RVX-208 Update, October 6 th , 2014 WWW.RESVERLOGIX.COM
Todays Presentation Points 1. Annual Milestone Review 2. Ongoing Biomarker & Genetic Pathway Analysis • Step 1: Analysis of all clinical data • Step 2: Further delineate mechanisms • Step 3: Design & launch next clinical trial 3. BET Bromodomain Opportunities 4. Milestones & Inflection Points Safe Harbor Statement. This presentation contains forward-looking statements that involve risks and uncertainties, which may cause actual results to differ materially from the statements made. For this purpose, any statements that are contained herein that are not statements of historical fact may be deemed to be forward- looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, the words "believes," "anticipates," "plans," "intends," "will," "should," "expects," "projects," and similar expressions are intended to identify forward- looking statements. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause actual results, future circumstances, or events to differ materially from those projected in the forward-looking statements. These risks include, but are not limited to, those associated with the success of research and development programs, the regulatory approval process, competition, securing and maintaining corporate alliances, market acceptance of the Company's products, the availability of government and insurance reimbursements for the Company's products, the strength of intellectual property, financing capability, the potential dilutive effects of any financing, reliance on subcontractors and key personnel. The forward- looking statements are made as of the date hereof, and 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. CONTACT: Donald J. McCaffrey 300, 4820 Richard Road SW, Calgary, Alberta T3E-6L1 Tel: (403) 254-9252, Fax:(403) 256-8495, http://www.resverlogix.com/
Annual Milestone Review Nature Publishing Group's SciBex Annual General reports RVX-208 is an Meeting - 2013 emerging first-in-class Oct 3 BET inhibitor RVX-208 annouced as RVX-208 May 21 effective in Atheroma gets European regression in High Risk CVD patients. Patent approval Combined Nov 4 trial data Mar 17 RVX secures $30MM confirm financing MACE reduction Jul 3 Jan 15 Feb 2013 2014 Oct Dec Apr Jun Aug Oct 2014 RVX closes a PLOS-ONE Journal Today Annual General $2.3MM insider publishes RVX-208 Meeting 2014 led private ApoA-I enhancer & Structural Oct 8 placement BET Bromodomain Genome Jun 11 Antagonist Consortium reports Jan 2 RVX-208 completes European Society of RVX-208, 1st Australian Diabetes Cardiology Selective BET trial presentation reports inhibitor 77% MACE reduction Mar 31 Australia Diabetes Oct 8 in Diabetes Mellitus Trial fully enrolled patients Dec 23 Sep 2 3
Recent RVX-208 Publications 4
Ongoing Biomarker & Genetic Pathway Analysis 5
Thinking Outside the Box to Expand Our World Leading Knowledge in Reader Epigenetics “I’m searching for my keys here because this is where the light is located.” RVX Internal Analysis 6
Critical steps required to maximize probability of success of future trials • Step 1 – Analyze all clinical data – Australia Diabetes Trial – ongoing, publication & oral presentations expected mid 2015 – SUSTAIN & ASSURE combined data analysis • Step 2 – Further delineate mechanisms driving MACE reduction – Microarray analysis of relevant cell types – Analysis of blood biomarker data to develop algorithms for identification of patients likely to respond to treatment – Proteomic analysis of archived clinical samples (from multiple trials) to investigate and possibly identify novel RVX-208 responsive biomarkers • Step 3 – Design and launch the next clinical trial – Utilize knowledge gained in steps 1 & 2 to enhance enrollment criteria – Hire a high caliber Chief Medical Officer – Plan additional smaller, less expensive trials for value creation purposes – Confirm clinical sites and PI’s RVX Internal Analysis 7
