Slide 1: Detailed Preliminary Results of BETonMACE
TSX: RVX Detailed Preliminary Results of BETonMACE Strengthening Opportunities Through Positive Findings & Synergy July, 2020
Slide 2: Forward Looking Statement
Forward Looking Statement 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",
Slide 3: Executive Summary (1)
Executive Summary (1) • Very Encouraging Cardiovascular Disease Efficacy Results – Narrow Miss on Primary Endpoint (CV Death, Non-fatal MI, and Stroke): 18% Hazard Reduction (HR: 0.82; 95% CI; 0.65-1.04) p=0.11 – Trending MACE Improvements on Multiple Endpoints with Survival Curves Consistently Sepa
Slide 4: Executive Summary (2)
Executive Summary (2) • Apabetalone treatment illustrated statistically significant improvements versus placebo (+ top standard of care) in patients with a baseline MoCA <22 : – 158% relative improvement in cognitive function in treated group compared to top standard of care placebo (comparing the m
Slide 5: Cardiovascular Disease Efficacy Results
Cardiovascular Disease Efficacy Results 5
Slide 6: Primary Endpoint
Cc ™™ RESVERLOGIX ™——__ Primary Endpoint
Slide 7: Primary Outcome Measure and Components
Primary Outcome Measure and Components Major Adverse Cardiac Events Apabetalone Placebo Endpoint, n(%) HR (95% CI) Log-rank p-value (N=1212) (N=1206) MACE 125 149 0.82 (0.65-1.04) 0.11 Non-fatal MI 77 94 0.80 (0.59,1.08) 0.15* Stroke 17 17 1.01 (0.52, 1.98) 0.99* CV Death 45 55 0.81 (0.54, 1.19) 0.2
Slide 8: Primary Endpoint: CV Death, Non-fatal MI, and Stroke
Primary Endpoint: CV Death, Non-fatal MI, and Stroke Sustained throughout the duration of the trial 18% Hazard Reduction Early separation of curves No. at Risk Placebo 1206 1135 1102 937 641 383 108 Apabetalone 1212 1151 1114 950 672 397 107 8
Slide 9: Secondary and Other Prespecified Endpoints
Secondary and Other Prespecified Endpoints
Slide 10: Cardiovascular Endpoints
Cardiovascular Endpoints Apabetalone Placebo Primary Endpoint Hazard Ratio (95% CI) P Value no. of events (%) First occurrence of primary endpoint: CV death, non-fatal MI and stroke 125 (10.3%) 149 (12.4%) 0.82 [0.65, 1.04] 0.11 Key Secondary Endpoints First occurrence of primary endpoint or hospita
Slide 11: Hospitalization for Congestive Heart Failure (CHF)
Hospitalization for Congestive Heart Failure (CHF)
Slide 12: Key Secondary Endpoint – First Hospitalizations for CHF
Key Secondary Endpoint – First Hospitalizations for CHF 41% Hazard Reduction No. at Risk Placebo 1206 1135 1102 937 641 383 108 Apabetalone 1212 1151 1114 950 672 397 107 12
Slide 13: Exploratory Endpoint – First Hospitalizations for CHF and CV Death
Exploratory Endpoint – First Hospitalizations for CHF and CV Death 27% Hazard Reduction No. at Risk Placebo 1206 1135 1102 937 641 383 108 Apabetalone 1212 1151 1114 950 672 397 107 Source: RVX Internal Analysis – Non-QC’d 13
Slide 14: Non-fatal MI, Stoke, CV Death, and Hospitalization for CHF
Non-fatal MI, Stoke, CV Death, and Hospitalization for CHF Apabetalone Placebo Endpoint, n(%) HR (95% CI) Log-rank p-value (N=1212) (N=1206) Non- Composite 139 173 0.79 (0.63, 0.98) 0.03* QC’d Non-fatal MI 77 94 0.80 (0.59,1.08) 0.15* CV Death 45 55 0.81 (0.54, 1.19) 0.29* Stroke 17 17 1.01 (0.52, 1
Slide 15: Non-fatal MI, CV Death, and Hospitalization for CHF – Survival Curve
Non-fatal MI, CV Death, and Hospitalization for CHF – Survival Curve Placebo + Top Standard of Care Cumulative Incidence of Event (%) Hazard Ratio = 0.79 (95% CI. 0.63 – 0.98) p=0.03 21% Hazard Reduction Apabetalone + Top Standard of Care No. at Risk Months Placebo 1206 1135 1102 937 641 383 108 Apa
Slide 16: Prespecified Subgroups
Prespecified Subgroups 16
Slide 17: Endpoint Significance Reached in Prespecified Subgroups
Endpoint Significance Reached in Prespecified Subgroups 0.25 0.5 1 2 17 Apabetalone Better Placebo Better
Slide 18: Apabetalone Overperforms in Patients with Renal Impairment
Apabetalone Overperforms in Patients with Renal Impairment (Baseline eGFR Below 60 mL/min)
Slide 19: Apabetalone Improved CVD Outcomes in Impaired Renal Subgroup
