Pharmacyclics

Corporate Presentation
March 2014

Safe Harbor Statement

During the course of this presentation we will make statements that constitute
forward-looking statements. These statements may include operating expense
projections, the initiation, timing and results of pending or future clinical trials,
the actions or potential action of the FDA, the status and timing of ongoing
research, corporate partnering activities and other factors affecting
Pharmacyclics financial condition or operations. Such forward-looking
statements are not guarantees of future performance and involve risks,
uncertainties and other factors that may cause actual results, performance or
achievements to vary materially from those expressed or implied in such
statements. These and other risk factors are listed from time to time in reports
filed with the Securities and Exchange Commission (SEC), including but not
limited to, reports on Forms 10-Q and 10-K. Pharmacyclics does not intend to
update any forward-looking information to reflect actual results or changes in
the factors affecting the forward-looking information.

Making a difference for the betterment of patients

Our Mission
To build a viable biopharmaceutical company that
designs, develops and commercializes novel therapies
intended to improve quality of life, increase duration of life
and resolve serious medical healthcare needs.
To identify and control promising product candidates
based on exceptional scientific development and
administrational expertise, develop our products in a
rapid, cost-efficient manner and to pursue
commercialization and/or development partners when and
where appropriate.
We exist to make a difference for the better and these are
important times to do just that.
3

PCYC Corporate Development

Jan 2006 to Dec 2008

SharePrice
$6
$4.92

04/10/06:
Assumptionof
Celeracompounds
BTK,FVIIa,HDAC

$5.07

$5

$4

$3

02/22/07:
FDARefusalto
file letterfor
Xcytrin

09/19/07:
BobDuggan
joinsPCYC
Board

10/21/07:
FDA Non
approvable
letterforXcytrin

05/01/08:
Offertopurchase
4M sharesat
$1.05/share
byRWDuggan

09/11/08:
PCYC Board&
Management
Transition

$2
$1.45

$0.79

$1

$0

PCYC Corporate Development

Jan 2009 to Mar 2014
11/13/13:
IMBRUVICA
approved forMCL
ptsw/atleastone
priortherapy.
PCYC'sfirstlabel.

SharePrice
$160

02/12/14:
IMBRUVICA
approved forCLL
ptsw/atleastone
priortherapy.

07/10/13: PCYCannounceditsfirstNDAfiling
ofibrutinib,fortreatmentofpatientswith
R/RCLLandR/RMCL.

$140

$120
2/12/13: PCYCreceivesBreakthrough
TherapyDesignationfromtheFDAforMCL
andWM. $70.37

$100

$80

$60

$40

$20

12/31/08
Price: $0.79
Employees:47
Mkt Cap:$20M
W.Cap: $7.2M
$6Mloanby
R.W.Duggan

8/5/2009
RightsOffering
22.5Mshares
soldat$1.28

$57.78
6/21/10: PCYC
raises$50.8M
netproceedsina
registereddirect
offering.
$6.74
$3.14

07/17/11:
Secondary
Offering
6.5Mshares
soldat$8.85

$14.82

12/8/11: PCYC
entersinto
collaboration
agreementwith
JanssenBiotech,
Inc.

$6.08

$0

IMBRUVICA Approved November 13, 2013 in MCL

and February 12, 2014 in CLL
4.5yearsfrom1st patientintoNDAfiling

4.5monthsfromfilingtofirstFDAapproval

Headlines and Highlights.Approval Grabs Attention

of Top Tier Media
[IMBRUVICA]isarevolutionary
bloodcancerdrug.

J&J-Pharmacyclics
Win U.S. Approval for
Breakthrough Drug

FDA speedily approves

Imbruvica, a treatment
for rare lymphoma
7

IMBRUVICA (ibrutinib)
Leads Our Oncology Pipeline
Molecule & Program / Indication

Discovery /
Preclinical

Phase
I

Phase
II

Phase
III

Ibrutinib (PCI-32765): Brutons tyrosine kinase (BTK) inhibitor for Oncology *

Chronic lymphocytic leukemia
Mantle cell lymphoma

APPROVED
APPROVED

Diffuse large B-cell lymphoma

Multiple myeloma
Follicular lymphoma
Waldenstroms Macroglobulinemia
Abexinostat HCI (PCI-24781): Histone deacetylase (HDAC) inhibitor for Oncology **
Follicular lymphoma and mantle cell
lymphoma
PCI-27483: Factor VIIa Inhibitor for Oncology
Pancreatic cancer
BTK inhibitor for Autoimmune Diseases
Autoimmune disease
*Janssen Biotech: global partnership
** Servier: ex-U.S. partnership
8

IMBRUVICA (Ibrutinib - PCI-32765)

IMBRUVICA is an oral therapy that targets an important

pathway in B-cell malignancies. Over 2800 patients
treated in company sponsored clinical trials.

