お知らせ • Jun 24
Revelation Biosciences Announces Phase 1 Clinical Study of Gemini Met the Primary Safety Endpoint and Showed Statistically Significant Biomarker Activity
Revelation Biosciences, Inc. 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. 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), neutrophil gelatinase lipocalin (NGAL) (p<0.01 at mid and high dose), c-reactive protein (CRP) (p<0.001 at mid and high dose), and IL-6 (p<0.01 at high dose). 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-a (p=0.51 at the highest dose) and IL-1ß (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 target indications including prevention of AKI following cardiac surgery and prevention of infection following surgery. IL-1RA has anti-inflammatory properties, as it binds to the IL-1 receptor, blocking IL-1a and IL-1ß, 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-a, 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. Reference is made to the announcement of the Company dated 25 March 2024 (the Announcement). As stated in the Announcement, following the resignation of Mr. Wong Yee Nok Enoch on 25 March 2024, the Company was unable to comply with the requirement under Rules 3.10, 3.10A, 3.21 of the Listing Rules. Following the above appointment, out of seven Directors, the Company has three independent non- executive Directors whom are all members of the Audit Committee, and as such, Rules 3.10, 3.10A, 3.21 are re-complied.