Roles of IK,ACh for perpetuating atrial fibrillation: Effects of atrial-selective K+ channel inhibitor AVE0118 and class I drugs on the persistent atrial fibrillation canine model

Article

Author: Kambayashi, Ryuichi ; Takei, Yoshinori ; Sugiyama, Atsushi ; Izumi-Nakaseko, Hiroko ; Goto, Ai ; Matsumoto, Akio ; Kawai, Shinichi

Since information is still limited whether atrial I_K,ACh may become a potential therapeutic target to terminate persistent atrial fibrillation (AF), we assessed it by using the persistent AF canine model with representative I_K,ACh inhibitor AVE0118 and class I drugs. AVE0118 (6 mg/kg, n = 7), disopyramide (3 mg/kg, n = 7) and cibenzoline (3 mg/kg, n = 6) terminated the AF in 3/7, 1/7 and 2/6 animals, respectively, whereas aprindine (3 mg/kg, n = 6) did not suppress it. These findings suggest that I_K,ACh inhibition in addition to open-state I_Na suppression with slow dissociation kinetics can synergistically exert potent antiarrhythmic action against persistent AF.

01 Jan 2021·Stem Cells Translational MedicineQ2 · MEDICINE

Drug screening platform using human induced pluripotent stem cell-derived atrial cardiomyocytes and optical mapping

Q2 · MEDICINE

ArticleOA

Author: Laksman, Zachary ; Lin, Eric ; Shafaattalab, Sanam ; Heims-Waldron, Danielle A. ; Sangha, Sarabjit S. ; Tibbits, Glen F. ; Gunawan, Marvin G. ; Bezzerides, Vassilios J.

AbstractCurrent drug development efforts for the treatment of atrial fibrillation are hampered by the fact that many preclinical models have been unsuccessful in reproducing human cardiac physiology and its response to medications. In this study, we demonstrated an approach using human induced pluripotent stem cell-derived atrial and ventricular cardiomyocytes (hiPSC-aCMs and hiPSC-vCMs, respectively) coupled with a sophisticated optical mapping system for drug screening of atrial-selective compounds in vitro. We optimized differentiation of hiPSC-aCMs by modulating the WNT and retinoid signaling pathways. Characterization of the transcriptome and proteome revealed that retinoic acid pushes the differentiation process into the atrial lineage and generated hiPSC-aCMs. Functional characterization using optical mapping showed that hiPSC-aCMs have shorter action potential durations and faster Ca2+ handling dynamics compared with hiPSC-vCMs. Furthermore, pharmacological investigation of hiPSC-aCMs captured atrial-selective effects by displaying greater sensitivity to atrial-selective compounds 4-aminopyridine, AVE0118, UCL1684, and vernakalant when compared with hiPSC-vCMs. These results established that a model system incorporating hiPSC-aCMs combined with optical mapping is well-suited for preclinical drug screening of novel and targeted atrial selective compounds.

01 Sep 2020·Heart and VesselsQ4 · MEDICINE

Analysis of electropharmacological effects of AVE0118 on the atria of chronic atrioventricular block dogs: characterization of anti-atrial fibrillatory action by atrial repolarization-delaying agent

Q4 · MEDICINE

Article

Author: Nunoi, Yoshio ; Izumi-Nakaseko, Hiroko ; Kambayashi, Ryuichi ; Hagiwara-Nagasawa, Mihoko ; Sugiyama, Atsushi ; Ichikawa, Tomoaki ; Goto, Ai ; Takahara, Akira ; Matsumoto, Akio ; Chiba, Koki

AVE0118, an inhibitor of I_Kur, I_to and I_K,ACh, was in the drug pipeline for atrial fibrillation. To investigate the limitation of AVE0118 as an anti-atrial fibrillatory drug, we studied its electropharmacological effects particularly focusing on the anti-atrial fibrillatory action as reverse translational research. We adopted the chronic atrioventricular block beagle dogs (n = 4), having a pathophysiology of bradycardia-associated, volume overload-induced chronic heart failure, in which the atrial fibrillation was induced by 10 s of burst pacing on atrial septum. AVE0118 in doses of 0.24 and 1.2 mg/kg, i.v. over 10 min hardly altered electrophysiological variables. Meanwhile, AVE0118 in a dose of 6 mg/kg, i.v. over 10 min delayed the inter-atrial conduction in a frequency-dependent manner and prolonged the atrial effective refractory period in a reverse frequency-dependent manner, whereas it did not significantly alter the duration of atrial fibrillation or its cycle length. The increment of atrial effective refractory period was 3.3 times greater compared with that of ventricular one at a basic cycle length of 400 ms. Torsade de pointes was not induced during the experimental period. Thus, AVE0118 may possess a favorable cardiac safety pharmacological profile, but its weak anti-atrial fibrillatory effect would indicate the limitation of atrial repolarization-delaying agents for suppressing atrial fibrillation.

