Cymabay Therapeutics (CBAY) 8-K This presentation contains "forward-looking" statements that involve risks, uncertainties

Cowen Health Care

Conference

March 4, 2015

Boston, MA

Harold Van Wart, Ph.D.

President and CEO

Exhibit 99.1

2

Safe Harbor Statement

This presentation contains "forward-looking" statements that involve risks, uncertainties

and assumptions, and actual results may differ substantially from those projected or

expected in the forward-looking statements.  Forward-looking statements include, but are

not limited to: any projections of financial information; any statements about future

development, clinical or regulatory events; any statements concerning CymaBay's plans,

strategies or objectives; and any other statements of expectation or belief regarding future

events. These statements are based on estimates and information available to CymaBay at

the time of this presentation and are not guarantees of future performance. Actual results

could differ materially from CymaBay's current expectations as a result of many factors

including, but not limited to: CymaBay's ability to obtain additional financing to fund its

operations; unexpected delays or results in clinical trials; uncertainties regarding obtaining

regulatory approvals; uncertainties regarding the ability to protect CymaBay's intellectual

property; uncertainties regarding market acceptance of any products for which CymaBay is

able to obtain regulatory approval; the effects of competition; and other market and general

economic conditions. You should read CymaBay's Quarterly Report on Form 10-Q filed with

the SEC on November 14, 2014, especially under the caption “Risk Factors,” which is

available on the SEC web site at http://www.sec.gov, for a fuller discussion of these and

other risks relating to an investment in CymaBay’s common stock.  CymaBay assumes no

obligation for and does not intend to update these forward-looking statements, except as

required by law.

3

CymaBay Highlights

•

Arhalofenate

is

the

first

drug

in

the

Urate

Lowering

Anti-Flare

Therapy

(ULAFT)

class for the treatment of gout

Reduces gout flares and lowers serum uric acid (sUA)

Refined product profile established in recently completed Phase 2 studies

Good overall and renal safety data in over 1,000 subjects

•

MBX-8025 is a potential novel treatment for rare or serious lipid and liver

disorders, including homozygous familial hypercholesterolemia (HoFH)

Positive effects on lipids and markers of liver health demonstrated in mixed

dyslipidemia Phase 2 trial

Focusing further development in rare or orphan diseases

•

Near-term, value-driving catalysts

Arhalofenate  End-of-Phase 2 meeting with FDA in 3Q 2015

Phase 2 trial initiation for MBX-8025 in HoFH expected in 1H 2015

Key Features of Gout

Hyperuricemia, urate crystal deposits and flares

Hyperuricemia

Serum Uric

Acid (sUA)

Mono Sodium

Urate (MSU)

crystal deposits

Inflammatory

response

IL-1

Painful flare

Therapeutic

targets

Joint

erosion

4

5

Current Treatment of Gout

Uric acid Lowering Therapies (ULTs) and anti-inflammatories

–

Treatment paradigm (ACR Guidelines)

–

Anti-inflammatory to treat the flare

–

ULT

is

initiated

to

address

the

hyperuricemia

with

a

goal

of

sUA

<

6

mg/dL

to

debulk offending MSU burden

–

Initiation

of

ULT

increases

flare

risk,

requiring

dose

titration

and

colchicine

prophylaxis

–

Anti-inflammatory drugs

–

Colchicine (Colcrys)

–

NSAIDs, steroids

–

Ilaris (anti-IL-1  biologic) approved in EU

•

ULTs

–

Xanthine oxidase (XO) inhibitors (allopurinol, febuxostat)

–

Uricosurics (probenecid, lesinurad in development)

–

Pegloticase (for severe treatment failure gout)

6

Gout Patients Are Poorly Served by Available Drugs

Need for more sUA lowering and better control of flares

•

More sUA lowering

–

~2

million

patients

do

not

reach

their

sUA

goal

on

their

current

ULT

•

<6 mg/dL for patients without tophi

•

<5 mg/dL for patients with tophi

–

~300 thousand patients are allopurinol intolerant

–

Inadequate responders to ULT continue to increase their MSU burden and

the disease continues to progress

•

Better flare control

–

~1 million patients experience    3 flares/year

–

Patients care about the pain, suffering and medical costs of flares

–

Colchicine,

NSAIDs

and

steroids

are

“strongly

contraindicated”

in

>40%

of

gout patients due to their comorbidities

–

Colchicine non-compliance is estimated to be ~40%

7

Arhalofenate

The First Urate Lowering Anti-Flare Therapy (ULAFT)

