Resverlogix BET Inhibition for Global Vascular Risk BIO CEO & Investor Conference February 12-13, 2018 New York, NY T S X : R V X
Forward Looking Statements This presentation 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 presentation includes forward looking information relating to the Company's clinical trials and the potential role of apabetalone in the treatment of CVD, DM, chronic kidney 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 presentation 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. 2 T S X : R V X R E S V E R L O G I X . c o m
Apabetalone Development Highlights • Apabetalone, the only-in-class BET inhibitor (BETi), reduces key risk factors Main Subject for high risk cardiovascular and renal patients resulting in reduction of Major Matter Adverse Cardiac Events (MACE), observed renal improvement markers • Epigenetic modulation of gene expression makes BETi a novel approach Advanced Mechanism – No known BETi competitor for next 9 plus years • Confirmed Proteomics, genomics, pathway analysis, mechanism of action are all very Science well understood • Phase 2b data – up to 62% RRR of MACE in high risk CVD patients Clinical • Phase 3 BETonMACE trial 90% enrolled Evidence – CVD/CKD risk biomarkers tracked to date - positive Corporate • Resverlogix corporate goal is to expand commercial partner program Expansion T S X : R V X R E S V E R L O G I X . c o m
Capitalization and Financial Profile RVX Top Shareholders Floating Founded 2001 Stock - Shenzhen Hepalink ~53M Pharmaceutical Co Ltd. Ticker TSX: RVX Shares Eastern Capital, Ltd. NGN Capital Market Cap ~C$300MM Donald J. McCaffrey 30.5% 42.9% Norman C.W. Wong Long Term ~C$0.0MM Debt Efung Capital 1.1% 12.7% CD Venture 2.3% 175.04MM Shares 1.7% Wayne Chiu (Co-founder) Outstand 1.8% Widely Held 2.6% 4.8% Cash Burn ~C$40.0M (Annual) • RVX shareholder base consists of several long term $87MM – Announced October investors who have been supportive over 10 years Finance 2017 • RVX maintains a diversified public market float of approximately 54M shares or ~$130MM 4 T S X : R V X R E S V E R L O G I X . c o m
2017 Major Accomplishments Four Publications in 2017, $68.8MM Long Term Debt Five already in the works Repaid – IP for 2018 unencumbered Q4 2017 Over $100MM in Financing Completed Q1-Q4 2017 Q3 & Q4 2017 Successful Data from Kidney Trial in New Additional Communications Zealand Q1 2017 Numerous additional news releases occuered in 2017new analysit reports. FDA approvals for a CKD Trial and BETonMACE Q1 & Q3 2017 5 T S X : R V X R E S V E R L O G I X . c o m
Upcoming Clinical Year Estimates Fabry’s Disease First Top Line Data for Patient Enrollment BETonMACE BETonMACE Enrollment Q4 2018 Completed Q2 2018 Q2 2018 Phase 2a Dialysis Study First Patient Randomized Additional Clinical Targets Q2 2018 Several additional targets exist and the order of launch may alternate First US Patient Randomized in Q1 2018 BETonMACE 6 T S X : R V X R E S V E R L O G I X . c o m
Apabetalone in the Clinic Apabetalone has been tested in multiple clinical trials with a good safety and efficacy profile 7 T S X : R V X R E S V E R L O G I X . c o m
BET Literature Impact Growing: CVD and Renal Risk HDAC1/2 P-TEFb BRD4 Ac Ac Decrease in TARGET Increase in CVD and CKD Complement Vascular GENE CVD and CKD RNA Pol II Risk Factors Risk Factors Inflammation Pathway Adapted from: Campbell, AE. et al. 2017 Adapted from: Campbell, AE. et al. 2017 Genes Genes Cell type Cell type Disease model Disease model Reference Reference Genes Cell type Disease model Reference Genes Cell type Disease model Reference Inflammation Vascular Calcification Fibrosis Complement cascade Reverse VCAM1, SELE, CCL2, CSF2, Human umbilical vein Atherosclerosis Brown et al, 2014 Mol Cell Coagulation IL6, ACTA2, PAI1, Human primary lung Bleomycin-induced Tang et al, 2013 AJP ALPL, OPG, RANKL, Primary human Basal conditions Gilham et al, 2017 AHA Epigenetic LTB, TNFAIP3, IRAK2, endothelial cells (hypercholesterolemic mice) MBL2, C9, C6, C8A, C4A-B, Human