Apabetalone Improved CVD Outcomes in Impaired Renal Subgroup Baseline eGFR Below 60 mL/min Endpoint Hazard Ratio (95% CI) P Value CV Death, Non Fatal MI and Stroke eGFR < 60 mL/min 0.50 [0.26, 0.96] 0.03 eGFR ≥ 60 mL/min 0.94 [0.73, 1.22] CV Death, Non Fatal MI and Stroke (Excl. Undetermined Death)
Slide 20: Renal Subgroup – CV death, Non-fatal MI, and Stroke
Renal Subgroup – CV death, Non-fatal MI, and Stroke Patients with eGFR < 60 at Baseline Patients with eGFR ≥ 60 at Baseline 50% Hazard Reduction Source: RVX Internal Analysis – Non-QC’d 20
Slide 21: Renal Subgroup – CV death, Non-fatal MI, Stroke, and Hosp. for CHF
Renal Subgroup – CV death, Non-fatal MI, Stroke, and Hosp. for CHF Patients with eGFR < 60 at Baseline Patients with eGFR ≥ 60 at Baseline 49% Hazard Reduction Source: RVX Internal Analysis – Non-QC’d 21
Slide 22: Surprise Finding!
Surprise Finding! Potential Synergy with New Generation of Diabetes Drugs 22
Slide 23: Baseline Characteristics: Cardiovascular and Diabetes Medications
Baseline Characteristics: Cardiovascular and Diabetes Medications Cardiovascular and Diabetes Medications Apabetalone (N=1212) Placebo (N=1206) Atorvastatin 621 (51.2) 620 (51.4) Rosuvastatin 591 (48.8) 586 (48.6) High intensity statin 1089 (89.9) 1092 (90.5) ACE inhibitors/ angiotensin II blockers
Slide 24: Comparison to Other Major Therapeutic Classes
Comparison to Other Major Therapeutic Classes Impact on MACE in Patients with Type 2 Diabetes Therapeutic Trial Name # Patients Effect on MACE Apabetalone BETonMACE 2,425 -18%* Apabetalone + SGLT2i BETonMACE 298 -60%** DDP-4 inhibitors1,2 CAROLINA 6,042 no effect Insulin3 ORIGIN 12,537 no effect SGL
Slide 25: SGLT2i or DPP4i – CV death, Non-fatal MI, Stroke, and Hosp. for CHF
SGLT2i or DPP4i – CV death, Non-fatal MI, Stroke, and Hosp. for CHF 63% Hazard Reduction No. at Risk Placebo 264 250 243 209 143 86 25 Apabetalone 265 257 251 219 156 90 25 Source: RVX Internal Analysis – Non-QC’d 25
Slide 26: CVD Endpoints with SGLT2 Inhibitors
CVD Endpoints with SGLT2 Inhibitors Apabetalone Placebo Endpoint, n(%) HR (95% CI) (N=150) (N=148) MACE 5 13 0.40 (0.16, 1.00) CV death, non-fatal MI and stroke Hospitalization for Congestive 1 2 0.49 (0.05, 4.73) Heart Failure (CHF) CV death, non-fatal MI stroke 5 15 0.35 (0.15, 0.85) and hospitali
Slide 27: Apabetalone and Empagliflozin (Jardiance)
Apabetalone and Empagliflozin (Jardiance) 66% Hazard Reduction Note: Based on Patients who were taking Empagliflozin for at least 30 days during the trial, and prior to their MACE No. at Risk Narrowly Defined MACE: Apabetalone 113 108 67 13 - CV Death - Non Fatal MI Placebo 115 104 59 18 - Stroke So
Slide 28: Market Growth of SGLT2 Inhibitors
Market Growth of SGLT2 Inhibitors Global Market Growth Jardiance Market Growth >USD 7.5Bn* USD 12.7Bn 2019-2024 CAGR: 15.78% USD 2.5Bn Source: *RVX Internal Estimate 28
Slide 29: Cognition Results
Cognition Results 29
Slide 30: Montreal Cognitive Assessment (MoCA)
Montreal Cognitive Assessment (MoCA)
Slide 31: Mean Change from Baseline to Last Value Captured (MoCA)
BETonMACE Cognition Findings - MoCA 4.0 * to Last Value Captured (MoCA) Mean Change from Baseline 3.0 Apabetalone + Top Standard of Care • Apabetalone treatment illustrates a statistically Placebo + Top Standard of Care significant (*p=0.02) improvement versus placebo in 2.0 MoCA in patients with a
Slide 32: Mean Change from Baseline to Last Value Captured (units of MoCA)
to Last Value Captured (units of MoCA) MoCA Domains in Patients with Baseline MoCA <22 4.0 Apabetalone + Top Standard of Care (N=30) * Mean Change from Baseline Placebo + Top Standard of Care (N=45) 3.0 • Analysis of MoCA domains illustrates a statistically significant improvement 2.0 (*p<0.05) in t
Slide 33: BETonMACE Cognition Findings – Additional Analysis
BETonMACE Cognition Findings – Additional Analysis • Apabetalone treatment illustrates a trend in the improvement of cognition when baseline MoCA was lower (MoCA < 22) Normal Mild Cognitive Decline High Risk MoCA >= 26 MoCA 25 - 22 MoCA < 22 28.0 28.0 28.0 Apabetalone + Top Standard of Care 26.0 26.
