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Item 1. Business

2026-02-26 compared with 2025-03-06 · 271 added, 181 removed, 454 unchanged (50% of the section changed)

Revelation is a clinical-stage life science company that is focused on rebalancing inflammation to optimize health using its proprietary formulation Gemini.

We have multiple ongoing programs to evaluate Gemini, including GEM-AKI as a prevention for acute kidney injury (“AKI”), GEM-CKD as a treatment for chronic kidney disease (“CKD”), and GEM-PSI as a prevention for post surgical infection (“PSI”).

We have multiple ongoing programs to evaluate Gemini, including GEM-AKI as a treatment for acute kidney injury (“AKI”) and GEM-CKD as a treatment for chronic kidney disease (“CKD”).

The Company was incorporated in the state of Delaware on November 20, 2019 (originally as Petra Acquisition, Inc.) and is based in San Diego, California.

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Recent Developments

2025 Reverse Stock Split

July 2025 and January 2026 Reverse Stock Splits

On June 23, 2025, at the annual meeting of stockholders, our stockholders granted discretionary authority to our board of directors to (i) amend our certificate of incorporation one or more times to combine outstanding shares of our common stock into a lesser number of outstanding shares, or a “reverse stock split,” at a specific ratio within a range of one-for-two to a maximum of a one-for-250 split, with the exact ratio to be determined by our board of directors in its sole discretion;

and (ii) effect the reverse stock split(s), if at all, within one year of the date the proposal is approved by stockholders

Following the annual meeting of stockholders and determination by the Board of Directors on the reverse split ratio, we filed a Certificate of Amendment which effected a 1-for-3 reverse stock split of our outstanding shares of common stock effective as of July 7, 2025.

Additionally, we filed a Certificate of Amendment effective which effected a 1-for-4 reverse stock split of our outstanding shares of common stock effective as of January 28, 2026, .

2025 Reverse Stock Splits

On January 17, 2025, at a special meeting of stockholders, our stockholders approved a Certificate of Amendment to our Third Amended and Restated Certificate of Incorporation to effect a reverse stock split of our outstanding shares of common stock at a specific ratio within a range of one-for-two (1-for-2) to a maximum of a one-for-fifty (1-for-50) split.

Following the special meeting of stockholders and determination by the Board of Directors on the reverse split ratio, we filed a Certificate of Amendment effective on January 28, 2025, which effected a 1-for-16 reverse stock split of our outstanding shares of common stock as of 12:01 a.m.

Eastern Standard Time on January 28, 2025.

Following the special meeting of stockholders and determination by the Board of Directors on the reverse split ratio, we filed a Certificate of Amendment which effected a 1-for-16 reverse stock split of our outstanding shares of common stock effective as of January 28, 2025.

2024 Reverse Stock Split

On January 17, 2024, at a special meeting of stockholders, our stockholders approved a Certificate of Amendment to our Third Amended and Restated Certificate of Incorporation to effect a reverse stock split of our outstanding shares of common stock at a specific ratio within a range of one-for-two (1-for-2) to a maximum of a one-for-fifty (1-for-50) split.

On January 22, 2024, we filed the Certificate of Amendment which effected a 1-for-30 reverse stock split of our outstanding shares of common stock as of 12:01 a.m.

Eastern Standard Time on January 25, 2024.

2023 Change in Authorized Shares and Reverse Stock Split

On January 30, 2023, at a special meeting of stockholders, our stockholders approved a Certificate of Amendment to our Third Amended and Restated Certificate of Incorporation to change the authorized common stock from 100,000,000 to 500,000,000 shares and effect a reverse stock split of our outstanding shares of common stock at a specific ratio within a range of one-for-twenty (1-for-20) to a maximum of a one-for-one hundred (1-for-100) split.

On January 30, 2023, we filed the Certificate of Amendment which set the authorized common stock to 500,000,000 and effected a 1-for-35 reverse stock split of our outstanding shares of common stock as of 12:01 a.m.

Eastern Standard Time on February 1, 2023.

On January 22, 2024, we filed the Certificate of Amendment which effected a 1-for-30 reverse stock split of our outstanding shares of common stock effective as of January 25, 2024.

Business Strategy and Pipeline

Revelation is developing a pipeline of potential high-value products based on Gemini.

Gemini is Revelation’s proprietary formulation of phosphorylated hexaacyl disaccharide (“PHAD ® ”) an established Toll-like receptor 4 (TLR4”) agonist that can stimulate the human body’s innate immune response to prevent and treat disease.

Our current Gemini based programs consist of:

Gemini-AKI, which is being developed for the prevention of AKI;

Gemini-CKD for the treatment of CKD;

and Gemini-PSI, which is being developed for the prevention of PSI.

Revelation is focused on developing potentially high-value products to address significant, unmet medical needs.

Revelation’s lead product candidate Gemini, is our proprietary formulation platform of phosphorylated hexaacyl disaccharide (“PHAD ® ”), an established Toll-like receptor 4 (“TLR4”) agonist that works by modulating and rebalancing a dysregulated inflammatory response.

Our lead Gemini programs have been derisked with preclinical and clinical data and are focused on disorders involving the kidneys including treatment or prevention of acute kidney injury (“AKI”) and treatment of chronic kidney disease (“CKD”).

In order to leverage our renal care focus and associated infrastructure, Revelation will look to add to its pipeline with technologies that address other kidney related issues.

Revelation’s pipeline is summarized in the figure below:

In addition to kidney care, Gemini’s unique immunomodulatory properties could lead to prevention and treatment of a variety of diseases ( Figure 1 ).

To realize and unlock the full potential of Gemini, Revelation may seek strategic opportunities including out-licensing and/or academic collaborations.

Potential Future Applications for Gemini

The Gemini Platform

Our current therapeutic candidates are all based on our proprietary Gemini formulation of PHAD ® , a synthetic version of monophosphoryl lipid A (“MPLA”), that is known to stimulate TLR4.

Stimulation of TLR4 via Gemini leads to a more controlled production of varied cytokines and chemokines which modulate the activity of the innate and adaptive immune response, relative to a lipopolysaccharide, a traditional TLR4 agonist.

This “Immunostimulatory Preconditioning” with Gemini prepares the body to better guard against a rapid upregulation of multiple pro-inflammatory and microbial gene products and proteins, such as pathogen-associated molecular patterns (“PAMPS”) and damage-associated molecular patterns (“DAMPS”) (damage-associated molecular proteins) (Zwirner 2017, Hernandez 2019, Ismaeli 2002).

Modulated activities may include stimulation and recruitment of infection fighting immune cells, reduction of inflammation, and/or regulation of inflammation depending on the degree and nature of the stimulation, which enables the multiple potential product candidates in development.

Our current therapeutic programs are based on our proprietary Gemini formulation of PHAD ® , a synthetic version of monophosphoryl lipid A (“MPLA”) with a well-established biology.

Chemically, PHAD is a small fragment of lipopolysaccharide (“LPS”) which is also called endotoxin.

Like LPS, PHAD stimulates TLR4, but unlike LPS, PHAD stimulation leads to controlled production of multiple cytokines and chemokines ( Figure 2 ) which modulate the activity of the innate and adaptive immune response to rebalance the inflammatory response and restore equilibrium ( Figure 3 ).

Interaction of PHAD with TLR4

The Gemini-AKI program is being developed as a potential therapy for the prevention of AKI due to external stress or insult (e.g.

surgical procedure, chemotherapy toxicity).

We believe immunologic preconditioning with Gemini prepares the body to handle biologic stress by redirecting the body’s immune system to have an attenuated response to the stress.

