Last update 19 Jun 2024

PIN-201104

Last update 19 Jun 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Synthetic peptide

Synonyms

Asp-Gly-Ser-Val-Val5-Val-Asn-Lys-Val-Ser10-Glu-Leu-Pro-Ala-Gly15-His-Gly-Leu-Asn-Val20-Asn-Thr-Leu-Ser-Tyr25-Gly-Asp-Leu-Ala-Ala30-Asp, 1104, ILR 201104

+ [5]

Target

Chaperonin

Mechanism

Chaperonin stimulators

Therapeutic Areas

Immune System DiseasesInfectious DiseasesDigestive System Disorders+ [3]

Active Indication

Rhinitis, Allergic, SeasonalEosinophilic Esophagitis

Inactive Indication

AsthmaCOVID-19

Originator Organization

Peptinnovate Ltd

Active Organization

Revolo Biotherapeutics Ltd.

Inactive Organization

Peptinnovate Ltd

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

Clinical Trials associated with PIN-201104

NCT05921591 / CompletedPhase 1

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate Safety, Tolerability, and Pharmacokinetics of IRL201104 in Healthy Volunteers

The purpose of this clinical study is to assess the safety, tolerability and pharmacokinetics of repeat doses of IRL201104 given to healthy volunteers.

Start Date26 May 2023

Sponsor / Collaborator

Revolo Biotherapeutics Ltd.

NCT05098522 / CompletedPhase 2

A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Allergen Challenge Trial of 6 Repeat Doses of IRL201104 in Adult Participants With Seasonal Allergic Rhinitis.

The purpose of this allergen challenge study is to assess the efficacy of IRL201104 compared with placebo in adult participants with seasonal allergic rhinitis.

Start Date04 Nov 2021

Sponsor / Collaborator

Revolo Biotherapeutics Ltd.

NCT05084963 / CompletedPhase 2

A Phase 2a, Double-blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy, Safety, and Tolerability of IRL201104 in Adult Participants With Active Eosinophilic Esophagitis (EoE)

The purpose of this study is to asses the efficacy, safety and tolerability of repeat doses of IRL201104 in Adult Participants with Active Eosinophilic Esophagitis (EoE)

Start Date29 Oct 2021

Sponsor / Collaborator

Revolo Biotherapeutics Ltd.

100 Clinical Results associated with PIN-201104

100 Translational Medicine associated with PIN-201104

100 Patents (Medical) associated with PIN-201104

Literatures (Medical) associated with PIN-201104

01 Nov 2021·American journal of physiology. Lung cellular and molecular physiologyQ2 · MEDICINE

A peptide derived from chaperonin 60.1, IRL201104, inhibits LPS-induced acute lung inflammation

Q2 · MEDICINE

Article

Author: Page, Clive P. ; Kanabar, Varsha ; Federici Canova, Donata ; Perretti, Mauro ; Gomes Ferreira, Sueli ; Riffo-Vasquez, Yanira ; Nadkarni, Suchita ; Man, Francis ; e-Lacerda, Rodrigo R.

