Revelation Biosciences announces topline results from PRIME study

Revelation Biosciences (REVB) announced safety and activity data for its Phase 1b PRIME clinical study in stage 3 and 4 chronic kidney disease patients. The primary endpoint to evaluate the safety and tolerability of escalating doses of Gemini was met. More importantly, Gemini significantly reduced inflammatory activity and restored normal cellular response to stimuli as measured in peripheral blood mononuclear cells isolated from patients at predose, 2, 24, and 168 hours post-dose, demonstrating Gemini’s ability to durably rebalance the inflammatory process at the cellular level. Revelation will host a corporate update webcast/conference call on Wednesday, September 10th at 8:30 am Eastern Time to review this top-line data and the potential impact of the use of Gemini for the treatment of acute and chronic inflammatory diseases. The PRIME study enrolled 40 patients from 32 to 78 years of age, at 3 US clinics located in San Diego and San Antonio, specializing in the care of patients with CKD. A total of 5 cohorts at 4 dose levels were enrolled: a subtherapeutic dose, a low dose, the target dose, and a high dose – an extension protocol was conducted to collect additional PBMC and biomarker samples in 8 Gemini naive or secondary naive patients. The primary endpoint was evaluation of safety. In addition to safety measures, patient PBMCs were isolated predose and at 2, 24, and 168 hours post-dose. PBMCs were analyzed ex vivo for background inflammation by measurement of IL-1beta, TNF-alpha, IL-6, IL-10, and IL-1RA. Cells were also assessed for response to stimulation by lipopolysaccharide or high mobility group box-1 protein. Subgroup analysis divided patients into two categories, those with PBMCs of minimal background inflammation activity and normal response to stimuli, and those with significant background inflammation activity and no response to stimuli. Approximately 50% of patients were in each group. In patients with high background PBMC activity, Gemini significantly reduced inflammation relative to placebo patient PBMCs post dose and remained significantly below their baseline value through 7 days. Background inflammation was reduced to levels comparable to PBMCs isolated from healthy subjects. Additionally, Gemini was able to demonstrate correction of the immunoparalysis typical to chronic disease. Gemini significantly increased the responsiveness to LPS stimulation in high background patient PBMCs relative to placebo at all timepoints. Gemini also significantly increased the responsiveness of patient PBMCs with high background vs placebo patient PBMCs with high background at all time-points to HMGB1 stimulation. The increased responsiveness was comparable to PBMCs isolated from healthy subjects. These results show the ability of Gemini to restore normal cell function, even as far as one week after a single dose. For the low background patients, as expected, Gemini does not increase inflammatory activity. Additional analysis on the effect of LPS or HMGB-1 stimulation is ongoing. Gemini administration was well-tolerated at the target dose with all events reported as mild. Adverse events observed at the target dose included transient headache, chills, loose stool, and body aches. Three adverse events at the highest dose were reported as severe, and included chills, nausea and vomiting, all resolving in 3 hours or less. Other reported events were either mild or moderate. All events corresponded with the previous healthy volunteer study, as well as with preclinical findings, and are consistent with the expected pharmacology of the drug. No serious adverse events were reported. Gemini administration did not result in clinically significant trends in clinical safety blood or urinalysis parameters. There were no clinically significant changes or trends in vital sign parameters or ECG assessments following administration of Gemini.