A Phase IIa, Placebo-controlled, Double Blind, Randomised Multicentre Pilot Study to Investigate the Efficacy, Safety and Tolerability of the Monoclonal Antibody ATH3G10 in Patients With ST-elevation Myocardial Infarction

Patients with ST-segment elevation myocardial infarction (STEMI) that have suffered a major anterior wall infarction or where coronary blood flow is less than normal in spite of successful percutaneous coronary intervention (PCI) have a poor prognosis. There are today no medical treatments that specifically reduce risk in these patients. The acute inflammatory reaction in conjunction with a STEMI and reperfusion by PCI determines the final size of the infarction and the signals leading to left ventricular remodelling.
This study is designed to assess the efficacy and safety of single intravenous injection with ATH3G10, a fully human IgG1 antibody against phosphorylcholine, in high-risk subjects with STEMI. ATH3G10 aims to reduce inflammation and thereby infarction size and remodeling.

Start Date29 Mar 2019

Sponsor / Collaborator

Athera Biotechnologies AB

NL-OMON44302 / CompletedPhase 2

Double-blinded, randomised, placebo-controlled, multicentre , Phase IIa study to investigate the effect, safety and tolerability of phosphorylcholine human monoclonal antibody (PC-mAb) 3G10 on arterial inflammation, together with safety and tolerability, in subjects with elevated lipoprotein a (Lp[a ]) - ATH-3G10-005

Start Date21 Dec 2017

Sponsor / Collaborator

Athera Biotechnologies AB

NCT03320265 / TerminatedPhase 2

Double-blind, Randomised, Placebo-controlled, Multicentre, Phase IIa Study to Investigate the Effect of PC-mAb on Arterial Inflammation in Subjects With Elevated Lipoprotein a

Inflammation and abnormal amount of lipids in the blood are key factors for the development and progression of atherosclerosis (thickening of the artery wall) and cardiovascular disease. Lipoprotein (a) is a pro-inflammatory plasma lipoprotein that is believed to be a risk factor for cardiovascular diseases. Vascular inflammation generates a range of effects, including endothelial dysfunction and migration of white blood cells into the vessel wall, which results in increased risk of cardiovascular events.
This study is designed to assess the effects of multiple monthly intravenous infusions with the fully human antibody called PC-mAb, in subjects with elevated lipoprotein (a).

Start Date11 Oct 2017

Sponsor / Collaborator

Athera Biotechnologies AB

100 Clinical Results associated with Athera Biotechnologies AB

0 Patents (Medical) associated with Athera Biotechnologies AB

Literatures (Medical) associated with Athera Biotechnologies AB

01 Dec 2020·JACC: Basic to Translational ScienceQ2 · MEDICINE

Phosphorylcholine Antibodies Preserve Cardiac Function and Reduce Infarct Size by Attenuating the Post-Ischemic Inflammatory Response

Q2 · MEDICINE

ArticleOA

Author: Atsma, Douwe E ; Pluijmert, Niek J ; Jukema, J Wouter ; de Vries, Margreet R ; Pettersson, Knut ; Quax, Paul H A ; de Jong, Rob C M

Phosphorylcholine monoclonal immunoglobulin G antibody attenuates the immediate post-ischemic inflammatory response by reducing the proinflammatory chemokine (C-C motif) ligand 2 chemokine and circulating Ly-6C^hi monocytes. This subsequently enhances the post-ischemic repair process, resulting in limited adverse cardiac remodeling and preservation of cardiac function. Therefore, phosphorylcholine monoclonal immunoglobulin G antibody therapy may be a valid therapeutic approach against myocardial ischemia-reperfusion injury.

01 Nov 2020·European Heart Journal

IgG1 phosphorylcholine ameliorates plaque stability via reduced intraplaque angiogenesis and intraplaque haemorrhage in a murine atherosclerosis model

Author: Quax, P.H.A ; Peters, H.A.B ; Petterson, K ; De Vries, M ; De Jong, R.C.M ; Baganha, F

AbstractBackgroundPhosphorylcholine, (PC) the polar headgroup of the dominating membrane phospholipid phosphatidylcholine, is one of the main oxLDL epitopes and an important pro-inflammatory damage associated molecular pattern. Experimental and epidemiologic data show that natural anti-PC IgM protect against cardiovascular disease. Within atherosclerotic lesions, inflammatory and angiogenesis processes are interdependent and contribute to plaque destabilization. Atherosclerotic lesion resident CD163+ macrophages promote leukocyte infiltration but also induce angiogenesis and vessel permeability by secreting VEGFA. PC antibodies are recognized for their anti-inflammatory properties. However, the effect of PC antibodies on intraplaque angiogenesis (IPA) and intraplaque hemorrhage (IPH), the main entrance route for inflammatory cells in advanced lesions, is unknown.PurposeTo investigate the therapeutic effect of a new IgG1 PC antibody (PCmAB) on lesion development, IPA and IPH in murine vein graft atherosclerosis.MethodsAll animal experiments were performed in compliance with Dutch government guidelines and the Directive 2010/63/EU of the European Parliament. Hypercholesterolemic male ApoE3*Leiden mice received a (donor) caval vein interposition in the carotid artery. Mice received weekly ip injections of (5mg/kg) PCmAb (n=11) or vehicle (n=12) until sacrifice at day 28. Immunohistochemistry was used to evaluate vein graft morphometry and lesion composition including IPA and IPH. PCmAB isolated effects on pro-angiogenic and pro-inflammatory behaviour was investigated in vitro in HUVECs and Hemoglobin (Hb):Haptoglobin (Hp)-cultured THP-1 macrophages.ResultsPCmAB treatment decreased vein graft media area (13%) and intima lesion (25%), but more importantly increased lumen area with 53% when compared to vehicle treatment. PCmAb improved lesion stability by increasing collagen content (18%) and by decreasing macrophages presence (31%). VCAM-1 and ICAM-1 expression in the vessel wall were also reduced (resp.29% and 36%) by PCmAb. PCmAb improved IPA by a significant reduction in neovessel density of 34%. This was supported in vitro by significant reduced EC proliferation and migration upon PCmAB with and without oxLDL stimulation. Moreover, PCmAb enhanced maturation of intraplaque angiogenic vessels by increasing neovessel pericyte coverage in vivo (31%). Together, this resulted in a reduction of IPH of 62% in the PCmAB group. PCmAb resulted in decreased macrophages CD163+ content in vein grafts by 23% whereas CD163 expression was reduced by PCmAb in Hb:Hp stimulated macrophages.ConclusionPCmAB is an effective inhibitor of atherosclerotic lesion formation in ApoE3*Leiden mice.PCmAb reduces IPA and IPH by decreased neovessel density and (CD163+) macrophages influx via reduced expression of VCAM-1 and ICAM-1, and increased neovessel maturation in vein graft atherosclerosis. PCmAB holds a promise as a new therapeutic approach for plaque stability.Funding AcknowledgementType of funding source: Public hospital(s). Main funding source(s): Leiden University Medical Center

01 Apr 2020·JACC: Basic to Translational ScienceQ2 · MEDICINE

Therapeutic Antibody Against Phosphorylcholine Preserves Coronary Function and Attenuates Vascular 18F-FDG Uptake in Atherosclerotic Mice

Q2 · MEDICINE

ArticleOA

Author: Saukko, Pekka ; Silvola, Johanna M U ; Roivainen, Anne ; Ståhle, Mia ; Liljenbäck, Heidi ; Ylä-Herttuala, Seppo ; de Jong, Alwin ; Kroon, Jeffrey ; Saraste, Antti ; Pettersson, Knut ; Stroes, Erik S G ; de Vries, Margreet ; Hellberg, Sanna ; Knuuti, Juhani ; Wickman, Anna ; Quax, Paul H A ; Abrahamsson, Tommy ; Rinne, Petteri ; Savisto, Nina

This study showed that treatment with a therapeutic monoclonal immunoglobulin-G1 antibody against phosphorylcholine on oxidized phospholipids preserves coronary flow reserve and attenuates atherosclerotic inflammation as determined by the uptake of ¹⁸F-fluorodeoxyglucose in atherosclerotic mice. The noninvasive imaging techniques represent translational tools to assess the efficacy of phosphorylcholine-targeted therapy on coronary artery function and atherosclerosis in clinical studies.

News (Medical) associated with Athera Biotechnologies AB

27 May 2021

·www.biospace.com

Betagenon AB announces new CEO and new Chairman of the Board

STOCKHOLM, May 27, 2021 /PRNewswire/ -- Betagenon AB, a Sweden-based company focused on development of AMPK activator compounds, today announced that James Hall BM, BCh, D.Phil has joined this month as CEO. Dr. Hall brings extensive senior healthcare and life science experience, including 12 years with AstraZeneca. While there, he held a number of commercial, R&D and Business Development roles, including VP Global Marketing for the CV/GI Therapy Area, Global Product VP for Crestor and VP Evaluation for the CV/Metabolism/Renal Therapy Area. Prior to this he was a member of the Pharmaceutical/Medical Products practice at McKinsey & Co. He has a BM, BCh in Clinical Medicine and a D.Phil in Cell Physiology from Oxford University where he was a Rhodes Scholar. Prof. Thomas Edlund, Ph.D., founder of Betagenon, will lead the ongoing scientific interrogation of the target as the Chief Scientific Officer, and joins the Board of Betagenon this month. "I am incredibly excited to join Betagenon as we build on the scientific leadership of Thomas and the team, and drive to clinical proof of concept and show what direct activation of AMPK can deliver to patients," said James. "Having known James professionally for a number of years, I am delighted that he has agreed to take the company and program forward in this next stage of development," said Thomas. Betagenon also announced that Dr. Gunnar Olsson, MD, Ph.D, has been elected as Chairman of the Board at the recent AGM. Dr. Olsson brings more than 30 years' experience in drug development, including 25 years at AstraZeneca. While at AstraZeneca Dr. Olsson held a number of senior roles in Global R&D including Senior VP and leader of the CV & GI Therapy Area. He certified in Cardiology and Internal Medicine in hospitals associated to Karolinska Institutet, where he was adjunct professor for 12 years. In recent years Dr Olsson has worked with innovative biotech companies in the Scandinavian region as board member or advisor. He is currently Chairman of the Board of IRLAB AB and Athera Biotechnologies AB and is a member of the Board of Gesynta AB. Dr. Olsson succeeds Andreas Nordberg as Chairman. Mr. Nordberg will continue as a member of the Board. Betagenon is a clinical stage company that develops its proprietary first in class AMPK activators as therapies for diseases and conditions associated with the global epidemic in metabolic disorders and an aging population. For more information, contact: James Hall, CEO Betagenon AB james.hall@betagenon.com This information was brought to you by Cision The following files are available for download: View original content: SOURCE Betagenon AB

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Drug(Targets)	Indications	Global Highest Phase

A-101(Anthera pharma) ( PLA2 )	Cardiovascular Diseases More	Discontinued
Phosphorylcholine monoclonal antibody (Athera Biotechnologies) ( PC )	Arteritis More	Discontinued
Dianexin (Athera Biotechnologies)	Acute Coronary Syndrome More	Pending

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