IRL201104 / Revolo Biotherap - LARVOL DELTA

IRL201104, A Novel Immunomodulatory Peptide, Shows a Wide Spectrum Long Lasting Effect on Inflammatory Endpoints Through the Sublingual Route in a Model of Allergic Inflammation (ATS 2025) - "As seen with other routes of administration, IRL201104 shows a similar wide spectrum long-lasting immunomodulatory profile when administered through an orally disintegrating tablet. The present work shows the potential of the sublingual route when administering 1104 in the treatment of asthma and other allergic and inflammatory diseases and validates our clinical formulations, supporting transition to this route of administration for future clinical trials.References: Riffo-Vasquez et al. Clin Exp Allergy."

Immunomodulating • Asthma • Eosinophilic Esophagitis • Gastrointestinal Disorder • Infectious Disease • Inflammation • Respiratory Diseases • Tuberculosis • CCL11 • IL13 • IL4 • IL5 • POSTN

A Study to Assess the Efficacy, Safety and Tolerability of IRL201104 in Adults With Active Eosinophilic Esophagitis (clinicaltrials.gov) - P2 | N=36 | Completed | Sponsor: Revolo Biotherapeutics | Phase classification: P2a ➔ P2

Phase classification • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Revolo to Present at the 2025 AAAAI / WAO Joint Congress (GlobeNewswire) - "Dr. De Alba will discuss preclinical studies that show the potential of the Company’s lead clinical asset, ‘1104, for treating atopic dermatitis (AD). In a chronic allergen-driven murine model of AD, ‘1104 significantly reduced skin thickness and skin pathology indicators. It also reduced allergen-driven Th2 cytokines and pro-inflammatory cytokines as well as serum biomarkers of AD to levels close to naïve controls and comparable to positive control individuals treated with the anti-inflammatory dexamethasone...Dr. De Alba will discuss preclinical data demonstrating the performance of subcutaneous ‘1104 in comparison to an intravenous formulation. Data from an ovalbumin (OVA) re-challenge model of allergic inflammation showed that ‘1104 significantly reduced inflammatory infiltration, pro-inflammatory cytokines, and OVA specific Immunoglobulin E (IgE)."

Preclinical • Atopic Dermatitis

IRL201104, A Novel Immunomodulatory Peptide, Shows Efficacy In An Allergen Driven Model Of Atopic Dermatitis (AAAAI-WAO 2025) - "Animals received vehicle, IRL201104 (80ug/kg or 2mg/kg iv) or dexamethasone (3mg/kg ip) from day 18-34. IRL201104 treatment showed significant dose response reduction on skin thickness, skin pathology and serum levels of OVA specific IgE and all cytokines/chemokines, comparable to dexamethasone. Conclusions This study shows the potential of IRL201104 as a novel first in class treatment for atopic dermatitis."

Clinical • Immunomodulating • Late-breaking abstract • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation • IL13 • IL17A • IL1B • IL4 • IL5 • TNFA

IRL201104, A Novel Immunomodulatory Peptide, Drives An Increase In T And B Regulatory Cell Phenotypes And Shows Long Lasting Efficacy Through Different Routes Of Administration In A Mouse Model Of Allergic Inflammation (AAAAI-WAO 2025) - "Conclusions This study shows that IRL201104 long pharmacodynamic effect is consistent with the induction of tolerogenic T and B regulatory cell phenotypes. The study also validates our two clinical subcutaneous formulations, supporting transition to this route of administration for future clinical trials."