Preclinical studies have demonstrated that preconditioning with PHAD significantly reduces the severity and duration of AKI following an ischemia of the kidney.

Additional data from these preclinical studies have been accepted for presentation at The International Conference on Advances in Critical Care Nephrology on March 12, 2024.

During 2024 we conducted a Phase 1 clinical study.

safety and biomarker activity data from our Phase 1 clinical study was announced in June of 2024, showing a significant increase in anti-inflammatory cytokines including IL-1RA and IL-10.

In January of 2025 we announced the start of our Phase 1b clinical study in CKD patients.

The Phase 1b clinical study will support further development of Gemini-AKI.

We expect data from our Phase 1b clinic study in the first half of this year.

The Gemini-CKD program is being developed as a potential therapy for preventing the progression of CKD.

We believe Gemini may modulate the immune response from a pro-inflammatory state to an anti-inflammatory (protective) state to rebalance the innate immune response and slow down or halt the progressive destruction and scarring of organ tissue, allowing the healing process to take place.

Preclinical studies have demonstrated that Gemini significantly reduces the degree of scar tissue formation in a hyperinflammatory kidney injury model.

In January of 2025 we announced the start of our Phase 1b clinical study in CKD patients.

The Phase 1b clinical study will support further development of Gemini-CKD.

We expect data from our Phase 1b clinic study in the first half of this year.

The Gemini-PSI program is being developed, through a license agreement with Vanderbilt University, as a potential therapy for the prevention or treatment of surgical site infection.

We believe immunologic preconditioning with Gemini prepares the body to resist infection by priming the body’s immune system to better and more rapidly respond to pathogen exposure.

Multiple preclinical studies have shown that systemic pretreatment with PHAD results in a significantly augmented immune response leading to significantly reduced duration and severity of infection following bacterial challenge with either gram-positive or gram-negative bacteria.

Our goal is to become a leading biopharmaceutical company focused on the development of therapeutics that modulate the immune system to prevent and treat conditions with significant unmet needs.

Gemini can rebalance cellular equilibrium, fostering healing processes

Gemini is being evaluated as an acute (short-term) treatment for AKI.

AKI is defined as a sudden and rapid loss in normal kidney function and currently the only treatment for AKI is supportive care and the use of renal replacement therapy (dialysis).

AKI can be caused by many different factors including severe infection, trauma, drug toxicity, etc.

Regardless of the initial insult, AKI is predominately driven by dysregulated hyperinflammation.

We believe the immunomodulatory action of Gemini can attenuate the excess inflammation associated with AKI and restore equilibrium.

Preclinical studies have demonstrated that Gemini can treat acute kidney injury driven by hyper inflammation.

In addition, clinical studies have demonstrated the immunomodulatory properties of Gemini in healthy individuals, and more importantly, Gemini was shown to durably normalize excessive background cellular inflammation and restore immunocompetence in patients with CKD.

Revelation met with FDA at the end of 2025 and obtained agreement on a single Phase 2/3 adaptive design study with a primary composite endpoint of death and/or dialysis for submission of a new drug application (NDA).

During 2026, the Company plans to build the necessary infrastructure to successfully run this clinical study including engagement of a scientific advisory board, engagement of a top-tier clinical research organization, and manufacture of blinded drug and placebo with the intention of starting the Phase 2/3 study as soon as feasible.

Gemini is also being evaluated as a chronic (long-term) treatment for CKD.

CKD is a progressive decline in kidney function ultimately resulting in the need for dialysis and/or a transplant (if eligible).

CKD can be caused my numerous conditions including diabetes, hypertension, prior episode of AKI, etc.

Like AKI, progression of CKD is predominately driven by dysregulated inflammation resulting in scarring of the kidney.

We believe the immunomodulatory action of Gemini can attenuate the dysregulated inflammation associated with CKD and restore equilibrium.

Preclinical studies have demonstrated that Gemini treatment can prevent scar tissue formation in hyper inflamed kidneys.

During 2026, Revelation intends to conduct preclinical toxicology studies to support a repeat dose Phase 2 study to allow further evaluation of Gemini in this high-need patient population.

Our goal is to become a leader in the treatment and prevention of kidney disease and conditions with significant unmet needs.

The key components of our strategy are to:

• Advance the development of Gemini for the prevention of acute kidney injury

• Advance the development of Gemini for the treatment of chronic kidney disease

• Advance the development of Gemini for the prevention and treatment of post surgical infection

• Conduct a phase 2/3 adaptive design study in patients with AKI and submit the data from this study in an NDA for marketing approval in the United States

• Conduct clinical studies to advance the development of Gemini for the treatment of chronic kidney disease

• Leverage our growing expertise and infrastructure in the kidney space by broadening our portfolio through identification and development of new additional technologies to treat other kidney related issues

• Strategically advance the development of Gemini for prevention and treatment of other non-kidney related conditions, through collaborations and out-licensing opportunities to maximize the potential for Gemini

Our Corporate History and Team

The Company was incorporated in the state of Delaware on November 20, 2019 (originally as Petra Acquisition, Inc.) and is based in San Diego, California.

We have assembled a management team of biopharmaceutical experts with extensive experience in drug development, manufacturing and commercialization of pharmaceutical products along with broad experience in building companies from inception, including La Jolla Pharmaceutical Company, Pluromed, Inc., and Horizon Pharma, Inc.

We are also supported by a group of directors and leading investors whose collective experience will assist us in realizing our corporate strategy.

The Gemini program was initiated in 2022.

We have assembled an entrepreneurial management team of biopharmaceutical experts with extensive experience in drug development, manufacturing and commercialization of pharmaceutical products.

We are also supported by a group of directors, leading investors and scientific advisors whose collective experience will assist us in realizing our corporate strategy.

Acute Kidney Injury Overview

AKI, also known as acute renal failure, is defined as a rapid loss of kidney function.

Acute Kidney Injury, or “AKI”, (also known as acute renal failure), is defined as a rapid loss of kidney function.

AKI causes a build-up of waste products in blood and makes it more difficult for kidneys to maintain the correct balance of fluid in the body.

AKI can also have a significant impact on other organs such as the brain, heart, and lungs.

Due to its severe nature, AKI represents a significant and increasingly frequent health problem, especially in patients with co-morbidities such as diabetes.

Approximately 1% of all hospitalized patients present with AKI upon admission.

Of these hospitalizations, rates of AKI increased 165% and 114% for diabetic men and women, respectively from the years 2000 to 2014 (Goyal 2023, Pavkov 2018).

During all hospitalizations, the approximate incidence of AKI is 2 to 5%.

Development of AKI is even more prevalent in patients admitted to the intensive care unit, occurring in up to 67% of patients admitted (Pavkov 2018, Workeneh 2022).

AKI can also significantly impact other organs such as the brain, heart, and lungs.

Severe AKI requiring dialysis significantly increases the likelihood of worse outcomes including longer time in an ICU, potential to develop chronic kidney disease, and death.

AKI is a major cause of morbidity and mortality, affecting more than 10% of all hospitalized patients and more than 50% of patients admitted to intensive care units.

Renal replacement therapy (dialysis) is still the only therapeutic option in the treatment of the consequences of severe AKI and is required in approximately 20% of all critically ill patients.

AKI is associated with high mortality rates, and even among those who survive, up to 40% later develop chronic kidney disease or progress to end-stage renal disease.

As such, new therapies to treat AKI are urgently needed.

AKI can develop as a result of many different causes including decreased blood flow to the kidneys, direct damage to the kidneys, or blockage of urine flow through the kidney.

