Blue Lake Biotechnology, Inc.

Advisors to the FDA had difficulty dissecting a small but concerning set of safety data from Moderna’s pediatric RSV vaccine data, largely concluding that other trials should continue to better inform immune responses in young kids. The FDA has flagged concerns based on severe cases of RSV seen in vaccinated children in Moderna’s Phase 1 study of two experimental vaccines, potentially due to vaccine-associated enhanced respiratory disease. The cases harken back to clinical studies in the 1960s, when two toddlers died in a vaccine trial, stalling pediatric RSV work for decades. Then, as now, severe RSV cases occurred in children who had never previously been infected with the virus. “We’re confronted by a very complicated situation,” said Arnold Monto, a professor emeritus of epidemiology at the University of Michigan. He suggested that the agency should consider safety for the individual platforms, but not the class as a whole. The Vaccines and Related Biological Products Advisory Committee wasn’t asked to vote Thursday, but rather to provide feedback on whether available data suggest a general safety risk to infants and toddlers or whether it’s unique to specific vaccine platforms. In July, the FDA put a clinical hold on Moderna’s study after severe RSV cases arose in five patients who received one of two vaccine candidates. By early August, the agency put a partial hold on other pediatric studies involving vaccine candidates that were not based on a live-attenuated vaccine. A sixth patient reported a severe RSV case months after completing vaccination and after the FDA placed the holds. The FDA didn’t respond to a question about how many studies were placed on a partial hold, but the agency outlined in briefing documents that 11 candidates that did not involve a live-attenuated vaccine candidate had pediatric studies. The holds weren’t disclosed by either the agency or the companies until the briefing materials were released ahead of the meeting this week. The FDA hasn’t yet identified a similar safety signal from other vaccine candidates, despite the partial hold. Octavio Ramilo, chair of infectious diseases at St. Jude Children’s Research Hospital, was brought on by the data safety monitoring board of Moderna’s trial to better understand the data. He acknowledged that the understanding of how to make a vaccine and leverage preclinical animal models was incomplete. “So I think there [are] a lot of gaps in our knowledge,” he said. ‘The monitoring here worked’ Moderna reported no cases of severe RSV hospitalization through March 2024 in the portion of the trial testing infants 8 to 23 months, and the company then moved to a younger cohort of patients who were 5 to 7 months old. Since the trial was halted, Moderna has also reported a case in the older population, which arose in August. Four of five severe cases included hospitalization, and all but one patient has gotten better. The most severe patient was hospitalized for 16 days, including 10 in the ICU, and that patient still had arterial hypertension. Moderna announced in September that it was not advancing the pediatric vaccine, but did not disclose at the time that it was under clinical hold. A spokesperson for the company declined to say why the hold wasn’t disclosed then when reached for comment earlier this week. The advisors seemed to largely endorse the regulatory safeguards in place, despite Moderna reporting encouraging preclinical safety data in cotton mice ahead of the clinical trials. Advisor Adam Berger said, “the monitoring here worked.” “The safety signal was identified. The sponsor halted the study. This is exactly the type of safeguards you want to see happen,” he said. Sarah Meyer, chief medical officer at the Immunization Services Division within the CDC, underscored that it’s difficult to assess trial safeguards without further understanding the mechanism of action that may have spurred the severe cases. Blue Lake Biotechnology, which was included in the subsequent partial hold, presented to the committee that it had not “detected any safety signals” of severe disease associated with its vaccine, according to Chief Medical Officer Henry Radziewicz. The company similarly had not publicly disclosed that it was on a partial hold before Thursday’s meeting. Sanofi also presented on its live-attenuated vaccine, currently in a Phase 3 study, saying that it had not seen any concerning safety signals. It’s not included in the FDA’s partial holds and committee members seemed to be assuaged by the fact that it has been given to many more patients in trials. “I’m not worried about the live-attenuated [vaccines] because of the long history of safety there,” said Tracy Ruckwardt, chief of the respiratory viruses core at the NIH’s Vaccine Research Center. Editor’s note: This story was updated to correct that Moderna’s trial was a Phase 1 study, not a Phase 1/2 study.

