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Jefferies 2015 Healthcare Conference Grand

Hyatt, New York

June 4th, 2015

Tobira Therapeutics: Targeting Serious Diseases of Immuno-inflammation and Fibrosis

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Forward-Looking Statements

This presentation and other matters discussed today or answers that may be given in response to questions may include statements that are, or may be deemed, “forward-looking statements.” Any statements that we make today, other than historical facts, are forward looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this presentation regarding our future results of operations and financial position, strategy and plans, and our expectations for future operations are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “design,” “intend,” “expect,” “could,” “plan,” “potential,” “predict,” “seek,” “should,” “would” or the negative version of these words and similar expressions intended to identify forward-looking statements, and similar expression and comparable terminology intended to identify forward-looking statements.

Forward-looking statements reflect management's current expectations, are based on certain assumptions and involve certain risks and uncertainties. Forward-looking statements include, but are not limited to, statements about: financial projections and estimates and their underlying assumptions, including, without limitation, sufficiency of our cash resources and needs for and ability to obtain additional financing; anticipated timing of patient enrollment in our clinical studies and availability of clinical data; anticipated timing of completing our clinical studies; the ability of CVC to treatother disease indications; the size and growth of our potential patient population; the mechanism of action of our product candidates; the ability to obtain and maintain regulatory approval of our product candidates; and the timing and success of the development and commercialization of our anticipated product candidates and the availability of alternative therapies for our target market. The Company's actual results could differ materially from those anticipated in these forward-looking statements as a result of various factors. Additional information regarding factors that could cause results to differ are available in the Company's other periodic filings with the SEC.

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Building a Leading Platform in Liver and Immuno-Inflammatory Disease with Cenicriviroc (CVC)

• Phase 2b in NASH, cornerstone therapy opportunityFast Track Designation for NASH with fibrosis

• CCR2/CCR5 direct role in immuno-inflammationInflammation is defining element of NASHDifferentiated approach to NASH therapy

• Once-daily oral dosing, extensive safety database

Potent CCR2/ CCR5 inhibitor, transformative

potential

Key expected near-term

value driving events

• 2015 Q2: Completion of merger with RegadoFunds Tobira programs into H2 2017

• 2015 Q4: Preliminary combination and ORION data

• Mid 2016: CENTAUR NASH P2b primary endpointStudy endpoints include NAFLD Activity Score (NAS), resolution of NASH, fibrosis scores

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• Merger with Regado completed May 4th. Company under Tobira leadership and name, focused on building a multi-indication platform with cenicriviroc (CVC)

• NASDAQ ticker symbol “TBRA”

• Approximately 17.4 million shares outstanding and $70 million cash, funding into the second half of 2017

• Leading CVC program targets inflammation and fibrogenesis, the key factors leading to liver damage in NASH

Tobira Therapeutics: Leader in Liver and Immuno-Inflammatory Diseases

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Leading NASH Program, Growth Potential Across Immuno-inflammatory Diseases

1 With potential strategic partner or non-dilutive financing

Key markers for kidney function to be measured in NASH P2b

Phase 2Phase 1Preclinical

Immuno-inflammatory & Fibrosis

NASH – CENTAUR Phase 2b

Diabetic nephropathy

Graft-vs-host disease (GVHD)

Oncology

Immunology

HIV - Fixed-dose backbone CVC/3TC and CVC/3TC/EFV

Phase 3

Enrolling

(Planning)1

ORION Phase 2a - Insulin Sensitivity, Biomarkers, Imaging

CVC + Pioglitazone PK and Safety Phase 1

Planning

Enrolled

Additional combinations

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NASH is Rapidly Growing, Driven by Obesity Epidemic

Liver Transplants - Average annual % change per waitlist year2

Incidence Rate Ratio (95% CI)

NASH +14.5%(12.4% - 16.6%)

HCV -1.0%(-2.0% - -0.06)

HBV -4.2%(-5.8% - -2.7%)

2 Wree, A, et al Nat. Rev. Gastroenterology Hepatology 2013;

JA Flemming et al, AASLD 2014

No Data

<10%

10%–14%

15%–19%

20%–24%

25%–29%

≥30%

Obesity Is Rapidly Increasing Among U.S. Adults1

1990

2000

2010

1 BMI 30, or about 30 lbs. overweight for 5’4” person

Source: Behavioral Risk Factors Surveillance System, CDC

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High Risk NASHNAFLD + Inflammation and Fibrosis

Type 2 Diabetes, High BMI

NASH is a Severe Form of NAFLDPotentially Progressive to Cirrhosis, Cancer or Death

Focus of CVC clinical developmentPhase 2b CENTAUR Study

NAFLD CirrhosisHealthy

~6-10M affectedAt greatest risk of progression to cirrhosis or

other serious liver conditions

NASHNAFLD + Inflammation

86 – 108M in US 9 – 15M in US

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Mechanisms of Therapies in Phase 2b StudiesCVC: Most Advanced Immunomodulator in NASH

Free Fatty Acids

Cytokines

Inflammatory Response

Stellate Cell Activation & Fibrogenesis

Cirrhosis / Fibrosis

Oxidative Stress

Mitochondrial Injury / Cell Death

Endoplasmic Reticulum Stress

InsulinInsulin

ResistanceSteatosis

Metabolic targeted agents (FXR, PPAR, ASBT, GLP-1)

NAFLD NASH

The presence of inflammation & ballooning are the defining factors that differentiate NASH from NAFLD

CVCCVC directly targets the cells promoting

inflammation and fibrosis in NASH

Collagen cross-linking(LOXL2)

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CVC First-in-Class Oral Agent Targeting Pathways of Inflammation and Fibrogenesis

Potent CCR2 antagonism

Potential impact on bacterial translocation

Mechanism of CVC Action in Fibrosis

Disruption of CCR2 and CCR5 signaling pathway

Anti-inflammatory effects in the liver

Reduced fibrogenesis in the liver

Additional anti-inflammatory effects

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CVC First-in-Class Dual MOA Targeting Fibrosis Generating Cells

• Chronic liver inflammation can lead to fibrosis, cirrhosis, ESLD, and HCC

• Chemokine receptors type 2 (CCR2) and type 5 (CCR5) are expressed on cells that promote fibrogenesis1–6, 8, 17

– Pro-inflammatory monocytes and macrophages– Kupffer cells and hepatic stellate cells (HSCs)

• Established roles of CCR2 and CCR5 in the pathogenesis of liver fibrosis1–7

– Promote the recruitment of monocytes and macrophages9,11,12 in the liver– Promote the activation and migration of Kupffer cells and HSCs during liver injury3,4,6

– Targeted deletion or inhibition of both CCR2 and CCR5 protects against hepatic fibrosis in mice3,4,7,10,11

• MCP-1 (CCR2 ligand) and RANTES (CCR5 ligand) are up-regulated in patients with liver fibrosis and cirrhosis13–16

1. Saiman and Friedman 2012; 2. Zimmermann and Tacke 2011; 3. Seki et al. 2009a; 4. Seki et al. 2009; 5. Miura et al. 2012; 6. Schwabe et al. 2003; 7. Mitchell et al. 2009; 8. Liaskou et al. 2012; 9. Egan et al. 2013; 10. Berres et al. 2010; 11. Baeck et al. 2012; 12. Baeck et al. 2014; 13. Bieche et al.2005; 14. Marra et al. 1998; 15. Asselah et al. 2005; 16. Zimmerman et al. 2010; 17. Marra and Tacke. 2014

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NASH Begins with Liver Injury

Bacterial translocation (leaky gut)

creates additional inflammation

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Kupffer Cells Initiate Immuno-inflammatory Response

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Hepatic Stellate Cells Initiate Fibrogenesis

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Cenicriviroc Inhibits the Immuno-inflammatory and Fibrogenesis Response to Injury

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CVC First-in-Class Dual CCR2/CCR5 Inhibitor - Ideal Drug Profile for NASH Clinical Development

• Oral dual CCR2/CCR5 antagonist with nanomolar potency

– CCR2: IC50 = 5.9 nM CCR5: IC50 = 3.1 nM

– Long plasma half-life (30-40 hours) supports once daily dosing

– Established dose to effectively block CCR2/CCR5 in patients

• Established favorable safety and tolerability profile to date

– Over 600 subjects treated, 115 up to 48 weeks

– Wide safety margin based on preclinical toxicology studies

• Manufacturing processes developed, differentiated by indication

– CVC 150 mg once-daily tablet

– Potential for fixed-dose combinations

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Broad Data Set Supporting CVC in NASH

Hepatic Impairment Safety P1

Over 600 Subjects Total in P1 & P2

HIV P2b: Inflammation & Fibrosis Biomarkers

NASH Mouse Model

Liver Fibrosis Rat Model

Kidney Fibrosis Mouse Model

Favorable change in sCD14, APRI, FIB-4, lipids

Few drug related AEs

Therapeutic dose established

Once-daily, 30-40 hour half life

Improvement in fibrosis across models

Improvement in NAFLD Activity Score

Reductions in monocyte-driven inflammation

CVC Program Supportive Data

Mouse Models of Inflammation

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NASH Mouse Model: CVC Shows a Significant Reduction in Fibrosis and NAFLD Activity Score

Mea

n (

±SD

) Si

riu

s re

d-p

osi

tive

are

a %

0

1

2

3

4

5

6

Interpretation performed by pathologist blinded to study group

0

.25

.5

.75

1

.61% ± .23%

.29% ± .14%

.20% ± .06%

p<.01

p<.001

VehicleN=6

CVC 20mg/kgN=6

CVC 100mg/kgN=6

VehicleN=6

CVC 20mg/kgN=6

CVC 100mg/kgN=6

52%reduction

67%reduction

CVC Shows a Significant Reduction in

NAFLD Activity Score (NAS)

p<.05

p<.01

CVC Shows a Significant Reduction in

Fibrosis

“Definite NASH”

“Borderline” or “Not NASH”

NA

FLD

Act

ivit

y Sc

ore

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Friedman et al. AASLD 2013. Abstract LB-7

Liver fibrosis model: CVC shows significant fibrosis reduction in rats

Sirius red – 100x

Vehicle Control CVC 30 mg/kg/day CVC 100 mg/kg/day

0

10

20

30

Vehicle 30 mg/kg/day 100 mg/kg/day

(%)

Relative fibrosis areap<0.001

p<0.001

49%reduction

38%reduction

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HIV Phase 2b Data to Support NASH:Favorable 48-week safety (combined with FTC/TDF)

Adverse Event, n (%)CVC 100 mg

N=58CVC 200 mg

N=57EFV

N=28

Subjects with at least 1 AE 51 (88%) 48 (84%) 27 (96%)

Grade 3 2 (3%) 3 (5%) 3 (11%)

Grade 4 - - 1 (4%)

AEs leading to discontinuation - 1 (2%) 6 (21%)

Serious AEs 1 (2%) 1 (2%) 1 (4%)

Deaths - - -

Any Grade 2 or higher treatment-related AE (occurring in ≥5%)

Abnormal dreams 1 (2%) - 3 (11%)

Insomnia - - 3 (11%)

Rash events 1 (2%) - 2 (7%)

Nausea - 2 (4%) 2 (7%)

Feinberg et al, EACS 2013, PS4/1, CVC Phase 2b Study 202

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HIV Phase 2b Data to Support NASH:Favorable Lipid Profile (combined with FTC/TDF)

Lower Total cholesterol on CVC

Mea

n c

han

ge f

rom

b

ase

line,

mg/

dL

(±SE

)

-40

-20

0

20

40

4 12 24 48

-40

-20

0

20

40

4 Weeks12 24 48

Lower Triglycerides on CVC

-20

-10

0

10

20

4 12 24 48

Lower LDL cholesterol on CVC

Mea

n c

han

ge f

rom

b

ase

line,

mg/

dL

(±SE

)

-20

-10

0

10

20

4 12 24 48

No Change in HDL cholesterol

CVC 100 mg CVC 200 mg EFV 600 mg

Feinberg et al, EACS 2013, PS4/1, CVC Phase 2b Study 202

CVC 200 mg

CVC 100 mg

CVC 200 mg

CVC 100 mg

CVC 200 mg

CVC 100 mg

CVC 200 mgCVC 100 mg

WeeksWeeks

Weeks

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Non-Invasive Serum Markers Associated with Severity of Inflammation and Fibrosis in NASH

1. Harte et al, Journal of Inflammation 2010; Ogawa et al, PLOS One 2013

2. Sebastiani et al, AASLD 2014

Increased sCD14 Serum Levels Associated with Severity of Inflammation and Fibrosis in NASH1

Me

an

log s

CD

14

leve

ls

*P < 0.05

-0.4

-0.2

0

0.2

0.4

12 48

wks

24

CVC 100 mg

CVC 200 mg

EFV

32

Me

an

Cha

nge

fro

m B

ase

line

in s

CD

14

,

log

10

x 1

06

pg/m

L (±

SE

)

HIV Phase 2b Data to Support NASH:CVC Lowers sCD14 (a marker of monocyte activation)

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Non-Invasive Serum Markers Associated with Severity of Inflammation and Fibrosis in NASH

1. Sebastiani et al, AASLD 2014

Greater FIB-4 and APRI Scores were Associated with Increased Progression to Negative Outcomes1

Note: Clinical outcomes were defined by death, liver transplantation, cirrhosis complications

FIB-4

APRI

10yr

10yr

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

Baseline Wk 24 Wk 48

APRI: CVC

0.5 - 1.5 >1.5

• 16-18% of patients had elevated scores at baseline which was reduced to 6%-9% at weeks 24 and 48

• Improvements in fibrosis scores correlated with patient decreases in sCD14 at week 48

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

Baseline Wk 24 Wk 48

FIB-4: CVC

1.45 - 3.25 >3.25

Exploratory Analysis from HIV P2b:CVC Lowers APRI and FIB4

(total N of CVC arms = 115)

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Global study, N = 252

Key Eligibility Criteria

• Biopsy diagnosis of NASH with fibrosis

• Enriched for patients with T2DM; high BMI with > 1 criteria of metabolic syndrome; bridging fibrosis and/or definite NASH

PLACEBO(n=126)

Primary endpoint biopsy1 year

ScreeningBiopsy

Final biopsy2 years

1 year Primary Endpoint

PLACEBO(n=63)

CVC 150 mg(n=126)

CVC 150 mg(n=63)

CVC 150 mg(n=126)

CENTAUR: NASH Phase 2b Study

NCT02217475

Endpoints

Primary:2 pt. Improvement in NAS

without worsening of fibrosis at Year 1

Key Secondary:Resolution of NASH without

worsening of fibrosis

OthersCollagen morphometry

Fibrosis stage α-SMA, CK-18

Validated fibrosis scoresNoninvasive imaging Biomarkers

Kidney function

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Improvement in NAS score ≥2pts without worsening of fibrosis

Phase 2b Studies in NASH Reinforce CENTAUR Study Design and Patient Focus (NASH with Fibrosis)

1. Sanyal et al. 2010; 2. Neuschwander-Tetri et al. 2014;

CENTAUR252 adults with NASH with fibrosis

Primary endpoint 1 year Secondary 2 years

Improvement in NAS score ≥2pts without worsening of fibrosis

NASH resolutionwithout worsening of fibrosis

Primary endpoint - 52 weeksGOLDEN (Genfit)275 adults with steatohepatitis

Disappearance of steatohepatitis without worsening of fibrosis

Primary endpoint - 72 weeksFLINT (NIDDK, ICPT)283 adults with NASH

Improvement in NAS score ≥2pts without worsening of fibrosis

+ 6 month follow-up

+ 3 month follow-up

Primary endpoint - 96 weeksPIVENS (NIDDK)247 non-diabetic adults with NASH

• Histologic improvement can be observed early, especially in patients with severe disease 1,2

• Longer-term treatment needed to show greatest benefit on NASH resolution and fibrosis 1,2

Other ongoing Phase 2b trials in related indications include 12 month study of RP103 (NIDDK) in pediatric NAFLD and 24 month study of simtuzumab(Gilead, injectable) for liver fibrosis due to NASH

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Profile of An Ideal Product for NASH

Ideal Attribute

Target cause of damage & fibrosis

Anti-fibrotic & anti-inflammatory

Safe for chronic setting

Oral, forgiving

CCR2 & CCR5 central in inflammatory and fibrotic pathways

Improvement in sCD14, APRI & FIB-4 in clinic

Reduced fibrosis across three animal models

600+ subjects treated to date, 115 up to 48 weeks

Few drug-related AEs; no MTD

30-40 hour half life

One pill, once-daily formulation

CVC Evidence

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Recent Milestones & Strategy to Build Value

2015 2016

Fast Track designation: CVC in NASH with fibrosis

ORION interim data(Q4 ‘15)

CENTAUR primary endpoint(Mid ‘16)

Initiate Phase 3 Planning(2H ‘16)

AASLD colloquium & EASL (Mar/Apr ‘15)

Explore HIV Partnership/Funding and Regado IP Partnership

Merger agreement with Regado(Jan ‘15)

Preliminary combination clinical & preclinical (2H ‘15)

Merger & financing, $70M(Q2 ‘15)

Third indication in clinic (1H ‘16)

CENTAUR enrollment complete (Q2 ‘15)

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Building a Platform with Cenicriviroc

• First-in-class immunomodulator for NASH– Targets inflammation and fibrosis generating cells

– Over 600 subjects treated, demonstrated activity in NASH and fibrosis models

– CENTAUR study enrolling, primary endpoint Mid 2016

• Potential across several additional indications– Broad implications of CCR2/CCR5 across multiple immuno-inflammatory diseases

– Exploring additional settings such as fibrosis, GVHD, oncology, HIV adjunctive therapy

• Management with deep expertise in developing and commercializing liver & HIV therapeutics

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Depth & Breadth in Team & Board

Management Board

Laurent Fischer, MDCEO & Board Member

Jennerex, Ocera, Roche, Dupont

Éric Lefebvre, MDChief Medical Officer

J&J, GSK

Chris PeetzCFO, Corporate Dev

Jennerex, Onyx, Abgenix

Helen JenkinsChief Operating Officer

Saegis, Genentech

Dennis Podlesak (Chairman)

Domain Associates

Carol Brosgart, MDGilead

Jeffrey CooperKalobios, BioMarin

Andrew J. FromkinClinical Data, DoctorQuality,

Patrick Heron, MBAFrazier Healthcare

Pierre Legault, MBA, CA, CPANephroGenex, Prosidion

Gwen MelincoffBTG, Shire, Adolor

Eckard Weber, MDDomain Associates

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Tobira Therapeutics: Targeting Serious Diseases of Immuno-inflammation and Fibrosis

Jefferies 2015 Healthcare Conference Grand

Hyatt, New York

June 4th, 2015