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NASDAQ:CNAT

Forward-looking Statements

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2 Portal Hypertension September 24, 2015

Cirrhosis of the Liver

Cirrhosis is scarring of the liver in response to a variety of insults (viral infection, alcohol, obesity, etc.) There are no approved drugs that prevent progression to cirrhosis if the insult persists Liver cirrhosis kills 32,000 Americans each year

The only “cure” is a transplant

Portal hypertension is a severe and almost unavoidable complication of cirrhosis

Responsible for the main clinical consequences including variceal bleeding, decreased liver function, ascites, and encephalopathy

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As Cirrhosis Progresses, Symptoms Worsen

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Spectrum of Liver Disease

Portal hypertension

Emricasan:

A drug candidate with potential to achieve long-term resolution

• f fibrosis and cirrhosis

Latest trial results:

Demonstrated emricasan’s ability to induce a rapid and clinically meaningful reduction of severe portal hypertension Set the stage for longer term, mixed etiology, Phase 2b studies Support the rationale for using HVPG as a registration endpoint

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Key Advances for Emricasan

Based on results from exploratory Phase 2 Portal Hypertension trial

September 24, 2015 Portal Hypertension

Open-label, multicenter (9 U.S. sites) pilot study 23 patients enrolled (22 evaluable)

Early stage cirrhosis patients Portal hypertension confirmed by HVPG (>5 mmHg) at baseline Mixed etiology of liver disease – most NASH or HCV (active or SVR)

28 day dosing at 25 mg emricasan twice daily Change from baseline in HVPG and cCK18 as primary endpoints

Two specified subgroups

Patients with baseline HVPG <12 mmHg Patients with baseline HVPG ≥12 mmHg

All sites trained on standardized HVPG measurement procedure All HVPG tracings evaluated by single independent expert reader Top-line data announced September 2015

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Exploratory Phase 2 Portal Hypertension Trial

Initiated September 2014

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Patient Group Mean Baseline HVPG Mean Change in HVPG HVPG ≥12 mmHg (N=12) 20.6 mmHg ‒ 3.7 mmHg (p<0.003) HVPG <12 mmHg (N=10) 8.1 mmHg + 1.9 mmHg (p=0.12) Total (N=22) 15.2 mmHg ‒ 1.1 mmHg (p=0.26)

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Phase 2 Portal Hypertension Pilot Study Top-line Results

Rapid, statistically significant and clinically meaningful reductions in severe portal pressure

September 24, 2015 Portal Hypertension

In severe PH patient group with baseline HVPG ≥12 mmHg:

8 of 12 achieved ≥10% reduction in HVPG 4 of 12 achieved ≥20% reduction in HVPG 2 of 12 achieved HVPG reductions to <12 mmHg Reducing HVPG by ≥10% or ≥20%, or to <12 mmHg is strongly associated with clinical benefit

In total evaluable patient population

cCK18 reduction was statistically significant (p<0.03)

Hepatic vein Sinusoid Portal vein Normal Liver Splenic vein Coronary vein

Normal Liver – Minimal Resistance to Blood Flow

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Liver functions:

• Process nutrients
• Produce essential substances
• Remove toxins

Gut vasculature:

Drains blood containing materials to be processed by the liver from the GI

• rgans into the portal vein

Total blood flow into the liver:

Averages about 1350ml/min or 27% of resting cardiac output

Cirrhotic Liver

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Varices Splenomegaly Hepatic vein Sinusoid Portal vein Splenic vein Coronary vein Cirrhotic Liver

Accumulating damage in the liver leads to Portal Hypertension (increased resistance to blood flow coming from the portal vein) and damage to the vessels that feed blood to the liver

Portal Hypertension

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↑ Resistance ↑ Flow GI vasodilation Hepatic vasoconstriction

Both resistance to blood flow in the cirrhotic liver and vasodilation in GI blood vessels outside the liver lead to increased portal pressure

Hepatic Venous Pressure Gradient (HVPG)

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HVPG is the measurement of the difference in pressure inside a hepatic vein with a balloon catheter inflated

• vs. deflated. This measurement

provides a good estimate of the elevation in pressure inside the portal vein vs. the pressure in unrestricted blood vessels. HVPG has been identified by the FDA as a validated, objective measure that may be acceptable as a surrogate endpoint for clinical trials of patients with liver cirrhosis.

Bosch, J et al. Nat Rev Gastroenterol Hepatol. 2009 Oct;6(10):573-82.

Portal Hypertension and Cirrhosis

Portal hypertension

HVPG ≥10 mm Hg defines clinically significant portal hypertension. Monitoring is indicated. HVPG ≥12 mm Hg defines severe portal hypertension with increased risk of blood vessel rupture. Treatment is indicated.

Causes

Fibrosis, restriction of blood flow (vasoconstriction) within the liver Vasodilation in the blood vessels feeding the liver caused in part by apoptotic microparticles derived from dying hepatocytes

Treatment

No current treatment addresses the vasoconstriction in the liver Beta blockers lower portal pressure through a systemic effect outside the liver to reduce blood flow into the liver

Associated with increased cardiovascular risks

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First-in-class, orally active, pan-caspase inhibitor

Suppresses apoptosis and inflammation Addresses all etiologies of cirrhosis

Pharmacodynamic effects

Inhibits the activation of stellate cells and decreases fibrosis Reduces apoptosis of hepatocytes which decreases the formation of vasoactive microparticles

Safe and well tolerated in fifteen clinical trials involving over 600 subjects

No dose-limiting toxicities or drug-related serious adverse events

Initial registration strategy to focus on cirrhosis

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Emricasan

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A novel treatment for cirrhosis

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Emricasan Addresses Two Main Drivers of Liver Damage Common Across Multiple Etiologies

Portal Hypertension

Various Insults

• Infections: HCV / HBV
• Obesity: NASH / NAFLD
• Alcohol-related conditions
• Autoimmune disorders

EMRICASAN

Excessive Apoptosis Plus Excessive Inflammation Rapid and sustained reductions in elevated biomarkers of apoptosis and inflammation

September 24, 2015

APOPTOTIC CASPASE ACTIVATION

ACTIVATED CASPASES 2 | 3 | 6 | 7 | 8 | 9 | 10

INFLAMMATORY CASPASE ACTIVATION

ACTIVATED CASPASES 1 | 4 | 5 Key biomarkers: ALT flCK18 (M65) Key biomarkers: Caspase 3/7 cCK18 (M30)

Apoptosis results in the release of pro-inflammatory, vasoactive microparticles

cCK18 is embedded in the microparticles

Increased inflammation exacerbates insult to liver and increases apoptosis

Greater severity of liver disease correlates with higher cCK18 levels

Emricasan reduces apoptosis, microparticle production, and related inflammation

Reductions in cCK18 levels confirm emricasan’s on target activity

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David McCarthy, Gut May 2008 57 (5)

Hepatocytes undergoing apoptosis Emricasan

X X X

cCK18 is a direct measure of microparticles

cCK18: A Measure of Microparticles

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Microparticles: Significance in Liver Disease

Important modulators of cell-to-cell communication in disease

Often associated with severity of disease stage

Biologically active substances are carried both on and in these particles

Contents and particle surface mirror the parent cell

Actively engulfed by Kupffer cells, stellate cells, endothelial cells

Excessive microparticle production overwhelms engulfment capacity

Caspase inhibition reduces the production of microparticles

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Barteneva, N et al. Circulating microparticles: square the circle. BMC Cell Biology 2013; 14:23

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Activated hepatic stellate cells constrict the capillaries in the liver of patients with cirrhosis, and restrict blood flow (in addition to the physical presence of collagen) Stellate cell activation is reversible Antifibrogenic activity through the reduced production of collagen – later phase response

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Emricasan Effects on Liver Vasculature

Emricasan inhibits the activation of hepatic stellate cells1

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1Canbay, A et al. Hepatology 2003, 38:1188.

Normal Liver Balanced vasoconstrictors and dilators Cirrhotic Liver Imbalance in vasoconstrictors and dilators

Iwakiri, Y et al. J of Hepatology 2014, 61:912.

↑ Resistance ↑ Flow

Emricasan May Have Multiple Opportunities to Benefit the Cirrhotic Liver

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• 1. Reduce vasodilation

and reduce inflow – in the short term

• 2. Reduce resistance and

improve liver function – in the medium term

• 3. Reduce collagen and

improve architecture – in the long term

↓ Flow GI vasodilation Hepatic vasoconstriction ↓ Resistance

Emricasan produced clinically meaningful and statistically significant reductions in HVPG in patients with liver cirrhosis dosed for 4 weeks

Significant reduction in HVPG in the severe patient population Significant reduction in cCK18 in the total evaluable patient population

Both NASH and HCV patients responded well Emricasan was safe and well tolerated consistent with prior trials The acute vasoactive effect of emricasan is unique and may greatly benefit patients with cirrhosis Sets the stage for longer term, mixed etiology, Phase 2b studies Supports the rationale for using HVPG as a registration endpoint

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Summary and Conclusions

Detailed results to be presented in future scientific forum

September 24, 2015 Portal Hypertension

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