Cymabay Therapeutics (CBAY) 8-K Regulation FD Disclosure

Corporate Presentation

January 2014

Exhibit 99.1

2

Safe Harbor Statements

This

presentation

contains

"forward-looking“

statements

that

involve

risks,

uncertainties

and

assumptions.

The

opinions,

forecasts,

projections,

or

other

statements

about

future

events

or

results,

are

forward-looking

statements.

If

the

risks

or

uncertainties

ever

materialize

or

the

assumptions

prove

incorrect,

CymaBay's

results

may

differ

materially

from

those

expressed

or

implied

by

such

forward-looking

statements.

Forward-looking

statements

include,

but

are

not

limited

to:

any

projections

of

financial

information;

any

statements

about

historical

results

that

may

suggest

trends

for

CymaBay's

business

and

results

of

operations;

any

statements

concerning

CymaBay's

plans,

strategies

or

objectives;

any

statements

of

expectation

or

belief

regarding

future

events;

any

statement

of

projected

sales

forecasts,

revenues

or

anticipated

or

projected

markets;

and

any

statements

of

assumptions

underlying

any

of

the

foregoing.

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

as

it

currently

expects;

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

market

acceptance;

the

effects

of

competition;

and

market

factors

and

general

economic

conditions.

You

should

read

CymaBay's

Form

10

and

S-1

registration

statements,

which

are

available

on

the

SEC

web

site

at

http://www.sec.gov,

including

the

Risk

Factors

set

forth

therein,

completely

and

with

the

understanding

that

our

actual

future

results

may

be

materially

different

from

what

we

expect.

CymaBay

assumes

no

obligation

for

and

does

not

intend

to

update

these

forward-looking

statements.

Nothing

contained

herein

is,

or

should

be

relied

on

as,

a

promise

or

representation

as

to

the

future

performance

of

CymaBay.

3

CymaBay Investment Highlights

•

Restructured company retaining the prior Metabolex pipeline and core

management team

–

Became public through Form 10 self registration route

–

$38M financing completed to fund arhalofenate development

–

Application to FINRA to trade on the OTCBB under review

–

Application for NASDAQ listing under review 

•

Arhalofenate is a potentially game changing dual-acting treatment for gout

–

Anti-flare activity of Colcrys (URL, acquired by Takeda for $800M)

–

Uricosuric activity of lesinurad (Ardea, acquired by AZ for $1.3B)

–

Large (>$500M peak sales) market opportunity

–

Highly de-risked asset with large clinical safety database

•

Other pipeline projects

–

MBX-2982 and MBX-8025 in Phase 2

4

CymaBay Leadership

Averages >20 years of drug development experience

Name

Title

Experience

Harold Van Wart

President, CEO              

Syntex, Roche

Sujal Shah

CFO

Credit Suisse, Citi

Charles McWherter

CSO       

Pfizer, Sugen

Mary Jean Stempien

Interim CMO

Roche, Tularik

Robert Martin

VP Project Management

Syntex, Roche

Patrick O’Mara

VP Business Dev.

Metabolex

Diana Petty

VP Human Resources

SmithKline, 3M

5

Preclinical

Phase 1

Phase 3

Phase 2

Lead Optimization

Arhalofenate

MBX-8025

MBX-2982

Gout

Diabetes

Diabetes

High Unmet Need/

Orphan Disease

Diabetes

Target

Novel Target

Diabetes

Targets

CymaBay

Pipeline, January 2014

Multiple partnered and unpartnered programs

6

Key Features of Gout

Hyperuricemia, urate crystal deposits and flares

Hyperuricemia

Serum Uric

Acid (sUA)

Mono Sodium

Urate (MSU)

crystal deposits

Inflammatory

Response

IL-1ß

Painful flare

Therapeutic

targets

Joint

erosion

7

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 Colcrys 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)

–

Pegloticase (for severe treatment failure gout)

8

The Big Paradox

Currently marketed ULTs increase flares

9

Gout Patients Are Poorly Served by Available Drugs

Need for better control of flares and sUA

•

Patients care about the pain, suffering and medical costs due to

flares

–

Despite ULT,  at least 1 million patients flare

3 times/year

–

More than 50% of patients on ULT do not reach the sUA goal of < 6

mg/dL and are unable to debulk  their MSU burden

–

Poor performance of available therapies leads to non-compliance

•

Current anti-inflammatory drugs have limitations for gout patients

–

Colcrys ($496M sales in 2012) has GI side effects, drug interactions

and is difficult to use in patients with comorbidities (CKD, CVD)