Slide 34: Summary
Summary • CVD primary endpoint was narrowly missed with consistent positive trend in key endpoints • Apabetalone overperfomed in pre-specified renal subgroup, reaching significance on multiple endpoints • Potential synergy discovered between Apabetalone and SGLT2 inhibitors • Apabetalone significant
Slide 35: Near Term Commercialization Steps
Near Term Commercialization Steps In the near term we will continue our multi-point approach to progressing our corporate commercial value. This approach involves aggressive exploratory development of the following: • Breakthrough Therapy Status Granted from FDA – February 2020 • Agreement reached w
Slide 36: Detailed Preliminary Results of BETonMACE
TSX: RVX Detailed Preliminary Results of BETonMACE Strengthening Opportunities Through Positive Findings & Synergy January, 2020
Slide 37: Appendix
Appendix 37
Slide 38: Study Design
Cc ™™ RESVERLOGIX ™——__ Study Design
Slide 39: BETonMACE Study Parameters
BETonMACE Study Parameters Primary Objective Primary Endpoint • To evaluate if treatment with apabetalone as • Time to first occurrence of adjudication-confirmed triple compared to placebo increases time to the first MACE occurrence of triple MACE. Triple MACE is defined as a single composite endpoi
Slide 40: BETonMACE a Global, Multi-centered Clinical Trial
BETonMACE a Global, Multi-centered Clinical Trial GERMANY NETHERLANDS POLAND RUSSIA BELGIUM SLOVAKIA UNITED STATES CROATIA BULGARIA TAIWAN SERBIA ISRAEL MEXICO HUNGARY ARGENTINA With 14 approved countries around the world, BETonMACE included patients randomized at 220 different sites 40
Slide 41: BETonMACE Study Design
BETonMACE Study Design Screening Follow-Up Treatment Period Period Period Active Arm: apabetalone 100 mg b.i.d + standard of care 1:1 Randomization End of Treatment N=2425 Statin Run-in 40-80 mg atorvastatin or Placebo Arm: 20-40 mg matching placebo rosuvastatin + standard of care 1-2 weeks Median 1
Slide 42: BETonMACE: Patient Disposition
BETonMACE: Patient Disposition Completed n = 1,083 Placebo (89.8%) n = 1,206 Reason for non-completion Randomized in error: 4 Adverse Event 3 Withdrew Consent 24 Screened Randomized Lost to Follow-up 13 n = 3,937 n = 2,425 Died 72 Other 15 Screen Failures n=1,512 HDL-C 998 Bilirubin 136 Apabetalone
Slide 43: Mean MoCA Score
MoCA in Patients with Baseline MoCA <22 Baseline versus Last Value Captured • Study duration was the same between treatment groups 30.0 Apabetalone + Top Standard of Care (N=30) Placebo = 702 days Placebo + Top Standard of Care (N=45) Mean MoCA Score 25.0 Apabetalone = 701 days * 20.0 21.7 19.5 18.3
Slide 44: Baseline Characteristics
Baseline Characteristics Overall Study Population
Slide 45: Baseline Characteristics, Prior Medical and Index ACS History
Baseline Characteristics, Prior Medical and Index ACS History Apabetalone Placebo (n=1212) (n=1206) Median age, yrs 62.0 62.0 Male sex- % 74.8 74.0 Body mass index, kg/m2 30.2 30.3 Hypertension - % 89.4 87.8 eGFR Mean ± SD, mL/min/1.73m2 104.9 101.7 Duration of diabetes – yrs 8.4 8.7 Index acute cor
Slide 46: Baseline Characteristics: Cardiovascular and Diabetes Medications