News (Medical) associated with AVE-0118

11 Apr 2023

·www.biospace.com

Mosanna Therapeutics Announces a Seed Extension Financing Round to Complete Preparations to Enter the Clinic with MOS-118 in Metabolic Obstructive Sleep Apnea

Company pursuing a highly differentiated small molecule MOS-118 in Metabolic Obstructive Sleep Apnea. New investors, Supermoon Capital and HTGF, join founding investor Forty51 Ventures to complete the Seed syndicate. Company will use the funds to IND in preparation for a proof of mechanism and proof of concept in the clinic. BASEL, Switzerland, April 11, 2023 /PRNewswire/ -- Mosanna Therapeutics AG, a Swiss Biotech company today announced that Supermoon Capital, a US based venture capital fund specializing in sleep, and the German investment firm, High-Tech Gründerfonds (HTGF), have invested in a Seed Extension round. The duo joins founding investor Forty51 Ventures to complete the Seed stage investment syndicate. Founded in 2022, Mosanna has quickly established a specialist core team and a reputable advisory Board and is on-track to submit an IND by the end of 2023. The company will utilize the funds for manufacturing and regulatory activities in preparation for a multi-study clinical development program. "We are extremely pleased with the data we are seeing in the lab and the technical performance of the product and this additional financing is testament to the potential the team sees for this to translate into significant clinical benefit for Sleep Apnea patients" said Jonathan Talbot, Co-Founder and CEO of Mosanna. Commenting on the investment, Supermoon Co-Founder Mike Masterson said: "Sleep Apnea therapy has historically been limited to a small handful of products that many patients find uncomfortable and undesirable. Mosanna's unique approach will expand the range of Sleep Apnea treatment options and provide therapy in a familiar, user-friendly modality." "This is a new frontier for Sleep Apnea and we are absolutely confident Mosanna will successfully develop MOS-118 and redefine standard of care." Said Laura Pedroza, Investment Manager at HTGF. "We are incredibly excited for Mosanna's truly novel therapeutic approach to enter the clinics early in 2024." Mosanna Therapeutics was co-founded by Forty51 Ventures, a Biotech Venture Capital fund focused on company formation in Biotech and its CEO, Jonathan Talbot. Forty51 Ventures led the Seed Financing. VISCHER advises Mosanna Therapeutics AG since its incorporation on all Swiss legal matters. The VISCHER team includes Matthias Staehelin (Partner) and Timothy Woodtli (Associate), both Corporate/M&A. About Metabolic Obstructive Sleep Apnea MOSA is characterized by obstruction of the upper airway during sleep that occurs when the muscles that support the soft tissues in the throat temporarily relax. Breathing is impaired or completely prevented causing blood oxygen levels to drop below the normal range. Low oxygen levels increase cardiac load and stress the nervous system which if left untreated increases significantly the risk for cardiovascular mortality. MOSA can also result in excessive daytime sleepiness and memory or concentration problems. Hundreds of millions of people around the globe are affected by MOSA. For further info please visit or email info@mosanna.com Logo -

13 Jul 2022

·www.prnewswire.com

Mosanna Therapeutics Announces a Seed Financing Round to Advance Development of MOS118 to Treat Metabolic Obstructive Sleep Apnea

Company pursuing an advanced small molecule MOS118 (formerly known as AVE0118) discovered by Sanofi Experienced team with strong background in Metabolic Diseases and Obstructive Sleep Apnea Seed financing led by Forty51 Ventures BASEL, Switzerland, July 13, 2022 /PRNewswire/ -- Mosanna Therapeutics AG, a Swiss Biotech company today announced that it has secured seed financing led by Forty51 Ventures to pursue the development of AVE0118 which will be referred to as MOS118 going forward, a small molecule developed by Sanofi S.A. (Paris, France). Mosanna will utilize the funds for formulation and manufacturing optimization and regulatory activities to enable the company's first Phase 1b clinical trial by end-2023. The company confirmed the appointment of co-founder Dr. Jonathan Talbot as Chief Executive Officer, who said, "I'm excited to develop a treatment for one of the modern world's growing, global health crises. Mosanna aims to bring the first, targeted precision medicine to Obstructive Sleep Apnea patients with a focus on the devastating cardiometabolic impact of this disease." Dr. Talbot brings broad industry experience with a strong track record in Pharma. The company also announced the appointment of industry veteran Ben Machielse as Chairman of the Board. Mr. Machielse's impressive career includes a former role as CEO of Vtesse, a company developing treatments for Niemann Pick Disease that was acquired by Sucampo in 2017, and COO at Omthera Pharmaceuticals, a company in the cardiovascular space acquired by AstraZeneca in 2013. Dr. Patrick Lévy, Professor at Université de Grenoble (France) and leading Key Opinion Leader in the field of Obstructive Sleep Apnea celebrated Mosanna's emergence saying, "I am delighted that all the excellent basic research and clinical work performed by Sanofi with this compound will now be taken forward by Mosanna with a focus on the important metabolic impacts of OSA." Mosanna Therapeutics was co-founded by Forty51 Ventures, a new Biotech Venture Capital fund focused on company formation in Biotech. Forty51 Ventures led the Seed Financing and will join the Board of Directors. About Metabolic Obstructive Sleep Apnea MOSA is characterized by obstruction of the upper airway during sleep that occurs when the muscles that support the soft tissues in the throat temporarily relax. Breathing is impaired or completely prevented causing blood oxygen levels to drop below the normal range. Low oxygen levels increase cardiac load and stress the nervous system which if left untreated increases significantly the risk for cardiovascular mortality. MOSA can also result in excessive daytime sleepiness and memory or concentration problems. Hundreds of millions of people around the globe are affected by MOSA. For further info please visit or email [email protected]. About Forty51 Ventures Forty51 is a recently founded Venture Capital firm focused on early stage venture creation in Europe backed by a strong investor syndicate with Stable Asset Management, several Pension funds, family offices and accomplished Biotech entrepreneurs. For further information please visit or email [email protected]. Logo - SOURCE Mosanna Therapeutics AG

Small molecular drug

100 Deals associated with AVE-0118

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Sleep Apnea, Obstructive	Preclinical	CH	Mosanna Therapeutics AGStartup	13 Jul 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

AVE-0118

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation