Delving into the Latest Updates on BI-1265162 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BI 1265162, BI1265162

Target

ENaC

Action

blockers

Mechanism

ENaC blockers(Epithelial sodium channel blockers)

Therapeutic Areas

Congenital DisordersDigestive System DisordersRespiratory Diseases+ [1]

Active Indication-

Inactive Indication

Cystic Fibrosis

Originator Organization

Boehringer Ingelheim GmbH

Active Organization-

Inactive Organization

Boehringer Ingelheim GmbH

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Investigation of Metabolism and Pharmacokinetics of BI 1265162 (C-14) After Intravenous Administration (Part 1) and Investigation of Metabolism and Pharmacokinetics of BI 1265162 (C-14) After Oral Administration (Part 2) in Healthy Male Subjects Following a Non-randomized, Open-label, Single-dose, Single Arm Per Trial Part Mass Balance Design

To investigate rates and routes of excretion, mass balance, pharmacokinetics of parent drug, any known metabolites, and total radioactivity, metabolite profiling, metabolite identification, if suitable assays are available, safety and tolerability in healthy male subjects.

Start Date18 Feb 2020

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT04059094

/ TerminatedPhase 2

A Randomised, Double-blind, Placebo-controlled and Parallel Group Trial to Evaluate Efficacy and Safety of Twice Daily Inhaled Doses of BI 1265162 Delivered by Respimat® Inhaler as add-on Therapy to Standard of Care Over 4 Weeks in Patients With Cystic Fibrosis - BALANCE - CF™ 1

The primary objective of this trial is to assess the efficacy, safety and pharmacokinetics of twice daily inhaled doses of BI 1265162 delivered by Respimat® inhaler versus placebo in adolescents and adult patients with cystic fibrosis.

Start Date16 Sep 2019

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT03907280

/ CompletedPhase 1

Absolute Bioavailability of BI 1265162 Following Oral and Inhaled Administration in Healthy Male Volunteers (an Open-label, Randomised, Single-dose, Three-period, Three-sequence Crossover Study Followed by a Fixed Treatment)

The main objective of this trial is to investigate the absolute bioavailability of BI 1265162 following administration of oral solution and inhaled (with and without charcoal) via Respimat.

Start Date23 Apr 2019

Sponsor / Collaborator

Boehringer Ingelheim GmbH

100 Clinical Results associated with BI-1265162

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100 Translational Medicine associated with BI-1265162

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100 Patents (Medical) associated with BI-1265162

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6

Literatures (Medical) associated with BI-1265162

01 Jan 2025·Journal of Cystic Fibrosis

ETD001: A novel inhaled ENaC blocker with an extended duration of action in vivo

Article

Author: Danahay, Henry ; Schofield, Thomas ; Gosling, Martin ; Salathe, Matthias ; McCarthy, Clive ; Collingwood, Stephen P ; Fox, Roy ; Charlton, Holly ; Sabater, Juan ; Baumlin, Nathalie ; Lilley, Sarah

BACKGROUND:

Inhibiting ENaC in the airways of people with cystic fibrosis (pwCF) is hypothesized to enhance mucociliary clearance (MCC) and provide clinical benefit. Historically, inhaled ENaC blockers have failed to show benefit in pwCF challenging this hypothesis. It is however unknown whether the clinical doses were sufficient to provide the required long duration of action in the lungs and questions whether a novel candidate could offer advantages where others have failed?

METHODS:

Dose-responses with the failed ENaC blockers (VX-371, BI 1265162, AZD5634, QBW276) together with ETD001 (a novel long acting inhaled ENaC blocker) were established in a sheep model of MCC and were used to predict clinically relevant doses that would provide a long-lasting enhancement of MCC in pwCF. In each case, dose predictions were compared with the selected clinical dose.

RESULTS:

Each of the failed candidates enhanced MCC in the sheep model. Translating these dose-response data to human equivalent doses, predicted that substantially larger doses of each candidate, than were evaluated in clinical studies, would likely have been required to achieve a prolonged enhancement of MCC in pwCF. In contrast, ETD001 displayed a long duration of action (≥16 h) at a dose level that was well tolerated in Phase 1 clinical studies.

CONCLUSIONS:

These data support that the ENaC blocker hypothesis is yet to be appropriately tested in pwCF. ETD001 has a profile that enables dosing at a level sufficient to provide a long duration of action in a Phase 2 clinical study in pwCF scheduled for 2024.

