SAN DIEGO--(BUSINESS WIRE)--Revelation Biosciences Inc. (Revelation), a clinical stage life sciences company focused on the development of immunologic-based therapies for the prevention and treatment of disease, announced today results from RVL‑NHV01, a Phase 1 clinical study of REVTx-99. RVL‑NHV01 was a single site, placebo‑controlled, single dose, escalating dose, followed by a multiple dose arm study to determine the pharmacodynamic effect, safety and tolerability of intranasal REVTx‑99 in healthy adult volunteers.
The primary pharmacodynamic endpoint was met, REVTx‑99 stimulated significant production of Interferon-Induced Protein-10 (IP-10) in a dose-dependent fashion. Intranasal IP-10 levels increased in a dose dependent manner to levels 13 times greater than pre-dose levels for the combined 50 and 100 μg dose groups vs. a 1.5-fold change for the placebo group (p=0.03). Increases in intranasal levels of additional, exploratory cytokines correlated with the increase in IP-10.
In the 50 μg REVTx‑99 treated group, there were significant response rates as measured by ≥5‑, 7‑, or 10‑fold change in IP‑10 from individual nostril pre-dose levels. A ≥5‑fold response was observed in 67% of the REVTx‑99 ‑treated group vs. 13% of the placebo‑treated group (p<0.01), a ≥7‑fold response was observed in 42% of the REVTx‑99 ‑treated group vs. 0% in placebo‑treated group (p<0.01), and a ≥10‑fold response was observed in 33% of the REVTx‑99 ‑treated group vs. 0% in placebo‑treated group (p<0.01).
Evaluation of an absolute change of >250 μg IP‑10/mL from baseline gave a response rate of 29% for the 50 and 100 μg dose groups combined, vs. a 4% response rate for the placebo group (p = 0.02). Evaluation of an absolute change of >200 μg IP-10/mL from baseline gave a response of 33% for the 50 and 100 μg dose groups combined, vs. a 4% response rate for the placebo group (p=0.01).
Overall, 38 adverse events (AE) were reported (20 test article-related, 18 not related). All adverse events were mild in nature (mild AEs being categorized as easily tolerated and did not interfere with normal daily activities) and did not require any medical intervention for complete resolution. The predominant adverse events included nasal bleeding at the time of sample collection (23% in treated vs. 20% in placebo), headache (3% in treated vs. 20% in placebo), nasal discomfort (7% in treated vs. 10% in placebo), and rhinorrhea (7% in treated vs. 0% in placebo).
"We are pleased with the outcome of the Phase 1 study and look forward to starting a Phase 2 viral challenge study later this year," said James Rolke, Chief Executive Officer of Revelation.
In this study 48 participants were dosed with REVTx‑99 (n=6) or placebo (n=2). The primary endpoints were to determine the safety and tolerability of escalating intranasal doses of REVTx‑99 in healthy adult volunteers, and to determine the pharmacodynamic effect of REVTx‑99 in healthy adult volunteers as measured by nasal and systemic cytokine levels throughout the course of treatment. Secondary and exploratory endpoints comprised change in serum cytokine levels, treatment emergent adverse events and plasma PK levels.
Revelation plans to initiate a Phase 2 viral challenge study to evaluate the potential utility of REVTx‑99 for preventing and treating respiratory viral infection. This study is on track to begin in the second half of 2021.
For more information on Revelation, please visit www.RevBiosciences.com.
About REVTx‑99
REVTx‑99 is a proprietary intranasal drop formulation in development for the prevention or treatment of respiratory viral infection and is broadly applicable to most infectious viruses including Influenza A, Influenza B, parainfluenza, rhinovirus, respiratory syncytial virus, SARS‑CoV‑2 and its variants. Influenza and SARS‑CoV‑2 have viral proteins that have been shown to block the production of interferons, a key part of the innate immune response to viral infection, resulting in worsened clinical outcomes. REVTx‑99 acts by stimulating the innate immune system at the site of infection via an alternative pathway (TLR4) to produce protective cytokines including Type I and Type II interferons.
The innate immune system is the first line of defense against invading pathogens such as bacteria and viruses. Toll-like receptors (TLRs) are associated with sentinel cells (e.g. macrophages, dendritic cells) and serve a vital role in the innate immune response. TLRs recognize repeated molecular patterns associated with pathogens (PAMPS). When a pathogen invades a subject, TLRs recognize PAMPS as foreign and activate the innate immune response, inducing the production of numerous cytokines to combat the invading pathogen and stimulate the adaptive immune response.
About REVDx‑501
REVDx‑501, a rapid point of care diagnostic product that can be used to detect any respiratory viral infection including influenza A, Influenza B, parainfluenza, respiratory syncytial virus, SARS-CoV-2, etc. The diagnostic is based on a lateral flow assay format, similar to a home pregnancy test with a simple to read visual readout that provides a result in less than 10 minutes without the need for specialized instrumentation or complicated sample collection. The commercial version of the kit is self-contained, portable, and able to be shipped anywhere. The instructions will direct users with a positive result to seek follow up confirmatory testing and/or medical treatment.
About Revelation Biosciences Inc.
Revelation Biosciences, Inc. is a clinical stage life sciences company focused on the development of immunologic‑based therapies for the prevention and treatment of disease. The Company has several product candidates in development. REVTx‑99, the lead therapeutic candidate, is an intranasal immunomodulator for the prevention or treatment of viral infections including Influenza A, Influenza B, parainfluenza, rhinovirus respiratory syncytial virus and SARS-CoV-2 including its variants. REVTx‑200 is an intranasal immunomodulator adjunct to be used in combination with an intramuscular vaccination for more complete immunity. REVTx‑200 is based on the same technology used in REVTx‑99. In addition to the Company’s therapeutic pipeline, Revelation is also developing REVDx‑501, a rapid point of care diagnostic that can be used to detect any respiratory viral infection, regardless of virus type or strain, without the need for specialized instrumentation. For more information on Revelation, please visit www.RevBiosciences.com.
Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. We caution investors that forward-looking statements are based on management’s expectations and are only predictions or statements of current expectations and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from those anticipated by the forward-looking statements. Revelation cautions readers not to place undue reliance on any such forward looking statements, which speak only as of the date they were made. These risks include, but are not limited to, risks relating to the development of REVTx‑99, including RVL‑NHV01: the clinical utility of an increase in intranasal IP-10 levels as a treatment for viral infections; the ability to complete planned clinical studies of REVTx‑99; expected initiation of the clinical studies, the timing of clinical data; the outcome of the clinical data, including whether the results of such study is positive or whether it can be replicated; the timing, costs, conduct and outcome of our other clinical studies; the anticipated treatment of future clinical data by the FDA, the EMA or other regulatory authorities, including whether such data will be sufficient for approval; the success of future development activities for REVTx‑99 and expanded indications, REVTx‑200, REVDx‑501, or any other product candidates; potential indications for which our product candidates may be developed; the potential impact that COVID‑19 may have on us, our suppliers, vendors, regulatory agencies, our employees and the global economy as a whole; and the expected duration over which the Company’s balance will fund us.
