Forward-looking Statements

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1 NASDAQ:CNAT

2 Forward-looking Statements This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, prospective products, product approvals, research and development costs, timing and likelihood of success, plans and objectives of management for future operations, and future results of current and anticipated products are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These known risks and uncertainties are described in detail in our filings made with the Securities and Exchange Commission from time to time. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and we undertake no obligation to revise or update this presentation to reflect events or circumstances after the date hereof. 2

3 Conatus Pharmaceuticals NASDAQ:CNAT San Diego, CA Publicly-traded development-stage biotechnology company Completed successful IPO in July 2013 Sufficient capital through next clinical data points Proprietary technology with long-term patent protection To 2028 in key global markets plus potential extensions Copyright 2013 The NASDAQ OMX Group, Inc. Balanced approach to product development Established in-house knowledge-based core competencies Outsourced infrastructure-based supporting capabilities Pursuing attractive commercial opportunities Initial small, targeted indications may offer accelerated regulatory pathways Additional indications may access much larger populations 3

4 Lead Compound: Emricasan (IDN-6556) Liver Disease: Various Insults Two Pathways One Drug First-in-class, orally active pan-caspase protease inhibitor Reduces activity of full family of enzymes involved in liver damage Indifferent to initial insult that causes liver disease Viral infection, alcohol, obesity, and autoimmune diseases all increase caspase activity leading to liver damage Addresses key underlying mechanisms of liver damage Caspases 2, 3, 6, 7, 8, 9 and 10 drive excessive apoptosis Caspases 1, 4 and 5 drive inflammation 4

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6 Caspase Activation Drives Two Pathways APOPTOTIC CASPASE ACTIVATION Various Insults Infections Obesity Alcohol-related conditions Autoimmune disorders INFLAMMATORY CASPASE ACTIVATION ACTIVATED CASPASES ACTIVATED CASPASES Measured as serum cck18 Excessive Apoptosis Plus Excessive Inflammation Measured as serum ALT Liver Fibrosis Cirrhosis/Failure 6

7 One Drug Addresses Both Pathways APOPTOTIC CASPASE ACTIVATION Various Insults Infections Obesity Alcohol-related conditions Autoimmune disorders INFLAMMATORY CASPASE ACTIVATION ACTIVATED CASPASES EMRICASAN ACTIVATED CASPASES Measured as serum cck18 Rapid and sustained reductions in elevated biomarkers of apoptosis and inflammation Measured as serum ALT 7

8 Apoptosis, Microvesicles and cck18 Caspase-driven apoptosis releases highly pro-inflammatory microvesicles Measured as elevated cck18 in serum by commercial laboratory test Increased inflammation escalates insult to liver Higher cck18 levels linked to greater severity of liver disease Emricasan reduces apoptosis and microvesicle production Confirmed by reduction of elevated cck18 levels Emricasan X X Hepatocytes undergoing apoptosis X David McCarthy, Gut May (5) 8

9 Sham Efficacious in Models of Liver Disease Control Emricasan Emricasan reduced hepatic injury and liver fibrosis in a model of cholestatic liver disease Emricasan inhibited apoptosis, fibrosis and inflammation in a model of NASH Control Emricasan Emricasan resolved hepatic steatosis and improved metabolic parameters in a model of NAFLD Control Emricasan 9

10 AFFLICTED POPULATION The Spectrum of Liver Disease NORMAL Various Insults INFLAMMATION NAFLD 147 Million 1 NASH 25 Million 1 NASH + Cirrhosis POLT-HCV-SVR 1.2 Million 3 47,500 2 FIBROSIS NASH + Fibrosis 8 Million 3 HCV-SVR + Cirrhosis 1.7 Million 4 AH 13 Million 5 COMPENSATED CIRRHOSIS AIH 83,000 6 CLF 774,000 7 DECOMPENSATED CIRRHOSIS ACLF Acute-on-Chronic Liver Failure AH Alcoholic Hepatitis AIH Autoimmune Hepatitis CLF Chronic Liver Failure HCV Hepatitis C Virus NAFLD Non-Alcoholic Fatty Liver Disease NASH Non-Alcoholic Steatohepatitis POLT Post Orthotopic Liver Transplant SVR Sustained Viral Response DISEASE SEVERITY HCV-RELATED LIVER TRANSPLANTATION 2,600/yr 8 Prevalence estimates are for US + Big 5 EU based on general population statistics and specific references: 1 Pascale 2010; Vernon Poordad 2014; Company-commissioned report Pascale Rajendra 2007; WHO Basra Freese 2002; Gleeson Moreau Adam 2003; OPTN 2011; ELTR ACLF 226,000 7 LIVER FAILURE 10

