0800 W 6 Conatus Pharma - Jefferies Group Pha… · Eight Phase 1 trials conducted in the US, EU...

NASDAQ:CNAT

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 Jefferies Global Healthcare Conference June 2015

Why NASH Cirrhosis? Why Now?

Liver disease patients typically have no symptoms until they progress to cirrhosis

There are no approved drugs that prevent progression to cirrhosis

Liver cirrhosis kills 32,000 Americans each year The only “cure” is a transplant

By 2020, the leading cause of liver transplants is expected to be NASH

3 June 2015 Jefferies Global Healthcare Conference

Why Conatus? Why Now?


First-in-class, small molecule, orally active, pan-caspase protease inhibitor Mechanism of action relevant regardless of etiology or disease severity Suppresses apoptosis and inflammation: two key drivers of liver disease

Activity confirmed by mechanism-specific biomarker cCK18 Baseline levels increase with disease severity Dose-related, rapid and sustained reductions even in severely ill patients

Safe and well tolerated in fourteen clinical trials involving over 550 subjects No dose-limiting toxicities or drug-related serious adverse events Important clinical trial readouts expected over next six months

Initial registration strategy to focus on NASH cirrhosis High medical need with large and growing patient population No current disease-modifying treatments Potential to access accelerated approval pathways Potential for registration strategy to include NASH fibrosis

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Lead Compound: Emricasan (IDN-6556)

Potential to address the full spectrum of liver disease with initial focus on NASH cirrhosis

June 2015 Jefferies Global Healthcare Conference

Key Drivers of Focus on NASH Cirrhosis

Potent mechanism with demonstrated activity across the full spectrum of liver disease Explicit regulatory pathway and high unmet need in cirrhosis Stable and compliant patient population in NASH


Liver Fibrosis Cirrhosis/Failure

Caspase Activation Drives Two Key Pathways

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

Jefferies Global Healthcare Conference 8 June 2015

Excessive Apoptosis Excessive Apoptosis Plus Excessive Inflammation

APOPTOTIC CASPASE ACTIVATION

ACTIVATED CASPASES

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

INFLAMMATORY CASPASE ACTIVATION

ACTIVATED CASPASES

1 | 4 | 5

Liver Fibrosis Cirrhosis/Failure

9

Interrupting the Pathways May Improve Outcome

Jefferies Global Healthcare Conference

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

June 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 highly pro-inflammatory 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 inflammatory microparticles

cCK18: A Biologically Plausible Marker of Improvement that is Objective, Measurable and Sensitive to Change*

June 2015

*Sanyal, AJ, et al. Hepatology 2015;61:1392-1405; doi: 10.1002/hep.27678

Eight Phase 1 trials conducted in the US, EU and Asia Healthy volunteers and patients with organ impairment Confirmed dosing for clinical studies

Six randomized, placebo-controlled Phase 2 trials conducted in the US and EU

Included patients with liver diseases due to a variety of causes Well tolerated, no drug-related serious adverse events

Biomarker results suggest disease-modifying potential

Levels of mechanism-specific biomarkers increase with disease severity Reproducible reductions in these biomarkers are achieved in patients across the full spectrum of liver disease

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Emricasan Clinical Experience to Date

Studied in over 550 patients


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Three Dosing Trials in Organ-impaired Patients

Established appropriate dosing in patients with varying degrees of liver impairment


● Moderate Hepatic Impairment

● Severe Hepatic Impairment

● Mild Hepatic Impairment

● Severe Hepatic Impairment + Acute Decompensation

● No Hepatic Impairment

DECOMPENSATED CIRRHOSIS

COMPENSATED CIRRHOSIS

LIVER FAILURE

ACLF Trial

Severe Renal Impairment Trial

Hepatic Impairment Trial

NORMAL

PK/PD data in five distinct patient populations has been evaluated in aggregate to inform dosing for future trials

Baseline biomarker data confirm MOA targeted by emricasan is highly engaged

Conclusions Safety

No dose-limiting toxicities or drug-related SAEs Drug Activity

Confirmed by reduction in elevated cCK18 levels Confirmed across all liver disease stages tested, even ACLF

