characteristics of the LXD-like motif present on the viral protein S2 subunit, also in other Coronaviruses. This evidence could open new scenarios in ‘pan-Coronavirus’ vaccination. We are excited to identify a path toward further refinement strategies to enable even more powerful benefits through future vaccination and booster initiatives”. ____________________________________________________________________________________ About Dompé Dompé is a private, rapidly scaling international biopharmaceutical company founded in Milan, Italy, with a 130-year legacy of medical innovation. The R&D department of the company is anchored by EXSCALATE, a structure-based virtual screening platform developed in-house that leverages one of the most powerful supercomputing and artificial intelligence platforms in the world. Today, Dompé employs more than 800 employees worldwide and maintains a US commercial operations hub in the San Francisco Bay Area as well as an R&D presence in Boston. Forward Looking Statements This press release refers to certain information that may not coincide with expected future results. Dompé firmly believes in the soundness and reasonableness of the concepts expressed. However, some of the information is subject to a certain degree of indetermination in relation to its research and development activities and the necessary verifications to be performed by regulatory bodies. Therefore, as of today, Dompé cannot guarantee that the expected results will be consistent with the information provided above. 1. SS Barbieri et al. Relevance of the viral Spike protein/cellular Estrogen Receptor-α interaction for endothelial-based coagulopathy induced by SARS-CoV-2 - Signal Transduction and Targeted Therapy - 2. Allegretti, M. et al. Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 370 infection. Cell Death Differ. 29, 156-166 (2022). 371 - 3. Wilcox et al. Sex Differences in Thrombosis and Mortality in Patients Hospitalized for COVID-19, Am J Cardiol. 2022 May 1; 170: 112–117 - 4. Science Advances - The SARS-CoV-2 spike protein binds and modulates estrogen receptors - eadd4150 (2022) 30 November 2022 -