Revelation Biosciences, Inc 8-K, filed Mar 12, 2024
Revelation Biosciences, Inc. (REVB)
About this 8-K
Revelation Biosciences, Inc filed this 8-K on March 12, 2024.
Items reported
- Item 7.01: Regulation FD disclosure
- Item 8.01: Other events
- Item 9.01: Financial statements and exhibits
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Securities registered pursuant to Section 12(b) of the Act:
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Item 7.01 Regulation FD Disclosure.
On March 12, 2024, Revelation Biosciences, Inc. (the “Company”) presented at the 29th International Conference on Advances in Critical Care Nephrology in San Diego, California. A copy of the poster and presentation is attached to this Current Report on Form 8-K as Exhibits 99.1 and 99.2 and is incorporated herein by reference.
The information in Item 7.01 and in Exhibits 99.1 and 99.2 will not be treated as “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section. This information will not be incorporated by reference into any filing under the Securities Act of 1933, as amended, or into another filing under the Exchange Act, unless that filing expressly incorporates this information by reference.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
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Exhibit No. |
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Description |
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104 |
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Cover Page Interactive Data File (embedded with the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
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REVELATION BIOSCIENCES, INC. |
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Date: |
March 12, 2024 |
By: |
/s/ Chester S. Zygmont, III |
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Chester S. Zygmont, III |
Gemini is a proprietary formulation of phosphorylated hexaacyl disaccharide (PHAD), a synthetic, detoxified version of lipopolysaccharide (LPS). PHAD stimulates TLR4 to precondition immune cells, including early, robust induction of IL-10, followed by an attenuated induction of IL-6, and TNF-a. Following injury (e.g. ischemia), immunostimulatory preconditioning contributes to mobilization of innate immune cells, a reduced pro-inflammatory response, and a reduction in reactive oxidative species. Immunostimulatory preconditioning was shown to provide significant improvement in function, less tissue damage, and accelerated resolution of injury in multiple models of kidney injury (I/R and UUO). Intravenous GeminiTM for Prevention of Acute Kidney Injury Prophylactic Administration of Gemini Reduces Tissue Damage and Improves Kidney Function in a Rat Model of Bilateral Ischemic Reperfusion Induced Acute Kidney Injury Robin Marsden1, James Rolke1, Jackson Stephens1, and Allie Zygmont1, 1Revelation Biosciences Robin Marsden1, James Rolke1 Jackson Stephens1, and Allison Zygmont1, 1Revelation Biosciences Purpose and Background The purpose of this study was to evaluate Gemini pretreatment in an ischemia reperfusion model of AKI. Due to its severe nature, AKI represents a significant health problem, especially in patients with co-morbidities such as diabetes. Approximately 1% of all hospitalized patients present with AKI upon admission. Phosphorylated hexaacyl disaccharide (PHAD), the active ingredient in Gemini, is a synthetic small molecule that preconditions the innate immune response via a more selective activation of toll-like receptor 4 (TLR4), characterized by an attenuated pro-inflammatory response relative to traditional TLR4 agonists such as lipopolysaccharide (LPS), while retaining the capacity to engage the innate immune response. We hypothesize that Gemini preconditioning will elicit an attenuated proinflammatory response following ischemic reperfusion (IR). Methods Rats were administered vehicle or Gemini intravenously at 0.07 and 0.35mg/kg at 24 and/or 48 hours prior to undergoing bilateral IR to induce acute kidney injury (AKI). A surgical sham group was also included. Blood and urine were collected pre-dose, and post-surgery at 24 and 72 hours (termination), and serum was assessed for BUN and creatinine levels. Urine was evaluated for c-reactive protein (CRP). Kidneys were evaluated for histological changes at 72 hours. Results Pretreatment with Gemini reduced serum BUN, serum creatinine and urine CRP in a dose dependent manner at 24 and 48 hours post-dose with significance at 0.35 mg/kg (p<0.05) relative to IR control. A single dose of 0.35mg/kg Gemini also significantly reduced the total degree of acute necrosis in cortical and medullary tubules (p<0.05). Neutrophil inflammation was significantly reduced (p<0.05) with