IMBRUVICA was approved for the treatment of

patients with mantle cell lymphoma who have received
at least one prior therapy

IMBRUVICA has demonstrated in clinical trials:

o Tumor reduction (response) in heavily pretreated patients
o Responses in patients previously treated with
chemotherapy and with aggressive disease
o Durable responses with many patients still on drug after
prolonged periods of time
o Patient tolerability demonstrated

BTK Signaling Pathway

10

Mechanism of BTK: IMBRUVICA (ibrutinib PCI-32765)

Blocks Malignant B-cell Growth and Proliferation

ChronicLymphocyticLeukemiaCell

LymphNode

PeripheralBlood

From: de Rooij et al, Blood 119: 2590-2594

11

B-Cell Development and

Origin of B-cell Malignancies
Normal :

Pre-B

Immature
B

Immature

Germinal
Center B

Memory
B

Plasma
Cell

antibody producing

Leukemia

Malignant:

Nave
B

Chronic
Lymphocytic
Leukemia (CLL)
un-mutated

Adopted from:
2012 Pan Pacific Lymphoma Conference
J Rubenstein, M.D., Ph.D.

Chronic
Lymphocytic
Leukemia
mutated
Mantle Cell Lymphoma
(MCL)

Multiple
Myeloma
(MM)
Follicular
Waldenstroms
Lymphoma (FL)
Macroglobulinemia (WM)
Diffuse Large B-Cell
Lymphoma (DLBCL)
12

Clinical Program Overview

13

Patient Populations in
Major Hematology Malignancies
US

All Major Markets*

Incidence

Prevalence

Incidence

Prevalence

CLL/SLL

16,0001

114,5002

40,0001

259,0001

MCL

2,9001

11,3002

6,0001

37,0001

WM

1,5004

12,0002

6,0004

23,0004

DLBCL

25,0001

112,0002

53,0001

356,0001

FL

13,0001

63,0002

28,0001

240,0001

MM

20,0001

77,0001

48,0001

183,0001

TOTAL

82,500

390,0002

181,000

1,100,0001

1 2013DR/DecisionResources,LLC.Allrightsreserved.Reproduction,distribution,transmissionorpublicationisprohibited. Reprintedwithpermission.FortheCLLdiagnosed
incidencetheUSNationalCancerInstituteestimationswereused
2 IMSpatientclaimsestimatesforJuly2012June2013.Note:ThisinformationisanestimatederivedfromtheuseofinformationunderlicensefromthefollowingIMSHealthIncorporated
informationservice:IMSOncologyTrackingReportsfortheperiodJuly2012toJune2013.IMSexpresslyreservesallrights,includingrightsofcopying,distributionandrepublication.
3 Majormarketsinclude:US,UK,Spain,Germany,France,Italy,andJapan4 WMFoundationestimate
Pharmacyclics,Inc.makesnorepresentationwithrespecttotheaccuracyorreliabilityofthisinformation. Investorsareadvisedtoindependentlyverifythisinformation
beforeusingittomakeinvestmentdecisions.

14

CLL/SLL & MCL US Patient Estimates

CLL/SLL

MCL

Diagnosed Incidence 1

16,000

2,900

Prevalence 2

114,500

11,300

No Therapy 2

50,600

2,000

1L Therapy 2

23,200

3,900

2L Therapy 2

9,300

1,300

3L+ Therapy 2

6,100

800

25,300

3,300

*Other 2 (All these patients are between lines

of therapy; 1/3 received maintenance, 2/3 were
not on therapy in observation period)
1

2013DR/DecisionResources,LLC.Allrightsreserved.Reproduction,distribution,transmissionorpublicationisprohibited. Reprintedwithpermission.FortheCLL
diagnosedincidencetheUSNationalCancerInstituteestimationswereused.
2 IMSpatientclaimsestimatesforJuly2012June2013.Note:ThisinformationisanestimatederivedfromtheuseofinformationunderlicensefromthefollowingIMS
HealthIncorporatedinformationservice:IMSOncologyTrackingReportsfortheperiodJuly2012toJune2013.IMSexpresslyreservesallrights,includingrightsof
copying,distributionandrepublication.
Pharmacyclics,Inc.makesnorepresentationwithrespecttotheaccuracyorreliabilityofthisinformation. Investorsareadvisedtoindependentlyverify
thisinformationbeforeusingittomakeinvestmentdecisions.
15