01 Feb 2024·European journal of medicinal chemistry

Discovery and development of BI 1265162, an ENaC inhibitor for the treatment of cystic fibrosis

Article

Author: Linehan, Brian ; Braun, Clemens ; Kley, Jörg T ; Linz, Günter ; Veser, Thomas ; Sieger, Peter ; Heckel, Armin ; Wiedenmayer, Dieter ; Betzemeier, Bodo

Lung selective inhibition of the endothelial sodium channel (ENaC) is a potential mutation agnostic treatment of Cystic Fibrosis (CF). We describe the discovery and development of BI 1265162, the first ENaC inhibitor devoid of the amiloride structural motif that entered clinical trials. The design of BI 1265162 focused on its suitability for inhalation via the Respimat® Soft Mist™ Inhaler and a long duration of action. A convergent and scalable route for the synthesis of BI 1265162 as dihydrogen phosphate salt is presented, that was applied to support clinical trials. A phase 2 study with BI 1265162 did not provide a clear sign of clinical benefit. Whether ENaC inhibition will be able to hold its promise for CF patients remains an open question.

01 Feb 2022·The European respiratory journalQ1 · MEDICINE

Efficacy and safety of inhaled ENaC inhibitor BI 1265162 in patients with cystic fibrosis: BALANCE-CF 1, a randomised, phase II study

Q1 · MEDICINE

Article

Author: Davies, Jane C ; Jain, Raksha ; Fajac, Isabelle ; Hsu, Ming-Chi ; Seibold, Wolfgang ; Mall, Marcus A ; Gupta, Abhya ; Sutharsan, Sivagurunathan ; Goss, Christopher H

Background:

Inhibition of the epithelial sodium channel (ENaC) in cystic fibrosis (CF) airways provides a mutation-agnostic approach that could improve mucociliary clearance in all CF patients. BI 1265162 is an ENaC inhibitor with demonstrated pre-clinical efficacy and safety already demonstrated in humans.

Objective:

We present results from BALANCE-CFTM1, a phase II, placebo-controlled, randomised, double-blind study of four dose levels of BI 1265162versusplacebo for 4 weeks on top of standard of care in adults and adolescents with CF.

Results:

Initially, 28 randomised subjects (BI 1265162 200 µg twice daily n=14, placebo twice daily n=14) were assessed at an interim futility analysis. Compared with placebo, numerical changes of –0.8% (95% CI –6.6 to 4.9%) in percentage predicted forced expiratory volume in 1s (ppFEV1) and +2.1 units (95% CI –2.4 to 6.5 units) in lung clearance index (LCI) were observed in the active group, meeting a pre-defined stopping rule; accordingly, the study was terminated. Recruitment had continued during the interim analysis and pending results; 24 patients were added across three dose levels and placebo. The final results including these patients (+1.5% ppFEV1, 200 µg twice-daily doseversusplacebo) were not supportive of relevant clinical effect. Furthermore, LCI change was not supportive, although interpretation was limited due to insufficient traces meeting quality criteria. A 9.4-point improvement in the Cystic Fibrosis Questionnaire – Revised Respiratory Domain was observed in the 200 µg twice daily dose groupversusplacebo. BI 1265162 up to 200 µg twice daily was safe and well-tolerated. Pharmacokinetics were similar to those in healthy volunteers.

Conclusion:

BI 1265162 was safe, but did not demonstrate a potential for clinical benefit. Development has been terminated.

1

News (Medical) associated with BI-1265162

12 Jun 2024

·www.biospace.com

Enterprise Therapeutics Publishes Preclinical Profile of ETD001, a Novel Inhaled ENaC Blocker

Low doses of ETD001 demonstrate exceptionally long duration of action in sheep model of airway mucus clearance Report in Journal of Cystic Fibrosis discloses best-in-class pro ETD001 ETD001 scheduled to commence Phase 2 clinical study in people with cystic fibrosis in summer 2024 BRIGHTON, England--(BUSINESS WIRE)-- Enterprise Therapeutics Ltd (Enterprise), a biopharmaceutical company dedicated to the discovery and development of novel therapies to improve the lives of people with respiratory diseases, today announced the publication of a peer reviewed study in the Journal of Cystic Fibrosis1. The paper describes low doses of the ENaC blocker ETD001, Enterprise’s lead asset, enhancing airway mucus clearance with an exceptionally long duration of action in a sheep model. This study indicates that ETD001, at a dose level that was well tolerated in healthy volunteer studies, provides an opportunity to test whether a long-acting ENaC blocker can deliver benefit to people with cystic fibrosis (pwCF). ETD001 is scheduled to commence a Phase 2 clinical study in pwCF in summer 2024, to understand whether 28 days of treatment will improve lung function. Blocking ENaC in the airways offers a novel approach to improve mucus clearance in pwCF, including in the ≥10% of individuals who are either intolerant of or genetically unsuited to CFTR modulators. Recently, several other ENaC blocking drugs (VX-371, AZD5634, BI 1265162, QBW276) failed to show any benefit in clinical trials. This study provides a potential explanation for these failures as data from the sheep model indicate that each may have been dosed in clinical trials at a dose too low to observe an extended duration of action on mucus clearance. Dr Henry Danahay, Head of Biology, Enterprise Therapeutics, and lead author of the paper, said: “This data provides strong evidence that ETD001 has a superior pro to other inhaled ENaC blockers. Along with the results from the Phase 1 trials where ETD001 was well-tolerated, this study supports our high level of confidence going into the Phase 2 clinical trial. We remain passionate in our drive to discover novel therapies that have the potential to transform the lives of all people with cystic fibrosis.” For more information about Enterprise Therapeutics, visit View source version on businesswire.com: Contacts Katie Odgaard Zyme Communications Tel: +44 (0)7787 502 947 Email: katie.odgaard@zymecommunications.com Source: Enterprise Therapeutics View this news release online at:

Phase 1Phase 2

100 Deals associated with BI-1265162

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cystic Fibrosis	Phase 2	United States	Boehringer Ingelheim GmbH	16 Sep 2019
Cystic Fibrosis	Phase 2	Belgium	Boehringer Ingelheim GmbH	16 Sep 2019
Cystic Fibrosis	Phase 2	Canada	Boehringer Ingelheim GmbH	16 Sep 2019
Cystic Fibrosis	Phase 2	France	Boehringer Ingelheim GmbH	16 Sep 2019
Cystic Fibrosis	Phase 2	Germany	Boehringer Ingelheim GmbH	16 Sep 2019
Cystic Fibrosis	Phase 2	Spain	Boehringer Ingelheim GmbH	16 Sep 2019
Cystic Fibrosis	Phase 2	Sweden	Boehringer Ingelheim GmbH	16 Sep 2019
Cystic Fibrosis	Phase 2	United Kingdom	Boehringer Ingelheim GmbH	16 Sep 2019

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03907280 (CTgov)	Phase 1	-	12	BI 1265162 (BI 1265162 as Infusion (R))	souztqghle(rubnofqasf) = naggjiqkfd hgwaommqhe (zjfnsfhhbo, NA) View more	-	06 Jul 2022
				BI 1265162 (BI 1265162 as Oral Solution (T1))	souztqghle(rubnofqasf) = hcqrdfvbkx hgwaommqhe (zjfnsfhhbo, NA) View more
NCT03576144 (CTgov)	Phase 1	-	50	BI 1265162 (Placebo Matching BI 1265162)	atmjhxvjnb = oqhjzuumcg bjpopjpofm (xginpqnfya, hekdyxjxnn - ktseawqljk) View more	-	23 Feb 2022
				BI 1265162 (10 Microgram (μg) BI 1265162)	atmjhxvjnb = gbxmkjgmcp bjpopjpofm (xginpqnfya, trhapniscq - ofougtccjz) View more
NCT03349723 (CTgov)	Phase 1	-	57	BI 1265162 (3 Microgram BI 1265162)	qnfpargmqz = ddopkkqszm jurqhxqgkl (urwzuaphfe, lvfhpgzhxd - qohpmjfsuh) View more	-	23 Feb 2022
				BI 1265162 (10 Microgram BI 1265162)	qnfpargmqz = rvorizbsrw jurqhxqgkl (urwzuaphfe, uunwlsbfbc - jonmrjxoqn) View more
NCT04267276 (CTgov)	Phase 1	-	7	BI 1265162	aljvqycgyo(bgzijwtrth) = nqwdrdzdxw oerbnzbsbs (wbcpnpphxu, 16.1) View more	-	23 Feb 2022
NCT04059094 (BALANCE-CFTM 1, Pubmed \| Clin Chest Med \| Eur Respir J) Manual	Phase 2	Cystic Fibrosis	28	BI 1265162	qfwuvwjjfe(kvpdlpjhdd) = dgiwoompaa byfnbnqbvl (ppjkbqmdei, -6.6 to 4.9) View more	Negative	12 Aug 2021
				placebo	-
NCT04059094 (BALANCE-CFTM 1 \| BALANCE-CF™ 1, CTgov)	Phase 2	Cystic Fibrosis	52	Placebo	fitgawllot(noqxnvgnmm) = baxuarxixt kxpqaehgzp (aosduhojse, 8.03) View more	-	04 Jun 2021
NCT03349723 \| NCT03907280 \| NCT03576144 (Pubmed \| ERJ Open Res) Manual	Phase 1	-	-	BI 1265162	qrmgidahuu(bltwnmoytr) = Adverse events were balanced across treatment groups, were of mainly mild or moderate intensity and resolved by trial-end. bhaaotwxmx (chcvzwpcay )	Positive	01 Feb 2021