Chaperonin 60.1 (Cpn60.1) is a protein derived from Mycobacterium tuberculosis that has been shown, along with its peptide fragment IRL201104, to have beneficial effects in models of allergic inflammation. To further investigate the anti-inflammatory properties of Cpn60.1 and IRL201104, we have investigated these molecules in a model of nonallergic lung inflammation. Mice were treated with Cpn60.1 (0.5–5,000 ng/kg) or IRL201104 (0.00025–2.5 ng/kg), immediately before intranasal instillation of bacterial lipopolysaccharide (LPS). Cytokine levels and cell numbers in mouse bronchoalveolar lavage (BAL) fluid were measured 4 h after LPS administration. In some experiments, mice were depleted of lung-resident phagocytes. Cells from BAL fluid were analyzed for inflammasome function. Human umbilical vein endothelial cells (HUVECs) were analyzed for adhesion molecule expression. Human neutrophils were analyzed for integrin expression, chemotaxis, and cell polarization. Cpn60.1 and IRL201104 significantly inhibited neutrophil migration into the airways, independently of route of administration. This effect of the peptide was absent in TLR4 and annexin A1 knockout mice. Intravital microscopy revealed that IRL201104 reduced leukocyte adhesion and migration into inflamed tissues. However, IRL201104 did not significantly affect adhesion molecule expression in HUVECs or integrin expression, chemotaxis, or polarization of human neutrophils at the studied concentrations. In phagocyte-depleted animals, the anti-inflammatory effect of IRL201104 was not significant. IRL201104 significantly reduced IL-1β and NLRP3 expression and increased A20 expression in BAL cells. This study shows that Cpn60.1 and IRL201104 potently inhibit LPS-induced neutrophil infiltration in mouse lungs by a mechanism dependent on tissue-resident phagocytes and to a much lesser extent, the proresolving factor annexin A1.

01 Apr 2020·Clinical and experimental allergy : journal of the British Society for Allergy and Clinical ImmunologyQ2 · MEDICINE

Modulation of allergic inflammation in the lung by a peptide derived from Mycobacteria tuberculosis chaperonin 60.1

Q2 · MEDICINE

Article

Author: Page, Clive P. ; Corrigall, Valerie ; Jackson, David J. ; Man, Francis ; Keir, Sandra D. ; e‐Lacerda, Rodrigo R. ; Riffo‐Vasquez, Yanira ; Kanabar, Varsha ; Coates, Anthony R. M.

Abstract:

Background:

We have previously demonstrated that Mycobacteria tuberculosis chaperonin 60.1 inhibits leucocyte diapedesis and bronchial hyperresponsiveness in a murine model of allergic lung inflammation.

Methods:

In the present study, we have investigated the effect of a shorter peptide sequence derived from Cpn 60.1, named IRL201104, on allergic lung inflammation induced by ovalbumin (OVA) in mice and by house dust mite (HDM) in guinea pigs, as well as investigating the action of IRL201104 on human cells in vitro.

Results:

Pre‐treatment of mice or guinea pigs with IRL201104 inhibits the infiltration of eosinophils to the lung, cytokine release, and in guinea pig skin, inhibits allergen‐induced vascular permeability. The protective effect of intranasal IRL201104 against OVA‐induced eosinophilia persisted for up to 20 days post‐treatment. Moreover, OVA‐sensitized mice treated intranasally with 20 ng/kg of IRL201104 show a significant increase in the expression of the anti‐inflammatory molecule ubiquitin A20 and significant inhibition of the activation of NF‐κB in lung tissue. Our results also show that A20 expression was significantly reduced in blood leucocytes and ASM obtained from patients with asthma compared to cells obtained from healthy subjects which were restored after incubation with IRL201104 in vitro, when added alone, or in combination with LPS or TNF‐α in ASM.

Conclusions:

Our results suggest that a peptide derived from mycobacterial Cpn60.1 has a long‐lasting anti‐inflammatory and immunomodulatory activity which may help explain some of the protective effects of TB against allergic diseases.

17 Mar 2020·Proceedings of the National Academy of Sciences of the United States of AmericaQ1 · CROSS-FIELD

The atomistic level structure for the activated human κ-opioid receptor bound to the full Gi protein and the MP1104 agonist

