Revelation Biosciences (NASDAQ:REVB) is a life sciences company focused on the development of immunologic-based therapies for the prevention and treatment of disease. Revelation has multiple product candidates in development that we believe have promising potential and are based on the biology of phosphorylated hexaacyl disaccharide (PHAD) and its effect on the innate immune system. The impact of PHAD on the immune system has been studied over multiple years and has been shown to have a positive effect on the human immune system. The company’s current therapeutic candidates are all based on the active ingredient PHAD, which is a synthetic version of MPLA, that is known to stimulate TLR-4. PHAD stimulation of TLR-4 leads to the production of multiple types of cytokines and chemokines which modulate the activity of the innate and adaptive immune response. Modulated activities may include stimulation and recruitment of infection fighting immune cells, down-regulation of inflammation, and/or upregulation of inflammation depending on the degree and nature of the stimulation which enables the multiple potential product candidates in development.
The current therapies being developed under the so-called Gemini project are:
REVTx‑300, which is being developed as a potential therapy for the treatment of acute and chronic organ disease including CKD, AKI and myocarditis.
REVTx‑100 is being developed as a prevention and treatment of infection.
The company just announced that studies have shown that Gemini priming reduces the inflammatory response in human peripheral blood mononuclear cells (PBMCs) that were exposed to clinically relevant molecules on inflammation. According to company management, in this study, human PBMCs were primed with either Gemini or placebo followed by challenge with clinically relevant promoter molecules of inflammation including high mobility box protein-1 (HMGB-1) and lipopolysaccharide (LPS) in vitro. HMGB-1 is an endogenous damage associated molecular pattern (DAMP) that is generated during tissue injury (e.g. during surgery) which drives the inflammatory response. LPS is an exogenous pathogen associated molecular pattern (PAMP) that is generated from a bacterial infection and drives the inflammatory response associated with infection (e.g. fever).
After exposure of Gemini-primed PMBCs to either HMGB-1 or LPS, levels of multiple proinflammatory and anti-inflammatory cytokines including IL-1 beta, TNF-alpha, IL-6, IL-1 Receptor Antagonist, and IL-10 were measured. Priming with Gemini significantly decreased proinflammatory cytokines and significantly increased anti-inflammatory cytokines, relative to placebo. According to management, this fundamental change in responsiveness at the cellular level demonstrates how Gemini will protect against inflammation-mediated damage. Revelation noted it intends to share the full results from this study in a future publication.
These results raise our optimism over the potential outcome from the ongoing, US-based Phase 1b clinical study to evaluate the potential of Gemini as a preconditioning treatment in patients with chronic kidney disease (CKD). This was extremely good news for the progression of this important treatment that has showed so much promise in earlier tests as we’ve discussed before.
According to the company, the multi-site, placebo-controlled Phase 1b clinical study is enrolling up to 40 subjects in up to 5 cohorts. The primary endpoint is evaluation of the safety and tolerability of a single dose of Gemini in patients with CKD. Secondary and exploratory endpoints will assess the pharmacokinetics, and the potential of Gemini to mobilize and attenuate the innate immune response to stress by measuring several predictive biomarkers of efficacy. The company also noted that topline data from the trial is expected to be announced mid-2025.
As a reminder, the company previously announced data from its Phase 1 trial of Gemini. This study involved 40 healthy individuals between the ages of 18 and 55 who were given placebo, low, mid and high doses. The primary purpose was to determine what the appropriate dosage was to use for further studies as well as evaluating the safety of Gemini. Those goals were both met, with the company noting that Gemini was generally well tolerated, with adverse events increasing as the dose increased. It’s important to note that Gemini administration did not result in any significant changes in clinical safety markers. The company also noted that the mid-level dose is now established as the maximum tolerated dose in healthy volunteers.
Another round of positive data from the upcoming Phase 1b study should then lead to, according to company management, a Phase 2 study of the treatment as a preconditioning treatment in patients with CKD to reduce the incidence, duration, and severity of acute kidney injury (AKI) in patients undergoing coronary artery bypass graft (CABG) and/or cardiac valve surgery.
As another reminder about issues we’ve written about, Gemini is also being developed for multiple indications, including as a pretreatment to prevent or reduce the severity and duration of acute kidney injury (GEMINI-AKI program), and as pretreatment to prevent or reduce the severity and duration of post-surgical infection (GEMINI-PSI program).
We are under no illusions that it’s easy to bring new therapies all the way to commercialization and Revelation will undoubtedly face challenges, but we believe that REVB is worth a look by investors due to the potential of the treatments being investigated, the science that has already been established behind those treatments, and the experienced management team the company has, headlined by the CEO who has overseen six INDs and two marketing approvals—experience we believe is needed to shepherd these treatments through the gauntlet of the FDA.
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