AKI inducing events may include shock (low blood pressure), blood or fluid loss (such as bleeding, severe diarrhea), heart attack, heart failure, and other conditions leading to decreased heart function, organ failure (e.g., heart, liver), overuse of pain medicines such as NSAIDs, severe allergic reactions, burns, injury, infection (sepsis), cancer, toxicity (e.g., chemotherapies), hereditary factors, or major surgery.

AKI is of particular concern after cardiac surgery.

Published evidence suggests that even slight postoperative increases in serum creatinine levels are associated with a significant increase in the risk of death.

Up to 31% of patients undergoing cardiac surgery with no prior CKD develop post operative AKI with a high mortality rate.

The average cost to treat AKI is about $42,600 and results in an approximate 4-7 day increase in hospitalization duration (Lysak 2017).

In this surgical setting, ischemia may be initiated intentionally, such as during a procedure that requires cardiopulmonary bypass.

Alternatively, ischemia may be the unintentional result of an untoward complication such as intraoperative hypotension.

Regardless of etiology, the ischemic event initially leaves the affected area(s) deprived of blood, oxygen, and other nutrients which then can exacerbate to injury when the blood supply returns to the site along with reactive oxygen species and other constituents that cause oxidative stress to the tissues.

There are no approved therapies for preventing AKI, including AKI due to cardiac surgery.

The American Hospital Association states that approximately 34 million people are admitted to US hospitals each year.

It was found that 20% or approximately 6.8 million patients admitted to hospitals had AKI by the University of Florida.

The CDC says Medicare in 2015 alone had an annual expenditure of over $10 billion and growing for AKI, with spending for AKI related costs of approximately $42,077 per patient.

The only treatment for severe AKI is dialysis which increases the potential for worse outcomes including death, therefore Gemini could be the first available therapy for this significant unmet medical need.

This data is an indication of how large the AKI market is and the potential for Gemini.

AKI is a serious and growing unmet medical need.

Aside from supportive care and the use of renal replacement therapy, there are no approved therapies for treating AKI.

Chronic Kidney Disease Overview

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Kidney disease is a major public health problem, affecting ~10% of populations in industrialized countries.

AKI, which affects 13.3 million people per year, may lead to CKD.

The damage suffered as a result of AKI, which affects 13.3 million people per year, often leads to CKD.

Both AKI and CKD are increasing worldwide.

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CKD can be initiated and propagated in several ways.

One prevalent condition is the high blood sugar levels associated with diabetes (either Type 1 or Type 2).

One prevalent condition is the high blood sugar levels associated with Type 1 or Type 2 diabetes.

High blood sugar is toxic to kidney cells creating stress which imitates the inflammatory process leading to the demise of these cells with subsequent fibrosis ultimately resulting in continuous loss of kidney function over time.

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As many as 9 to 10 adults with CKD as well as about 2 in 5 adults with severe CKD do not know they have the disease.

Kidney diseases are the leading cause of death in the United States.

Kidney diseases are a leading cause of death in the United States.

The CDC estimates Medicare costs in excess of $87 billion and continues to promote reduced costs including better management of CKD.

Post Surgical Infection Overview

Despite efforts to monitor and prevent infection in hospital care settings, infections arise from a range of different causes including surgery, burn wounds, central line catheters or urinary catheters, and sepsis, as well as long courses of antibiotic treatment, which may lead to the development of methicillin-resistant Staphylococcus aureus resistant infection (“MRSA”).

According to the most recent prevalence study data published by the Center for Disease Control and Prevention in 2015, approximately 3% of hospital patients suffered at least one infection, and there were approximately 687,000 infection cases in acute care settings resulting in approximately 72,000 deaths.

According to the CDC, on any given day about 31 hospital patients has at least one healthcare-associated infection.

A World Health Organization cooperative study which included 55 hospitals in 14 countries from four regions, approximately 8.7% of hospitalized patients developed infection within 48 hours of hospitalization (Tikhomirov 1987).

The most common healthcare-associated infections are bloodstream infection, pneumonia, urinary tract infections, and surgical site infections.

Current Prevention, Treatment, and Detection Options

Prevention and Treatment of AKI

Current Treatment

There are currently no therapeutics to prevent or treat AKI.

Treatment for AKI requires hospitalization and intensive supportive care until kidney function recovers.

Treatment for AKI requires hospitalization and intensive care support until kidney function recovers.

In more serious cases, dialysis may be needed to help replace kidney function until kidneys can recover.

The main treatment is to address what is causing the acute kidney injury.

Prevention and Treatment of Chronic Kidney Disease

Current treatments only address what is causing the acute kidney injury.

In April 2021, The FDA approved the use of Farxiga (Dapagliflozin) to reduce the risk of kidney function decline, kidney failure, cardiovascular death and hospitalization for heart failure in adults who are at risk of disease progression.

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Avoiding conditions or exposures that can harm the kidneys like certain medications or kidney infections is also beneficial.

Still, at this time, there is a significant unmet need for therapies that slow disease progression and improve outcomes of patients with chronic kidney disease.

Prevention of Post Surgical Infection

There are no approved therapies currently available for the prevention of infection outside of pre- and post-surgical administration of antibiotics and commonly recommended procedures for the preventing the transmission of bacteria including hand washing, mask wearing, and cleaning the surgical site pre- and post-surgery.

In the case of antibiotic pretreatment, the typical course of treatment may require an initial empiric broad-spectrum antibiotic, later targeted to an organism if detected, with consideration for the presence of multidrug resistant pathogens, specifically MRSA.

Antibiotic resistance has become a major consideration in the need for pretreatment of yet-to-be diagnosed infections, as the number of antibiotic resistant strains have increased, and the over prescription of antibiotics further contributes to resistance.

At this time, there are no approved therapies for CKD that target the underlying inflammation associated with the progression of this disease.

REVELATION’S PROGRAMS

Gemini Platform

Our current therapeutic candidates are all based on Gemini, our proprietary formulation of PHAD ® , a synthetic version of MPLA, that is known to stimulate the innate immune response via TLR4.

The innate immune system is our first line of defense against stress such as trauma, infection and acute and chronic disorders.

The innate immune system responds to stress (e.g.

infection) by producing and releasing various types of cytokines.

The innate immune system responds to stress by producing and releasing various types of cytokines.

Cytokines are proteins that direct different activities in cells and can be inflammatory or protective, meaning they may be able to modulate certain established cellular activities.

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damage associated molecular patterns).

Revelation believes immunostimulatory preconditioning with Gemini prepares the body to respond better to stress due to infection, trauma, or other acute and chronic disorders.

Modulated activities may include stimulation and recruitment of infection fighting immune cells, reduction of inflammation, and/or regulation of inflammation depending on the degree and nature of the stimulation which enables the multiple potential product indications in development.

Gemini is our proprietary formulation platform of PHAD ® , a synthetic version of MPLA with a well-established biology.

Chemically, PHAD is a small fragment of LPS, which is also called endotoxin.

Like LPS, PHAD stimulates TLR4, but unlike LPS, PHAD stimulation leads to controlled production of multiple cytokines and chemokines ( Figure 4 ) which modulate the activity of the innate and adaptive immune response to rebalance the inflammatory response and restore equilibrium ( Figure 5 ).

Revelation believes the immunomodulatory action of Gemini can be used to treat disease and conditions driven by a dysregulated inflammatory response.

Numerous acute and chronic kidney conditions are driven by dysregulated inflammation.