primary Atherosclerosis Gilham et al, 2016 Cholesterol COL1A1, FN1 fibroblasts pulmonary fibrosis CSF2RB, CXCR7, CXCL1, MCP1, IL8, BMP2, OPN hepatocytes C4BPB, C5, C1S, C8G, C2, hepatocytes and Atherosclerosis Kulikowski et al, 2017 Pathway ICOSLG COL1A1, ACTA2, Human activated Carbon tetrachloride (CCl 4 ) Ding et al, 2015 PNAS Regulation CFH whole blood Pathway ERA-EDTA COL1A2, DES, PDGFRB, hepatic stellate cells mouse model of liver injury TNFA, IL1B, IL6, CCL2 Murine bone marrow- Endotoxemic (LPS-induced Belkina et al, 2013 J Immunol CCND1, FBN1, FN1, (HSCs) (LX-2 cell MCP1, OPN U937 macrophages Inflammation (LPS “cytokine storm”) Gilham et al, 2017 AHA MBL2, C1S, C2, C3, C4, C9, (MCP-1), IL10 derived macrophages Human primary CVD Wasiak et al, 2017 JCTR TIMP1, TGFB1 line) C6, C8A, SAP, CRP, C5a, hepatocytes, chimeric stimulation) CCL2, CCL5 (RANTES), IL6, Human tubular Unilateral ureteral Suarez-Alvarez, 2017 JASN Kulikowski et al, 2017 C3b, C5b-C6, COLEC11 mice w. humanized CSF2, CCL20, LTB, epithelial cells (HK2 obstruction Primary mouse HSCs on ERA-EDTA livers, CVD patient ICOSLG, IL8 cell line) Systemic infusion of ANGII TS2, HNF4A, JUNB, Human lung cancer Chang et al, 2016 NAR plasma RUNX2, ALPL, OPG rVSMS and Osteogenic and calcifying Gilham et al, 2017 AHA Nephrotoxic serum nephritis Journal of Translational FOXP1, CDH2 A549 cell line Cardiovascular Research IL6, TIMP1, NOX4, COL8A1, HCASMSs Neonatal rat conditions Transverse aortic Falkenberg et al, 2014 Nat Kulikowski et al, 2017 Acute phase response ACTA2, COL1A1, P53, Renal interstitial Unilateral ureteral Xiong et al, 2016 CCL21A, CTGF ventricular constriction (TAC) (cardiac Rev Drug Disc Vascular ERA-EDTA FBN1, SMAD7, CCL2, c- fibroblast cells (NRK- obstruction Oncotarget cardiomyocytes hypertrophy) MBL2, C9, CP, IRAK1, LBP, Human primary Metabolism Atherosclerosis Gilham et al, 2016 MYC 49F) (NRVM) ALPL, OPG, OPN Serum CVD patients Gilham et al, 2017 AHA Atherosclerosis C5, AHSG, KLKB1, APCS, Calcification hepatocytes and Hyperlipidemic apoE - / - mice F9, F7, F11, PROC, Haptoglobin, VCAM1, IL18, Human primary Serum, HAEC, U937 (ASSERT/ASSURE phase Atherosclerosis Gilham et al, 2016 Jahagirdar et al, 2014 ITIH2, OSMR, F2, SHC, whole blood Kulikowski et al, 2017 SAP, MIP1 MCP1, IL6 cells Atherosclerosis KLKB1, TRPI, F12, F13B, hepatocytes and Atherosclerosis SERPINE1, C2 2 clinical trials) ERA-EDTA F2, A2M whole blood Carotid artery ligation Th-17 cell differentiation and activation OPN Serum Stage 4 CKD patients Kulikowski et al, 2017 Thrombin, F9, F10, F11, Human primary CVD Wasiak et al, 2017 JCTR FN1, CCL2, CCL8, CCL7, Human primary Atherosclerosis Gilham et al, 2016 F12, KLKB1 hepatocytes, chimeric (Phase 1 PK trial) ERA-EDTA CCL18, SPP1, CCL23, IL17A, IL21, IL22, IL23R, hepatocytes and Human Th-17 Collagen-induced arthritis Atherosclerosis Mele et al, 2013 J Exp Med mice w. humanized RORc, RORγt, GMCSF, PIK3R3, FCGR1A, ITGA9, whole blood Baud’huin et al, 2017 Bone NFATc1, RUNX2 Osteoclasts, differentiated cells Post-ovariectomy (CIA) livers, CVD patient IL2RA, F13A1, PROK2, BATF Experimental autoimmune osteoblasts osteoporosis plasma CXCL1 encephalomyelitis (EAE) 8 T S X : R V X R E S V E R L O G I X . c o m
Unique Mechanism of Action Genome Editing The mechanism is based on cutting and pasting undesired/desired sequences into or out of the DNA, thereby altering the gene sequence and then re-introducing the modified DNA into the body. CRISPR – gene editing within a cell sub population Transcriptional Regulation Mechanism is based on changing the levels of disease causing proteins by modulating their expression at the gene level Apabetalone – reduces expression of disease mediators Protein Targeting Focus on reducing or blocking the activity of one disease protein by using an inhibitor or antibody Antibody or Inhibitor – blocks activity of one mediator of disease 9 T S X : R V X R E S V E R L O G I X . c o m
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