Breakthrough Therapy Designations

and Regulatory Progress
IMBRUVICATM approved on November 13, 2013 for the treatment of
patients with MCL who have received at least one prior therapy and on
February 12, 2014 for the treatment of patients with CLL, who have
received at least one prior therapy.
New Drug Application (NDA) submitted in relapsed/refractory MCL
and relapsed/refractory CLL on July 10, 2013. NDA was accepted on
August 27, 2013 - Priority Review was granted with a PDUFA of Feb
28, 2014.
FDA approved Breakthrough Designations for IMBRUVICA in:
o Relapsed/Refractory Mantle Cell Lymphoma (MCL) Feb 2013
o Waldenstroms Macroglobulinemia (WM) Feb 2013
o Chronic Lymphocytic Leukemia (CLL) with deletion 17p Mar 2013

16

Clinical Development Plan: Select Studies of

IMBRUVICA in CLL/SLL Patients
PCYC/JNJ
/ISTs

Phase

Study ID

Status

Line of
Therapy

#of
Patients

Trial 1st
Released

PCYC1108

compl

RR

33

Feb11

i+FCR; i+BR

PCYC1103

active

RR

200

Jun10

RollOver Study

PCYC1117
RESONATE17

active

RR

111

Jan13

Monotherapy in17p

PCYC1102

compl

TN/RR

133

May10

Monotherapy

BurgerMDACC

active

RR

40

Feb12

i+R inhighriskpts

BurgerMDACC

recruit

RR

208

Dec13

ivs iR

PCYC1112
RESONATE

active

RR

350

Jun12

i vsOfa
(Crossoveradded8/13/13)

PCYC1115
RESONATE2

active

TN

272

Jan13

i vsChlorambucil inElderly

HELIOS

recruit

RR

580

Sept12

i+BR

CLL3002

notyet

RR

150

Oct13

i vs R(in China)

Woyach

notyet

TN

523

Jun13

ivsiR vsBRinElderly

CLL12

notyet

TN

302

ASH13

ivsPlacebo;Watch&Wait(German
StudyGroup)

ECOG

notyet

TN

519

ASH13

iR vs.FCR;YoungFit

II

CLL

III

StudyDesign

17

The Brutons Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765)

Monotherapy Demonstrates Long-Term Safety and Durability of
Response in Chronic Lymphocytic Leukemia/Small Lymphocytic
Lymphoma Patients in an Open-Label Extension Study (OBrien, ASH 2013)

A total of 148 patients TN or

R/R CLL/SLL received ibrutinib
monotherapy in a phase 1
multiple ascending dose study
(PCYC-04753)3 or phase 1b/2
continuous-dosing study
(PCYC-1102),4 and were
continued on a long-term
extension study for follow-up for
safety and efficacy with ibrutinib
monotherapy

Median Duration of Response

(DOR) was not reached for
either Treatment Nave (TN) or
Relapsed/Refractory (R/R)
responders achieving partial
response or better, after a
median follow-up of 28.1 and
23.9 months.

At 30 mos, 95.8% of TN and 69.7% of R/R

responders were alive without disease
progression.

18

The Brutons Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765)

Monotherapy Demonstrates Long-Term Safety and Durability of
Response in Chronic Lymphocytic Leukemia/Small Lymphocytic
Lymphoma Patients in an Open-Label Extension Study (OBrien, ASH 2013)

The percentage of patients with

a serious Adverse Events grade
3 declined from 43% within
the first year of study treatment
to 32% after the 1st year of
treatment.

Grade 3 AEs (severe) and serious

AEs (life threatening) declined from
24% to 7% and serious AEs
declined from 8 % to 0% from
the first year of treatment to
after the first year of treatment.

Safety: Treatment-Emergent Related AEs Grade 3 With Incidence 2%

AEs

Efficacy: Best Overall Response (ORR)

ResponseRate

AEs leading to ibrutinib

discontinuation occurred in
8.1% (12/148) of patients
within the first year of treatment
and declined to 5.5% (6/109) of
patients after the first year of
treatment.