Interaction of PHAD with TLR4

Revelation Biosciences

Gemini-AKI Program

Gemini is being evaluated as a potential therapy for the prevention of AKI due to external stress (e.g.

surgical procedure, chemotherapy toxicity).

We believe immunologic preconditioning with Gemini prepares the body to handle biologic stress by directing the body’s immune system to have an attenuated response to the stress.

Gemini is being evaluated as a potential therapy for the prevention of AKI.

Preclinical studies have shown that pretreatment with PHAD results in significantly decreased severity and duration of acute kidney injury due to ischemia.

PHAD Pretreatment Reduces AKI in a Unilateral Ischemia/Reperfusion Model 1

1 Mice pretreated with intravenous PHAD at 2, 20, and 200 µg/mouse or vehicle control, 48 and 24 hours prior to undergoing right nephrectomy followed by clamping of the left renal pedicle for 28 minutes.

A) Blood was analyzed for BUN and creatinine at baseline (D0), and post-injury day 1 and 3.

Results expressed as means +/-SEM with N = 8.

Two-way ANOVA was used to compare differences between PHAD- and vehicle-treated mice over time, with p values indicated;

B) Representative images of periodic acid-Schiff staining (PAS) sections of the outer medulla at Day 3 after injury in sham, vehicle- and PHAD-treated mice.

Arrows point to casts within the collecting tubules.

Scale bar, 100 µm.

C) Pretreatment with PHAD reduced tubular injury in a dose dependent manner as visualized (PAS).

Hernandez A, Patil N, et.

Pretreatment with a novel Toll-like receptor 4 agonist attenuates renal ischemia-reperfusion injury.

American Journal of Physiology-Renal Physiology 2023 324:5, F472 – F482

PHAD Pretreatment Reduces AKI in a Bilateral Ischemia/Reperfusion Model

Mice were pretreated with intravenous PHAD at 200 µg/mouse or vehicle control, 48 and 24 hours prior to undergoing bilateral renal pedicle clamping for 24 minutes.

A) Blood was analyzed for BUN and creatinine at baseline (0), and post-injury day 1 and 3.

Results expressed as means +/-SEM with N = 10.

Two-way ANOVA was used to evaluate between group differences over time (p <0.05 for both BUN and serum creatinine), with p values shown after Sidak’s correction for multiple post hoc between group comparisons at each time point;

B) Tubular injury scores in the outer stripe of the outer medulla from PAS-stained sections Day 3 after injury;

C) Apoptosis in the outer stripe of the outer medulla from TUNEL stained sections Day 3 after injury.

Hernandez A, Patil N, et.

Pretreatment with a novel Toll-like receptor 4 agonist attenuates renal ischemia-reperfusion injury.

American Journal of Physiology-Renal Physiology 2023 324:5, F472 – F482.

Clinical Development Plan

During 2024 we conducted a Phase 1 clinical study.

Subsequently, safety and biomarker activity data from our Phase 1 clinical study was announced in June of 2024, showing a significant increase in anti-inflammatory cytokines including IL-1RA and IL-10.

In January of 2025 we announced the start of our Phase 1b clinical study in CKD patients.

The Phase 1b clinical study will support further development of Gemini-AKI.

We expect data from our Phase 1b clinic study in the first half of this year.

The Phase 1b study in CKD patients will be followed by a Phase 1b study in patients undergoing cardiac surgery to establish dose and dosing regimen in preparation for Phase 2.

The primary readout will be safety with exploratory endpoints to evaluate biomarkers and rate, duration, and severity of AKI.

Gemini-CKD Program

Gemini is being evaluated as a potential therapy for preventing the progression of CKD.

Revelation conducted a nonclinical study to evaluate the potential of Gemini to prevent kidney fibrosis due to excess inflammation.

Specifically, a range of daily systemic dosing levels of Gemini were tested in a rat unilateral urethral obstruction (“UUO”) model.

Gemini can rebalance cellular equilibrium, fostering healing processes

Gemini-AKI and CKD Programs

Gemini is being evaluated as an acute (short-term) treatment for AKI.

AKI is defined as a sudden and rapid loss in normal kidney function.

Currently the only treatment for AKI is supportive care and the use of renal replacement therapy (dialysis).

AKI can be caused by many different factors including severe infection, trauma, drug toxicity, etc.

Regardless of the initial insult, AKI is predominately driven by dysregulated hyperinflammation.

We believe the immunomodulatory action of Gemini can attenuate the excess inflammation associated with AKI and restore equilibrium.

Preclinical studies have demonstrated that Gemini can treat acute kidney injury driven by hyperinflammation.

During 2026, the Company plans to build the necessary infrastructure to successfully run this clinical study including engagement of a scientific advisory board, engagement of a top-tier clinical research organization specializing in renal studies, and manufacture of blinded drug and placebo with the intention of starting the Phase 2/3 study as soon as feasible.

Gemini is also being evaluated as a chronic (long-term) treatment for CKD.

CKD is a progressive decline in kidney function ultimately resulting in the need for dialysis and/or a transplant (if eligible).

CKD can be caused my numerous conditions including diabetes, hypertension, prior episode of AKI, etc.

Like AKI, progression of CKD is predominately driven by dysregulated inflammation resulting in scarring of the kidney.

We believe the immunomodulatory action of Gemini can attenuate the dysregulated inflammation associated with CKD and restore equilibrium.

Preclinical studies have demonstrated that Gemini treatment can prevent scar tissue formation in hyper inflamed kidneys.

During 2026, Revelation intends to conduct preclinical toxicology studies to support a repeat dose Phase 2 study to allow further evaluation of Gemini in this high-need patient population.

Preclinical Studies Supporting the development of Gemini for AKI and CKD

Preclinical studies have shown that Gemini can attenuate the inflammatory response resulting in reduce severity and duration of acute kidney injury as well as prevention of scarring associated with AKI and CKD.

Unilateral Urethral Obstruction Model

Revelation tested Gemini in the Unilateral Urethral Obstruction (“UUO”) model of AKI and CKD to evaluate the potential of Gemini to prevent kidney fibrosis and correct excess inflammation.

The 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 obstructed 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 picrosirius red stained histology sections assessed at three different sampling depths.

The study demonstrated a dose-dependent reduction in scar tissue formation in the Gemini treated groups ( Figure 6 ) and a dose dependent decrease in inflammation markers with a.

subsequent increase in inflammation resolving and protective markers ( Figure 7 ).

Gemini Treatment Reduces Fibrosis in Acute and Chronic Kidney Model (UUO in Rats)

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TGF-β is pro-fibrotic and is directly linked to the propagation of fibrosis.

The positive control is an established TGF-β blocker.

The positive control is a well-established TGF-β blocker.

IL-10 is a key driver for the reduction and resolution of inflammation, and NGAL is an important defense for preventing excessive oxidative damage resulting from injury/ongoing inflammation.

Development Plan

In January of 2025 we announced the start of our Phase 1b clinical study in CKD patients.

The Phase 1b clinical study will support further development of Gemini-AKI.

We expect data from our Phase 1b clinic study in the first half of this year.

Revelation will continue evaluating the potential of Gemini in additional preclinical models of CKD to identify optimal dosing conditions and conduct the preclinical testing required for chronic dosing in patients.

Gemini-PSI Program

Gemini is being evaluated as a potential therapy for the prevention or treatment of post surgical infection.

We believe immunologic preconditioning with Gemini prepares the body to resist infection by priming the body’s immune system to respond to pathogen exposure more rapidly.

