Revelation Biosciences Inc. announced statistically significant results in a validated preclinical model of acute and chronic kidney disease. This mechanistic biomarker data further supports the potential clinical utility of REVTx-300 previously announced on November 18, 2022. In this validated preclinical model, administration of REVTx-300 caused significant reduction in circulating transforming growth factor-ß (TGF-ß) in a dose dependent manner relative to the positive control group.

In addition, REVTx-300 significantly increased circulating anti-inflammatory interleukin-10 (IL-10), hepcidin, and neutrophil gelatinase-associated lipocalin (NGAL) in all groups in a dose dependent manner, relative to the positive control group (the unilateral ureteral obstruction (UUO) model, described below). TGF-ß is a key driver of fibrogenesis and contributes directly to the deposition of collagen through excessive production of extracellular matrix. IL-10 is characterized as an anti-inflammatory cytokine, due to its capability to reduce the generation of pro-inflammatory mediators.

Hepcidin and NGAL sequester iron to prevent iron-mediated reactive oxygen tissue damage. There were no significant increases in markers of inflammation. These results provide mechanistic evidence for the reduction in fibrosis observed in the UUO model in response to treatment with REVTx-300.

Revelation plans to seek publication of the full results during 2023. Revelation originally released positive results from the preclinical model of acute kidney injury (AKI) and chronic kidney disease (CKD). Additional analysis announced on November 18, 2022 found that treatment with REVTx-300 significantly reduced new collagen deposition (fibrosis) in the renal cortex in a dose dependent manner in the medium and high dose groups (42.1% reduction (p <0.05) and 56.7% (p < 0.05), respectively).

The reduction in new collagen formation was calculated for each treatment group vs the UUO control group after correction for the normal collagen levels observed in the sham control. Fibrosis, or the formation of scar tissue, is the final, common pathway of many diseases which can have devastating effects, including acute kidney injury, chronic kidney injury, nonalcoholic steatohepatitis, myocarditis, and cancer. Revelation intends to further investigate the potential anti-inflammatory and anti-fibrotic benefit of PHAD, including its effect on NLRP3-mediated inflammasome activation in animal models of AKI, CKD, nonalcoholic steatohepatitis (NASH), and cancer.

About REVTx-300 Preclinical Study: The unilateral ureteral obstruction (UUO) model is appropriate for studying the anti-inflammatory and anti-fibrotic effects of potential new therapies for acute and chronic kidney disease as complete ureteral obstruction of one kidney results in significant inflammation and subsequent fibrosis of the affected kidney over a 7-day period. The present study consisted of 6 groups with the following outcomes on renal cortical fibrosis as measured by detection of collagen deposition using picosirius red stained histology sections assessed at three different sampling depths. Group 1 animals had surgery with no UUO (Sham) and received vehicle only (collagen deposition: 2.36 ± 0.44%).

Group 2 animals had UUO surgery and received vehicle only (collagen deposition: 4.88 ± 0.51%). Group 3 animals had UUO surgery and received SB-525334, a known TGF-ß inhibitor of fibrosis (new collagen deposition: 3.02 ± 0.37%, 75% reduction vs Group 2 - Sham, p < 0.05). Group 4 animals had UUO surgery and received 0.1 mg/kg REVTx-300 (new collagen deposition: 4.96 ± 0.95 %, 1% reduction vs Group 2 – Sham).

Group 5 animals had UUO surgery and received 0.3 mg/kg REVTx-300 (new collagen deposition: 3.82 ± 0.91%, 42% reduction vs Group 2 – Sham, p < 0.05). Group 6 animals had UUO surgery and received 0.9 mg/kg REVTx-300 (new collagen deposition: 3.45 ± 0.54%, 57% reduction vs Group 2 – Sham, p < 0.05). About REVTx-300: REVTx-300 is a proprietary formulation for systemic administration of PHAD and is being developed as a potential therapy for the treatment of acute and chronic organ disease including chronic kidney disease (CKD), acute kidney injury (AKI), myocarditis, and nonalcoholic steatohepatitis (NASH).

Chronic disease of an organ, due to chronic inflammation and subsequent fibrosis, follows a pattern of perpetual and ongoing destruction of living functional cells and subsequent replacement by the non-functional protein, collagen, resulting in fibrosis (scar tissue) (Wilson). The establishment of fibrosis and subsequent death of the organ is driven by ongoing inflammatory processes and reactive oxygen species associated with the innate immune response. Revelation believes that redirection of the innate immune response with REVTx-300 from a pro-inflammatory state to an anti-inflammatory (protective) state may rebalance the innate immune response to slow down or halt the progressive destruction and scarring of organ tissue, allowing the healing process to take place.

Revelation plans to initiate clinical studies in 2023.