-Gemini administration induced statistically
significant, dose dependent changes in key biomarkers of
activity-
-Gemini was safe and well tolerated at
pharmacologically active doses-
-Phase 1 results enable further development
across multiple indications-
Revelation Biosciences, Inc. (NASDAQ: REVB) (the “Company” or
“Revelation”), a clinical-stage life sciences company that is
focused on harnessing the power of trained immunity for the
prevention and treatment of disease, today announced safety and
biomarker data for its Phase 1 clinical study (RVL-HV02). The
primary endpoint to evaluate the safety and tolerability of
escalating doses of Gemini was met and a maximum tolerated dose in
healthy volunteers was identified. Additionally, statistically
significant dose dependent upregulation of key biomarkers
demonstrating the immunostimulatory preconditioning effect of
Gemini were observed. The study, which enrolled 40 healthy
individuals 18 to 55 years of age, was conducted in Australia and
evaluated escalating doses (placebo, low, mid and high dose) of
intravenously administered Gemini.
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Administration of Gemini induced significant, dose dependent
changes in key circulatory biomarkers of activity that reflect the
expected pharmacology of Gemini-specific toll-like receptor 4
(TLR4) stimulation. Intravenous Gemini induced significant
increases in interleukin-1RA (IL-1RA) (p<0.001 at mid and high
dose, Figure 1), neutrophil gelatinase lipocalin (NGAL) (p<0.01
at mid and high dose, Figure 2), c-reactive protein (CRP)
(p<0.001 at mid and high dose, Figure 3), and IL-6 (p<0.01 at
high dose, Figure 4). Significant, dose dependent mobilization of
innate immune cell populations was observed, specifically
neutrophils (p<0.001 at mid-dose and high dose) and monocytes
(p<0.001 at mid and high dose). Importantly, Gemini
administration did not induce significant increases in serum TNF-α
(p=0.51 at the highest dose) and IL-1β (p=0.89 at the highest
dose). This attenuated pro-inflammatory activity and corresponding
significant upregulation of beneficial cytokines is unique to
Gemini and facilitates the reprogramming of the innate immune
response for resolution of inflammation and promotion of the
healing process.
These changes in biomarkers are consistent with the changes
observed in preclinical models in which Gemini demonstrated
remarkable activity (ischemia/reperfusion model of acute kidney
injury and unilateral ureteral obstruction model of kidney injury)
and are highly predictive of clinical efficacy, thus demonstrating
the potential for Gemini in our target indications including
prevention of AKI following cardiac surgery and prevention of
infection following surgery.
Figures 1 through 4 illustrate the reprogramming of the innate
immune response after Gemini administration in multiple biomarkers
of TLR4 stimulation. IL-1RA has anti-inflammatory properties, as it
binds to the IL-1 receptor, blocking IL-1α and IL-1β, major drivers
of the inflammation cascade. NGAL sequesters iron and is an
important defense for preventing excessive oxidative damage
resulting from injury and/or ongoing inflammation. CRP plays an
important role in resolving acute inflammation through increased
phagocytosis, clearing cellular debris. IL-6 at low concentrations
facilitates multiple activities associated with the resolution of
inflammation, including stimulation of IL-1RA and IL-10. IL-10
levels trended higher with increasing dose but did not reach
significance vs placebo (data not shown). While significance was
not observed at the time points evaluated, IL-10 activity is
inferred by the significant upregulation of IL-1RA as well as the
lack of significant upregulation of TNF-α, as both activities are
impacted by IL-10.
Gemini administration was generally well-tolerated. The
frequency and severity of adverse events corresponded with
increased dose, with the mid-level dose being established as the
maximum tolerated dose in healthy volunteers. Adverse events
observed included transient headache, chills, body aches/pain, and
vomiting, and are consistent with preclinical findings and the
expected pharmacology of the drug. Gemini administration did not
result in significant changes in clinical safety markers (e.g.
markers of organ function including creatinine, BUN, etc.) or
hematologic parameters (aside from immune cell mobilization). There
were no clinically significant findings with other safety measures
including vital signs, ECG, urinalysis and physical exam. These
results and the maximum tolerated dose will be used to guide dose
level selection in a planned randomized, placebo-controlled Phase
1b study in patients with chronic kidney disease.