In addition to post surgical infection, we believe Gemini may also have utility for post-burn infection, urinary tract infection (e.g.

as a result of hospital-based or outpatient catheterization), sepsis, and antibiotic-resistant infection.

Revelation is developing Gemini for the prevention of infection through a license agreement with Vanderbilt University.

Preclinical studies

Multiple preclinical studies have shown that pretreatment with PHAD results in significantly augmented immune response with significantly reduced duration and severity of infection following bacterial challenge with either gram-positive or gram-negative bacteria as indicated in the following figures.

Pretreatment with PHAD Impart Protection from Gram Negative Bacterial Infection

Pretreatment with PHADs Impart Protection from Gram Positive Bacterial Infection

Clinical Development Plan

During 2024 we conducted a Phase 1 clinical study.

We are evaluating the next steps to be taken in the development of Gemini-PSI.

Ischemia-Reperfusion Model

Gemini Pretreatment Reduces AKI in a Unilateral Ischemia/Reperfusion Model

Revelation tested Gemini pretreatment in a bilateral ischemia-reperfusion model (I/R).

In this model, rats were pretreated with:

• single dose of intravenous Gemini at 1000 or 350 µg/kg or vehicle control (2.18% HP-b-CD and 5% dextrose in sterile water), at 3 or 24 and/or 48 hours prior to undergoing bilateral ischemia for 30 minutes followed by reperfusion.

• two doses of intravenous Gemini at 350 or 70 µg/kg or vehicle control (2.18% HP-b-CD and 5% dextrose in sterile water), at 24 and 48 hours prior to undergoing bilateral ischemia for 30 minutes followed by reperfusion.

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.

The results from this study demonstrated pretreatment with Gemini at least 24 hours prior to surgery significantly improved kidney function as demonstrated by reductions in serum BUN and creatinine vs pretreatment with vehicle only ( Figures 8a and 8b ).

Additional renal function findings (data not shown) included improved creatinine clearance and excretion relative to the vehicle group.

In addition, Gemini pretreatment reduced cortical and medullary tubular injury ( Figure 9a and 9b ).

Lastly, Gemini pretreatment showed a reduction in several markers of inflammation including CRP, IL-6, and neutrophilic inflammation ( Figures 10a - 10d ).

Figure 8a and 8b:

Gemini Preserves Kidney Function (Serum Creatinine and Serum BUN) in a Rat Bilateral Ischemia/Reperfusion Model of AKI

Gemini reduced serum creatinine levels (left) and BUN levels (right) at 24 and 72 hours post IR surgery as measured by histopathology when dosed 24 and/or 48 hours prior to IR.

A similar trend was observed at the 70µg/kg dose level (data not shown).

Figure 9a and 9b:

Gemini Reduces Injury (Acute Cortical Tubular Necrosis and Medullary Tubular Necrosis) in a Rat Bilateral Ischemia/Reperfusion Model of AKI

Gemini reduced injury to the cortical (left) and medullary tubules (right) at 72 hours post IR surgery as measured by histopathology when dosed 24 hours prior to IR.

A similar trend was observed for 70 mg/kg (data not shown).

Figure 10a-10d:

Gemini Significantly Reduces Inflammatory Response in a Rat Bilateral Ischemia/Reperfusion Model of AKI

Pretreatment with Gemini (350 µg/kg) at 24 and/or 48 hours prior to IR significantly reduced multiple markers of local inflammation at 24 and/or 72 hours in urine (Figure 10a and 10b, 72-hour data not shown).

Pretreatment with Gemini (350 µg/kg) significantly reduced a key marker (CRP) of systemic inflammation at 72 hours in serum (Figure 10c).

Pretreatment with Gemini 24 hours prior to surgery also significantly reduced markers of cellular inflammation as observed via reduced neutrophilic inflammation at 72 hours (Figure 10d).

Clinical Studies Supporting the development of Gemini for AKI and CKD

Phase 1 Clinical Study in Healthy Volunteers

Administration of Gemini to healthy volunteers 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-10 (IL-10) (p<0.0.05, Figure 11 ), interleukin-1 Receptor Antagonist (IL-1RA) (p<0.001 at mid and high dose, Figure 12a ), neutrophil gelatinase lipocalin (NGAL) (p<0.01 at mid and high dose, Figure 12b ), c-reactive protein (CRP) (p<0.001 at mid and high dose, Figure 12c ), and IL-6 (p<0.01 at high dose, Figure 12d ).

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-α (p=0.51 at the highest dose) and IL-1β (p=0.89 at the highest dose).

This attenuated pro-inflammatory activity and corresponding significant upregulation of anti-inflammatory cytokines is unique to Gemini, and evidence of the reprogramming of the innate immune response for resolution of inflammation and promotion of the healing process.

Upregulation of IL-10 at 2 Hours Post Intravenous Administration of Gemini

Figure 12a-12d:

Peak Increase in IL-1RA, NGAL, CRP, and IL-6

Figures 12a through 12d illustrate the reprogramming of the innate immune response after Gemini administration in multiple biomarkers of TLR4 stimulation.

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-1b and TNF-a 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.

IL-1RA has anti-inflammatory properties, as it binds to the IL-1 receptor, blocking IL-1a and IL-1b, 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.

The pharmacologic effects observed in healthy volunteers was consistent with the pharmacologic effects observed in healthy animals ( Figure 13 ).

Importantly, this consistent effect was observed in the same species used in the preclinical AKI models, (unilateral ureteral obstruction model of kidney injury and ischemia/reperfusion model of acute kidney injury) where Gemini demonstrated significant activity as a treatment for AKI.

Cytokine Upregulation in Healthy Humans Agrees with Cytokine Upregulation in Healthy Animals

Figure 13 demonstrate the cytokine and cellular response in healthy volunteers is comparable to the cytokine and cellular response observed in healthy rats, the same species used for the preclinical pharmacology studies.

Phase 1b Clinical Study in patients with stage 3 and stage 4 chronic kidney disease

Stage 3 and Stage 4 CKD patient peripheral blood mononuclear cells (PBMCs) were isolated predose and at 2, 24, and 168 hours post-dose of either Gemini or placebo.

PBMCs were analyzed ex vivo for background inflammation by measurement of IL-1β, TNF-α, IL-6, IL-10, and IL-1RA.

Cells were also assessed for response to stimulation by lipopolysaccharide (LPS, also known as endotoxin) or high mobility group box-1 protein (HMGB-1).

On average, patients enrolled in the study had at least 3 elevated cytokines at baseline with a majority (>50%) of all patients in the placebo and target groups having greater than 4 elevated cytokines, and greater than 80% of patients having least 1 elevated cytokine at predose ( Table 1a ).

In particular, elevated IL-1b and IL-6 were observed in >60% of patients ( Table 1b ).

In addition to having a high cytokine background, PBMCs were also not responsive to additional stimulation to either LPS ( Table 2a and 2b ) or HMGB-1 ( Table 3a and 3b ), demonstrating a form of immunoparalysis or immune cell tolerance, often observed in chronic disease.

Table 1a and 1b:

Elevated Cytokines in PBMC Samples

Table 2a and 2b:

Response to LPS Stimulation in predose PBMC Samples

Table 3a and 3b:

Response to HMGB-1 Stimulation in predose PBMC Samples

Treatment with Gemini significantly reduced the number of elevated cytokines vs baseline at all timepoints post-dose, demonstrating a durable response ( Figure 14a ), while placebo resulted in no significant change from baseline ( Figure 14b ).

Figure 14a and 14b:

Elevated Cytokines in Target Dose Group and Placebo Group Over Time

Figures 14a and 14b are box and whisker plots of all data in the specified group at the specified time.

2 hr, p<0.01, 24 hr p<0.02, 168 hr p<0.03.

2 hr, NS, 24 hr NS, 168 hr NS.

NS=not significant.

P-values generated using two-tailed t-test with alpha at 5%.

In addition, treatment with Gemini significantly restored normal responsiveness to LPS stimulation ( Figure 15a and 15b ) and trended to improved responsiveness to HMGB-1 at 24 hours vs baseline values, p=0.06 for Treated and p=0.45 for Placebo ( Figure 16a and 16b ) correcting the immunoparalysis observed predose, demonstrating Gemini is not simply acting as an immunosuppressive agent.

Figure 15a and 15b:

Cytokines stimulated by LPS in Target Dose Group and Placebo Group Over Time

Figures 15a and 15b are box and whisker plots of all data in the specified group at the specified time.

2 hr, NS, 24 hr p<0.02, 168 hr p<0.03.

2 hr, NS, 24 hr NS, 168 hr NS.

NS=not significant.

P-values generated using two-tailed t-test with alpha at 5%.

Figure 16a and 16b:

Cytokines stimulated by HMGB-1 in Target Dose Group and Placebo Group Over Time

Figures 16a and 16b are box and whisker plot of all data in the specified group at the specified time.

2 hr, NS, 24 hr p<0.06, 168 hr NS.

2 hr, NS, 24 hr NS, 168 hr NS.

NS=not significant.

P-values generated using two-tailed t-test with alpha at 5%.

Patient PBMCs with high background inflammation tended to be resistant to LPS or HMGB-1 stimulation.

As such, an analysis was done on patients with high IL-1b (>12 pg/mL IL-1β) and high IL-6 at predose.

In these patients, Gemini significantly reduced the background inflammation relative to placebo patient PBMCs post dose (IL-1β:

p<0.001) and remained significantly below their baseline value through day 7.

Background inflammation was reduced to levels comparable to PBMCs isolated from healthy subjects.

In addition, Gemini significantly increased the responsiveness to LPS ( Figures 17a-17f ) and HMGB-1 stimulation ( Figures 18a-18f ) relative to placebo at all timepoints.

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.

As expected, Gemini administration had no significant effect on patients with low background inflammation (e.g.

it did not increase background inflammation).

Figure 17a-17f:

Gemini Restored Response to LPS Stimulation in High Predose Background Patients

Figures 17A-F show the cytokine response of isolated PMBCs to stimulation with LPS which had an initial high background of IL1- b .

NS=not significant.

P-values generated using two-tailed t-test with alpha at 5%.

Figure 18a-18f:

Gemini Restored Response to HMGB-1 Stimulation in High Predose Background Patients

Figures 18A-F show the cytokine response of isolated PMBCs to stimulation with HMGB-1 which had an initial high background of IL1- b .

P-values generated using two-tailed t-test with alpha at 5%.

Development Plans

Revelation met with FDA at the end of 2025 and obtained agreement on a single Phase 2/3 adaptive design study comprising approximately 300 patients with AKI and a primary composite endpoint of death and/or need for dialysis, the data from which can be used for submission of a new drug application (NDA).

During 2026, the Company plans to build the necessary infrastructure to successfully run this clinical study including engagement of a scientific advisory board, engagement of a top-tier clinical research organization specializing in renal studies, and manufacture of blinded drug and placebo with the intention of starting the Phase 2/3 study as soon as feasible.

During 2026, Revelation intends to conduct preclinical toxicology studies to support a multiple-dose Phase 2 study to allow further evaluation of Gemini in this high-need patient population.

Additional clinical studies will be necessary to obtain approval of Gemini in this indication

The biopharmaceutical industry is intensely competitive and subject to rapid innovation and significant technological advancements.

We believe the key competitive factors that will affect the development and commercial success of our Gemini based programs and any future Program Product candidates are efficacy, safety and tolerability profile, reliability, convenience of dosing, price, the level of generic competition, and reimbursement.

We believe the key competitive factors that will affect the development and commercial success of our Gemini based programs and any future product candidates are efficacy, safety and tolerability profile, reliability, convenience of dosing, price, the level of generic competition, and reimbursement.

Our competitors include multinational pharmaceutical companies, specialized biotechnology companies, universities, and other research institutions.

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Smaller or earlier-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies.

Given the high incidence of AKI and CKD, and the rate of surgical site infections, it is likely that the number of companies seeking to develop products and therapies for the prevention or treatment of such, will increase.

If Gemini-AKI is approved for prevention of acute kidney injury, we would face competition that could arise from products currently in development.

Given the high incidence of AKI and CKD, it is likely that the number of companies seeking to develop products and therapies for the prevention or treatment of such will increase.

If Gemini-AKI is approved for treatment of acute kidney injury, we would face competition that could arise from products currently in development.

If Gemini-CKD is approved for treatment of chronic kidney disease, we would face competition from currently approved and marketed products including Farxiga®.

We would also have future competition that could arise from products currently in development.

If Gemini-PSI is approved for prevention of surgical site infection, we would face competition from currently approved and marketed products including many antibiotics that are effective against non-resistant strains of bacteria.

We would also have future competition that could arise from products currently in development.

Many of our competitors have substantially greater financial, technical, human, and other resources than we do and may be better equipped to develop, manufacture, and market technologically superior products.

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In addition, many competitors have greater name recognition and more extensive collaborative relationships.

As a result, our competitors may obtain regulatory approval of their products more rapidly than we do or may obtain patent protection or other intellectual property rights that limit our ability to develop or commercialize our Program Products or any future product candidates.

Our competitors may also develop and succeed in obtaining approval for drugs that are more effective, more convenient, more widely used and less costly or have a better safety profile than our products and these competitors may also be more successful than we are in manufacturing and marketing their products.

If we are unable to compete effectively against these companies, then we may not be able to commercialize our product candidate or any future product candidates or achieve a competitive position in the market.

If we are unable to compete effectively against these companies, then we may not be able to commercialize our Product Candidates or any future product candidates or achieve a competitive position in the market.

This would adversely affect our ability to generate revenue.

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Manufacturing and Supply

We do not own or operate manufacturing facilities for the production of our Program Products or any other product candidates, nor do we have plans to develop our own manufacturing operations in the foreseeable future.

We currently rely, and expect to continue to rely, on third parties for the manufacturing of our Program Products or any other product candidates for preclinical and clinical testing, as well as for commercial manufacturing if Gemini or any future product candidate receives marketing approval.

We do not own or operate manufacturing facilities for the production of our Product Candidates or any other product candidates, nor do we have plans to develop our own manufacturing operations in the foreseeable future.

We currently rely, and expect to continue to rely on, third parties for the manufacturing of our Product Candidates or any other product candidates for preclinical and clinical testing, as well as for commercial manufacturing if Gemini or any future product candidate receives marketing approval.

Also, there is only one supplier for PHAD ® , Avanti Polar Lipids, Inc., with whom we do not have a long-term supply agreement.

Currently we have purchased enough material for our planned clinical studies through purchase orders.

Currently, we have purchased enough active pharmaceutical ingredients for our planned clinical studies through purchase orders.

Strategic Acquisitions and In-Licensing

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The license grants Revelation the use of issued US patent 11,389,465.

We are obligated to use commercially reasonable efforts to (i) develop, commercialize, market and sell licensed products in a manner consistent with a development plan submitted to Vanderbilt by April 2023 and (ii) achieve certain financing, development, regulatory and clinical milestone events, including, among other things, raising $5 million in financing to advance the development program, commencement of various clinical trials by target dates according to the development plan and the filing of an Investigational New Drug Application (“IND”) by the end of 2032.