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12 Emricasan Clinical Experience to Date Studied in 500+ patients Six Phase 1 trials conducted in the US, EU and Asia Predominantly healthy volunteers Four randomized, placebo-controlled Phase 2 trials conducted in the US and EU Included patients with liver diseases due to a variety of causes Emphasis on HCV infection Clinically relevant results Reproducible reductions in elevated biomarkers of inflammation and apoptosis 12

13 Emricasan Reduces Key Biomarkers Phase 2b Studies Statistically significant, consistent, rapid and sustained reductions in elevated levels of ALT and cck18 Use of ALT in clinical trials: Elevation at baseline: identifies patients with liver disease Reduction in elevated levels: primary endpoint in completed Phase 2 trials Use of cck18 levels in clinical trials: Reduction in elevated levels: key biomarker in Phase 2b and planned trials 13

14 Acute-on-Chronic Liver Failure (ACLF) Rapid Deterioration of Liver Function Follows acute event in patients with underlying cirrhosis Morbidity and mortality is high In-hospital mortality rate can be greater than 50% Current intervention involves treatment of underlying cause of acute event and support for failing organs Liver transplantation may be required to improve survival and QOL NEED: Prevent catastrophic organ failure 14

15 ACLF Phase 2b Goals Understand the PK/PD in this patient population Data to support dosing in patients with a combination of hepatic and renal impairment Supplemental PK/PD studies ongoing in patients with single organ failure Provide exploratory information on efficacy Relationship between reductions in biomarkers and improvement in functional parameters and time to clinical worsening Understand the complexities of the patient population to inform Phase 3 Clinical event rate Regional variation in precipitating causes, co-morbidities and concomitant medications Challenges of conducting studies in the population Heterogeneity of population based on disease etiology 15

16 ACLF Emricasan Phase 2b 60-patient, 28-day PK study Objectives Confirm safe dose for future studies Changes in organ function (e.g., creatinine, bilirubin, INR) Changes in biomarkers (ALT, cck18, Caspase 3/7, IL-18) Time to clinical worsening (TTCW) Screening Phase Screen R A N D O M I Z A T I O N Treatment Phase Emricasan: 5 mg BID N=15 Emricasan: 25 mg BID N=15 Emricasan: 50 mg BID N=15 Placebo BID N=15 Follow-Up Phase Follow- Up Trial initiated September 2013 Day 1 M1 / Day 28 M2 M3 & M6 Phase 2b trial results expected 2H14 16

17 Chronic Liver Failure (CLF) Late-stage Liver Disease Rationale for Chronic Liver Failure/chronic cirrhosis study Include patients with late-stage liver failure Different etiologies PK/PD data from ongoing studies should allow inclusion of patients with a broad range of organ dysfunction Potentially for both listed and not suitable for listing for transplant Could potentially use results to support ACLF MAA/NDA NEED: Stabilize/improve organ function Phase 2b trial expected to initiate 2H14 17

18 Post Orthotopic Liver Transplant (POLT) Patients Reinfected with HCV, Then Cleared with HCV Antivirals Well characterized and closely monitored patient population New antivirals increase HCV sustained viral response rate in POLT patients Environment remains pro-fibrogenic and pro-inflammatory Existing collagen deposition (scar) Abnormal extracellular matrix (ECM) Steatosis / NASH Emricasan actively reduces inflammation Expected to accelerate resolution of collagen matrix NEED: Prevent or delay progression of fibrosis to cirrhosis TGF-β TNF-α Inflammatory cytokines } Stellate cell Matrix growth Hepatocyte Cell death 18

19 POLT-HCV-SVR Phase 2b Trial 60-patient, 2-year double-blind sponsor-open dosing study Primary objective To assess effect on fibrosis using the Ishak Fibrosis Score Secondary objectives To assess effect on necroinflammatory sub-score To assess effects on biomarkers of cell death and inflammation biomarkers To assess safety and tolerability Screening Phase Screen R A N D O M I Z A T I O N Treatment Phase Emricasan: 25 mg BID N=40 Placebo BID N=20 Screening Bx 1 Yr Bx 2 Yr Bx Wk -6 to Day 0 Day M6 - - M M24 Follow-Up Phase Follow- Up 4 Wk The sponsor-open design may allow interim data analyses and periodic disclosures on trial progress 19

20 Nonalcoholic Steatohepatitis (NASH) An Emerging Large Market Opportunity Preclinical studies suggest therapeutic potential for emricasan in NASH Compelling preclinical data in models of NASH and NAFLD Clinical trial tracking fibrosis in NASH patients is currently a challenge Fibrosis progression rate not well characterized Data from longitudinal patient databases not yet available Some insight may come from ongoing studies NASH regulatory pathway still being defined NEED: Prevent or delay progression of fibrosis to cirrhosis 20