Drug Exposure Systemic drug levels increased with severity of hepatic impairment Appropriate dosing confirmed across spectrum of hepatic impairment

38 patients with NAFLD/NASH and persistently elevated ALT 28-day double-blind, placebo-controlled Objectives

Confirm safety, dosing, and tolerability in target population

Efficacy variables - primary Change from Baseline in ALT

Efficacy variables - secondary Change from Baseline in cCK18, AST, caspase 3/7, flCK18 Change from Baseline in HOMA-IR

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NAFLD/NASH Phase 2 Trial

Understanding dosing in patients with different etiologies


Top-line results announced 1Q15 Detailed results presented at EASL in April

Screening Phase Treatment Phase

Emricasan: 25 mg BID N=19

Placebo BID N=19

Follow-Up Phase

Follow-Up

Screen

RANDOMIZATION Day 1 M1 / Day 28 M2

Met primary endpoint Statistically significant (p<0.05) reduction in ALT compared to placebo control ALT reduction of ~39% in treatment arm vs reduction of ~14% in placebo arm

Key secondary serum biomarkers – cCK18, AST, caspase 3/7, flCK18 Elevations at baseline confirm engagement of apoptosis and inflammation Statistically significant reductions from baseline confirm drug activity cCK18 reduction of ~30% in treatment arm vs increase of ~4% in placebo arm

Emricasan was safe and well tolerated No dose-limiting toxicities or drug-related serious adverse events No adverse effects on lipid levels or insulin sensitivity

Conclusions Confirmed that optimal dose of emricasan is consistent across etiologies Demonstrates that the mechanism is relevant in NASH Opened the door for more advanced studies in NASH

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NAFLD/NASH Phase 2 Trial Results

Top-line results in March 2015; detailed results at EASL Annual Meeting in April 2015


Comments on the Model for End-Stage Liver Disease (MELD) Objective measure, validated MELD score >10 linked to negative liver-related clinical outcome 2 point change in MELD score or lack of progression to MELD score of 15 as potential surrogate endpoints

Comments on the Child-Pugh-Turcotte (CPT) score Objective-subjective measure, validated 2 point change in CPT score or lack of progression from CPT-A to CPT-B potential surrogate endpoints

Comments on Hepatic Venus Pressure Gradient (HVPG) Objective measure, validated HVPG >10 mm Hg linked to negative liver-related clinical outcome Lowering to or lack of progression to HVPG >10 mm Hg potential surrogate endpoints

Comments on cCK18 utility Objective measure, sensitive to change Levels correspond to improvement in liver histology in NASH

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Manuscript from AASLD/FDA Joint Workshop*

Published online December 2014


*Sanyal, AJ, et al. Hepatology 2015;61:1392-1405; doi: 10.1002/hep.27678

Ongoing Phase 2 Portal Hypertension (PH) clinical trial ~20 patients, open-label pilot study

Early stage cirrhosis in patients with evidence of portal hypertension; mixed etiology of liver disease Most subjects HVPG baseline value expected to be >10 mm Hg Change in HVPG and cCK18 as endpoints One month dosing at 25 mg emricasan twice daily Top-line data expected 3Q15

Ongoing Phase 2 Liver Cirrhosis (LC) clinical trial ~80 patients, double-blind, placebo-controlled 1st phase + open-label 2nd phase

Cirrhosis with MELD score at entry from 11-18; mixed etiology of liver disease Changes in MELD score, CPT score and cCK18 as endpoints Three month dosing at 25 mg emricasan twice daily First stage top-line data expected 4Q15

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Clinical Development in Cirrhosis On Target

Trials initiated September 2014


Feedback on proposed registration trial patient populations and methods of measuring and analyzing validated surrogate endpoints of MELD, CPT, and HVPG in patients with NASH cirrhosis

Design details for registration trials to be finalized based on results from two ongoing cirrhosis trials and additional feedback from regulatory agencies

Evaluating opportunity to include a clinical trial in patients with NASH fibrosis as a component of overall registration strategy