Grade3=SevereGrade4=LifeThreatening

n(%)

TN65years
(n=31)

R/R
(n=117)

Total
(N=148)

ORR

25(80.6%)

98(83.8%)

123(83.1%)

27(87.1%)

104(88.9%)

131(88.5%)

ORR+PRL
(PartialResponsewith
Lymphocytosis)

19

Single Agent Ibrutinib Achieves Equal Responses in CLL

Patients With and Without Deletion 17p (Farooqui, ASH 2013)
Patient Population: 53 Total Patients

Non-Heme Toxicity

Normal (NL) 17p = 24 pts (8 pts TN/16 pts R/R)

Del 17p = 29 pts (15 pts TN/14 pts R/R)

Evaluable at 6 Mo: 47 pts (only 1 PD)

Est. Event Free Survival at 14 mo is 93%
4 pts (20%) had no evidence of 17p after 6 mos
Del17p does not confer resistance to ibrutinib
Responses

Progression Free Survival

(MedianFollowup:14mos)

20

Ibrutinib in combination with rituximab (iR) is well tolerated and induces

a high rate of durable remissions in patients with high-risk CLL: new,
updated results of a Phase II trial in 40 patients (Burger, ASH 2013)
i+R resulted in a ORR of 95% in high risk pts.
78% of patients were progression free after
18 mos.
The ORR in the 20 pts with del17p or TP53
mutation was 90% (16 PR, 2 CR).
Questionnaires revealed significantly
improved overall health and quality of life
after 6 months, which coincided with a
significant weight gain
at 3 and 6 months.
Treatment generally was well tolerated, with
infectious complications (6 cases of
pneumonia and 3 cases of upper respiratory
infections) being the most common
complication. There were two Grade 3,
possibly related AEs: mucositis (n=1), and
peripheral neuropathy (n=1). Milder toxicities
included Grade 1-2 bruising (n=7), Grade 1
subdural hematoma (n=1), fatigue (n=2),
bone pain, myalgias, and arthralgia (n=5), or
diarrhea (n=1).
21

21

Ibrutinib as initial therapy for elderly patients with chronic

lymphocytic leukaemia or small lymphocytic lymphoma:an
open-label, multicentre, phase 1b/2 trial (OBrien, Lancet 2013)

31 treatment nave pts

treated with ibrutinib
monotherapy.

After median follow-up of

22.1 mos, ORR was 71%
(13% CR)

Est. PFS: 96.3% at 24

mos (Figure A)

Est. Overall Survival:

96.6% at 24 mos
(Figure B)

22

Ibrutinib as initial therapy for elderly patients with chronic

lymphocytic leukaemia or small lymphocytic lymphoma:an
open-label, multicentre, phase 1b/2 trial (OBrien, Lancet 2013)

Toxicity was mainly of mild-to-moderate severity (grade 12). Three (10%)

patients developed grade 3 infections, although no grade 4 or 5 infections
occurred. One patient developed grade 3 neutropenia, and one developed grade 4
thrombocytopenia.
Improvements in hemoglobin, platelet counts, and absolute neutrophil counts
were observed in patients treated with ibrutinib
Median serum IgA, IgM, and IgG levels also showed significant improvement.

23

Clinical Development Plan: Select Studies of

IMBRUVICA in MCL patients

PCYC/JNJ
Phase
/ISTs

II

MCL
III
IV

#of
Patients

Trial 1st
Released

StudyDesign

Study ID

Status

Line of
Therapy

PCYC1104

active

RR

115

Feb11

Monotherapy

SPARK

active

RR

120

Aug12

Monotherapy;FailedBR

Wang
MDACC

recruit

RR

50

Jul13

i+R

RAY

recruit

RR

280

Dec12

Monotherapy vs.Temsirol

SHINE

recruit

TN

520

May13

i+BR inelderly

MCL4001

recruit

RR

250

Apr13

Monotherapy

24

Highlights EHA 2013: Phase II Monotherapy Trial in

Relapsed/Refractory MCL Patients-Long Term Follow
Up (Rule, EHA 2013)
PATIENTCHARACTERISTICSFORALLTREATEDPOPULATION
BortezomibNave
(N=63)

BortezomibExposed
(N=48)

Total
(N=111)

MedianAge, yrs(Range)

66(4683)

69(4084)

68(4084)

Gender:Male

46(73%)

39(81%)

85(77%)