•

Lowers sUA by improving uric acid excretion in

the kidney (uricosuric effect)

–

Blocks urate reabsorption by URAT1

–

Same target as lesinurad

–

Very favorable PK for a uricosuric drug

•

50 hour half-life produces gradual

changes in serum and urinary UA with

small intraday fluctuations

•

Avoids “hyperuricosuria”

•

Reduces flares through anti-inflammatory                       

properties and long plasma half-life                                                      

–

Suppresses MSU crystal-induced

IL-1  in gouty joints

–

No systemic suppression of IL-1   and no

infection risk

Human

URAT1

Arhalofenate Acid (M)

10

-6

10

-5

10

-4

10

-3

0

20

40

60

80

100

IC

50

=

92

M

* NHANES 2008

** Source Healthcare  2012

Gout Population Segregated by sUA Status

Treating inadequate responders with a uricosuric drug

Uricosuric drug

Uricosuric drug

Uricosurics in Development:

Lesinurad (ULT)

Arhalofenate (ULAFT)

The original positioning of

arhalofenate was for the ~1M

patients flaring >3 times/year

Allopurinol

Intolerant

~300 K

Diagnosed

Gout*

8.3 M

ULT Treated**

>90% Allopurinol

~3.3 M

Inadequate

Responders

~2 M

Responders

~1.3 M

8

9

Arhalofenate Phase 2 Clinical Program for Gout

•

Five Phase 2 studies completed

–

Monotherapy with and without colchicine

–

Combination with febuxostat and allopurinol

–

Arhalofenate doses of 400, 600 and 800 mg

•

Summary of results

–

Very effective sUA lowering in combination with febuxostat (40 or 80 mg)

–

Arhalofenate monotherapy is an alternative for the XOI intolerant patients

–

Arhalofenate has anti-flare activity

•

Provides the symptomatic relief that patients really want

•

Helps patients in which colchicine is contraindicated or not tolerated

–

Does not require dose titration

•

Refined product positioning

–

Recent arhalofenate Phase 2 data and lesinurad news has shifted

positioning to address the larger sUA inadequate responder segment

10

Arhalofenate Febuxostat Phase 2 Study

•

Objectives

–

Assess sUA reductions of different dose combinations

–

Measure the interday and intraday fractional excretion of UA (FEUA)

–

Assess if there is a drug-drug interaction

–

Additional safety data for arhalofenate/febuxostat combination

N = 16 per cohort ; PK from cohort 2 at Weeks 2, 4 and 6

All patients received colchicine for flare prophylaxis

Cohort 1

Cohort 2

Weeks 1-2

Week 3

Week 4

Weeks 5-6

Arhalofenate 600

Febuxostat 80 +

Arhalofenate 600

Febuxostat 40 +

Arhalofenate 600

Febuxostat 40

Arhalofenate 800

Febuxostat 40 +

Arhalofenate 800

Febuxostat 80 +

Arhalofenate 800

Febuxostat 80

Arhalofenate Febuxostat Phase 2 Study

Changes in sUA for treatment phases

sUA = -33%

RR = 43%

sUA = -24%

RR = 100%

Arhalofenate decrease sUA

by an additional 24% and

increases the Responder

Rate from 43 to 100%

Baseline

Fbx (40 mg)

Fbx (40 mg) +

Arhalo (800 mg)

0

2

4

6

8

10

12

11

12

Arhalofenate Febuxostat Phase 2 PK/PD Study

sUA responder rate for febuxostat 40 mg treatments

< 6.0 mg/dL            < 5.0 mg/dL              < 4.0 mg/dL    

< 3.0 mg/dL  

Febuxostat (40 mg) +

Arhalofenate (800 mg)

Febuxostat (40 mg) +

Arhalofenate (600 mg)

Febuxostat (40 mg)

N                 15                                            14

15

p-values reflect comparisons vs. febuxostat 40 mg. McNemar’s exact  test and Fischer’s

exact test were used for comparisons within and between cohorts,

respectively.