Q1 · CROSS-FIELD

Article

Author: Goddard, William A. ; Mafi, Amirhossein ; Kim, Soo-Kyung

The kappa opioid receptor (κOR) is an important target for pain therapeutics to reduce depression and other harmful side effects of existing medications. The analgesic activity is mediated by κOR signaling through the adenylyl cyclase-inhibitory family of Gi protein. Here, we report the three-dimensional (3D) structure for the active state of human κOR complexed with both heterotrimeric Gi protein and MP1104 agonist. This structure resulted from long molecular dynamics (MD) and metadynamics (metaMD) simulations starting from the 3.1-Å X-ray structure of κOR–MP1104 after replacing the nanobody with the activated Gi protein and from the 3.5-Å cryo-EM structure of μOR–Gi complex after replacing the 168 missing residues. Using MD and metaMD we discovered interactions to the Gi protein with strong anchors to two intracellular loops and transmembrane helix 6 of the κOR. These anchors strengthen the binding, contributing to a contraction in the binding pocket but an expansion in the cytoplasmic region of κOR to accommodate G protein. These remarkable changes in κOR structure reveal that the anchors are essential for activation.

News (Medical) associated with PIN-201104

14 May 2024

·www.globenewswire.com

Revolo Biotherapeutics to Present at Upcoming Medical Meetings in May

GAITHERSBURG, Md. and CAMBRIDGE, United Kingdom, May 14, 2024 (GLOBE NEWSWIRE) -- Revolo Biotherapeutics (“Revolo” or the “Company”), a company developing therapies that reset the immune system to achieve superior remission for patients with autoimmune and allergic diseases, today announced that it will present at two medical meetings in May: The American Thoracic Society (ATS) 2024 International Conference and the 6th Treg Directed Therapies Summit. ATS 2024 – May 17-22, San DiegoFormat: Poster PresentationTitle: 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 ExacerbationPoster Number: 804Session: D21 - Terminator: Control of Airway Inflammation and Immune Response in AsthmaPoster Discussion Date and Time: Wednesday, May 22, 8:15-10:15 a.m. PTRoom: San Diego Convention Center, Room 31A-C (Upper Level)Presenter: Jorge De Alba, Vice President of Discovery and Translational Science, Revolo More information about the ATS 2024 can be accessed here. 6th Treg Directed Therapies Summit – May 21-23, BostonFormat: Oral PresentationTitle: ‘1104, an immune-resetting peptide, for the treatment of allergic diseaseTrack: Non-Cell Based ApproachesSession: Utilizing Novel Platform Technology to Amplify Treg Induction In-VivoPresentation Date and Time: Wednesday, May 22, 12:00-12:30 p.m. ETPresenter: Roly Foulkes, Chief Scientific Officer, Revolo More information about the 6th Treg Directed Therapies Summit can be accessed here. Revolo BiotherapeuticsRevolo Biotherapeutics is developing therapies that reset the immune system to achieve remission for patients with autoimmune and allergic disease, without the immune system suppression seen with current therapies. Its two drug candidates, ‘1805 and ‘1104, reset the immune system from a pro-inflammatory state to a regulated homeostatic state, by inducing T regulatory and B regulatory cells after just one dose. ‘1104, a first-in-class peptide, has been evaluated in two Phase 2a trials: one in patients with eosinophilic esophagitis (EoE) and another in patients with allergen sensitivity. ‘1104 is now advancing towards evaluation in a Phase 2b trial in EoE and a Phase 2a trial in atopic dermatitis or asthma, while the company explores its additional potential for other allergic diseases. ‘1805, a modified analogue of a key protein in immune function, is planned to be assessed in a second Phase 2 clinical trial in patients with moderate-to-severe rheumatoid arthritis and a Phase 2a clinical trial for ulcerative colitis. The disease-agnostic mechanism of action of Revolo Biotherapeutic’s assets provides a potential platform for the development of treatments for multiple autoimmune and allergic diseases. For further information, please visit www.revolobio.com. Company ContactWoody Bryan, Ph.D.President and CEOwbryan@revolobio.com Media ContactMichael RubensteinLifeSci Communications+1 561-289-7981mrubenstein@lifescicomms.com

