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Resverlogix Provides Groundbreaking Results in Patients with Severe Kidney Impairments

T.RVX

Several Key Proteins That Drive Kidney (Renal) Disease and Dialysis Risk are Downregulated After a Single Dose of Apabetalone

PR Newswire

CALGARY, Alberta, Jan. 23, 2017 /PRNewswire/ -- Resverlogix Corp. ("Resverlogix" or the "Company") (TSX: RVX) today announced preliminary results from the New Zealand based Phase 1 trial with severe kidney (renal) impaired patients. The data showed remarkable results in reducing inflamed protein biomarkers in patients with severe kidney impairment versus healthy control patients. It is believed that this is the first time in medical history that a direct connection of this type can be made between epigenetic regulation and its potential for positive disease impact. Both the healthy group and the severely impaired kidney group received equal amounts of apabetalone.

"It was shocking and highly encouraging to see the direct comparison of the protein data ranked by magnitude of effect in the two groups. For the first time, epigenetic and BET inhibition clinical data has been shown to differentially affect genes and proteins between advanced chronic kidney disease (CKD) patients and normal subjects," stated Donald McCaffrey, President and CEO.

Dr. Kamyar Kalantar-Zadeh, Chairman of the Renal Clinical Advisory Board and member of the BETonMACE Clinical Steering Committee stated, "These early results help provide a first understanding of the potential rapid effects of BET inhibition and apabetalone on key proteins that drive risk and death in Stage 4 CKD and potentially dialysis patients. Late Stage 4-5 CKD and dialysis patients represent very important groups whom currently have limited therapeutic strategies that can improve their outcomes and quality of life," Dr. Kalantar-Zadeh added.

Ongoing expanded analysis of this exploratory data is also planned which will look at Ingenuity Pathway Analysis (IPA). The quick onset of action and improvement of reported CKD risk factors are encouraging for the Company in their planned expansion beyond its current cardiovascular and diabetes program. Detailed data will be submitted for peer reviewed publications. 

Clinical Trial Highlights

The study explored acute changes in biomarkers relevant to subjects with Stage 4 CKD. Plasma components were analyzed using the SOMAscan® assay, a sensitive, quantitative and reproducible proteomic tool for measuring 1,310 proteins in the human proteome. Eight patients with previously diagnosed Stage 4 CKD not on dialysis (estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73m2) were compared to eight matched healthy individuals with normal renal function (eGFR range > 90 mL/min/1.73m2).

Protein data was collected following a single oral administration of 100mg of apabetalone before and after multiple time points in both cohorts. Protein levels of 289 proteins were significantly different at baseline between the two groups (p<0.05). Initial findings from this study revealed a highly differential protein signature at baseline between CKD patients and controls. Following a single dose administration of apabetalone in the Stage 4 CKD patients, the levels of multiple plasma proteins were changed within 12 hours after dosing, demonstrating a fast onset of drug action. Analysis of the changes in protein levels at the 12-hour time point revealed that, in the Stage 4 CKD patients, 33 percent of proteins had statistically significant changes (p<0.05) compared to only 10 percent in the controls. Of these significant proteins, several established renal biomarkers such as interleukin 6 (IL6) and osteopontin, were regulated positively with respect to disease severity and progression.

About Advanced CKD & Dialysis

Advanced CKD encompasses Stages 4 & 5, and it can be alternatively defined as an estimated glomerular filtration rate (eGFR) of <30 ml/min/1.73m2. As reported in the 2016 United States Renal Data System (USRDS) Annual Report, approximately 1.4 million patients in the US have advanced CKD, 474,000 of which are on dialysis treatment. According to the USRDS, advanced CKD cost the US healthcare system approximately US$17 billion in 2014, with an average annual cost exceeding US$28,000 per patient. Additionally, dialysis treatment costs the US Medicare system approximately US$28 billion with an average annual cost exceeding US$80,000 per year. Currently there are no known agents that improve Major Adverse Cardiac Events (MACE) in CKD or dialysis patients.

About Resverlogix

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, 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.

Follow us on Twitter: @Resverlogix_RVX (https://twitter.com/resverlogix_rvx), or on our blog at http://www.resverlogix.com/blog

For further information please contact:

Investor Relations
Email:
ir@resverlogix.com
Phone: 403-254-9252

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 Company's Phase 2 Renal Impairment trial and Phase 3 clinical trial, and the potential role of apabetalone in the treatment of CVD, DM, chronic kidney disease, 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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