Baseline Characteristics: Cardiovascular and Diabetes Medications Cardiovascular and Diabetes Medications Apabetalone Placebo (%) (N=1212) (N=1206) Atorvastatin 51.2 51.4 Rosuvastatin 48.8 48.6 High intensity statin 89.9 90.5 ACE inhibitors/ angiotensin II blockers 92.3 92.0 Beta blockers 91.0 90.2
Slide 47: BETonMACE: Baseline Laboratory Parameters
BETonMACE: Baseline Laboratory Parameters Apabetalone Placebo Baseline Laboratory Parameters (n=1212) (n=1206) Serum glucose, mg/dL 152.2 ± 60.7 150.7 ± 62.5 eGFR, ml/min/1.73m2 † 104.9 ± 39.3 101.7 ± 38.6 Total cholesterol, mg/dL 134.8 ± 35.3 136.8 ± 38.2 LDL cholesterol, mg/dL 69.7 ± 29.8 70.9 ± 3
Slide 48: Biochemical Parameters at 100 weeks and changes from baseline
Biochemical Parameters at 100 weeks and changes from baseline Biochemical parameters Apabetalone (N=1212) Placebo (N=1206) P value HDL cholesterol, mg/dL 38.1 (+16.4%) 36.4 (+10.4%) 0.001 LDL cholesterol, mg/dL 69.6 (+11.5%) 72 (+14.9%) 0.35 eGFR, ml/min/1.73m2 104.3 (-0.4) 105.2 (+2.1) 0.03 Alkalin
Slide 49: Safety Results
Cc ™™ RESVERLOGIX ™——__ Safety Results
Slide 50: Top Line Data: Safety
Top Line Data: Safety Variable Apabetalone (N=1212) Placebo (N= 1207) Adverse events - n (%) Patients with at least one adverse event 830 (68.5) 820 (67.9) Adverse event leading to discontinuation 114 (9.4) 69 (5.7) Serious adverse events – n (%) Patients with at least one SAE 354 (29.2) 339 (28.1)
Slide 51: Top Line Data: Safety
Top Line Data: Safety Adverse Events, System Organ Classes with at least one AE > 2% incidence either group* System Organ Class, Adverse Event Apabetalone (N=1212) Placebo (N= 1207) Infections and Infestations 291 (20.6) 296 (19.3) Nasopharyngitis 46 (3.8) 56 (4.6) Urinary tract infection 58 (4.8) 4
Slide 52: Background Slides
Cc ™™ RESVERLOGIX ™——__ Background Slides
Slide 53: BETonMACE: Background & Rationale – Apabetalone Mechanism of Action
BETonMACE: Background & Rationale Apabetalone Mechanism of Action DNA Genome Editing Altering the sequence of DNA itself and then reintroducing modified genes into the body There are currently no FDA-approved Transcription therapies based on gene editing Transcriptional Regulation RNA Adjusting the
Slide 54: BETonMACE: Background & Rationale
BETonMACE: Background & Rationale Epigenetics Regulate Gene Activity Chromosome Chromatin Fiber Nucleosome Writers • Epigenetics refers to modifications to chromatin that regulate it’s activity Histone Tail • Transcription is regulated by addition, removal, or Erasers recognition of these modificati
Slide 55: Apabetalone Mechanism of Action
Apabetalone Mechanism of Action BET P-TEFb Protein TF Pol II Transcription Activated Apabetalone Treatment TF Transcription 55 Inhibited
Slide 56: Apabetalone Impacts the Pathways that Drive Disease
Apabetalone Impacts the Pathways that Drive Disease Apabetalone reduces the Treatment with apabetalone expression of multiple reduces mediators that drive components of the complement endothelial activation, cascade Complement Vascular monocyte recruitment and plaque destabilization Wasiak et al. 20
Slide 57: Addressing Critical Unmet Needs
Addressing Critical Unmet Needs Cardiovascular Disease Diabetes Epidemic Still the number one killer of both males and females and costs the US healthcare system over $500B per year Current CVD Therapies - 30% Statins are the top medication used to treat CVD 60% Despite maximized use, Opportunity cu