"Apabetalone, a selective bromodomain extra-terminal (BET) protein inhibitor that significantly decreases abundance and activity of complement proteins"
CALGARY, May 24, 2016 /PRNewswire/ - Resverlogix Corp. ("Resverlogix" or the "Company") (TSX:RVX) announces that new data was presented at the ERA-EDTA Congress in Vienna, Austria in a poster titled: "Apabetalone (RVX-208), a Selective Bromodomain and Extra-Terminal (BET) Protein Inhibitor, Decreases Abundance and Activity of Complement Proteins in Vitro, in Mice and in Clinical Studies". The Company is also pleased to announce the formation of an International Renal Clinical Advisory Board (RCAB) for the future development of apabetalone into expanded renal indications.
New Complement Data Announced at ERA-EDTA Congress – Vienna, Austria
The immune system is the body's way of protecting itself from attacking foreign invaders, such as bacteria, viruses, illness, and disease. The complement cascade is part of this protective response, however pathological activation of the cascade underlies multiple human diseases including several inflammatory, autoimmune, neurodegenerative and infectious diseases.
New data demonstrated that when exposed to apabetalone, primary human liver cells significantly downregulate the expression of complement components. This was observed at both the gene expression and protein level, and occurred at steady state (when unstimulated) and when the cells were stimulated with factors known to cause inflammation and immune response activation. This is particularly important in conditions where these factors are overactive or present in excessive quantities. Moreover, in an apabetalone treated mouse model, where mouse liver cells are replaced with human liver cells, reductions in expression of components C4, C9 and MBL2 mRNA of the complement cascade, decreased by 36 percent, 46 percent and 61 percent respectively. To establish if the observed decrease in protein abundance affected activity, hemolytic assays were performed on 11 plasma samples from patients with cardiovascular disease (CVD) at baseline, and after 26 weeks of apabetalone treatment. Results showed a significant decrease in activity of approximately 26 percent (p<0.01) in both assays. No increase in infections was reported in phase 2 trials.
This effect of apabetalone treatment on complement component expression and cascade activity may have an impact on the pathologic activation of this cascade in Chronic Kidney Disease (CKD). The potential of apabetalone for the treatment of high-risk diabetes and CKD patients is currently being explored in the Company's Phase 3 BETonMACE clinical study.
Dr. Kamyar Kalantar-Zadeh, Chairman of the RCAB, stated, "BET inhibition with apabetalone represents a novel and compelling approach for diabetes and CKD treatment. This data in combination with previously published findings on novel biomarkers and pathways affected by select BET inhibition with known roles in CVD and CKD such as, coagulation, vascular calcification and inflammation, provide a potentially unique and multifactorial approach to disease reduction. The RCAB intend to examine expanded opportunities in renal disease where patients have a significant risk for major adverse cardiac events (MACE) such as death, stroke, heart failure and myocardial infarction".
"This new data is an important step for the Company as we continue to develop our proprietary BET data for high risk CVD patients and apply these learnings into additional indications in kidney and renal orphan diseases," said Mr. Donald McCaffrey, President and CEO. "The data showing that select BET inhibition is modulating key pathways and proteins known to play a role in renal disease, is directly responsible for attracting world-class leaders in the field of renal disease research to help expand and direct our efforts."
Members of the Resverlogix International Renal Clinical Advisory Board:
Dr. Kamyar Kalantar-Zadeh (Chair): Dr. Kalantar-Zadeh is Professor and Chief, Division of Nephrology and Hypertension at University of California, Irvine. Dr. Kalantar-Zadeh is the founder and director of the Harold Simmons Center for Kidney Disease Research and Epidemiology. Among his numerous appointments in the renal field Dr. Kalantar-Zadeh is Associate Editor of several peer-reviewed journals including Nephrology Dialysis Transplantation (NDT), American Journal of Kidney Diseases (AJKD), Cardiorenal Medicine (CRM), Seminars in Dialysis, sarcopenia and Muscle (JCSM), and a member of the editorial board of Journal of Kidney International (KI), Journal of American Society Nephrology (JASN), Nature Reviews Nephrology, American Journal of Nephrology (AJN). Dr. Kalantar-Zadeh has authored 3 textbooks and over 500 peer reviewed publications.
Dr. Carmine Zoccali: Dr. Zoccali is a specialist in Renal Diseases (Pisa University) and Hypertension. Dr. Zoccali's appointments include: Director, Division of Nephrology, Hypertension and Renal Transplantation, Ospedali Riuniti, Reggio Cal, Italy; Chief, CNR-IBIM Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension; Professor, Postgraduate Schools of Nephrology, Palermo, Catania and Messina Universities. Dr. Zoccali's current editorial positions include: Editor in Chief, Nephrology Dialysis and Transplantation, Academic Editor, (Nephrology) PlosOne, and Editorial Board member, Journal of the American Society of Nephrology (JASN). Editorial Board member, Clinical Journal of the American Society of Nephrology (cJASN) and Editorial Board member, Kidney International (KI). Dr. Zoccali has over 402 papers in international peer-reviewed, Pubmed indexed journals.
Dr. Marcello Tonelli: Dr. Tonelli is Associate Vice-President (Research) at the University of Calgary. Dr. Tonelli was the recipient of the 2013 United States National Kidney Foundation Medal for Distinguished Service and the Kidney Foundation of Canada's 2013 Medal for Research Excellence for changing nephrology practice in Canada and beyond. Along with the two other team co-leads, he received a Top Canadian Achievements in Health Research Award from the CIHR-CMAJ in 2013 for his work with the Interdisciplinary Chronic Disease Collaboration. He was elected a fellow of the Canadian Academy of Health Sciences in 2012 and a member of the American Society for Clinical Investigation in 2014. He was named a "Highly Cited" researcher in 2015 by Thomson-Reuters, corresponding to a rank in the top 1% by citations of all researchers worldwide for field and publication year.
Dr. Vincent Brandenburg: Dr. Brandenburg is Nephrologist, Associate Professor and Senior Consultant at the Department of Cardiology, Intensive Care Medicine and Vascular Medicine, University Hospital of the RWTH Aachen, Germany. Dr. Brandenburg has been leader of the German Calciphylaxis registry (www.calciphylaxie.de) since 2007. He is a board member of the ERA-EDTA scientific working group Chronic Kidney Disease – Mineral and Bone Disorder (CKD-MBD). Dr. Brandenburg has authored or co-authored over 140 articles in peer-reviewed journals. These articles have had the primary focus upon chronic kidney disease – mineral and bone disorder, cardiorenal syndrome, and calciphylaxis. He is a member of the German and European Societies of Nephrology and the Societies of Cardiology.
Dr. Srinivasan Beddhu: Dr. Beddhu, MD is a tenured Professor of Medicine at the University of Utah School of Medicine. He is Board Certified in Internal Medicine and Nephrology. Dr. Beddhu received his medical degree from Stanley Medical College, Chennai, India. His clinical and research interests include hypertension, chronic kidney disease progression and complications and end-stage renal disease. Dr. Beddhu's research is funded primarily by NIH grants. He has served in several national committees including NIH panels, American Society of Nephrology Research Committee and NKF clinical practice guidelines committee. Dr. Beddhu has published about 100 articles including peer-reviewed publications, editorials and book chapters.
Dr. Mathias Haarhaus: Dr. Haarhaus is a Consultant Nephrologist at the Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden, where he is head of the Bone and Mineral Program. His research at the Division of Renal Medicine, Karolinska Institutet, mainly focuses on the link between skeletal disorders and cardiovascular complications in chronic kidney disease, with a special focus on alkaline phosphatase. He is an active member of the Chronic Kidney Disease – Mineral and Bone Disorder (CKD-MBD) working group of the European Renal Association – European Dialysis and Transplantation Association (ERA-EDTA) and a member of the Guidelines Committee of the Swedish Society of Nephrology.
Resverlogix is developing apabetalone (RVX-208), a first-in-class, small molecule that is a selective BET (bromodomain and extra-terminal) inhibitor. BET bromodomain inhibition is an epigenetic mechanism that can regulate disease-causing genes. Apabetalone is the first and only BET inhibitor selective for the second bromodomain (BD2) within the BET protein called BRD4. This selective inhibition of apabetalone on BD2 produces a specific set of biological effects with potentially important benefits for patients with diseases such as high-risk cardiovascular disease (CVD), diabetes mellitus (DM), chronic kidney disease (CKD), Alzheimer's disease, Orphan diseases, and peripheral artery disease, while maintaining a well described safety profile. Apabetalone is the only selective BET bromodomain inhibitor in human clinical trials, currently in a Phase 3 trial BETonMACE in high-risk CVD patients with type 2 DM and low high-density lipoprotein (HDL).
Resverlogix common shares trade on the Toronto Stock Exchange (TSX:RVX).
For further information please visit www.resverlogix.com.
This news release may contain certain forward-looking information as defined under applicable Canadian securities legislation, that are not based on historical fact, including without limitation statements containing the words "believes", "anticipates", "plans", "intends", "will", "should", "expects", "continue", "estimate", "forecasts" and other similar expressions. In particular, this news release includes forward looking information relating to the potential role of apabetalone in the treatment of CVD, DM, CKD, complement component expression, Alzheimer's disease, Orphan diseases, and peripheral artery disease. Our actual results, events or developments could be materially different from those expressed or implied by these forward-looking statements. We can give no assurance that any of the events or expectations will occur or be realized. By their nature, forward-looking statements are subject to numerous assumptions and risk factors including those discussed in our Annual Information Form and most recent MD&A which are incorporated herein by reference and are available through SEDAR at www.sedar.com. The forward-looking statements contained in this news release are expressly qualified by this cautionary statement and are made as of the date hereof. The Company disclaims any intention and has no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
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SOURCE Resverlogix Corp.