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Regulatory Clarity on Initial Registration Pathway

Met with FDA in May 2015


Fibrosis Compensated Cirrhosis

Decompensated Cirrhosis Transplant

U.S. Patients (Diagnosed) 1,617K 1,077K 230K 6.5K

EU5 Patients (Diagnosed) 628K 617K 191K 5.3K

Cost per Patient (U.S.) <$5K $22K $66K $600K

Fibrosis Compensated Cirrhosis

Decompensated Cirrhosis Transplant

U.S. Patients (Diagnosed) 1,617K 1,077K 230K 6.5K

EU5 Patients (Diagnosed) 628K 617K 191K 5.3K

Cost per Patient (U.S.) <$5K $22K $66K $600K

As Liver Disease Progresses to Cirrhosis, Symptoms and Healthcare Costs Increase


Sources: P Byass 2014, CPMC, and Conatus sponsored market analysis Cost per Patient figures are annual except for Transplant, which is one-time

Spectrum of Liver Disease

Uniquely Positioned to Address Both Medical Need and Efficiency of Development


• Approved drugs address symptoms or complications of liver disease, not underlying mechanisms

• Medical need shifts from symptoms

to clinical outcomes with cirrhosis

• Validated clinical endpoints for advanced cirrhosis patient populations may allow more efficient drug development

• Conatus is initially targeting high medical need patients with cirrhosis for whom emricasan may modify the course of disease

Liver Failure

Decompensated Cirrhosis

Asymptomatic Symptomatic

Other Companies

Disease Severity

Relat

ive U

nmet

Nee

d

Relative Disease Prevalence Size (directional, not to scale) Sources: Clinicaltrials.gov; company websites

Fibrosis

Cirrhosis

Based on three factors: 1) understanding how to dose emricasan in patients

with different levels of liver impairment

2) understanding how to dose emricasan in patients with different etiologies of liver disease

3) regulatory clarity on endpoints suitable for registration trials, in particular those potentially useful in accelerated approval pathways

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Emricasan Initial Registration Strategy

Focus on NASH cirrhosis supplemented with data in patients with NASH fibrosis


1) addressed with results from three organ impairment trials announced in January 2015

2) addressed with results from NAFLD/NASH trial announced in March 2015

3) addressed in meeting with FDA in May 2015 with feedback on proposed patient populations and validated surrogate endpoints

Emricasan Initial Registration Status

Finalizing design details by year-end 2015 for registration trial in NASH-driven cirrhosis Evaluating opportunity to include NASH-driven fibrosis trial in overall registration strategy


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Emricasan: Clinical Milestones

Goals: Define dosing, broaden safety database, show activity against validated endpoints


Post Liver Transplant HCV Clearance with Unresolved Fibrosis/Cirrhosis (POLT-HCV-SVR)

Phase 2b initial baseline data expected 2Q15

Liver Cirrhosis (LC)

Phase 2 first stage top-line data expected 4Q15

Portal Hypertension (PH)

Phase 2 top-line data expected 3Q15

Target Population Preclinical Phase 1 Phase 2 Importance Next Milestone

Long term safety with histology endpoints

Validated Surrogate endpoint

Validated Surrogate endpoint

Emricasan: Investment Highlights

Large market opportunity in cirrhosis with potential future opportunities in larger liver disease indications

Mechanism applies across the entire spectrum of liver disease, regardless of cause or stage of progression

Clinical data has shown consistent safety and statistically significant reductions in key biomarkers of liver cell death and inflammation

Near-term milestones with two cirrhosis trials measuring validated surrogate endpoints

Regulatory feedback confirmed opportunity in cirrhosis and provided clarity on analysis of surrogate endpoints in the context of potential accelerated approval

Inclusion of NASH fibrosis provides supplemental safety and could provide early entry into key area of liver disease spectrum

IP protection through 2028 (US) and 2027 (International), without extension

June 2015 Jefferies Global Healthcare Conference 26

0800 W 6 Conatus Pharma - Jefferies Group Pha… · Eight Phase 1 trials conducted in the US, EU...

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