–

Steroids and NSAIDs are also problematic

–

Ilaris is an expensive injectable with risk of infections

•

Unmet needs

–

Better flare control

–

Additional sUA lowering, but not if it causes more flares

10

The Arhalofenate Solution

The only therapy that reduces flares while lowering sUA

•

Reduces flares through anti-inflammatory                       

properties and long plasma half-life                                                      

–

Suppresses MSU crystal-induced

IL-1ß

in gouty joints

–

No systemic suppression of  IL-1   and      

no infection risk

–

50 hour half-life “buffers”

sUA levels

to minimize intraday fluctuations

•

Lowers sUA by improving uric acid excretion

in the kidney

–

Blocks urate reabsorption by URAT1

–

Same mechanism for lowering sUA as

lesinurad

–

Retains uricosuric activity in CKD patients

11

Allopurinol

Intolerant

~300 K

Diagnosed

Gout*

8.3 M

ULT Treated**

~3.3 M

Mild & Moderate

~581K

Severe

~282K

Arhalofenate

Arhalofenate

+ Febuxostat

Arhalofenate

* NHANES, 2008

** Source Healthcare 2012

*** BioTrends

Target

Population

~ 1M patients

3 flares/yr***

Arhalofenate Target Population

Three or more flares a year or allopurinol intolerant

CymaBay/Biotrends

Market Research:

PCPs cite 3 flares/year

as the threshold for

trying a new therapy

12

Switch Strategy is Made Possible by Patient Presentations

Repeat visits to PCPs due to flare recurrence

Allopurinol

Intolerant

~300K

Steady State

XO-Treated

3.3M

Untreated Gout

Patients

5.3-5.8M

Discontinuations

~1.2M/year*

Restarts

~0.75M/year*

Newly

Diagnosed

New Starts

~200K/year**

* Sarawate et al. (2006)

** NHANES data

~20K/year

13

Market Opportunity

Arhalofenate’s unique profile creates large opportunity

•

Arhalofenate offers what patients care about –

relief from flares and pain

–

US Colcrys sales ($496M) in 2012 validate value of flare reduction

–

Pharmacoeconomic argument for payers on reduced healthcare costs

•

25% of patients with

3 flares/yr need an ER visit or hospitalization*

•

Hospitalizations have a mean length of stay of 4 days**

•

Arhalofenate US Sales forecast (Sage Path Partners)

–

Peak sales >$500M

•

Pure ULTs that lack anti-flare activity have not been commercially successful

–

Allopurinol is an inexpensive entrenched generic (>90% market share)

–

Febuxostat sales of only ~$216M/year is due to minimal differentiation

–

Lesinurad may face the same challenges

*  BioTrends, 2012

** Mandell BF et al

14

Discovery and History of Arhalofenate

Single enantiomer of halofenate

•

Halofenate

–

Racemic drug studies by Merck in late 1970s

–

1200 patient year clinical database with effective reduction in sUA

and triglycerides and good overall safety (studies up to 4 years)

–

Lowered glucose in diabetics

–

Discontinued due to GI side effects associated with S-enantiomer

•

Arhalofenate

–

R

-enantiomer

of

halofenate

partnered

with

JnJ

for

type

2

diabetes

–

Eight Phase 1 and four Phase 2 studies (3-6 months) completed

–

Total of 873 patients studied giving ~165 patient-years of exposure

–

Decreases in HbA1c fell short of commercial target

–

Now being repurposed for gout

15

Phase 2 Gout Studies Conducted with Arhalofenate

Strong support for monotherapy and febuxostat combination

•

Monotherapy study (64 patients, 4-week treatment)

–

Arhalofenate (400 or 600 mg) or placebo

–

Reductions in sUA lowering and flare parameters

•

Febuxostat combination study (11 patients; up-titration over 5 weeks)

–

80 mg febuxostat plus arhalofenate (400 or 600 mg)

–

Percentage of patients that reach sUA goals (< 6, < 5, < 4 and <

3 

mg/dL) and decrease in flare parameters

•

Allopurinol combination study (95 patients, 4 weeks of treatment)

–

Patients on allopurinol (300 mg) not reaching sUA < 6 mg/dL

received arhalofenate (400 or 600 mg) or placebo

–

Reductions in flare parameters

–

Effect on sUA partially offset by drug interaction with oxypurinol

16

Arhalofenate Phase 2 Monotherapy Study

Gradual dose-dependent reductions in sUA

Weeks of treatment

Baseline sUA                 9.7                       9.4     

9.8

No. of patients               22                        20     

22

17

Incidence (%)

Duration (Days)

Combined Score

(Incidence x Duration)