We are obligated to use commercially reasonable efforts to (i) develop, commercialize, market and sell licensed products in a manner consistent with a development plan submitted to Vanderbilt in April 2023 and (ii) achieve certain financing, development, regulatory and clinical milestone events, including, among other things, raising $5 million in financing to advance the development program, commencement of various clinical trials by target dates according to the development plan and the filing of an Investigational New Drug Application (“IND”) by the end of 2032.

Under the license agreement we are obligated to make payments to Vanderbilt based upon achievement of certain milestones including achievement of various clinical trial events, regulatory approval and sales levels.

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We also rely on trade secret protection of our confidential information and know-how relating to our proprietary technology, platforms, and Product Candidates.

As of March 3, 2025, our patent portfolio includes one patent family directed to MPLA formulations, including Gemini.

As of February 23, 2026, our patent portfolio includes one patent family directed to MPLA formulations, including Gemini.

This patent family includes one U.S.

application, one European Patent Organization (“EPO”) application, and one Canadian application.

Our portfolio additionally includes a Patent Cooperation Treaty (“PCT”) application directed to methods of using MPLA formulations, including Gemini, as an adjuvant to traditional allergy immunotherapy, such as oral allergy immunotherapy.

Our portfolio additionally includes a second patent family, consisting of a U.S application and a Canadian application directed to methods of using MPLA formulations, including Gemini, as an adjuvant to traditional allergy immunotherapy, such as oral allergy immunotherapy.

Our portfolio also includes a U.S.

provisional patent application covering dosing regimens of MPLA formulations.

Regarding our GEM-AKI and GEM-CKD programs, our portfolio also includes a patent family directed to the use of MPLA formulations for the prevention of loss of function associated with acute organ disease and chronic organ disease.

This patent family includes one application in the U.S., as well as applications filed in the EPO, China, Japan, South Korea, and Canada.

This patent family includes one application in the U.S., as well as applications filed in the EPO, China, Hong Kong, Japan, South Korea, and Canada.

Finally, we have licensed from Vanderbilt University a patent directed to methods of using PHAD for treating or preventing infections.

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We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems.

As of March 3, 2025, we had 8 full-time employees and one part-time employee, 5 of whom are engaged in research and development activities or operations and 4 of whom are engaged in general and administrative activities or operations.

As of February 23, 2026, we had 8 full-time employees and one part-time employee, 5 of whom are engaged in research and development activities or operations and 4 of whom are engaged in general and administrative activities or operations.

None of our employees are represented by a labor union or covered by a collective bargaining agreement.

We consider our relationship with our employees to be good.

We consider our relationship with our employees to be positive.

Government Regulation

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Our Product Candidates must be approved for therapeutic indications by the FDA before they may be marketed in the United States.

For drug product candidates regulated under the FD&C Act, FDA must approve a New Drug Application (“NDA”).

For Product Candidates regulated under the FD&C Act, FDA must approve a New Drug Application (“NDA”).

The process generally involves the following:

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More than one adequate and well-controlled Phase 3 clinical study may be required by the FDA for approval of an NDA.

Pursuant to FDORA and subsequent FDA guidance, sponsors of certain Phase 3 clinical trials or other pivotal studies are required to submit Diversity Action Plans describing strategies to enroll representative populations, including racial and ethnic minorities and other underrepresented populations.

The FDA has indicated that failure to submit or adequately implement such plans may delay review or approval.

These requirements may increase development complexity and cost.

Progress reports detailing the results of clinical studies involving an IND must be submitted at least annually to the FDA and more frequently if serious adverse events occur.

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Similarly, an IRB can suspend or terminate approval of a clinical study at its institution if the clinical study is not being conducted in accordance with the IRB’s requirements or if the drug or biologic product has been associated with unexpected serious harm to patients.

Concurrent with clinical studies, the company usually complete additional animal studies, develop additional information about chemistry and physical characteristics of the product candidate, and finalize a process for manufacturing the drug product in commercial quantities in accordance with cGMP requirements.

Concurrent with clinical studies, the Company usually completes additional animal studies, develop additional information about chemistry and physical characteristics of the product candidate, and finalize a process for manufacturing the drug product in commercial quantities in accordance with cGMP requirements.

The manufacturing must be capable of consistently producing quality batches of the product candidate and manufacturers must develop, among other things, methods for testing the identity, strength, quality and purity of the final drug product.

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HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA and seek attorneys’ fees and costs associated with pursuing federal civil actions.

In addition to HIPAA and HITECH, many state laws govern the privacy and security of health information in specified circumstances, many of which differ from each other in significant ways, are often not pre-empted by federal law, and may have a more prohibitive effect than federal law, thus complicating compliance efforts.

In addition to HIPAA and HITECH, numerous states have enacted comprehensive consumer privacy statutes that may apply to health-related data even where HIPAA does not, imposing additional data governance, cybersecurity, and consumer rights compliance obligation, many of which differ from each other in significant ways, are often not pre-empted by federal law, and may have a more prohibitive effect than federal law, thus complicating compliance efforts.

We may develop products that, once approved, may be administered by a physician.

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In order to distribute products commercially, we must comply with state laws that require the registration of manufacturers and wholesale distributors of drug and biological products in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state.

Some states also impose requirements on manufacturers and distributors to establish the pedigree of product in the chain of distribution, including some states that require manufacturers and others to adopt new technology capable of tracking and tracing product as it moves through the distribution chain.

Some states also impose requirements on manufacturers and distributors to establish the pedigree of product in the chain of distribution.

These requirements have been further expanded under the Drug Supply Chain Security Act (DSCSA), which mandates interoperable electronic tracing at the package level and enhanced product verification, including interoperable electronic tracing at the package level, became effective in November 2023, subject to phased enforcement.

Manufacturers must ensure serialization, product tracing, and verification compliance, including some states that require manufacturers and others to adopt new technology capable of tracking and tracing product as it moves through the distribution chain.

Several state and local laws have been enacted requiring pharmaceutical and biotechnology companies to establish marketing compliance programs, file periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, clinical studies and other activities, and/or register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing certain physician prescribing data to pharmaceutical and biotechnology companies for use in sales and marketing, and to prohibit certain other sales and marketing practices.

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Additionally, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.

On August 16, 2022, President Biden signed the Inflation Reduction Act of 2022, or IRA, into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and through a newly established manufacturer discount program.

It is unclear how other healthcare reform measures, if any, will impact our business.

Any reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payments from private payors.

The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our products.

Such reforms could have an adverse effect on anticipated revenue from product candidates that we may successfully develop and for which we may obtain regulatory approval and may affect our overall financial condition and ability to develop product candidates.

On August 16, 2022, President Biden signed the Inflation Reduction Act of 2022, or IRA, into law.

The IRA extended enhanced premium tax credits for individuals purchasing health insurance coverage through ACA marketplace plans through plan year 2025.

The enhanced premium tax credits expired on December 31, 2025.

The expiration of these subsidies may reduce enrollment in ACA marketplace plans and decrease access to subsidized health insurance coverage.

Changes in the number of insured individuals or in reimbursement structures could affect demand for pharmaceutical products reimbursed through such plans.