* p < .05   ** p < .01  *** p < .001

*

**

***

0

20

40

60

80

100

13

< 6.0 mg/dL            < 5.0 mg/dL              < 4.0 mg/dL    

< 3.0 mg/dL  

Febuxostat (80 mg) +

Arhalofenate (800 mg)

Febuxostat (80 mg) +

Arhalofenate (600 mg)

Febuxostat (80 mg)

N                    14                                         

16                                               14

Arhalofenate Febuxostat Phase 2 PK/PD Study

sUA responder rate for febuxostat 80 mg treatments

*

* p < .05  for comparison vs. febuxostat 80 mg; McNemar’s exact  test

0

20

40

60

80

100

14

Time Period

*** p < 0.001

Matched pairs

t-test

Fractional Excretion of Uric Acid (FEUA)

Normal Range*

* Perez-Ruiz et al.,

Arthr. Rheum. 47, 610

(2002)

Day 0   (n = 8)

Day 14 (n = 8)

Mean ±

SE

9 am to

3 pm

3 pm to

9 pm

9 pm to

9 am

***

***

***

2

3

4

5

6

7

8

9

10

Arhalofenate Febuxostat Phase 2 PK/PD Study

Intraday and interday variation in FEUA for arhalofenate (800 mg)

14

•

Design

–

Randomized double blind placebo-

and active-controlled study

–

12-week duration

–

248 gout patients who had  >3 flares in prior year

•

Goal for arhalofenate

–

Establish statistically significant reduction in gout flares

–

Show anti-flare effect in the absence of colchicine

•

Primary end point

–

Mean flares/patient

•

Secondary end point

–

Reduction in sUA

Arhalofenate Phase 2b Flare Study

Arhalofenate flare study

Electronic diary

for patient flare

reporting

16

Arhalofenate Phase 2b Study Design

Primary Endpoint:

Reduction in flare

rate for arhalofenate

compared to allopurinol

n = 25

n = 50

n = 50

n = 50

n = 50

Allopurinol  300 mg + Colchicine

Allopurinol 300 mg

Arhalofenate 600 mg

Placebo

Flare Rescue

3 Month Treatment Phase

2 Week

Follw-up

Arhalofenate 800 mg

Arhalofenate Phase 2b Flare Study

Most frequent adverse events and safety summary

Placebo

Arhalofenate

600 mg

Arhalofenate

800 mg

Allopurinol

300 mg + COL

Allopurinol

300 mg

N

28

53

51

53

54

AEs

17 (60.7%)

24 (45.3%)

21 (41.2%)

24 (45.3%)

22 (40.7%)

SAEs

0

1

0

1

3

Discon due to

AE or Lab

1

1

1

5

3

CK increased

0

3 (5.7%)

2 (3.9%)

3 (5.7%)

3 (5.6%)

URT

Infection

2 (7.1%)

3 (5.7%)

2 (3.9%)

2 (3.8%)

0

Headache

1 (3.6%)

3 (5.7%)

2 (3.9%)

0

2 (3.7%)

Hypertension

2 (7.1%)

1 (1.9%)

2 (3.9%)

2 (3.8%)

1 (1.9%)

Creatinine 

>1.5X and

>ULN

0

0

0

0

0

17

Arhalofenate Phase 2b Flare Study

Arhaolfenate 800 mg dose met the primary flare end point

Arhalofenate (800 mg)

vs.  allopurinol (300 mg) + colchicine

were not statistically different

(p = .091)

-46%

p= 0.0056

Arhalofenate

(600 mg)

Allopurinol

(300 mg)

Placebo

Allopurinol

(300 mg) +

Colchicine

Arhalofenate

(800 mg)