21 Nonalcoholic Steatohepatitis (NASH) Patient Populations and Measures of Activity NAFLD and NASH Biomarkers (i.e., ALT, cck18), metabolic panels (i.e., HOMA), FibroScan, NAFLD Activity Score (NAS) NASH with fibrosis All of the above plus: Fibrosis component of NAS, Ishak fibrosis score, morphometric quantitative collagen NASH with compensated cirrhosis All of the above plus: Hepatic Venous Pressure Gradient (HVPG) NASH with decompensated cirrhosis All of the above plus: Liver function tests (i.e., bilirubin, INR) Clinical outcomes 21

22 Nonalcoholic Steatohepatitis (NASH) Emricasan Phase 2 40 patient study Objectives Confirm safety and tolerability in target population Changes in biomarkers (ALT, AST, cck-18, Caspase 3/7, HOMA-IR) Position emricasan as fast follower once Phase 3 endpoint is defined Screening Phase Screen R A N D O M I Z A T I O N Treatment Phase Emricasan: 25 mg BID N=20 Placebo BID N=20 Follow-Up Phase Follow- Up Day 1 M1 / Day 28 M2 Trial initiated March 2014 Phase 2 trial results expected 2H14 22

23 Emricasan Development Target Population Preclinical Phase 1 Phase 2 Phase 3 Next Milestone Acute-on-Chronic Liver Failure (ACLF) Phase 2b trial results expected 2H14 Chronic Liver Failure (CLF) Phase 2 trial expected to initiate 2H14 Post Liver Transplant HCV Clearance with Unresolved Fibrosis (POLT-HCV-SVR) Phase 2b trial initial interim data expected 1H15 Nonalcoholic Steatohepatitis (NASH) Phase 2 trial results expected 2H14 Also supporting pilot clinical study funded by National Institute on Alcohol Abuse and Alcoholism in patients with severe alcoholic hepatitis 23

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25 AFFLICTED POPULATION The Spectrum of Liver Disease NORMAL Various Insults INFLAMMATION NAFLD 147 Million 1 NASH 25 Million 1 NASH + Cirrhosis POLT-HCV-SVR 1.2 Million 3 47,500 2 FIBROSIS NASH + Fibrosis 8 Million 3 HCV-SVR + Cirrhosis 1.7 Million 4 AH 13 Million 5 COMPENSATED CIRRHOSIS AIH 83,000 6 CLF 774,000 7 Current Emricasan Trials DECOMPENSATED CIRRHOSIS ACLF Acute-on-Chronic Liver Failure AH Alcoholic Hepatitis AIH Autoimmune Hepatitis CLF Chronic Liver Failure HCV Hepatitis C Virus NAFLD Non-Alcoholic Fatty Liver Disease NASH Non-Alcoholic Steatohepatitis POLT Post Orthotopic Liver Transplant SVR Sustained Viral Response DISEASE SEVERITY HCV-RELATED LIVER TRANSPLANTATION 2,600/yr 8 Prevalence estimates are for US + Big 5 EU based on general population statistics and specific references: 1 Pascale 2010; Vernon Poordad 2014; Company-commissioned report Pascale Rajendra 2007; WHO Basra Freese 2002; Gleeson Moreau Adam 2003; OPTN 2011; ELTR ACLF 226,000 7 LIVER FAILURE 25

26 Unmet Need in Chronic Liver Disease Prevalence Estimates in US + Big 5 EU Acute-on-Chronic Liver Failure (ACLF) Post Liver Transplant HCV Clearance with Unresolved Fibrosis (POLT-HCV-SVR) Autoimmune Hepatitis Chronic Liver Failure (CLF) HCV-SVR + Cirrhosis Non-Alcoholic Steatohepatitis (NASH) Non-Alcoholic Fatty Liver Disease (NAFLD) Alcoholic Hepatitis <½ MILLION PATIENTS ~ 35 MILLION PATIENTS ~ 160 MILLION PATIENTS Overall, chronic liver diseases cause ~32,000 deaths per year in the US 1 and ~170,000 deaths per year in the EU 2 1 U.S. Centers for Disease Control and Prevention 2 World Health Organization 26

27 Value Proposition NASDAQ:CNAT San Diego, CA Emricasan is first-in-class, oral pan-caspase protease inhibitor Caspases play central role in underlying mechanism of disease in liver Clinical programs in areas of high unmet medical need, attractive market potential Near-term milestones Potential to treat broad spectrum of liver diseases Conatus has extensive experience in caspase inhibition Successful IPO; well-funded to near-term milestones 27

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