“We are pleased that the biomarker data generated in healthy
volunteers is consistent with our preclinical studies. This
confirms the potential utility of Gemini as a single-dose
preconditioning therapy in our target indications.” said James
Rolke, Chief Executive Officer of Revelation. “With this new data,
we are excited and committed to moving rapidly into a Phase 1b
study in patients late 2024.”
For more information on Revelation, please visit
www.RevBiosciences.com.
About Gemini
Gemini is the Company’s proprietary formulation of
phosphorylated hexaacyl disaccharide (PHAD®), a toll-like receptor
4 (TLR4) agonist. TLR4 stimulation with PHAD potentially
preconditions the innate immune system to respond to a subsequent
stress, such as ischemia (loss of blood flow) or bacterial
infection. Gemini is initially being developed as a single dose
preconditioning therapy for two target indications: as a
pretreatment to prevent or reduce the severity of acute kidney
injury due to cardiac surgery (GEMINI-AKI program) and as a
pretreatment to reduce the incidence, duration, and severity of
post-surgical infection (GEMINI-PSI program). In addition, Gemini
has the potential to be a long-term treatment to stop or slow the
progression of chronic kidney disease (GEMINI-CKD program).
Revelation believes Gemini works through trained immunity, which
redirects and attenuates the innate immune response to external
stress (infection, trauma, etc.). Preclinical studies evaluating
models of AKI or bacterial infection have demonstrated pretreatment
with Gemini can reduce the severity and duration of AKI or
bacterial infection, respectively. Additionally, preclinical
studies evaluating a model of CKD demonstrate the potential of
Gemini as a treatment to prevent kidney tissue scarring following
the onset of severe inflammation.
About the Phase 1 Study Data Analysis
For all reported biomarkers except IL-1RA, the reported p-values
were based on a two-tailed t-test assuming equal variances between
data sets and an alpha of 0.05 for the peak change from baseline in
treated subjects (by dose vs peak change in baseline in placebo
subjects). For IL-1RA, a two-tailed t-test assuming equal variances
between data sets and an alpha of 0.05 using a binary responder
analysis of no change vs baseline and change vs. baseline was used.
For each analysis there were 9 subjects in the placebo group, 12
subjects in the low dose group, 13 subjects in the mid dose group
and 5 subjects in the high dose group.
About Revelation Biosciences, Inc.
Revelation Biosciences, Inc. is a clinical stage life sciences
company focused on harnessing the power of trained immunity for the
prevention and treatment of disease using its proprietary
formulation Gemini. Revelation has multiple ongoing programs to
evaluate Gemini, including as a prevention for post-surgical
infection, as a prevention for acute kidney injury, and for the
treatment of chronic kidney disease.
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. These forward-looking statements are generally
identified by the words "anticipate", "believe", "expect",
"estimate", "plan", "outlook", and "project" and other similar
expressions. 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. The following factors,
among others, could cause actual results to differ materially from
those described in these forward-looking statements: the ability of
Revelation to meet its financial and strategic goals, due to, among
other things, competition; the ability of Revelation to grow and
manage growth profitability and retain its key employees; the
possibility that the Revelation may be adversely affected by other
economic, business, and/or competitive factors; risks relating to
the successful development of Revelation’s product candidates; the
ability to successfully complete planned clinical studies of its
product candidates; the risk that we may not fully enroll our
clinical studies or enrollment will take longer than expected;
risks relating to the occurrence of adverse safety events and/or
unexpected concerns that may arise from data or analysis from our
clinical studies; changes in applicable laws or regulations;
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 outcome of data collected, including whether the results of
such data and/or correlation 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 its product candidates; potential indications for
which product candidates may be developed; the ability of
Revelation to maintain the listing of its securities on NASDAQ; the
expected duration over which Revelation’s balances will fund its
operations; and other risks and uncertainties described herein, as
well as those risks and uncertainties discussed from time to time
in other reports and other public filings with the SEC by
Revelation.
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version on businesswire.com: https://www.businesswire.com/news/home/20240624937640/en/
Sandra Vedrick Vice President, Investor Relations & Human
Resources Revelation Biosciences Inc. Email:
svedrick@revbiosciences.com
and
Chester Zygmont, III Chief Financial Officer Revelation
Biosciences Inc. Email: czygmont@revbiosciences.com
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