Clinical study supported by BARDA under Project NextGen to compare CVXGA to mRNA vaccine ATHENS, GA & SAN JOSE, CA, USA I December 09, 2024 I CyanVac LLC, a clinical-stage biotechnology company developing intranasal vaccines using a transformational parainfluenza virus 5 (PIV5)-based vector, announced today that the first participant has been dosed in a Phase 2b clinical study of CVXGA, its intranasal COVID-19 vaccine candidate. The study, supported by the U.S. Government’s (USG) Project NextGen , is designed to evaluate CVXGA against a U.S. Food and Drug Administration (FDA)-approved injectable mRNA-based COVID-19 vaccine, with both CVXGA and the comparator mRNA-based vaccine targeting the omicron variant KP.2 strain of SARS-CoV-2. Approximately 400 participants initially will be enrolled in sentinel and safety lead-in cohorts. Once an independent Data and Safety Monitoring Board (DSMB) reviews the safety data of the participants, and the Center for the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response (ASPR) within the Department of Health and Human Services (HHS) provides approval, enrollment of approximately 9,600 additional participants for the second part of the trial will proceed. “This phase 2b trial represents a major milestone for our proprietary PIV5-based vaccine platform,” said Biao He, Ph.D., founder and CEO of CyanVac. “Recently we reported positive results from an earlier Phase 2a trial of CVXGA involving 227 adult volunteers. We expect this new Phase 2b trial to play a key role in confirming these results and validating the potential of our PIV5-based vaccine platform.” The Phase 2b study is being conducted through BARDA’s Clinical Studies Network and is expected to enroll approximately 10,000 adults representative of the U.S. population including people at high risk for severe COVID-19. Participants will be followed for evidence of SARS-CoV-2 infection for 12 months after vaccination. The study is designed to assess the relative efficacy of CVXGA versus mRNA vaccine in the prevention of symptomatic COVID-19. The study also will evaluate CVXGA’s ability to prevent asymptomatic infections, which could be an indicator of the vaccine’s ability to prevent the transmission or spread of this respiratory pathogen. This project is being funded with federal funds from HHS, ASPR, BARDA, under Other Transaction (OT) number 75A50123D00005. 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 high efficacy and durability with few vaccine-related side effects. Learn more at CyanVac and Blue Lake Biotechnology . SOURCE: CyanVac

ATHENS, Ga. & SAN JOSE, Calif.--( BUSINESS WIRE )--CyanVac LLC, a clinical-stage biotechnology company developing intranasal vaccines using a transformational parainfluenza virus 5 (PIV5)-based vector, announced today that the first participant has been dosed in a Phase 2b clinical study of CVXGA, its intranasal COVID-19 vaccine candidate. The study, supported by the U.S. Government’s (USG) Project NextGen , is designed to evaluate CVXGA against a U.S. Food and Drug Administration (FDA)-approved injectable mRNA-based COVID-19 vaccine, with both CVXGA and the comparator mRNA-based vaccine targeting the omicron variant KP.2 strain of SARS-CoV-2. Approximately 400 participants initially will be enrolled in sentinel and safety lead-in cohorts. Once an independent Data and Safety Monitoring Board (DSMB) reviews the safety data of the participants, and the Center for the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response (ASPR) within the Department of Health and Human Services (HHS) provides approval, enrollment of approximately 9,600 additional participants for the second part of the trial will proceed. “This phase 2b trial represents a major milestone for our proprietary PIV5-based vaccine platform,” said Biao He, Ph.D., founder and CEO of CyanVac. “Recently we reported positive results from an earlier Phase 2a trial of CVXGA involving 227 adult volunteers. We expect this new Phase 2b trial to play a key role in confirming these results and validating the potential of our PIV5-based vaccine platform.” The Phase 2b study is being conducted through BARDA’s Clinical Studies Network and is expected to enroll approximately 10,000 adults representative of the U.S. population including people at high risk for severe COVID-19. Participants will be followed for evidence of SARS-CoV-2 infection for 12 months after vaccination. The study is designed to assess the relative efficacy of CVXGA versus mRNA vaccine in the prevention of symptomatic COVID-19. The study also will evaluate CVXGA’s ability to prevent asymptomatic infections, which could be an indicator of the vaccine's ability to prevent the transmission or spread of this respiratory pathogen. This project is being funded with federal funds from HHS, ASPR, BARDA, under Other Transaction (OT) number 75A50123D00005. 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 high efficacy and durability with few vaccine-related side effects. Learn more at CyanVac and Blue Lake Biotechnology .