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

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4 Transformational Collaboration for Conatus Subject to Novartis License Option Exercise A Conatus and Novartis collaboration would: Cover emricasan single-agent indications and future emricasan combination products Assign full responsibility to Novartis for emricasan Phase 3 and all combination product development and commercialization Provide an option to co-commercialize in the United States with shared costs and revenues in lieu of US royalties Allow Conatus to apply its expertise to develop other caspase inhibitors as well as develop some retained preclinical compounds Provide near-term capital and Phase 2b cost-sharing sufficient through completion of Conatus-led Phase 2b development Fully fund ongoing operations through

5 Agreement Overview Subject to Novartis License Option Exercise Validates Conatus approach with a small-molecule pan-caspase inhibitor Conatus to lead Phase 2b development of emricasan as a single agent treatment for NASH cirrhosis in both compensated and decompensated patients and in NASH fibrosis Novartis to lead Phase 3 development of emricasan as a single agent and development of oral combination products for the treatment of NASH FXR agonists from Novartis designed to reduce the severity of the insult (steatosis and fibrosis) Pan-caspase inhibitor from Conatus designed to reduce the severity of the consequences of the insult (excessive cell death and inflammation) Conatus to provide collaborative expertise 5

6 Agreement Key Financial Terms Near-term $50 million upfront $7 million if Novartis exercises license option Up to $15 million in a convertible note Long-term Up to $650 million in development, regulatory and commercial milestones Conatus to lead Phase 2b emricasan development with 50% reimbursement of costs after license option exercise Novartis to assume full responsibility and costs for Phase 3 emricasan and all combination product development Conatus eligible to receive tiered double digit royalties on emricasan single agent sales and tiered single to double digit royalties on sales of combination products containing emricasan 6

7 Collaborative Synergies Strengths Novartis brings to collaboration Substantial financial, research, developmental and commercial resources Expertise in liver portfolio and industry-leading pipeline Proven record of success in drug development Strengths Conatus brings to collaboration Comprehensive expertise with emricasan Deep understanding of caspase inhibition and its role in diseases Relevant experience in liver disease Agile and purpose-driven development team Parties work together through Joint Steering Committee 7

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9 December 20, 2016 Collaboration and License Agreement 9

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11 Emricasan: Potential to Modify Disease Outcome First-in-class, orally active, pan-caspase inhibitor Suppresses apoptosis and inflammation Addresses all etiologies of cirrhosis Efficacy Safety Potent mechanism with multiple disease intervention points Demonstrated activity across broad spectrum of chronic liver disease Clinically meaningful reductions in validated surrogate cirrhosis endpoints Rapidly improves both portal hypertension and key measures of liver function 650+ subjects exposed (450+ with liver disease) across 16 clinical trials Up to 50mg BID for 12 weeks currently testing 25mg BID for 2 years Serious adverse event and adverse event profiles similar in placebo and emricasan treated patients 11

12 Caspase Activation Drives Two Key Pathways APOPTOTIC CASPASE ACTIVATION ACTIVATED CASPASES Various Insults Infections: HCV / HBV Obesity: NASH / NAFLD Alcohol-related conditions Autoimmune disorders INFLAMMATORY CASPASE ACTIVATION ACTIVATED CASPASES Excessive Apoptosis Plus Excessive Inflammation Liver Fibrosis Cirrhosis/Failure 12

13 Interrupting the Pathways May Improve Outcome APOPTOTIC CASPASE ACTIVATION ACTIVATED CASPASES Key biomarkers: Caspase 3/7 cck18 (M30) Various Insults Infections: HCV / HBV Obesity: NASH / NAFLD Alcohol-related conditions Autoimmune disorders EMRICASAN Rapid Excessive and sustained Apoptosis reductions Plus in elevated Excessive biomarkers Inflammation of apoptosis and inflammation INFLAMMATORY CASPASE ACTIVATION ACTIVATED CASPASES Key biomarkers: ALT flck18 (M65) 13

14 Activated Biomarkers: Measure of Microparticles Apoptosis results in the release of pro-inflammatory, vasoactive microparticles Activated Caspase 3/7, cck18, IL-1β and other biomarkers are embedded Increased inflammation exacerbates insult to liver and increases apoptosis Greater severity of liver disease correlates with higher biomarker levels Emricasan reduces apoptosis, microparticle production, and related inflammation Reductions in biomarker levels confirm emricasan s on-target activity Emricasan X X David McCarthy, Gut May (5) Hepatocytes undergoing apoptosis X Biomarkers are direct measures of circulating microparticles 14

15 Circulating microparticles carry apoptosis markers CK-18 and Caspase-3/7 which are reduced by treatment with emricasan in subjects with cirrhosis. Akiko Eguchi 1, Davide Povero 1, Hirokazu Yamashita 1, Casey D Johnson 1, Patricia C Contreras 2, Alfred P Spada 2, Ariel E. Feldstein 1 1 Department of Pediatrics, University of California San Diego, La Jolla, USA, 2 Conatus Pharmaceuticals Inc., San Diego, USA AASLD Poster #2098 CONCLUSIONS This study shows that subjects with severe hepatic injury have elevated levels of MPs in the bloodstream and that MPs carry CK-18 and Caspase 3/7. Additionally, treatment with pancaspase inhibitor emricasan, reduced to some extent the level of MP-encapsulated CK-18 and Caspase 3/7. 15