Immunomodulating • Preclinical • Inflammation • FOXP3 • IL10 • IL13 • IL4 • IL5

Revolo Announces New Preclinical Data Supporting Subcutaneous ‘1104 for Atopic Dermatitis and Other Clinical Programs (GlobeNewswire) - "Key results when comparing SQ versus IV administration in a murine allergen-driven model of AD: Comparable reductions in inflammatory biomarkers in serum, reaching levels similar to naïve control individuals and equivalent to those observed in positive control individuals treated with the anti-inflammatory dexamethasone; This includes key T helper 2 (Th2) cytokines, like interleukin 4 (IL-4), IL-5, and IL-13, to cytokines specific to AD, including CCL17 and CCL22, and IL-31, a cytokine specific to itch, overall consistent with the mechanism of action for ‘1104...Key results of single-dose toxicity studies evaluating tolerability and pharmacokinetics (PK) of the SQ formulation in two preclinical models: There were no local tolerability adverse effects (redness or swelling) in preclinical models administered the SQ formulation at dose levels substantially higher than planned for clinical evaluation."

Preclinical • Atopic Dermatitis • Immunology

IRL201104, A Novel Immunomodulatory Peptide, Shows Efficacy on Inflammatory Endpoints and Airway Hyperresponsiveness in a House Dust Mite Driven Model of Allergic Inflammation With or Without Poly I:C Exacerbation (ATS 2024) - "IRL201104 showed efficacy on inflammatory markers and lung function in a HDM drivel model of allergic inflammation. Unlike steroid dexamethasone, 1104 maintained its efficacy even after Poly I:C exacerbation. The present work shows the potential of IRL201104 in asthma and other allergic inflammatory diseases even in phenotypes that do not respond to steroids."

Clinical • Immunomodulating • Asthma • Inflammation • Pulmonary Disease • Respiratory Diseases • CCL11 • IL13 • IL4 • IL5

Revolo Biotherapeutics Receives Orphan Drug Designation from the U.S. FDA for its First-in-Class Peptide as a Potential Treatment for Eosinophilic Esophagitis (GlobeNewswire) - "Revolo Biotherapeutics...announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to ‘1104, a first-in-class immune-resetting peptide being developed as a potential treatment for eosinophilic esophagitis (EoE). Revolo submitted its original request prior to the initiation of its Phase 2a EoE study (RVLO 121-04) and submitted an amended request following positive results from an additional Phase 2 study....Based on the results from RVLO 121-04, Revolo plans to initiate a Phase 2b trial of ‘1104 in adults with active EoE in 2024."

New P2b trial • Orphan drug • Eosinophilic Esophagitis • Immunology

Efficacy and Safety of IRL201104, a Novel Peptide Immunomodulator, in a Phase 2a, Double-Blind, Placebo-Controlled Multi-Center Study in Patients With Active Eosinophilic Esophagitis (ACG 2023) - P2a | "There were no serious adverse events (SAEs), discontinuations from AEs, or safety signals in this study (Table 1). Most frequent AEs were constipation, nausea, headace, and fatigue. Most AEs were mild or moderate, with no severe related AEs."

Clinical • Immunomodulating • P2a data • Constipation • Eosinophilic Esophagitis • Fatigue • Gastrointestinal Disorder • Immunology • Inflammation • CD8

Revolo Biotherapeutics to Present Data from Phase 2a Clinical Trial of ‘1104 in Eosinophilic Esophagitis at ACG 2023 (GlobeNewswire) - "Revolo Biotherapeutics...announced that it will present the previously announced Phase 2a trial data evaluating its immune-resetting drug candidate, ‘1104, in people with eosinophilic esophagitis (EoE), via a poster at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting in Vancouver, Canada, from October 20-25."

P2a data • Eosinophilic Esophagitis • Immunology

Safety, Tolerability, and Pharmacokinetics of IRL201104 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Revolo Biotherapeutics | Recruiting ➔ Completed

Trial completion

Revolo Biotherapeutics Announces the Completion of Phase 1 Multiple Ascending Dose Clinical Trial of ‘1104 (GlobeNewswire) - P1 | N=24 | NCT05921591 | Sponsor: Revolo Biotherapeutics | "Revolo Biotherapeutics...today announced the completion of a Phase 1 multiple ascending dose (MAD) clinical trial evaluating the safety and tolerability of the Company’s immune-resetting drug candidate, ‘1104, in healthy volunteers. The study showed no clinically significant adverse safety findings at any of the doses evaluated (16, 32, and 64 mg). The results support the evaluation of ‘1104 at doses above those administered in clinical trials to date....'We anticipate that higher doses administered over a longer duration of treatment could potentially result in a superior efficacy profile. We are working diligently to initiate a Phase 2b EoE trial in H1 2024.'"