-68%

p < 0.0001

-41%

p = 0.049

0.00

0.25

0.50

0.75

1.00

1.25

1.50

N       53            51               53              54      

28

1.13

1.04

0.66

1.24

0.40

18

Arhalofenate Phase 2b Flare Study

Mean lowering of serum uric acid

8 weeks

p < .01 vs. Pbo

for all changes

12 weeks

Arhalofenate

(600 mg)

Allopurinol

(300 mg)

Placebo

Allopurinol

(300 mg) +

Colchicine

Arhalofenate

(800 mg)

Baseline sUA        9.1               9.0                   9.1

9.2                    9.1  

16-20% drop in sUA

projected to give RR = 100%

in combo with Fbx

(40 mg)

-30

-20

-10

0

19

N                     28               53                     51

53                    54

20

Allopurinol

Intolerant

~300 K

Inadequate

Responders

~2 M

Arhalofenate (800 mg)

+ Febuxostat (80 mg)

Arhalofenate

(800 mg)

Arhalofenate Target Population

Major target is inadequate responders on current ULT

Patients

w/o Tophi

~1.6 M

Patients

with Tophi

~ 0.4 M

Arhalofenate (800 mg)

+ Febuxostat (40 mg)

Great majority reach their sUA goal

Experience fewer flares

Don’t need colchicine prophylaxis

No need for dose titration

A fixed dose combination

pill is in development for

patient convenience

Benefits to Patient

21

Comparison of Arhalofenate with Lesinurad

Arhalofenate (800 mg)

Lesinurad (200 mg)

sUA lowering                                   16-24% (Ph 2)

Monotherapy for                                    

allopurinol intolerant

Responder Rate (< 6 mg/dL)                                     

increase with XOI             

On top of Allo (300 mg)

On top of Fbx (40 mg)                 

Flare benefit                                            

Colchicine

Prophylaxis needed                               

Renal safety                                        

* Ardea presentation materials  **ACR presentation, 2014

No signal

No

Yes

57% (Ph 2)

Yes

No**

38% (Ph 2)*; 25% (Ph 3)**

No**

16% (Ph 2)*

22

Arhalofenate Clinical Studies

Safety summary

•

Completed 9 Phase 2 clinical studies (200-800 mg)

–

More than 1,000 subjects exposed to arhalofenate for up to 6 months

•

General safety

–

Adverse events similar to placebo and balanced across dose groups

–

Low incidence of asymptomatic liver transaminase elevations

–

No change in neutrophils or increase in infections

•

Renal safety

–

No kidney stones or decrease in urine pH

–

No creatinine signal

•

No dose-limiting toxicity has been identified

23

Arhalofenate Nonclinical Studies

Non-clinical

development status

•

Drug materials

–

Economical, proprietary synthesis

–

Tablet formulations developed

–

Fixed dose formulation with febuxostat in development

•

Completed preclinical safety package

–

Sub-chronic and chronic toxicology

–

Safety pharmacology and reproductive toxicology

–

Two-year carcinogenicity studies

–

Carcinogenicity and CV safety review by FDA completed

•

All results support further development

24

•

Non-tophaceous gout (n = 1,000) in allopurinol inadequate responders

–

Febuxostat (40 mg) + colchicine vs. febuxostat (40 mg) + arhalofenate (800 mg)

for 6 months + 6 month safety extension

–

Primary endpoint: sUA responder rate (< 6 mg/dL) at 6 months

–

Secondary end point: average flares/patient at 6 months

•

Tophaceous gout (n = 300) in allopurinol inadequate responders

–

Febuxostat (80 mg) + colchicine vs. febuxostat (80 mg) + arhalofenate (800 mg)

for 6 months

–

Primary endpoint: sUA responder rate (< 5 mg/dL) at 6 months

–

Secondary endpoints: flare rate and tophi resolution at 12 months

•

Patients intolerant to allopurinol (n = 200)

–

Placebo and arhalofenate (800 mg) for 6 months with 6-month safety extension

–

Primary endpoint: average flares per patient at 6 months

–

Secondary end point: sUA responder rate (< 6 mg/dL) at 6 months

Phase 3 Program for Arhalofenate

Preliminary study design

25

MBX-8025

•

MBX-8025

–

Potent selective PPAR-

agonist

–

Once daily orally administered

•

Status 

–

Originally in development for mixed dyslipidemia

–

Phase

2

study

demonstrated

favorable

effects

on

lipids

and

liver

biomarkers

–

FDA now requiring a preapproval CV outcome study for this indication

•

Redirecting  program to higher unmet need indications

–

Homozygous familial hypercholesterolemia (HoFH)

–

Primary biliary cirrhosis (PBC)

–

Severe refractory hypertriglyceridemia (SHTG)

–

Nonalcoholic steatohepatitis (NASH)

O

HO

O

S

O

O

CF

3

(R)

26

•

Orphan disease affecting 1 in 1 million

–

Markedly elevated LDL-C (>500 mg/dL) caused by                                       

loss-of-function mutations in LDL receptor (LDL-R)

–

Cardiovascular disease (MI, stroke, CAD) before the age of 20

–

Mean age of death is in the 30s

–

Current therapy is focused on lowering LDL-C

•

Therapies that raise LDL-R activity are minimally effective

–

Statins, bile acid sequestrants, cholesterol absorption        

inhibitors, PCSK9 inhibitors

•

Current therapeutic options

–

LDL apheresis

–

Juxtapid (lomitapide)

–

Kynamro (mipomersen)

28 year-old female with

cutaneous xanthoma

Homozygous Familial Hypercholesterolemia (HoFH)

Rare disease of impaired cholesterol metabolism

27

Unmet Medical Need in HoFH Remains High

Patients need more effective and better tolerated  therapies

•

LDL apheresis is inconvenient and has many complications

•

Juxtapid (Microsomal Transfer Protein Inhibitor)

–

Only 28% of patients achieve LDL < 100 mg/dL

–

Dose limiting GI tolerability

–

Risk of hepatotoxicity due to increase in hepatic fat

–

Black box and REMs requiring monthly liver testing 

•

Kynamro (oligonucleotide inhibitor of apo-B synthesis)

–

Risk of hepatotoxicity due to increase in hepatic fat

–

Black box and REMs requiring monthly liver testing

–

Flu-like symptoms and injection site reactions

28

MBX-8025 Phase 2 Mixed Dyslipidemia Study

Change in LDL-C as a function of baseline LDL-C

-60

-50

-40

-30

-20

-10

0

Placebo

MBX-8025 (50 mg)

MBX-8025 (100 mg)

LDL-C range

83-242

175

180

190

195

Mean LDL-C

159-169

186-197

189-205

195-207

197-215

N

28,27,32

8,10,11

6,9,10

3,7,9

2,5,6

29

Effect of MBX-8025 in the WHHL Rabbit Model of HoFH

Significant and sustained reductions in LDL-C

The Watanabe

Heritable

Hyperlipidemic

(WHHL) rabbit

has low (<5%)

LDL-R activity

LDL-C

(Mean

±

SD, n = 5)

1

2

3

4

5

6

7

-60

-40

-20

0

20

MBX-8025

Time (weeks)

Washout

30

MBX-8025 for the Treatment of HoFH

Rationale and pilot study design

•

Rationale

–

MBX-8025 exhibited a strong anti-atherogenic profile in patients with

mixed dyslipidemia including reductions in LDL-C

–

Data from the WHHL rabbit model suggest that the decreases in

LDL-C would be retained in the setting of low LDL-R activity

characteristic of HoFH

•

Pilot study design

–

Open label dose escalation study in up to 8 patients

–

Doses are 50, 100 and 200 mg

–

Study duration of 3 months

–

Study to be conducted in 2-3 countries in Europe

–

Start of study planned for 1H 2015

31

CymaBay Projected Milestones

•

Arhalofenate

–

Dose first patient in Phase 2b study

1H 2014

–

Phase 2 febuxostat combo headline data

1Q 2015

–

Phase 2b flare study headline data

2Q 2015

–

End-of-Phase 2 meeting

2H 2015

–

Start Phase 3

1H 2016

•

MBX-8025

–

Select indication for proof-of-concept

2H 2014

–

Start pilot study in HoFH

1H 2015