Medivation 8-K Regulation FD Disclosure

Talazoparib (MDV3800):

A Potentially Best-in-Class PARP Inhibitor

July 2016

Exhibit 99.1

WELCOME TO MEDIVATION

2

Forward-Looking Statements

Forward-looking

statements

are

made

throughout

this

presentation.

The

forward-looking

statements

in

this

presentation

include,

but

are

not

limited

to,

estimates

and

other

speculative

statements

regarding

the

potential

for

the

PARP

inhibitor

class

in

general

and

talazoparib

in

particular

and

how

it

will

drive

growth

for

Medivation;

potential

clinical

trial

design,

initiation,

enrollment

and

results;

potential

regulatory

approvals;

and

talazoparib’s

addressable

market

in

terms

of

indications,

patients

and

product

sales

and

are

made

pursuant

to

the

safe

harbor

provisions

of

the

Private

Securities

Litigation

Reform

Act

of

1995.

These

forward-looking

statements

may

also

be

identified

by

words

such

as

“expect,”

believe,”

“should,”

“potential,”

“suggest”

or

similar

expressions.

All

forward-looking

statements

are

subject

to

risks

and

uncertainties

which

may

cause

actual

results

to

differ

significantly

from

those

expressed

or

implied

by

such

forward-looking

statements.

Factors

that

could

cause

or

contribute

to

such

differences

include,

but

are

not

limited

to,

the

risk

that

clinical

trials

of

talazoparib

will

be

unsuccessful,

the

inherent

uncertainty

associated

with

the

regulatory

approval

process

and

the

related

risk

of

failure

to

obtain

marketing

approval

for

talazoparib

for

its

target

(or

any)

patient

populations

and

indications;

the

risk

that

competitive,

regulatory

or

other

factors

could

negatively

impact

the

pricing

of

talazoparib,

if

approved;

the

risk

that

unexpected

adverse

events

could

impact

sales

of

talazoparib,

if

approved;

competition

from

other

approved

or

generic

products

similar

to

talazoparib,

if

approved;

failure

to

cost-

effectively

manufacture

talazoparib,

if

approved;

general

economic

conditions;

and

other

risks

detailed

in

Medivation’s

filings

with

the

Securities

and

Exchange

Commission,

or

SEC,

including

its

annual

report

on

Form

10-K

for

the

year

ended

December

31,

2015,

which

was

filed

on

February

26,

2016,

and

its

latest

Quarterly

Report

on

Form

10-Q.

You

are

cautioned

not

to

place

undue

reliance

on

the

forward-looking

statements,

which

speak

only

as

of

the

date

of

this

presentation.

Medivation

disclaims

any

obligation

or

undertaking

to

update,

supplement

or

revise

any

forward-looking

statements

contained

in

this

presentation.

Talazoparib: A Potentially Best-in-Class PARP Inhibitor

(PARPi)

3

Significantly greater potency

in vitro

and

lowest clinical dose relative

to other PARPi’s in clinical development

Superior PARP trapping

ability

Differentiated

Mechanism of Action

Compelling Clinical

Data

High & differentiated response rates

observed in patients with ovarian

and breast cancers

Potential beyond HRD (homologous recombination deficiency) cancers

Phase 3 Data

Approaching

Phase 3 EMBRACA trial in BRCA-mutated breast cancer expected to

complete enrollment in 2016, top-line data expected 1H 2017

Blockbuster

Potential

DNA repair and PARP trapping relevant to multiple tumor types

Numerous potential opportunities as a single-agent, in combination with

low-dose chemotherapy or radiation, or other combinations

High Probability of

Success

PARPi class validated through FDA approval

(despite historical

failure of iniparib incorrectly believed to be a PARPi)

Clinical efficacy appears to correlate better with PARP trapping than

PARP enzyme inhibition and talazoparib

is the best PARP trapper in

development

Most potent PARP inhibitor reported

Strongest tumor cell killing ability

Highest efficiency at PARP trapping

Highly selective for PARP1 and PARP2

Clinical proof-of-concept established 

as a monotherapy and combination

therapy in multiple indications

Lowest clinical dose with most

convenient dosing regimen (1mg daily

dosing vs. 300-1,200mg given daily to

twice daily dosing for others)

Competitive safety profile

Talazoparib is Distinguished from Other PARP Inhibitors by

Several Important Characteristics

Talazoparib Appears to be the Most Optimized PARP Inhibitor in Development

4

Introduction to Talazoparib

PARP Inhibitors Could be the Next Major Class of

Therapeutics in Oncology

Recent Equity Research Highlight the Excitement of PARP Inhibitors

6

“PARP

inhibitors

may

have

broad

applicability

in

cancer

therapies

beyond

the initial indications in a subset of high-

grade ovarian cancers.”

-

William Blair 04/11/16

“Given the potential breadth of action, we

estimate that PARP inhibitors could have a

large

addressable

market

of

c$20bn

across

ovarian,

breast,

pancreatic

and

prostate

cancers.”

-

BofA Merrill Lynch 06/10/16

“Upside

PARP

Potential

in

Other

Cancers

or Combinations: We believe the PARP

class of drugs in cancer has promise in

more

than

just

ovarian….

PARP market is one of the next big

categories in cancer.”

-

Credit Suisse 05/12/16

“Data suggests high potential for

Talazoparib”

-

BofA Merrill Lynch 06/29/16

“Tesaro announced positive phase 3 top-line data

for

niraparib

–

further

validating

the

“PARP”

class,

a novel DNA pathway repair inhibitor, which

includes Medivation’s talazoparib.”

-

Leerink

06/29/16

We

think

the

PARP Inhibitors Act Through Dual Cytotoxic Mechanisms

National Cancer Institute Research (Yves Pommier)

7

Source:

Murai

et

al.