The IRA also eliminated the Medicare Part D coverage gap beginning in 2025, caps beneficiary out-of-pocket costs, establishes a manufacturer discount program that increases manufacturer liability in certain phases of the Part D benefit, authorizes the Secretary of HHS to negotiate maximum fair prices for certain high-expenditure single-source drugs and biologics covered under Medicare, with the first negotiated prices taking effect in 2026 for selected Medicare Part D drugs and additional products to be selected annually thereafter, and imposes inflation-based rebate obligations under Medicare Parts B and D.

These provisions are being implemented through agency guidance and rulemaking and is expected to affect pricing and reimbursement dynamics for pharmaceutical products.

Further legislation or regulation could be passed that could harm our business, results of operations and financial condition.

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In January 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

More recently, on May 30, 2018, the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017, or the Right to Try Act, was signed into law.

In 2018, the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017, or the Right to Try Act, was signed into law.

The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase I clinical trial and that are undergoing investigation for FDA approval.

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Individual states in the United States have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

There have been a number of recent Presidential Executive Orders that have or may have an effect on the pharmaceutical and biotechnology industries.

In 2025, the Trump Administration issued Executive Orders and pursued legislative initiatives that could materially affect our business operations and product development strategy.

On May 12, 2025, President Trump signed an Executive Order requiring that U.S.

prices for prescription drugs not exceed the lowest price ordered in other developed nations (Most-Favored-Nation or “MFN” pricing).

In September 2025, President Trump announced a 100% tariff on all "branded or patented" imported drugs effective October 1, 2025, which manufacturers could avoid by building manufacturing facilities in the United States.

This tariff regime significantly increases costs for manufacturers relying on foreign manufacturing, potentially making our reliance on third-party manufacturers for clinical and commercial supply more expensive if those manufacturers do not rapidly establish or expand U.S.

production capabilities.

Additionally, on May 5, 2025, President Trump signed an Executive Order directing the FDA to streamline and accelerate approval of domestic pharmaceutical manufacturing by eliminating unnecessary regulatory barriers and increasing fees for foreign manufacturing facilities.

On August 13, 2025, President Trump signed an Executive Order establishing a Strategic Active Pharmaceutical Ingredients Reserve, which may affect the availability and cost of critical raw materials, including the PHAD lipid our GEM Program Products require.

The Trump Administration has pursued a deregulatory agenda requiring agencies to eliminate 10 existing regulations or guidance documents for every new regulation issued.

This regulatory framework may slow FDA issuance of guidance and reduce the agency’s capacity for routine functions, potentially extending our IND review timelines and clinical study authorization processes.

Additionally, uncertainty regarding how FDA will interpret and apply these new policies, combined with reduced agency staffing due to budget constraints, may create delays or unpredictable regulatory outcomes for our clinical programs.

Enhanced FDA oversight of foreign contract manufacturing organizations and contract research organizations may increase the cost of engaging foreign CDMOs and CROs and potentially limit our access to certain foreign suppliers if they do not meet enhanced FDA requirements or choose to cease U.S.

operations due to increased compliance burden.

On October 1, 2025, the Administration launched TrumpRx.gov, a government-operated direct-to-consumer platform allowing individuals to purchase select medications at discounted prices from participating manufacturers.

These initiatives could fundamentally change the traditional pharmaceutical distribution model, bypass traditional pharmacy benefit managers and wholesalers, and require us to establish new compliance and operational infrastructure if we choose to participate.

Alternatively, exclusion from these channels could disadvantage us competitively relative to manufacturers participating in these programs.

In December 2025, Congress expanded the orphan drug exclusion to the Medicare Drug Price Negotiation Program, allowing drugs with multiple rare disease indications to maintain pricing protection if each indication is for a rare disease.

This change may benefit our GEM-AKI program if it qualifies for orphan designation, though it also reflects continued Congressional interest in restricting pharmaceutical pricing through the Medicare program, creating ongoing uncertainty regarding how future policy changes may affect our products if approved.

On December 1, 2025, the U.S.

and United Kingdom announced an agreement to increase net prices of new prescription drugs by 25% in the U.K., reflecting efforts to ensure foreign countries contribute more fairly to pharmaceutical innovation.

These bilateral price negotiations may complicate our international commercialization strategy and pricing discussions in foreign markets, requiring coordination between domestic MFN pricing requirements and foreign price negotiations.

We cannot predict whether these 2025 policy initiatives will be maintained, expanded, modified, or reversed by future administrations, Congress or the courts.

The evolving regulatory landscape creates material uncertainty regarding whether and when our manufacturing costs will increase.

Any of these developments could materially and adversely affect our business model, cost structure, development timeline, manufacturing strategy, regulatory approvals, commercialization approach, and financial projections.

We will need to maintain flexibility in our development and commercialization strategies to adapt to these policy changes, but such adaptation may require significant operational and financial adjustment

We expect additional state, federal and foreign healthcare reform measures to be adopted in the future, any of which could limit the amounts that federal, state and foreign governments will pay for health products, which could result in reduced demand for our products, if approved or additional pricing pressure.

For instance, in December 2021, the European Union (“EU”) Regulation No 2021/2282 on Health Technology Assessment, or HTA, amending Directive 2011/24/EU, was adopted.

While the Regulation entered into force in January 2022, it will only begin to apply from January 2025 onwards, with preparatory and implementation-related steps to take place in the interim.

Once the Regulation becomes applicable, it will have a phased implementation depending on the concerned products.

This regulation is intended to boost cooperation among EU member states in assessing health technologies, including new medicinal products, as well as certain high-risk medical devices, and providing the basis for cooperation at the EU level for joint clinical assessments in these areas.

The regulation will permit EU member states to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovative health technologies with the most potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas.

Individual EU member states will continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technologies, and making decisions on pricing and reimbursement.

For instance, the EU Regulation (EU) 2021/2282 on Health Technology Assessment (“HTA Regulation”), amending Directive 2011/24/EU, was adopted in December 2021 and entered into force in January 2022.

The HTA Regulation became applicable in January 2025 for certain medicinal products, including certain oncology and advanced therapy medicinal products, with phased expansion to additional products thereafter.

The regulation establishes a framework for joint clinical assessments at the EU level, which Member States are required to consider in their national pricing and reimbursement decisions.

The HTA Regulation is intended to enhance cooperation among EU Member States in the assessment of health technologies by providing common tools, methodologies and procedures, including joint clinical assessments, joint scientific consultations, identification of emerging health technologies, and continued voluntary cooperation in other areas.

While clinical assessment activities will be coordinated at the EU level, individual Member States will remain responsible for evaluating non-clinical aspects, such as economic, social and ethical considerations, and for making final pricing and reimbursement decisions.

Additional Regulation

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Accelerated approval is usually contingent on a sponsor’s agreement to conduct additional post-approval studies to verify and describe the product’s clinical benefit.

In December 2022, the Food and Drug Omnibus Reform Act (FDORA) amended the accelerated approval framework to provide the FDA with enhanced authority to require that confirmatory trials be underway prior to approval, to mandate timely completion of such trials, and to expedite withdrawal procedures if confirmatory trials fail to verify clinical benefit.

These changes could increase regulatory oversight and post-approval compliance obligations for products approved under accelerated pathways.

In addition, unless otherwise informed by the FDA, the FDA currently requires, as a condition for accelerated approval, that all advertising and promotional materials that are intended for dissemination or publication be submitted to FDA for review before the initial dissemination or publication.

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• injunctions or the imposition of civil or criminal penalties.

The FDA closely regulates the marketing, labeling, advertising and promotion of biologic regulations prohibiting the promotion of off-label uses.

The FDA closely regulates the marketing, labeling, advertising and promotion of biologics, including regulations prohibiting the promotion of off-label uses.

Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business