a single pretreatment of Gemini at 0.35mg/kg. Conclusion Pretreatment with Gemini significantly improved kidney function as demonstrated by reductions in BUN, creatinine and CRP, and reduced kidney injury as evident in the reductions in cortical and medullary tubular necrosis. Gemini also reduced AKI-related inflammation attributed to neutrophils in the kidney. These results demonstrate the premise of trained immunity as a means of prevention of AKI. The collective improvement in renal function along with the reductions in cellular necrosis and neutrophilic inflammation demonstrate Gemini pretreatment attenuates the severity of IR AKI. Administration of Gemini 24 hours prior to IR reduced kidney injury as demonstrated in the significantly reduced tissue injury, improved renal function, and attenuation of inflammatory markers. Specifically, as CRP is a general marker of inflammation, the reduction in urinary and serum CRP demonstrate an overall reduction of local and systemic inflammation. The 0.07 mg/kg dose group also demonstrated non-statistically significant dose dependent reduction in Creatinine and BUN – data not shown. Preconditioning with Gemini reduces tissue damage and improves kidney function in a rat model of bilateral ischemic reperfusion induced acute kidney injury Study limitations: rodent to human translation, sample timing and volume (limited), magnitude of effect of treatment corresponds to AKI severity Improved kidney function and reduced necrosis likely due to reduction in pro-inflammatory activities, as observed in reduced neutrophil inflammation and reduced local and systemic CRP and IL-6 levels Gemini may halt necroinflammation feedback loop by reducing proinflammatory signals that contribute to cellular necrosis, effectively improving organ health Additional indications of improved kidney health include local and systemic changes in NGAL and HO-1 (results not reported here) Phase 1 clinical studies with Gemini initiated in February 2024 Figure 3a. Acute Cortical Tubular Necrosis. Figure 3b. Acute Medullary Tubular Necrosis. Figure 4a. Change in Serum Creatinine. Figure 4b. Change in Serum BUN. Figure 5a. Urinary CRP at 24 hours. Ϯ Ϯ Ϯ Figure 1. Selective TLR4 Stimulation with Gemini promotes healing. Figure 2. AKI model timeline. Animals in treatment groups were dosed 48 and/or 24 hours prior to IR. Rats (n=8-28 per group) were administered vehicle or Gemini 24 and/or 48 hours prior to IR surgery (30-minute ischemia) at different dose levels (0.07 and 0.35mg/kg). In addition to clinical observations, rats were evaluated for kidney function and functional biomarkers at 24 and 72 hours post surgery, and kidney damage at 72 hours (sacrifice) post surgery. Figure 5d. Neutrophilic Inflammation in Kidney. Figure 5b. Serum CRP at 72 hours. Figure 5c. Urinary IL-6 at 24 hours.
Oral Presentation at the 29th International Conference on Advances in Critical Care Nephrology: AKI and CRRT - March 2024 Intravenous GeminiTM for Prevention of Acute Kidney Injury Prophylactic Administration of Gemini (intravenous PHAD®) Reduces Tissue Damage and Improves Kidney Function in a Rat Model of Bilateral Ischemic Reperfusion Induced Acute Kidney Injury (AKI) Presented by Robin Marsden, Senior Vice President, Biology
Introduction Gemini is a proprietary formulation of phosphorylated hexaacyl disaccharide (PHAD), a synthetic, detoxified version of lipopolysaccharide (LPS). PHAD stimulates TLR4 to precondition immune cells, including early, robust induction of IL-10, followed by an attenuated induction of IL-6, and TNF-a. Gemini Reprograms Toll-Like Receptor 4 Signaling Methods: Ischemia/Reperfusion AKI Model1 Rats (n=8-28 per group) were administered vehicle or Gemini 24 and/or 48 hours prior to I/R surgery (30-minute ischemia) at different dose levels (0.07 and 0.35 mg/kg). In addition to clinical observation, rats were evaluated for kidney function and functional biomarkers at 24 and 72 hours post surgery and kidney damage at 72 hours (sacrifice) post surgery. Oral Presentation at the 29th International Conference on Advances in Critical Care Nephrology: AKI and CRRT - March 2024 1 Skrypnyk NI, et. al. Ischemia-reperfusion model of acute kidney injury and post injury fibrosis in mice. J Vis Exp. 2013 Aug 9;(78):50495. doi: 10.3791/50495. PMID: 23963468; PMCID: PMC3854859. Following injury (e.g. ischemia), immunostimulatory preconditioning contributes to mobilization of innate immune cells, a reduced pro-inflammatory response, and a reduction in reactive oxidative species. Immunostimulatory preconditioning was shown to provide significant improvement in function, less tissue damage, and accelerated resolution of injury in multiple models of kidney injury (I/R and UUO).
Gemini Preserves Kidney Function and Reduces Injury Kidney Function at 24 and 72 hours Kidney Injury at 72 hours Gemini pretreatment (0.35 mg/kg) significantly preserved kidney function with return to base line faster relative to untreated control animals (Figure 1a and 1b). A similar trend was observed for 0.07 mg/kg (data not shown). Additional renal function findings (data not shown) included improved creatinine clearance and excretion relative to the untreated group Oral Presentation at the 29th International Conference on Advances in Critical Care Nephrology: AKI and CRRT - March 2024 Figure 2a. Acute Cortical Tubular Necrosis2 Figure 2b. Medullary Tubular Necrosis2 Figure 1b. Change in BUN1 Figure 1a. Change in Creatinine1 1N=16-28, dosed 24 and/or 48 hours prior to surgery. 2N=8-14, dosed 24 hours prior to surgery. Gemini reduced injury to the cortical and medullary tubules as measured by histopathology (Figure 2a and 2b). A similar trend was observed for 0.07 mg/kg (data not shown). Additional findings: Gemini did not significantly lower cortical or medullary tubular degeneration or tubular protein casts included (data not shown) relative to the untreated group.
Gemini Significantly Attenuates Inflammatory Response Oral Presentation at the 29th International Conference on Advances in Critical Care Nephrology: AKI and CRRT - March 2024 Figure 3d. Neutrophilic Inflammation at 72 hours2 Figure 3a. Urinary CRP at 24 hours1 1N=16-28, dosed 24 and/or 48 hours prior to surgery. 2N=8-14, dosed 24 hours prior to surgery. Figure 3b. Urinary IL-6 at 24 hours1 Figure 3c. Serum CRP at 72 hours1 Pretreatment with Gemini (0.35 mg/kg) significantly reduced multiple markers of local inflammation at 24 and/or 72 hours in urine (Figure 3a and 3b, 72-hour data not shown). Pretreatment with Gemini (0.35 mg/kg) significantly reduced a key marker (c reactive protein, CRP) of systemic inflammation at 72 hours in serum (Figure 3c). Pretreatment with Gemini also significantly reduced markers of cellular inflammation as observed via reduced neutrophilic inflammation (Figure 3d). Additional markers of reduced cellular inflammation observed (data not shared).
Gemini Clinical Evaluation Initiated Discussion Improved kidney function and reduced necrosis likely due to reduction in pro-inflammatory activities, as observed in reduced neutrophil inflammation and reduced local and systemic CRP and IL-6 levels Gemini may halt necroinflammation feedback loop by reducing proinflammatory signals that contribute to cellular necrosis, effectively improving organ health Additional indications of improved kidney health include local and systemic changes in NGAL and HO-1 (results not reported here) Study limitations: rodent to human translation, sample timing and volume (limited), magnitude of effect of treatment corresponds to AKI severity Conclusions Immunologic preconditioning with Gemini reduces tissue damage and improves kidney function in a rat model of bilateral ischemic reperfusion induced acute kidney injury Phase 1 clinical studies with Gemini initiated in March 2024 Oral Presentation at the 29th International Conference on Advances in Critical Care Nephrology: AKI and CRRT - March 2024