New P2b trial • P1 data • Trial completion • Eosinophilic Esophagitis • Immunology

Revolo Biotherapeutics to Host Virtual KOL Event on ‘1104: A First-in-Class Peptide for Eosinophilic Esophagitis (EoE) and Allergic Disease (GlobeNewswire) - "Revolo Biotherapeutics...today announced it will host a virtual KOL event on ‘1104, a first-in-class peptide for eosinophilic esophagitis (EoE) and allergen sensitivity on Tuesday, August 29, 2023, at 11:00 AM – noon ET. The event will feature Evan Dellon, MD, MPH (University of North Carolina School of Medicine in Chapel Hill) and Mohamed Shamji, PhD (Professor of Immunology and Allergy at Imperial College London). The event will discuss disease pathogenesis, the unmet medical needs, the current treatment landscape, and Revolo’s recent positive phase 2a clinical data in patients suffering from EoE as well as the broad mechanistic effects of ‘1104 in allergy."

Clinical • P2a data • Eosinophilic Esophagitis • Immunology

Revolo Biotherapeutics Announces Additional Data from Phase 2a Trial of ‘1104 in Adults with Active Eosinophilic Esophagitis (GlobeNewswire) - P2a | N=36 | NCT05084963 | Sponsor: Revolo Biotherapeutics | "Revolo Biotherapeutics...announced additional data from its proof of concept, 2-week, 3-dose, Phase 2a clinical trial evaluating the efficacy, safety, and tolerability of the company’s immune-resetting drug, ‘1104, in adults with active eosinophilic esophagitis (EoE)....Patient reported dysphagia median symptom scores ('DSQ') showed a sustained statistically significant improvement from baseline vs placebo that continued for four weeks after the last dose; Eosinophil count showed a ~50% statistically significant reduction from baseline as measured by flow cytometry; 8mg ‘1104 showed a statistically significant ~58% increase in T regulatory cells, that act to suppress inflammatory immune responses, taken from esophageal biopsies....Safety assessment showed no serious adverse events and there were no study drug discontinuations due to drug-related adverse events..."

P2a data • Eosinophilic Esophagitis • Immunology

Safety, Tolerability, and Pharmacokinetics of IRL201104 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Revolo Biotherapeutics

New P1 trial

IRL201104 inhibits pro- inflammatory T cell responses and induce regulatory T cell: A novel therapeutic approach for allergic rhinitis (EAACI 2023) - "Conclusion IRL201104 exhibit immunomodulatory properties with the capacity to suppress pro-allergic T cell responses (Th2, Th2A and Tfh), induce immune deviation towards Th1 response, and modulate Treg cells. These highlight the potential of IRL201104 for seasonal allergic rhinitis and other allergic diseases."

Late-breaking abstract • Allergic Rhinitis • Immune Modulation • Immunology • Inflammation • FOXP3 • IL10 • IL4 • SATB1

Tolerogenic properties of IRL201104, a novel heat shock- derived peptide, for the treatment of seasonal allergic rhinitis (EAACI 2023) - "Unbiased clustering analysis supported this observation, revealing 3 metaclusters denoting each one of the monocyte subsets with increasing population abundance in response to IRL201104 stimulation. Conclusion IRL201104 is tolerogenic and can induce the generation of IL-10-producing monocytes and Breg cells, making it a potential candidate for the treatment of seasonal allergic rhinitis and other allergic diseases."