16 Emricasan s Mechanism of Action Addresses Both Intrahepatic and Extrahepatic Disease Effects Extrahepatic effects Increased cardiac output GI vasodilation Intrahepatic effects Impaired hepatocyte function Synthetic function - decreased clotting factors - decreased albumin Excretory function - increased total bilirubin Increased MELD and Child-Pugh scores Portal hypertension Variceal bleeding Ascites Encephalopathy Increased HVPG 16

17 The pan caspase inhibitor emricasan improves the hepatic microcirculatory dysfunction of CCl 4 -cirrhotic rats leading to portal hypertension amelioration and fibrosis reduction Jordi Gracia-Sancho 1, Patricia C Contreras 2, Sergi Vila 1, Héctor García-Calderó 1, Alfred Spada 2, Jaime Bosch 1 1- Barcelona Hepatic Hemodynamic Lab. IDIBAPS Biomedical Research Institute & CIBEREHD. Barcelona, Spain. 2- Conatus Pharmaceuticals, San Diego, CA AASLD Poster #

18 Regardless of Etiology, Liver Disease Follows the Same Pathway of Progression NORMAL INFLAMMATION Various Insults FIBROSIS COMPENSATED CIRRHOSIS AFFLICTED POPULATION LIVER TRANSPLANTATION DECOMPENSATED CIRRHOSIS LIVER FAILURE DISEASE SEVERITY 18

19 Emricasan Clinical Trials Across the Spectrum of Liver Disease Various Insults NAFLD/NASH Severe Renal Impairment ENCORE-NF POLT-HCV-SVR AFFLICTED POPULATION Planned Confirmatory Trials Ongoing Efficacy Trials Completed POC Trials Completed Biomarker Trials ACLF Acute on Chronic Liver Failure HCV Hepatitis C Virus LC Liver Cirrhosis LF Liver Function NAFLD Non-Alcoholic Fatty Liver Disease NASH Non-Alcoholic Steatohepatitis NF NASH Fibrosis PH Portal Hypertension POLT Post Orthotopic Liver Transplant SVR Sustained Viral Response DISEASE SEVERITY Portal Hypertension ENCORE-PH Liver Cirrhosis ENCORE-LF Hepatic Impairment ACLF 19

20 Emricasan Has Unique Potential to Improve Both Portal Hypertension and Liver Function in Patients with Cirrhosis Clinical trial results in support emricasan development as a treatment for cirrhosis Organ impairment PK/PD clinical trials Permits dosing to efficacy in patients with mild, moderate, or severe liver function impairment NAFLD/NASH Phase 2 clinical trial Confirmed that emricasan is as effective in NAFLD/NASH patients as previously shown in patients with other (i.e. HCV) etiologies of liver disease Portal Hypertension Phase 2 clinical trial Clinically meaningful reductions in a validated surrogate endpoint of portal hypertension (HVPG) in patients with cirrhosis and severe portal hypertension after only one month of dosing with emricasan Liver Cirrhosis Phase 2 clinical trial Clinically meaningful reductions in validated surrogate endpoints of liver function (MELD and Child-Pugh) in high-meld and NASH subgroups of after only three months of treatment with emricasan with continued directional improvements after six months of treatment 20

21 Emricasan (IDN-6556) Orally for 6 Months in Patients with Cirrhosis and Elevated MELD Score Improves Liver Function Catherine Frenette 1, Giuseppe Morelli 2, Mitchell Shiffman 3, R. Todd Frederick 4, Raymond A. Rubin 5, Michael Fallon 6, James Robinson 7, Mason Yamashita 7, Alfred P. Spada 7, Jean L. Chan 7, David T. Hagerty Scripps Clinic, La Jolla, CA, 2 - University of Florida, Gainesville, FL, 3 - Liver Institute of Virginia, Richmond, VA, 4 - California Pacific Medical Center, San Francisco, CA, 5 - Piedmont Transplant Institute, Atlanta, GA, 6 - University of Texas Health Science Center, Houston, TX, 7 - Conatus Pharmaceuticals Inc., San Diego, CA 21

22 Emricasan (IDN-6556) Orally for 6 Months in Patients with Non-alcoholic Steatohepatitis (NASH) Cirrhosis Decreases the Progression of MELD Score and Improves Liver Function Catherine Frenette 1, Giuseppe Morelli 2, Mitchell Shiffman 3, R. Todd Frederick 4, Raymond A. Rubin 5, Michael Fallon 6, James Robinson 7, Mason Yamashita 7, Alfred P. Spada 7, Jean L. Chan 7, David T. Hagerty Scripps Clinic, La Jolla, CA, 2 - University of Florida, Gainesville, FL, 3 - Liver Institute of Virginia, Richmond, VA, 4 - California Pacific Medical Center, San Francisco, CA, 5 - Piedmont Transplant Institute, Atlanta, GA, 6 - University of Texas Health Science Center, Houston, TX, 7 - Conatus Pharmaceuticals Inc., San Diego, CA 22

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24 Nonalcoholic Steatohepatitis (NASH) A progressive disease associated with hepatocyte injury, inflammation and scarring Normal Estimated US + EU5 prevalence NAFLD 125 million NASH Fibrosis 15 million NASH Cirrhosis 0.9 million Graphic from Cohen JC, et al. Science Prevalence estimates from company commissioned report

25 There Are No Approved Treatments for NASH Strongly linked to obesity, Type 2 diabetes, cardiovascular disease and metabolic syndrome Slowly Normal progressive disease typically asymptomatic until cirrhosis Increasingly linked to mortality as disease progresses NASH projected as leading cause of liver transplants by 2020 NAFLD NASH with mild fibrosis (F1) may benefit from treating underlying pathology Hyperlipidemia, diabetes, obesity, lifestyle modifications NASH Fibrosis Largely undiagnosed NASH with moderate/severe fibrosis (F2/F3) may benefit from treatment NASH Cirrhosis NASH with cirrhosis (F4) are highest medical need population 25

26 Medical Need, Market Opportunity, and Efficiency of Development Intersect at Cirrhosis Decompensated Cirrhosis Liver Failure Other Companies Cirrhosis Approved drugs address insults, symptoms, or complications of liver disease Relative Unmet Need Fibrosis Asymptomatic Symptomatic Medical need shifts from symptoms to clinical outcomes with cirrhosis Opportunities to use validated surrogate endpoints (i.e. HVPG) for compensated cirrhosis patients coupled with the potential to use clinical endpoints in decompensated cirrhosis patients allow for an efficient drug development strategy Disease Severity Sources: Clinicaltrials.gov; company websites Relative Disease Prevalence Size (directional, not to scale) 26

27 NASH Fibrosis / Cirrhosis Competition Emricasan s mechanism of action is powerful enough to address more advanced disease Emricasan is the only oral drug in development for NASH cirrhosis Key to market share in NASH fibrosis may be in combination therapies Novartis FXR agonist/conatus caspase inhibitor potentially ideal oral combination as a treatment for NASH fibrosis ~20 Drugs for NASH Fibrosis in Development 2 Drugs for NASH Cirrhosis in Development 27

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29 Building a Portfolio of Indications with NASH Cirrhosis Targeted for Initial Registration EmricasaN, a Caspase InhibitOR, for Evaluation (ENCORE) Phase 2b Trials ENCORE-LF Target Populations Decompensated NASH cirrhosis N = TBD Treatment Durations 48 weeks ENCORE-PH NASH cirrhosis +CSPH ~ weeks HVPG Key Endpoints Composite clinical endpoint ENCORE-NF NASH fibrosis ~ weeks NASH CRN Histology POLT-HCV-SVR Post-transplant HCV- SVR with fibrosis or cirrhosis ~60 2 years Ishak Fibrosis Score Conatus continues to drive Phase 2b development through completion CSPH: Clinically Significant Portal Hypertension HVPG: Hepatic Venous Pressure Gradient CRN: Clinical Research Network POLT: Post Orthotopic Liver Transplant HCV: Hepatitis C Virus SVR: Sustained Viral Response 29

30 Emricasan: Current Clinical Milestones Goals: Define dosing, broaden safety database, show activity against multiple endpoints Target Population Preclinical Phase 1 Phase 2 Importance Next Milestone ENCORE-LF (NASH Cirrhosis) Composite clinical endpoint Phase 2b initiation expected 1H17 ENCORE-PH (NASH Cirrhosis) Validated surrogate endpoint Phase 2b top-line data expected 2018 ENCORE-NF (NASH Fibrosis) Relevant histology endpoint Phase 2 top-line data expected 2018 Post Liver Transplant HCV Clearance with Unresolved Fibrosis/Cirrhosis (POLT-HCV-SVR) Established histology endpoint Phase 2b top-line data expected 1H18 Four clinical trials, 2 in cirrhosis and 2 in fibrosis, using endpoints tailored to each patient population, offer multiple opportunities for successful readouts beginning in

31 Transformational Collaboration for Conatus Subject to Novartis License Option Exercise A Conatus and Novartis collaboration would: Cover emricasan single-agent indications and future emricasan combination products Assign full responsibility to Novartis for emricasan Phase 3 and all combination product development and commercialization Provide an option to co-commercialize in the United States with shared costs and revenues in lieu of US royalties Allow Conatus to apply its expertise to develop other caspase inhibitors as well as develop some retained preclinical compounds Provide near-term capital and Phase 2b cost-sharing sufficient through completion of Conatus-led Phase 2b development Fully fund ongoing operations through

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