All patients received Colcrys for flare prophylaxis

Arhalofenate  Phase 2 Monotherapy Study

Decrease in flare incidence, duration and  combined score

Pbo            400 mg               600 mg

p = 0.08

p = 0.16

18

Arhalofenate Phase 2 Monotherapy Study

Decreases in flare severity

Placebo

400 mg

600 mg

Mild

Moderate

19

Lesinurad Phase 2 Monotherapy Study (Ardea*)

Increases in flare incidence, duration and combined score

* 28-day study up-titration of lesinurad from 200 to 400 to 600 mg

Incidence (%)

Duration (Days)

Combined Score

(Incidence x Duration)

Placebo           Lesinurad

All patients received Colcrys for flare prophylaxis

20

Arhalofenate Phase 2 Febuxostat Combination Study

Best-in-class sUA responder rate

6.0 mg/dL               5.0 mg/dL             

4.0 mg/dL             

3.0 mg/dL  

Febuxostat (80 mg)

Febuxostat (80 mg) +

Arhalofenate (400 mg)

Febuxostat (80 mg) +

Arhalofenate (600 mg)

~10-fold

increase vs.

febuxostat

(p = 0.013)

Baseline sUA = 9 mg/dL

Week 1

Week

2-3

Week

4-5

21

Arhalofenate Phase 2 Febuxostat Combination Study

Decrease in flare incidence and duration

Febuxostat   Plus 400 mg   Plus 600 mg       Post-

Alone        Arhalofenate   Arhalofenate  Treatment

Week 1

Weeks 2-3

Weeks 4-5

Weeks 6-7

All patients received

Colcrys for flare

prophylaxis through

post-treatment phase

22

Arhalofenate Clinical Studies

Efficacy summary

•

Consistent reductions in flare parameters in all three studies

–

Incidence, severity and duration

–

Effects comparable to the anti-IL-1   biologics

–

Effects achieved without need for dose titration

•

Consistent reductions in sUA

–

Up to 27% with monotherapy

–

Up to 60% in combination with febuxostat

–

Subset analyses show that sUA reductions are retained in:

•

Patients with Stage 2 and 3 CKD

•

Patients taking diuretics and aspirin

•

Favorable effects on metabolic comorbidities

–

Lowers triglycerides and reverses insulin resistance

23

Arhalofenate Clinical Studies

Safety summary

•

Completed 15 clinical studies

–

Nearly 1000 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 increase in infections, no changes in neutrophils

•

Renal safety

–

No kidney stones, decrease in urine pH or effect on eGFR

–

No creatinine signal (no grade 3 or 4 elevations)

•

No dose-limiting toxicity has been identified

24

Arhalofenate Clinical Studies

Development status

•

Drug materials

–

Economical, proprietary synthesis

•

200 kg of drug substance in hand

–

Commercial tablet formulation developed

•

200, 300, 400 and 600 mg strengths

•

Completed preclinical safety package

–

Sub-chronic and chronic toxicology in rat and monkey

–

Safety pharmacology and reproductive toxicology

–

Two-year carcinogenicity studies in rodents

–

Carcinogenicity and CV safety review by FDA completed

–

All studies satisfactorily completed and support further development

•

Additional Phase 2/3 study to refine product profile

25

•

12-week study in gout patients experiencing

3 flares in the prior year

•

Goals for arhalofenate

–

Prevent flares without colchicine prophylaxis

–

800 mg lowers  sUA comparable to allopurinol (300 mg)

–

Generate safety data with 800 mg dose

•

Primary endpoint

–

Mean flares/patient for arhalofenate (800 mg) vs. allopurinol (300 mg)

–

>80% power to detect a 50% decrease in flares

•

Secondary endpoint

–

sUA responder rate (<6 mg/dL) for arhalofenate (800 mg) vs. placebo

–

>90% power to detect a responder rate of 40%

Replace

allopurinol -

Colcrys

Arhalofenate Phase 2/3 Study

26

Arhalofenate Phase 2/3 Study Design

Screening

Run-in

3 Month Treatment Phase

1 Month

Run-in

Flare Rescue

Arhalofenate 600 mg

Arhalofenate 800 mg

Allopurinol  300 mg + Colchicine

Allopurinol 300 mg

Placebo

n = 25

n = 50

n = 50

n = 50

n = 50

1 Month

Follow-up

27

CymaBay Milestones for Arhalofenate

•

Dose first patient in Phase 2/3 study

1H 2014

•

Phase 2/3 headline data

1H 2015

•

End-of-phase 2 meeting

2H 2015

•

Start Phase 3

1H 2016