Late-breaking abstract • Allergic Rhinitis • Immune Modulation • Immunology • Inflammation • CD14 • CD27 • CD40LG • IL10

IRL201104, a Novel Immunomodulatory Peptide, Prevents Inflammatory Infiltration and Proinflammatory Cytokine Release in a New Model of ARDS Associated to Influenza Infection (ATS 2023) - "We have established a new model of influenza exacerbation that mimics certain aspects or ARDS associated to IAV infection. In this model, IRL201104, unlike dexamethasone, significantly inhibits inflammatory infiltration and relevant pro-inflammatory cytokines such us TNF-α, IL-1β, IL-6, MCP-1 or MIP-1α showing the potential of the molecule to be used in the treatment of ARDS associated to viral infection."

Immunomodulating • Acute Respiratory Distress Syndrome • Immune Modulation • Infectious Disease • Inflammation • Influenza • Pneumonia • Pulmonary Disease • Respiratory Diseases • CSF2 • CXCL8 • IFNG • IL10 • IL17A • IL1B • IL6 • TNFA

Allergen Challenge Trial of IRL201104 in Seasonal Allergic Rhinitis (clinicaltrials.gov) - P2a | N=63 | Completed | Sponsor: Revolo Biotherapeutics | Active, not recruiting ➔ Completed

Trial completion • Allergic Rhinitis • Immunology • Inflammation

Revolo Biotherapeutics Announces Positive Topline Data from Phase 2a Trial of ‘1104 in Adults with Active Eosinophilic Esophagitis (GlobeNewswire) - P2a | N=36 | NCT05084963 | Sponsor: Revolo Biotherapeutics | "Revolo Biotherapeutics... announced positive topline data from its proof of concept Phase 2a clinical trial evaluating the efficacy, safety, and tolerability of the company’s immune-resetting drug, ‘1104, in adults with active eosinophilic esophagitis (EoE). Despite the short duration of treatment, patients treated with ‘1104 showed a dose dependent numeric reduction from baseline in the peak esophageal intraepithelial eosinophil count compared to the placebo group. In addition, ‘1104 treated patients showed positive results on a broad array of other biologic measures thought to be key drivers of EoE. Importantly, ‘1104 treated patients showed an increase in both Regulatory B cells (Bregs) and Regulatory T cells (Tregs) that act to suppress inflammatory immune responses."

P2a data • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

IRL201104, A Novel Immunomodulatory Peptide, Shows A Long Lasting Reduction In Anaphylaxis Symptoms And Allergy Biomarkers In A Murine Model Of Food Allergy (AAAAI 2023) - "This study highlight the great potential of IRL201104 as an alternative non-allergen specific therapy for the treatment of food allergy."

Immunomodulating • Preclinical • Allergy • Food Hypersensitivity • Immune Modulation • Immunology • Inflammation • CCL11 • IL13 • IL4 • IL5

Allergen Challenge Trial of IRL201104 in Seasonal Allergic Rhinitis (clinicaltrials.gov) - P2a | N=60 | Active, not recruiting | Sponsor: Revolo Biotherapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Allergic Rhinitis • Immunology • Inflammation

A Study to Assess the Efficacy, Safety and Tolerability of IRL201104 in Adults With Active Eosinophilic Esophagitis (clinicaltrials.gov) - P2a | N=36 | Completed | Sponsor: Revolo Biotherapeutics | Active, not recruiting ➔ Completed

Trial completion • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Revolo Biotherapeutics Announces That the Last Patient in its Phase 2a Trial of ‘1104 in Eosinophilic Esophagitis has Completed the Study (GlobeNewswire) - "Revolo Biotherapeutics...today announced that the last patient has completed a Phase 2a proof of concept clinical study investigating its immune-resetting molecule, ‘1104, for the treatment of patients with eosinophilic esophagitis (EoE)....'The last patient out marks a key milestone in our Phase 2a trial in EoE, and we are looking forward to announcing topline data early next year,'..."

P2a data • Eosinophilic Esophagitis • Respiratory Diseases

A Study to Assess the Efficacy, Safety and Tolerability of IRL201104 in Adults With Active Eosinophilic Esophagitis (clinicaltrials.gov) - P2a | N=36 | Active, not recruiting | Sponsor: Revolo Biotherapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology