Revelation Biosciences’ Gemini Induces Dose Dependent Significant Increases in IL-10

Rhea-AI Summary

Revelation Biosciences (NASDAQ: REVB) announced statistically significant, dose-dependent increases of interleukin-10 (IL-10) in response to Gemini treatment, using a high sensitivity analysis. This follows the previously reported positive topline data from the Phase 1 clinical study. Key findings include:

- Gemini induced significant changes in circulatory IL-10 at 2 hours post-dose across all dose levels (p-value < 0.05)
- IL-10 increases were 27-fold, 162-fold, and 309-fold for low, mid, and high dose groups, respectively
- No significant increase in pro-inflammatory IL-1β and TNF-α was observed
- Results confirm TLR4 binding unique to Gemini and reprogramming of innate immune response
- Findings are consistent with prior preclinical studies

The company plans to move rapidly into a Phase 1b study in late 2024, focusing on potential benefits for patients, including prevention of AKI following cardiac surgery.

Positive

• Statistically significant, dose-dependent increases in IL-10 observed across all dose levels
• Substantial fold increases in IL-10: 27-fold (low dose), 162-fold (mid dose), and 309-fold (high dose)
• No significant increase in pro-inflammatory cytokines, confirming Gemini's unique TLR4 binding
• Results consistent with prior preclinical studies, supporting potential efficacy in target indications
• Plans to advance to Phase 1b study in late 2024

Negative

• None.

Insights

Medical Research Analyst

The new data on Gemini's ability to induce significant increases in IL-10 is promising for Revelation Biosciences' pipeline. Key points:

• Dose-dependent increases in IL-10 were observed 2 hours post-administration, with fold changes of 27x, 162x and 309x for low, mid and high doses respectively.
• IL-10 is an anti-inflammatory protein that helps resolve inflammation, suggesting Gemini could modulate immune responses beneficially.
• The lack of increase in pro-inflammatory cytokines indicates Gemini's unique TLR4 binding and potential to reprogram innate immunity.
• Results align with preclinical data, supporting Gemini's potential in target indications like preventing acute kidney injury after cardiac surgery.

While encouraging, this is still early-stage data. The planned Phase 1b study in late 2024 will be important to further validate Gemini's clinical potential and safety profile. Investors should monitor upcoming trial results closely, as positive outcomes could significantly impact REVB's value proposition in the immunomodulation space.

Biotech Industry Analyst

This new data strengthens Revelation's position in the competitive immunomodulation field:

• The statistically significant, dose-dependent IL-10 increases demonstrate Gemini's mechanism of action and potential efficacy.
• The 309-fold increase at the highest dose is particularly notable, suggesting potent anti-inflammatory effects.
• Consistency between human and preclinical data reduces translational risk, a common hurdle in drug development.
• The unique TLR4 binding profile differentiates Gemini from other immunomodulators, potentially offering a competitive edge.

For a small-cap biotech ($3.2M market cap), positive early-stage data is crucial. This news could attract investor interest and potential partnerships. However, REVB still faces significant clinical and regulatory hurdles. The upcoming Phase 1b study will be a key value inflection point, determining whether Gemini's promising mechanism translates to clinical benefit in patients.

SAN DIEGO--(BUSINESS WIRE)-- 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 statistically significant, dose dependent increases of interleukin-10 (IL-10) in response to Gemini treatment, using a high sensitivity analysis. This additional positive data follows the previously reported positive topline data from the Phase 1 clinical study of Gemini released on June 24, 2024.

Figure 1. Upregulation of IL-10 at 2 Hours Post Intravenous Administration of Gemini (Graphic: Business Wire)

Using high sensitivity serum IL-10 biomarker analysis to gain further insight into Gemini’s capability for resolution of inflammation, Revelation tested samples from the Phase 1 clinical study. It was found that Gemini induced statistically significant, dose dependent changes in circulatory IL-10 at 2 hours post-dose, with a p-value of < 0.05 or greater, at each of the low, mid, and high dose levels, as shown in Figure 1. The change in IL-10 observed for treatment groups relative to placebo, were a 27-fold increase, 162-fold increase, and 309-fold increase for the low, mid, and high dose groups, respectively.

IL-10 is a potent anti-inflammatory protein that downregulates pro-inflammatory cytokines and is an active contributor to initiating reduction of inflammation. The significant increase of anti-inflammatory IL-10 with no significant increase in pro-inflammatory IL-1β and TNF-α confirms TLR4 binding unique to Gemini, and is further evidence of the reprogramming of the innate immune response, enabling Gemini to initiate resolution of inflammation and promote the healing process.

The observed increase of IL-10 in humans is consistent with prior preclinical studies performed by Revelation where an increase in IL-10 was observed in healthy animals as well as efficacy models, including the ischemia/reperfusion model of acute kidney injury and unilateral ureteral obstruction model of kidney injury. This demonstrates the potential for Gemini in our target indications, including prevention of AKI following cardiac surgery.

“We are very pleased to see such a clear increase in interleukin-10 levels. This confirms how we can use Gemini to fine tune the innate immune response and speed the healing process through immunostimulatory preconditioning,” said James Rolke, Chief Executive Officer of Revelation. “This new data underlines the potential benefit of Gemini for patients, and we are committed to moving rapidly into our Phase 1b study in 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

The Phase 1 study 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. The primary endpoint was to evaluate the safety and tolerability of escalating doses of Gemini. Additionally, multiple biomarkers of clinical activity were evaluated.

As previously reported, 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. In addition, Gemini administration engaged multiple beneficial markers of the innate immune system, including mobilization of innate immune cells, and increased IL-10, Interleukin-1 Receptor Antagonist (IL-1RA), Neutrophil Gelatinase Associated Lipocalin (NGAL), and relatively low levels of Interleukin-6 (IL-6). Importantly, Gemini administration did not induce significant increases in serum TNF-α or IL-1β, markers associated with inflammatory damage.

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 prevention of post-surgical infection, prevention of 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240924064564/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

Source: Revelation Biosciences, Inc.

FAQ

What were the key findings of Revelation Biosciences' Gemini treatment study?

The study found statistically significant, dose-dependent increases in interleukin-10 (IL-10) levels in response to Gemini treatment. The increases were 27-fold, 162-fold, and 309-fold for low, mid, and high dose groups, respectively, with no significant increase in pro-inflammatory cytokines.

How does Gemini's effect on IL-10 impact inflammation?

Gemini's ability to increase IL-10, a potent anti-inflammatory protein, while not increasing pro-inflammatory cytokines, suggests it can reprogram the innate immune response to initiate resolution of inflammation and promote healing.

What are the next steps for Revelation Biosciences (REVB) regarding Gemini?

Revelation Biosciences plans to move rapidly into a Phase 1b study of Gemini in late 2024, focusing on potential benefits for patients, including the prevention of acute kidney injury (AKI) following cardiac surgery.

How do the Gemini study results compare to Revelation's preclinical studies?

The observed increase of IL-10 in humans is consistent with Revelation's prior preclinical studies, where an increase in IL-10 was observed in both healthy animals and efficacy models, including models of acute kidney injury.