Phase 2Immunotherapy

14 May 2024

·www.biospace.com

Revolo Biotherapeutics to Present at Upcoming Medical Meetings in May 2024

GAITHERSBURG, Md. and CAMBRIDGE, United Kingdom, May 14, 2024 (GLOBE NEWSWIRE) -- Revolo Biotherapeutics (“Revolo” or the “Company”), a company developing therapies that reset the immune system to achieve superior remission for patients with autoimmune and allergic diseases, today announced that it will present at two medical meetings in May: The American Thoracic Society (ATS) 2024 International Conference and the 6th Treg Directed Therapies Summit. ATS 2024 – May 17-22, San Diego Format: Poster Presentation Title: 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 Poster Number: 804 Session: D21 - Terminator: Control of Airway Inflammation and Immune Response in Asthma Poster Discussion Date and Time: Wednesday, May 22, 8:15-10:15 a.m. PT Room: San Diego Convention Center, Room 31A-C (Upper Level) Presenter: Jorge De Alba, Vice President of Discovery and Translational Science, Revolo More information about the ATS 2024 can be accessed here. 6th Treg Directed Therapies Summit – May 21-23, Boston Format: Oral Presentation Title: ‘1104, an immune-resetting peptide, for the treatment of allergic disease Track: Non-Cell Based Approaches Session: Utilizing Novel Platform Technology to Amplify Treg Induction In-Vivo Presentation Date and Time: Wednesday, May 22, 12:00-12:30 p.m. ET Presenter: Roly Foulkes, Chief Scientific Officer, Revolo More information about the 6th Treg Directed Therapies Summit can be accessed here. Revolo Biotherapeutics Revolo Biotherapeutics is developing therapies that reset the immune system to achieve remission for patients with autoimmune and allergic disease, without the immune system suppression seen with current therapies. Its two drug candidates, ‘1805 and ‘1104, reset the immune system from a pro-inflammatory state to a regulated homeostatic state, by inducing T regulatory and B regulatory cells after just one dose. ‘1104, a first-in-class peptide, has been evaluated in two Phase 2a trials: one in patients with eosinophilic esophagitis (EoE) and another in patients with allergen sensitivity. ‘1104 is now advancing towards evaluation in a Phase 2b trial in EoE and a Phase 2a trial in atopic dermatitis or asthma, while the company explores its additional potential for other allergic diseases. ‘1805, a modified analogue of a key protein in immune function, is planned to be assessed in a second Phase 2 clinical trial in patients with moderate-to-severe rheumatoid arthritis and a Phase 2a clinical trial for ulcerative colitis. The disease-agnostic mechanism of action of Revolo Biotherapeutic’s assets provides a potential platform for the development of treatments for multiple autoimmune and allergic diseases. For further information, please visit . Company Contact Woody Bryan, Ph.D. President and CEO wbryan@revolobio.com Media Contact Michael Rubenstein LifeSci Communications +1 561-289-7981 mrubenstein@lifescicomms.com