Step 1: Determined that RVX-208 lowered MACE by 77% in CVD patients with diabetes mellitus RVX-208 (N=127) Placebo (N=65) RVX-208, DM pts (n=127) Placebo, DM pts (n=65) 21.0% RVX-208 (n=331) Placebo (n=168) Cummulative Event Rate (%) 18.0% 77% RRR 15.0% p = 0.01 diabetes 12.0% 55% RRR mellitus p = 0.02 9.0% 6.0% 3.0% 0.0% 0 30 60 90 120 150 180 210 Days Since Randomization Source: RVX data on file – ASSURE and SUSTAIN Safety Population. Log-Rank test for between group comparison 8
Additional knowledge gained from clinical data analysis Placebo (n=166) RVX-208 (n=331) Biomarker Percent p value vs. Percent p value vs. Change baseline Change baseline HDL Cholesterol, (mg/dL) 0.0 0.59 +7.69 <0.0001 ApoA-I, (mg/dL) +3.8 0.0003 +10.3 <0.0001 Total HDL particles, ( mol/L) +0.40 0.61 +6.51 <0.0001 HDL particle size, (nm) 0.0 0.30 +1.16 <0.0001 Large HDL particles, ( mol/L) +4.11 0.02 +30.71 <0.0001 hsCRP, (mg/L) -22.4 0.0002 -28.4 <0.0001 Alkaline phosphatase, (U/L) -3.23 0.03 -11.0 <0.0001 Results expressed as median percentage change from baseline Source: RVX data on file – ASSURE and SUSTAIN mITT Population. 2-sided Van Elteren test of RVX-208 vs placebo, stratified by study RVX Internal Analysis 9
SUSTAIN & ASSURE: Pooled Analysis of Biomarkers • Reverse Cholesterol transport markers measured : ApoA-I, ApoB, cholesterol, HDLc, HDLc (total), HDL particles (total), HDL size, IDL particles, large HDL particles, large LDL particles, large VLDL & chylomicron particles. LDLc, LDL particles (total), LDL size, medium HDL particles, medium VLDL particles, non-HDL cholesterol, small HDL particles, small LDL particles, small VLDL particles, triglycerides, triglycerides (total), VLDL & chylomicron particles, VLDL & chylomicron triglyceride, VLDL size • Inflammatory markers measured : hsCRP, IL-6 • Metabolic markers measured : glucose, HbA1c • Chemistry markers measured : albumin, alkaline phosphatase blood urea nitrogen, calcium, chloride, creatinine, creatine kinase, lactate dehydrogenase, phosphate, potassium, total protein, sodium, granular casts ‡ , hyaline casts ‡ , ketones ‡ , specific gravity ‡ , pH ‡ , waxy casts ‡ , triphosphate crystals ‡ • Liver safety markers measured : ALT, AST, total bilirubin, direct bilirubin, GGT • Atheroma markers measured : PAV † , TAV † , 10MTAVMX † • Hematology markers measured : hematocrit, hemoglobin, mean corpuscular volume, percent basophils, percent eosinophils, percent lymphocytes, percent monocytes, percent neutrophils, platelets, RBCs, WBCs, RBC casts ‡ • Vital Signs measured : diastolic BP, systolic BP, weight RVX ASSURE only † SUSTAIN only ‡ 10
ASSURE & SUSTAIN: Biomarker Rank RVX-208 (n=331) Placebo (n=166) p value Rank Biomarker vs Change from Change from p value vs. p value vs. placebo baseline baseline baseline baseline (% ▲ ) (% ▲ ) <0.0001 -8.0 (-11.0) <0.0001 -2.0 (-3.2) 0.03 1 Alkaline phosphatase (U/L) 0.0003 2 HDL-C (mg/dL) +3.0 (+7.69) <0.0001 0.0 (0.0) 0.59 0.005 3 ApoA-I (mg/dL) +12.3 (+10.3) <0.0001 +4.8 (+3.8) 0.0003 Glucose † (mmol/L) 0.008 4 -0.3 (-4.69) 0.25 +0.9 (+10.3) 0.06 Large HDL particles ( mol/L) 0.03 +0.8 (+30.7) <0.0001 +0.1 (+4.11) 0.02 5 HDL particle size (nm) 0.049 6 +0.1 (+1.16) <0.0001 0.0 (0.0) 0.30 Total HDL particles ( mol/L) 7 +1.9 (+6.51) <0.0001 +0.1 (+0.40) 0.61 0.07 -0.36 (-28.4) <0.0001 -0.33 (-22.4) 0.0002 0.67 8 hsCRP (mg/L) Ranking based on statistical significance vs placebo Results expressed as median percentage change from baseline † Significance vs placebo observed in diabetes population with baseline HDL<40 mg/dL Source: RVX data on file – ASSURE and SUSTAIN mITT Population. 2-sided Van Elteren test of RVX-208 vs placebo, stratified by study RVX Internal Analysis 11
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