Cancer

Res

2012,

72(21)

5588-99;

and

Medivation. 

Mechanism 1:

PARP Enzyme

Inhibition

Mechanism 2:

PARP

Trapping

Cell death in DNA

damage repair

deficient cells

(e.g. BRCA-mutation)

DNA Damage

(Single-Strand)

DNA Damage

(Double-Strand)

Trapping of

PARP on DNA

Enhanced cell death in

any tumor cell with

single-strand DNA

damage

Talazoparib

PARP

Enzyme

Mechanism 1: Inhibition of PARP Enzyme

PARP Inhibitors Prevent DNA Damage Repair Leading to Tumor Cell Kill

8

Cancer cells replicate

frequently and make many

errors in DNA that require

repair for survival

PARP is the major DNA

repair enzyme

Tumors have many DNA

repair defects, such as

BRCA-mutations and other

HRD (homologous

recombination deficiency)

Tumors with HRD struggle

to repair and replicate DNA

When HRD is combined

with PARP inhibition, DNA

repair is so compromised

that tumors can no longer

survive

Source: Sonnenblick et al. Nature Reviews Clinical Oncology 2015; 12: 27–41.

9

Source:

Shen

et

al.

Clin

Cancer

Res

2013;

19:5003–15.

Note: PARP inhibition represents relative concentration for 50% inhibition in PARP1 enzyme assay.

Most Potent

PARP Enzyme Inhibitor

(~3x–8x)

Relative Potency for

PARP Enzyme Inhibition

Mechanism 1: Talazoparib is the Most Potent Inhibitor of

PARP Enzyme in Clinical Development

All PARP inhibitors inhibit

PARP enzyme…

10

Source:

Shen

et

al.

Clin

Cancer

Res

2013;

19:5003–15.

Note: PARP inhibition represents relative concentration for 50% inhibition in PARP1 enzyme assay; antitumor activity represents relative concentration

for 50% Capan-1 cell survival reduction in single-agent cytotoxicity assay.

Most Potent

PARP Enzyme Inhibitor

(~3x–8x)

Most Potent

Antitumor Activity

(~50x–2,000x+)

Relative Potency for

PARP Enzyme Inhibition

Relative Potency for

Cytotoxicity

If Talazoparib

is

3X

–

8X

More

Potent

than

Other

PARP

Inhibitors in

PARP Inhibition, Why is it 2,000X Better at Killing Cancer Cells in Vitro?

All PARP inhibitors inhibit

PARP enzyme…

…but potency of PARP enzyme

inhibition does not correlate

with antitumor activity…

And Why is Talazoparib Orders of Magnitude More Potent

than Olaparib in Cancer Xenograft Models?

BRCA-Mutated Breast Cancer Xenograft Mouse Model

11

Talazoparib 0.1 mg/kg

Talazoparib 0.33 mg/kg

Olaparib 100 mg/kg

Vehicle

Source: Shen et al. Clin Cancer Res 2013; 19:5003–15.

Note: MX-1 tumor xenograft model.  MX-1 is a human mammary carcinoma cell line that harbors BRCA1 deletion events and is BRCA1 deficient.

Because PARP Enzyme Inhibition is Not Key:  Olaparib Maximally Inhibits

PARP Enzyme Even at 40 mg, a Dose That is Clinically Ineffective

Current Olaparib Clinical Dose is 300-400mg BID

12

Source: Fong et al. NEJM 2009; 361: 123-134.

Maximum PARP

enzyme inhibition

evidenced by virtual

elimination of PAR in

human tumors

Because PARP Enzyme Inhibition is Not Key:  Rucaparib Maximally Inhibits

PARP Enzyme Even at 92 mg, a Dose That is Clinically Ineffective

Current Rucaparib Clinical Dose is 600mg BID

13

Phase 2 multi-center trial

investigating intermittent and

continuous dosing schedules

of rucaparib in germline BRCA-

mutation carriers with

advanced ovarian and breast

cancer.

Scatter plot showing % PARP

enzyme inhibition levels

relative to pretreatment levels

in patients’ peripheral blood

lymphocytes following

treatment with rucaparib.

Samples were analyzed using

a validated assay that uses

quantitative immunologic

detection of ex vivo

poly(ADPribose) formation.

Source: Drew et al. Br J Cancer. 2016;114:723-30.

Source: Shen et al. Clin Cancer Res 2013; 19:5003–15.

Note: PARP inhibition represents relative concentration for 50% inhibition in PARP1 enzyme assay; antitumor activity represents relative concentration

for 50% Capan-1 cell survival reduction in single-agent cytotoxicity assay; and temozolomide potentiation represents the relative concentration that,

when combined with 200 µmol/L of temozolomide, resulted in 50% growth inhibition of LoVo cells in a temozolomide potentiation assay.

All PARP inhibitors inhibit

PARP enzyme…

…but potency of PARP enzyme

inhibition does not correlate

with antitumor activity…

…while PARP trapping ability

is better correlated to

antitumor activity

Most Potent

PARP Enzyme Inhibition

(~3x–8x)

Most Potent

Antitumor Activity

(~50x–2,000x+)

Most Effective

PARP Trapping

(~50x–2,000x)

Relative Potency for

PARP Enzyme Inhibition

Relative Potency for

Cytotoxicity

Relative Potentiation of

Chemotherapy (Temozolomide)

Because

Cancer Cell Cytotoxicity Correlates Better with

PARP Trapping

than PARP Enzyme Inhibition

14

Mechanism 2: Talazoparib, When Bound to PARP, Traps

PARP Protein on Single-Strand DNA Breaks

15

PARP

PARP

PARP

PARP

Temozolomide             Radiation

Single-Strand DNA Breaks

PARP Trapping

Enhanced PARP-dependent cell killing

Talazoparib

Alkylation chemotherapies and radiation

create single-strand DNA breaks which

become sites for PARP trapping

Source: Medivation.

Publications Support PARP Trapping as a Better Correlate

with Tumor Cell Killing than PARP Inhibition

PARP Inhibitors Differ Markedly in PARP Trapping Ability

16

“Trapped PARP–DNA complexes

were more cytotoxic

than…PARP inactivation”

“a new mechanistic foundation

for the rational application of

PARP inhibitors in cancer

therapy”

“potency in trapping PARP

differed markedly among

inhibitors…, a pattern not

correlated with the catalytic

inhibitory properties for each

drug.”

“[Talazoparib] is the most potent

clinical PARP inhibitor tested to

date with the highest efficiency at

trapping PARP-DNA complexes”

Source: Murai et al. Cancer Res 2012, 72(21) 5588-99; and Murai et al. Molecular Cancer Ther 2014, 13 (2): 433–443.

Talazoparib is the Most Potent and Niraparib is the Second

Most Potent PARP Trapper in Clinical Development

Slide 20, Yves Pommier, 13th International Congress on Targeted Anticancer Therapies, March 2015

17

Source: Pommier,13th International Congress on Targeted Anticancer Therapies (TAT 2015), Paris, March 2015, Slide 20.

Talazoparib is the Most Potent and Niraparib is the Second

Most Potent PARP Trapper in Clinical Development

Source: Murai et al, Cancer Res 2012; Murai et al, Molecular Cancer Ther 2014.

18

Niraparib

is

2x more potent

at PARP trapping than Olaparib

Talazoparib

is

100x more potent

at PARP trapping than Olaparib

By inference, Talazoparib

is

50 fold more potent

at PARP trapping than Niraparib

PARP Trapping Potency Appears to Correlate Better with

Clinical Outcomes than PARP Enzyme Inhibition Potency

PARP Assays

1

Ovarian PFS

2

PARP-1

Enzyme

Inhibition

(IC50, nM)

Cytotoxicity

(IC90, nM)

Relative PARP

Trapping

Activity

BRCA-

Mutated

Patients

Non-BRCA

Mutated

Patients

Olaparib

6

4500

1

11.2 vs. 4.3

months

7.4 vs. 5.5

months

Niraparib

60

2300

2

21.0 vs 5.5

months

†

9.3 vs 3.9

months

Talazoparib

4

40

100

1

Data from:

Pommier,13th International Congress on Targeted Anticancer Therapies (TAT 2015), Paris, March 2015.

Cytotoxicity with DT40 cells.

2

Data from:

Ledermann et al, Lancet Oncol. 2014 Jul;15(8):852-61.

Company filings and press releases.

† Only includes gBRCA-mutated patients.

Only excludes gBRCA-mutated patients.

PFS = progression-free survival.

19

PARP trapping also

appears to be correlated

with better responses

beyond BRCA and HRD

Lower IC50s & IC90s

mean higher potency

50-100x better than

Niraparib and Olaparib

at PARP trapping

The Multi-Log Superiority of Talazoparib Over Olaparib in PARP

Trapping Correlates with a Multi-Log Superiority in NON-HRD Cell Kill*

20

(1) Cosmic database, Wellcome Trust Sanger Institute; CCLE database, Broad Institute.

*These cell lines have NO detectable mutations in the most common HRD genes:

ATM, ATR, BRCA1, BRCA2, FANCA, FANCD2, MRE11A, NBN, PALB21

Prostate cancer PC-3 cells

Ovarian cancer OvCAR3 cells

Niraparib, a More Potent PARP Trapper than Olaparib,

Resulted in Longer PFS than Olaparib

21

NIRAPARIB

(NOVA)

OLAPARIB

Sponsor

Tesaro

AstraZeneca

Trial

Phase 3 ovarian cancer trial

Phase 2 ovarian cancer trial

Setting

Maintenance following response to

platinum in recurrent ovarian cancer

Maintenance following response to

platinum in recurrent ovarian cancer

Design

Placebo-controlled

N>500 (target 490)

2:1 randomization

Two independent cohorts based on

gBRCA status

Placebo-controlled

N=265

1:1 randomization

One cohort including patients with

BRCA mutation

Dosing

300 mg QD (3 pills per day)

400 mg BID (16 pills per day)

Primary Endpoint

PFS

PFS

Drug vs. Placebo PFS

by Patient Subgroup

gBRCA: 21.0 vs 5.5 months

g/sBRCA:

11.2 vs 4.3 months

non-gBRCA:

9.3 vs 3.9 months

non-g/sBRCA:

7.4 vs 5.5 months

non-gBRCA HRD+: 12.9 vs 3.8 months

Source: Ledermann et al, Lancet Oncol.

2014 Jul;15(8):852-61. Company filings and press releases.

Note:  gBRCA = germline BRCA mutation; sBRCA = somatic BRCA mutation; PFS = progression-free survival

22

Single-Strand DNA Breakers (e.g., Low-Dose Chemo) Can

FURTHER Amplify Talazoparib’s Superior PARP Trapping

Potentially Registrational Studies to Evaluate Combination to Begin by YE 2016

Source: Medivation.

Note:

NCI-H209

SCLC

xenograft

model.

Talazoparib

and

temozolomide

were

administered

orally,

once

daily

for

4

days

x

3

as

indicated. 

Temozolomide dose was 3mg/kg and talazoparib dose was 0.25 mg/kg.

Vehicle

Temozolomide

Talazoparib

Talazoparib + Temozolomide

Single-Strand DNA Breakers (e.g., Low-Dose Radiation) Can

FURTHER Amplify Talazoparib’s Superior PARP Trapping

23

Source:

Wong

et

al.

Potent

anti-tumor

activity

of

talazoparib

(BMN673)

in

combination

with

radiation

for

squamous

cell

carcinoma

of

the

head

and

neck.

AACR 2015.  Note: DMSO: vehicle; IR only: radiation only:

Enhancement of Head and Neck Cancer Cell Kill with

Talazoparib in Combination with Low-Dose Radiation

Talazoparib is the Most Specific PARP Inhibitor for PARP1

and PARP2 in Clinical Development

PARP1 and PARP2 are the PARP Isoforms Used Most by Cancers

24

Source: Poster presented by Herwig Schuler at the 2014 PARP meeting. Wahlberg et al. Nature Biotech 2012; 30: 283-289.

Specificity: Talazoparib > Veliparib > Olaparib > Rucaparib

Olaparib

Veliparib

Rucaparib

Talazoparib is a Highly Specific PARP Inhibitor and has

Lower Off-Target Cell Toxicity

Cell Viability Assay in PARP1/2 Deficient Cells

25

Source:

Murai

et

al.

Mol

Cancer

Ther

2014,

13

(2):

433–443.

Note: DT40 PARP1-/-

avian B lymphoblast cells used are equivalent to PARP1 and PARP2 double knockout cells and do not have detectable levels

of PARP activity.

Talazoparib has less effect on PARP1 and PARP2 deficient cells than other PARP inhibitors in

clinical development, showcasing greatly reduced off-target toxicity

Talazoparib

Olaparib

Rucaparib

Talazoparib’s Cell Killing Effects are More PARP-Specific

than Niraparib in TK6 Human Lymphoblastoid Cells

26

TALAZOPARIB

NIRAPARIB

A cell line lacking PARP1 suffers little toxicity from Talazoparib at clinically effective doses

Source: Pommier lab, NCI, unpublished data.

Third-Party Comparison of Adverse Event Profile of

Talazoparib vs. Other PARP Inhibitors

Talazoparib: >10% pts

Niraparib: >10% pts

Olaparib: >15% pts

Rucaparib: >15% pts

Note: Compiled by BioMarin.  Source: Wainberg et al. ASCO 2014 (1mg patients), Kaufman et al. ASCO 2013 (400mg patients), Sandu et al. Lancet

Oncology

2013 (290-300mg patients), and Swisher et al. SGO 2015 (600mg patients).

12%

4%

5%

33%

30%

23%

25%

16%

10%

2%

Anemia

Thrombocytopenia

Neutropenia

Lymphopenia

Nausea

Vomiting

Constipation

Anorexia

Diarrhea

Dyspepsia

Dysgeusia

Fatigue

Insomnia

Alopecia

ALT/AST Increased

0%

10%

20%

30%

40%

50%

60%

70%

Talazoparib

Gr

1–2

Talazoparib Gr 3–4

16%

59%

35%

21%

26%

17%

16%

53%

17%

2%

1%

6%

Anemia

Thrombocytopenia

Neutropenia

Lymphopenia

Nausea

Vomiting

Constipation

Anorexia

Diarrhea

Dyspepsia

Dysgeusia

Fatigue

Insomnia

Alopecia

ALT/AST Increased

0%

10%

20%

30%

40%

50%

60%

70%

47%

25%

24%

15%

56%

25%

36%

27%

49%

13%

11%

15%

5%

2%

2%

2%

5%

Anemia

Thrombocytopenia

Neutropenia

Lymphopenia

Nausea

Vomiting

Constipation

Anorexia

Diarrhea

Dyspepsia

Dysgeusia

Fatigue

Insomnia

Alopecia

ALT/AST Increased

0%

10%

20%

30%

40%

50%

60%

70%

Niraparib

Gr

1–2

Niraparib Gr 3–4

10%

59%

20%

28%

26%

16%

36%

43%

19%

4%

2%

1%

2%

1%

6%

Anemia

Thrombocytopenia

Neutropenia

Lymphopenia

Nausea

Vomiting

Constipation

Anorexia

Diarrhea

Dyspepsia

Dysgeusia

Fatigue

Insomnia

Alopecia

ALT/AST Increased

0%

10%

20%

30%

40%

50%

60%

70%

Rucaparib

Gr

1–2

Rucaparib

Gr

3–4

30%

7%

Olaparib

Gr

1–2

Olaparib Gr 3–4

27

Clinical Data and Development Plans

Talazoparib

(MDV3800)

Talazoparib Will Be Tested Across Multiple Solid Tumor

Indications

Current Talazoparib Clinical Development Plan

29

Phase 1

Phase 2

Phase 3

Breast Cancer

(Germline BRCA-Mutation) (EMBRACA)

Potential Addressable

Patient Population

1

10K

Reviewed with FDA

Potentially registrational

Prostate Cancer

(Monotherapy, Genetically-selected)

Select optimal

regimen for Phase 3

Prostate Cancer

(Monotherapy & Low-dose

Combo Chemo, All-comers)

140K

Small Cell Lung Cancer

(Monotherapy & Low-dose

Combo Chemo, All-comers)

Reviewed with FDA

Registrational

80K

Select optimal

regimen for Phase 3

Breast Cancer

(Monotherapy & Low-Dose

Combo Chemo, All-comers)

140K

Potentially registrational

Ovarian Cancer

(PARP-failures & TBD)

100K

Note: Light blue shading indicates trials expected to be initiated in 2016. Further clinical development plans under review.  Last updated July 6, 2016. 

1

Addressable patient population defined as all lines of treatable metastatic patients in U.S. and Europe in 2016. Source: © 2016 DR/Decision

Resources, LLC.  All rights reserved.  Reproduction, distribution, transmission or publication is prohibited.  Reprinted with permission.

Talazoparib: The Leading Breast Cancer PARPi Program

30

Note: gBRCA = germline BRCA; BRCAm = BRCA-mutated; ORR = objective response rate; CBR = clinical benefit response

RATIONALE

DESIGN

OUR

OPPORTUNITY

EMBRACA

BREAST

CANCER

BEYOND

gBRCA

High ORR / CBR in phase

1 in gBRCA-mutated

patients, as monotherapy

Phase 3 randomized (2:1)

trial vs. physician’s choice

in gBRCA-mutated locally

advanced and/or

metastatic breast cancer

Powered to show overall

survival (OS) benefit

Potentially superior PFS

prolongation relative to

other PARP inhibitors

Largest BRCAm

breast

cancer trial, potentially

best-powered to show an

OS advantage

Preclinical data supporting

activity in non-gBRCA-

mutated patients  

Multi-arm Phase 2 study,

testing talazoparib

monotherapy

and in

combination with low-dose

chemotherapy, with the

primary endpoint of PFS

Study in a broad breast

cancer population (non-

genetically selected)

Only combination with

chemotherapy study in this

indication

Talazoparib was Studied in a Phase 1 Trial as a

Monotherapy in BRCA-Mutated Cancer Patients

Evaluated 46 Germline BRCA-Mutated Breast and Ovarian Cancer Patients

31

Note: Asterisk indicates Talazoparib.

Safety and Antitumor Activity of the PARP inhibitor BMN 673

*

in a Phase 1

Trial Recruiting Metastatic Small-Cell Lung Cancer (SCLC) and Germline BRCA

Mutation Carrier Cancer Patients

1

David

Geffen

School

of

Medicine

at

University

of

California,

Los

Angeles,

CA,

2

Institute

of

Cancer

Research,

Royal

Marsden

NHS

Foundation

Trust,

Sutton,

United

Kingdom,

3

Virginia

G.

Piper

Cancer

Center

at

Scottsdale

Healthcare/TGen,

Scottsdale,

AZ,

4

Indiana

University,

Indianapolis,

IN,

5

University

of

Texas

MD

Anderson

Cancer

Center,

Houston,

TX,

6

University

of

Michigan,

Ann

Arbor,

MI,

7

BioMarin

Pharmaceutical,

Novato,

CA

Zev

A.

Wainberg

1

,

Saeed

Rafii

2

,

Ramesh

K.

Ramanathan

3

,

Lida

A.

Mina

4

,

Lauren

Averett

Byers

5

,

Rashmi

Chugh

6

,

Jonathan W. Goldman

1

, Jasgit

Sachdev

3

, Daniela Matei

4

, Jennifer J. Wheler

5

, Joshua W. Henshaw

7

, Charlie Zhang

7

, Gilles

J.A. Gallant

7

, Johann S. de Bono

2

Talazoparib Demonstrated Compelling Activity in BRCA-

Mutated Breast Cancer Patients

RECIST Response in Germline BRCA-Mutated Breast Cancer

32

At the 1 mg/day Phase 3 dose:

7/14 had an objective response (ORR = 50%)

12/14 had a clinical benefit response (CBR = 86%)

Source: Wainberg et al. ASCO 2014.

Note: CR = complete response, PR = partial response, SD = stable disease and PD = progressive disease.

Genetic Status

N

CR

PR

SD <24

weeks or

PD

7

11

0

1

2

5

1

1

4

4

Deleterious BRCA1 mutation

Deleterious BRCA2 mutation

Total

18

1

(6%)

7

(39%)

5

(28%)

RECIST Response

5

(28%)

SD   24

weeks

Kaplan-Meier Estimates:

Median duration of response: 32.0 weeks

95% C.I.: 19.9 –

40.3 weeks

Median progression-free survival: 32.1 weeks

95% C.I. 13.1 –

43.4 weeks 

Talazoparib Demonstrated Strong Objective Responses in

BRCA-Mutated Breast Cancer Patients

BRCA-Mutated Breast Cancer RECIST Response Waterfall Plot

33

Source: Wainberg et al. ASCO 2014.

Note: Asterisks indicate treatment ongoing at the time of data cutoff (April 18, 2014).

-100

-80

-60

-40

-20

0

20

Dose (mg/day)

0.9

1.0

1.1

BRCA 1

BRCA 2

Third-Party Analysis of PARP Inhibitors in BRCAm Breast

Cancer Supports Talazoparib’s Best-In-Class Potential

Comparison of Single-Agent Activity in BRCA-Mutated Breast Cancer

34

Source:

Barclays

Research;

Kaye

et

al.

J

Clin

Oncol

2012

Feb

1;

30

(4):

372;

company

reports.

Olaparib

Niraparib

Talazoparib

Phase 2 Breast POC

Phase 2

Phase 1/2

Phase 1

Dosing

100mg BID

400mg BID

400mg BID

Various

0.9–1.1mg QD

1mg QD

Size, n

27

27

62

4

18

14

Prior Regimens,

median

3

3

4.6

5

3

Platinum

22%

30%

33%

ORR, %

22%

41%

13%

50%

44%

50%

CR

–

4%

–

6%

7%

PR

22%

37%

13%

50%

39%

43%

CBR, %

67%

85%

60%

72%

86%

SD

44%

44%

47%

28%

36%

(>23wks)

(>23wks)

(>8wks)

(>24wks)

(>24wks)

PFS (months)

3.8

5.7

8.0

EMBRACA: Talazoparib Phase 3 Study in Germline BRCA-

Mutated Metastatic Breast Cancer is Ongoing

Note: Enrollment Initiated in October 2013.

Compare PFS of patients treated with monotherapy

talazoparib relative to those treated with protocol-specified

physician’s choice single-agent chemotherapy

Up to 430 women with gBRCA-mutated locally advanced

and/or metastatic breast cancer

Powered for hazard ratio = 0.67

Two-arm study:  Talazoparib 1 mg per day vs protocol-

specified physician’s choice of chemotherapy

Primary endpoint: Progression-free survival (PFS)

Radiographic progression determined by blinded independent

central radiology review

35

GOAL

Phase 3 EMBRACA is Similar to Competitors’ Trials, but

More Conservatively Designed and Higher-Powered

Comparison of Phase 3 BRCA-Mutated Breast Cancer Trial Designs

36

BRAVO

(Niraparib)

OlympiAD

(Olaparib)

EMBRACA

(Talazoparib)

Sponsor

Tesaro

AstraZeneca

Medivation

Phase 3 Dose Same as Phase 2 Dose?

Yes

No

Yes

Clinical Dose

300mg QD

300mg BID

1mg QD

Target Hazard Ratio (control / active)

0.5

NA

0.67

Target Enrollment

306

310

429

Accrual

Enrolling through

2016

Enrollment

complete

Complete

enrollment in 2016

Option to read out early

Reduce target

number of events

Source: Medivation, company filings and presentations, ClinicalTrials.gov, and Balmana et al. SABC 2015 Poster OT1-03-05.

Talazoparib is Being Studied in a Phase 2 Trial for the

Treatment of Breast Cancer Beyond BRCA-Mutation

37

Source: Medivation and ISPYTrials.org.

I-SPY 2 trial sponsored by QuantumLeap Healthcare Collaborative.  Talazoparib arm of Phase 2 trial activated in May 2016.

"The

I-SPY

2

TRIAL

is

designed

to

rapidly

test

promising

agents

to

reduce

the

cost,

time

and

number

of

patients

needed

to

bring

new

therapies

to

breast

cancer

patients

who

urgently

need

new

treatment

options.”

“We

are

very

excited

to

initiate

a

new

trial

arm

of

talazoparib

that

is

designed

to

optimize

our

understanding

of

this

investigational

drug

and

avoid

some

of

the

complications

of

paclitaxel,

which

is

part

of

the

current

standard

treatment."

Laura J. Esserman, M.D.

Principal Investigator of I-SPY 2

I-SPY 2 Trial

Talazoparib + Irinotecan in Neoadjuvant Breast Cancer

GOAL Compare pCR rates in women with early breast

cancer when treated in the neoadjuvant setting with

either talazoparib + irinotecan or paclitaxel followed by

standard chemotherapy

Neoadjuvant setting in patients with newly-diagnosed,

locally-advanced breast cancer

Up to 75 patients with HER-2 negative breast cancer will be

enrolled in the talazoparib arm

Talazoparib arm: 1 mg talazoparib once-daily + low-dose

irinotecan followed by standard chemotherapy

Talazoparib arm activated in May 2016

Control arm: paclitaxel followed by standard chemotherapy

Primary endpoint: Pathologic complete response

Therapies found effective in I-SPY 2 can move onto a

more focused Phase 3 registration trial (I-SPY 3)

Talazoparib: The Leading Prostate Cancer PARPi Program

MONO-

THERAPY

STUDY

Single-arm study in post-

NHT / post-chemotherapy

mCRPC patients

Patients selected for DNA

repair defects

Alignment on trial design

with FDA reached,

potential for accelerated

approval

CHEMO-

COMBINATION

STUDY

Monotherapy and in

combination with low-dose

chemotherapy in mCRPC

non-genetically defined

patients

Phase 2 trial with data in

2017

DESIGN

Potential to be the first

PARPi approved for

prostate cancer

Leverages existing

development and

commercial expertise and

capabilities

OUR

OPPORTUNITY

Study in a broad prostate

cancer population (non-

genetically selected)

Compelling response rates

were observed with a

PARPi in heavily pre-

treated mCRPC patients

Johnson & Johnson in-

licensing of a PARPi for

prostate cancer provides

further validation (up to

$500m in payments plus

royalties)

Strong synergistic effect

with temozolomide

demonstrated in preclinical

prostate cancer model

RATIONALE

38

Note: mCRPC = metastatic castration-resistant prostate cancer; NHT = novel hormonal therapy.

Investigator-Initiated Study of a PARPi in Advanced Prostate Cancer

39

Source:

Mateo

et

al.

N

Engl

J

Med

2015

Oct

29;

373(18):1697-708.

Study:

A Phase 2

Trial of Olaparib in

Patients With Advanced Castration

Resistant Prostate Cancer

(TOPARP)

Sponsor:

Institute of Cancer

Research, United Kingdom

Collaborator:

Royal Marsden NHS

Foundation Trust

Principal Investigator:

Johann de

Bono

Enrollment:

50 patients

Data Presentation:

AACR 2015

Publication:

NEJM October 2015

FDA Breakthrough Therapy:

Granted in January 2016

The TOPARP Study Demonstrated the Potential of PARP

Inhibitors in the Treatment of Prostate Cancer

Data from TOPARP Study with PARPi in Advanced Prostate Cancer

Patients dosed

50

Evaluable for response        

49

Prior lines of treatment

n (%)

Docetaxel

50 (100%)

Cabazitaxel

29 (58%)

Zytiga

(abiraterone)

48 (96%)

Xtandi (enzalutamide)

14 (28%)

40

Heavily pre-treated patient

population

Prior Zytiga and/or

Xtandi 49/50 (98%)

Response rate: 33%

(16/49 patients)

13/16 responders dropped

circulating tumor cells

(CTCs) to zero

Median duration of treatment

in responders was 40 weeks

Striking Effects were Observed in Heavily Pre-treated,

Advanced Metastatic Prostate Cancer Patients

Source: Mateo et al. N Engl J Med 2015 Oct 29; 373(18):1697-708.

Strong Activity Occurred in Most Patients with DNA Repair Defects

41

16/49 (33%) of patients

were identified as

having DNA-repair

defects

Of these 16 patients,

14 patients had a

response (88%)

All 8 patients with a

BRCA1 or BRCA2 loss

had a response

PARP Inhibition Even More Effective in Patients with HRD

in TOPARP

Source:

Mateo

et

al.

N

Engl

J

Med

2015

Oct

29;

373(18):1697-708.

Radiologic Progression-Free Survival: Biomarker+ vs. Biomarker-

42

PARP Inhibition Even More Effective in Patients with HRD

in TOPARP

Hazard Ratio: 0.24 (95% CI, 0.11 –

0.50)

Source:

Mateo

et

al.

N

Engl

J

Med

2015

Oct

29;

373(18):1697-708.

Selected Talazoparib Preclinical Prostate Cancer Data

43

Talazoparib’s Potency and PARP Trapping Ability Could

Make It Best in Class for the Treatment of Prostate Cancer

Source: Medivation, unpublished data.

Note: Monotherapy study in LNCaP cells, which are patient-derived prostate cancer cell line with pathogenic mutations in DNA repair genes including

ATM, CHEK2, ERCC2, ERCC3, FANCA, and HDAC2. 

Talazoparib Appears Significantly More Potent than Olaparib

as a Monotherapy in Prostate Cancer Cells

Low-Dose Temozolomide Potentiates the Anti-tumor Effects of

Sub-Maximal Talazoparib Doses in Prostate Cancer Cells

Talazoparib Single-Agent

Low-Dose Talazoparib with Temozolomide

Concentration tested for temozolomide potentiation

Source: Medivation, unpublished data.

Note: Temozolomide combination study in PC-3 prostate cancer cells.

44

Talazoparib: The Leading Small Cell Lung Cancer (SCLC)

PARPi Program

1L

MAINTENANCE

STUDY

Phase 3 maintenance

study after first-line

chemotherapy

Monotherapy and in

combination with low-dose

temozolomide

Alignment with FDA

reached

DESIGN

Potentially first

registrational study in a

broad lung cancer

population (all-comers,

non-genetically selected)

OUR

OPPORTUNITY

10% ORR

1

observed with

talazoparib as

monotherapy in phase 1

study

Significant synergy

observed between

talazoparib and low-dose

temozolomide in

preclinical models

Temozolomide is used in

SCLC

PR observed in IST

evaluating talazoparib +

irinotecan in SCLC patient

RATIONALE

45

1

Calculated as the ORR of evaluable patients.

Source: Wainberg et al. ASCO 2014, and Medivation.

Note: ORR = objective response rate; PR = partial response; IST = investigator-sponsored trial

46

Talazoparib Demonstrated Single-Agent Activity in Patients

with Advanced Previously-Treated Small Cell Lung Cancer

Source: Wainberg et al. ASCO 2014, and Medivation.

-75

-50

-25

0

25

50

75

Dose (mg/day)

1.0

Small Cell Lung Cancer RECIST Response Waterfall Plot

Kaplan-Meier Estimates:

Median duration of response: 13.6 weeks

95% C.I.: 12.0 –

15.3 weeks

Median progression-free survival: 11.1 weeks

95% C.I. 4.3 –

13.0 weeks 

Talazoparib’s PARP Trapping Activity Synergizes Effectively

with Low-Dose Temozolomide in SCLC Animal Model

47

Vehicle

Temozolomide

Talazoparib

Talazoparib + Temozolomide

Source: Medivation.

Note: NCI-H209 SCLC xenograft model.  Talazoparib and temozolomide were administered orally, once daily for 4 days x 3 as indicated.  

Temozolomide dose was 3mg/kg and talazoparib dose was 0.25 mg/kg.

Talazoparib: Exploiting PARP Trapping in Ovarian Cancer

PARP-

FAILURE

&

PARP-

SENSITIVE

STUDY

Potentially registrational

study with multiple arms

testing monotherapy and

combination low-dose

chemotherapy in both

PARP-sensitive and

PARP-failure patients

DESIGN

Potentially first

registrational study to

show activity in PARP-

failures

Potentially rapid path to

approval

OUR

OPPORTUNITY

48% ORR observed in

heavily treated patients in

Phase 1 (n=12)

57% ORR (4/7) observed

in non-gBRCA ovarian

patients in IST (+ low-dose

chemotherapy)

2 ovarian olaparib

failures experienced 6+

months SD (ASCO, 2016)

Responses observed in

both platinum-sensitive

and platinum-resistant

patients

RATIONALE

48

Source: Wainberg et al. Oral presentation, AACR 2016, and Medivation.

Note: ORR = objective response rate; SD = stable disease; IST = investigator-sponsored trial.

Talazoparib Demonstrated Compelling Activity in BRCA-

Mutated Ovarian Cancer Patients

RECIST Response in Germline BRCA-Mutated Ovarian Cancer

49

Clinical benefit response rate (CR, PR, SD

24 weeks): 23/28 (CBR = 82%)

Source: Wainberg et al. ASCO 2014.

Note: ORR = objective response rate, CR = complete response, PR = partial response, SD = stable disease and PD = progressive disease.

(1)

25 of 28 patients measurable by RECIST.

(2)

27 of 28 patients evaluable for CA-125.

Deleterious Mutation

N

Response

CR/PR

SD

>

24 weeks

SD < 24

weeks/PD

RECIST

(1)

CA-125

(2)

BRCA1

20

8

13

4

3

BRCA2

8  

4

6

0

2

Total

28*

12

(48% ORR)

19

(70% ORR)

4

(14%)

5 

(18%)

Talazoparib Demonstrated Compelling Activity in BRCA-

Mutated Ovarian Cancer Patients (continued)

BRCA-Mutated Ovarian Cancer RECIST Response Waterfall Plot

50

Source: Wainberg et al. ASCO 2014.

Note: Asterisks indicate treatment ongoing at the time of data cutoff (April 18, 2014).

Kaplan-Meier Estimates:

Median duration of response: 26.9 weeks

95%

C.I.:

15.9

–

28.1

weeks

Median progression-free survival: 32.9 weeks

95%

C.I.

28.1

–

40.4

weeks 

-100

-80

-60

-40

-20

0

20

Dose (mg/day)

0.1

0.2

0.4

0.6

0.9

1.0

1.1

BRCA 1

BRCA 2

Talazoparib Plus Low-Dose Chemotherapy Clinical Data (AACR 2016)

51

Superior PARP Trapping May Lead to Improved Clinical Outcomes

in Broad Patient Populations as Seen in Ovarian Cancer

Phase 1 data from a 40 patient study of

talazoparib in combination with low-dose

chemotherapy in heavily pre-treated

advanced malignancies

4/7

objective

responses

in

non-

BRCA

mutated ovarian cancer patients

1 responder did not even have HRD

suggesting possibilities of treating

patients without genetic selection

Additional responses in Ewing’s

sarcoma, cervical adenocarcinoma,

SCLC and TNBC

Olaparib was approved based on 34%

objective

response

rate

(ORR)

in

BRCA-

mutated ovarian cancer

Talazoparib is active in tumors with defects in DNA repair genes beyond BRCA-mutations

(larger market than BRCA) and possibly even without HRD (largest market)

All

(CBR)

Ovarian Cancer, non-BRCA-mutated

(ORR)

(CBR)

(>50%   CA-125)

Source: Wainberg et al. Oral presentation, AACR 2016, and FDA product label for olaparib.

Note: Chemotherapy regimens included temozolomide and irinotecan.  HRD = homologous recombination deficiency and CBR = clinical benefit rate.

Phase 1 Response Data

(talazoparib with low-dose chemotherapy)

58%

57%

86%

86%

Talazoparib Investigator-Sponsored Trials

52

Talazoparib is Being Further Explored Across Indications

through Several Investigator-Sponsored Studies

Investigator

Institution

Phase

Indication

Other

Wainberg

UCLA

Phase 1

Advanced solid

tumors

Combination with irinotecan or temozolomide

Piha-Paul

MD Anderson

Phase 2

Advanced cancers

Somatic BRCA-mutations and deletions

HRD

positive

PTEN deficiency

gBRCAm (not breast or ovarian)

Munster

UCSF

Phase 1

Triple negative breast cancer

Combination

with carboplatin

Triple negative breast cancer with BRCAness

Other tumors with BRCAm

Chen

NCI

Pilot

Advanced solid tumors

Deleterious BRCAm

Lee

NCI

Phase 2

Advanced solid tumors

Deleterious BRCAm

Prior

PARP inhibitor treatment

Litton

MD Anderson

Pilot

Neoadjuvant breast

cancer

Invasive

breast cancer with deleterious BRCAm

Federico

St. Jude

Phase 1

Pediatric solid tumors

Combination with irinotecan +/-

temozolomide

Telli

Stanford

Phase 2

Triple negative breast cancer

HER2-negative

breast cancer

HRD positive

Wisinski

University of Wisconsin

Phase 1

Advanced solid tumors

Combination

with carboplatin and paclitaxel

Schafer

Baylor

Phase

1/2

Pediatric malignancies

Combination with temozolomide

Esserman

Multisite

Phase 2

Neoadjuvant breast

cancer

Combination with irinotecan (I-SPY 2)

Owonikoko

Multisite

Phase 2/3

Non-small cell lung cancer

2nd-line, HRD positive patients (LUNG MAP)

Note: Includes collaborative/cooperative-group studies (I-SPY 2 and LUNG MAP).  HRD = homologous recombination deficiency.

Multiple Indications to Pursue as Monotherapy or Combination Therapy

53

Talazoparib Holds the Potential to Address Multiple Tumor

Types and a Large Commercial Opportunity

Potential Addressable Patient Population

(U.S. and Europe)

Phase

Potential

Launch

2022-23

2022-23

P2

ready

P3

ready

2020-21

P2/3

ready

2019-22

P3

2018

~760k

P2

ready

2021-22

P2

ready

2022-23

Addressable Market

(U.S. and Europe)

Talazoparib

Opportunity

>$30bn

Note:

Addressable

patient

population

defined

as

all

lines

of

treatable

metastatic

patients

in

2016.

Dollar

figures

reflect

current

PARP

inhibitor

pricing.

Source:

Medivation;

Peshkin

et

al.

Breast

Dis

2010;

TCGA,

Nature

2012;

Mateo

et

al.

N

Engl

J

Med

2015;

and

TCGA

Nature.

2011;

and

© 2016 DR/Decision Resources, LLC.  All rights reserved.  Reproduction, distribution, transmission or publication is prohibited.  Reprinted with permission.

Breast

(gBRCAm)

Prostate

SCLC

Ovarian

P2

ready

NSCLC

10k

140k

80k

100k

140k

60k

230k

Current Patient

Opportunity

Breast

(Beyond BRCAm)

Glioblastoma