Phase 2Immunotherapy

31 Jan 2024

·www.pharmaceutical-technology.com

Revolo advances plans to tackle eosinophilic esophagitis with orphan drug tag

Eosinophilic esophagitis can be triggered by a food allergy, acid reflux, or seasonal allergies. Credit: CGN089 via Shutterstock. Revolo Biotherapeutics plans to initiate a Phase IIb clinical trial investigating immune-resetting peptide ‘1104 (IRL-201104) in eosinophilic esophagitis (EoE) following an orphan drug designation from the US Food and Drug Administration (FDA). Revolo initially submitted a request before the initiation of the Phase IIa trial but then sent a revised request following the results of an additional Phase II study. The biotech is headquartered in both New Orleans, US, and London, and is focused on targeting the immune system for treating autoimmune and allergic conditions. Positive results from the Phase IIa RVLO 121-04 trial (NCT05084963), demonstrated efficacy, safety, and tolerability of ‘1104 in adults with active EoE. Results included improvements in patient-reported dysphagia symptoms, reductions in eosinophils and other immune cells in the oesophageal tissue and increase in regulatory immune cells. Revolo reported interim data in April 2023, where the trial met its primary endpoint. The company initially failed to disclose whether or not ‘1104 had met its secondary endpoint—dysphagia median symptom scores (DSQ)—the symptom scale that earned Sanofi and Regeneron’s Dupixent approval. However, Revolo confirmed in July with additional data that this all-important endpoint had been met. If approved, Revolo’s candidate would be on track to challenge Sanofi and Regeneron’s Dupixent (dupilumab), the only FDA-approved drug for EoE. See Also: Almirall and Microsoft partner for dermatological drug development Defender’s plans for motion sickness nasal gel stop with FDA rejection Dupixent, which is approved for treating four conditions, including EoE, generated $8.29bn in 2022, as per Sanofi’s 2022 full year report. According to an analyst consensus forecast on GlobalData’s Pharma Intelligence Center, Dupixent is forecast to generate to $20.4bn by 2029. GlobalData is the parent company of Pharmaceutical Technology. ‘1104 is a synthetic peptide that reduces neutrophil recruitment into the lung, decreasing inflammation. The Phase IIb trial will evaluate increased dose levels of ‘1104 and a longer duration of therapy. EoE is a chronic allergic condition that causes inflammation in the oesophagus due to reactions to certain foods or allergens. It leads to symptoms like difficulty swallowing and chest pain, with dietary changes and medications used to manage inflammation. Revolo also investigated the drug candidate in another Phase IIa trial (NCT05098522) for patients with allergen sensitivity, reporting positive topline data in October 2023. In the announcement accompanying the ODD, principal investigator for the Phase IIa clinical trial Evan Dellon said: “1104 is a promising EoE therapeutic with a novel mechanism of action. Based on the proof-of-concept data from the Phase 2a study, I am eager to see this molecule move forward into the next stage of development.”

Phase 2Clinical ResultOrphan DrugDrug ApprovalImmunotherapy

100 Deals associated with PIN-201104

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Rhinitis, Allergic, Seasonal	Phase 2	GB	Revolo Biotherapeutics Ltd.	04 Nov 2021
Eosinophilic Esophagitis	Phase 2	US	Revolo Biotherapeutics Ltd.	29 Oct 2021
COVID-19	Phase 1	GB	Revolo Biotherapeutics Ltd.	29 Jan 2021
Asthma	Phase 1	GB	Peptinnovate Ltd	01 Jan 2017

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05098522 (GlobeNewswire) Manual	Phase 2	Rhinitis, Allergic, Seasonal	63	1104	qepzsqigoh(jxpftxsgvx) = not observed olfcskvjga (mesasrkoki )	Positive	25 Oct 2023
NCT05084963 (GlobeNewswire) Manual	Phase 2	Eosinophilic Esophagitis	36	IRL201104	yzmmjulcno(kpakrmiuaw) = fkeqthicqw xhbrrzbvsl (jdjzxpjlrx )	Positive	18 Jul 2023
				Placebo	-
NCT05084963 (NEWS \| Corporate Publications) Manual	Phase 2	Eosinophilic Esophagitis	36	IRL-201104	ogtxkbkkcc(fkztpmjsoi) = shows achievement of primary endpoint of decreasing esophageal intraepithelial eosinophil count and positive impact on an array of histological measures of EoE anqskkzhfi (acshhcnpkl ) Met View more	Positive	19 Apr 2023
				Placebo
Phase I clinical trial (ERS2018)	Phase 1	Asthma	-	PIN201104	kddadrbily(cksvztwffc) = 104 (≤10µg/ml), overall, did not affect antigen-induced cell proliferation or IFN-γ release in human T cells. In contrast, the steroid dexamethasone led to nearly 100% reduction in antigen-induced IFN-γ release and >50% reduction in cell proliferation, for 2 out of 3 donors ztgbvzzxtc (zgcmrzbdur ) View more	Positive	15 Sep 2018

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PIN-201104

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