ECOGStatus:
01
2
>2

53(84%)
9(14%)
1(2%)

46(96%)
2(4%)
0(0%)

99(89%)
11(10%)
1(1%)

Prior Regimens:
Median(Range)
3regimens

2(15)
31(49%)

3(15)
30(63%)

3(15)
61(55%)

MedianMonthsSince
Diagnosis(Range)

29(3213)

48(7223)

42(3223)

25

Highlights EHA 2013: Treatment Related and

Unrelated AEs Occurring in >15% of MCL Patients
(Rule, EHA 2013)
HematologicalAE
Neutropenia
Thrombocytopenia
Anemia
0%

10%

20%

30%

40%

50%

60%

Bleedingeventsgrade3occurredin5%ofpatients

NonHematologicalAE
Diarrhea
Fatigue
Nausea
Oedema peripheral
Dyspnea
Constipation
Upperrespiratorytractinfection
Vomiting
Decreasedappetite
Cough
Pyrexia
Abdominalpain
Contusion
Rash
0%

Grade1
Grade2
Grade3
Grade4
Grade5

10%

20%

30%

40%

50%

60%
26

Highlights EHA 2013: Phase II Monotherapy Trial in

Relapsed/Refractory MCL PFS and Duration of
Response (Rule, EHA 2013)
ProgressionFreeSurvival,%

100
80
60
40
20
0
PatientsAliveWithoutProgression,%

All
BortezomibExposed
BortezomibNave
Censored

Est.medianPFS=13.9mos
63
48
111

44
37
81

28
29
57

19
14
33

12
10
22

0
2
2

0
0
0

12

16

20

24

MonthsFromFirstDose
All
BortezomibExposed
BortezomibNave
Censored

100
80
60

Est.medianDOR=17.5mos

40
20
0

43
32
75

30
26
56

23
17
40

15
9
24

3
3
6

0
0
0

12

16

20

MonthsFromFirstResponse

27

Highlights EHA 2013: Phase II Monotherapy Trial in

Relapsed/Refractory MCL Patients-Long Term Follow
Up (Rule, EHA 2013)
ImprovementofCompleteandOverall
ResponseRatesOverTime

BestResponse
100
68

67

60
40

49

44

47

20

62.2

60

66.7

68

46.0

47.3

64

64.9

50.5

47.8

17.1

20.7

20.7

12

15

52.3

40

53.2
48.7

20
19

23

21
0

0
CR
PR

80

68
ResponseRate,%

Patients,%

80

100

Bortezomib
Nave
(n=63)

Bortezomib
Exposed
(n=48)

Total
(n=111)

3.6

9.0

13.5

Time,months

EfficacyPopulationn=111,EstimatedMedianFollowup15.3months
28

Clinical Development Plan: Select Studies of

IMBRUVICA in DLBCL patients

PCYC/JNJ

DLBCL

Phase

II

III

#of
Patients

Trial 1st
Released

Study ID

Status

Line of
Therapy

DLB1002

active

TN

32

Jun12

i+RCHOP;DLBCL,MCL,FL

PCYC1106

recruit

RR

125

May11

Monotherapy

PCYC1123

Notyet

RR

110

ASH13

i+R+Len vs.i+Len

PCYC1124

Notyet

RR

56

ASH13

i+Len+DAEPOCHR

DBL3001

recruit

TN

800

Sept13

i+RCHOP vs. RCHOP

StudyDesign

29

Highlights EHA 2013: Phase II Monotherapy Trial

in Relapsed/Refractory DLBCL Patients
(Vos, EHA 2013)

MolecularSubtypePredictsOutcomewithRCHOP

Background:

Sub-typed for activated B-cell

(ABC) or Germinal Center B
(GCB)
Median of 3 prior therapies (1-7)

Results:

ABC ORR 41%, CR 17%.

Additional Ongoing Studies:

Phase Ib dose escalation with CHOP-R (ORR 100%)

Randomized Phase III Frontline CHOP-R+/IMBRUVICA in non- GCB (800 patients)

30

Combining Ibrutinib With Rituximab, Cyclophosphamide, Doxorubicin,

Vincristine, and Prednisone (R-CHOP): Updated Results From a Phase
1b Study in Treatment-Nave Patients With CD20-Positive B-cell NonHodgkins Lymphoma (NHL) (Younes, ASH 2013)
Study Results:

560 mg + R-CHOP resulted in high responses in both GCB and non-GCB pts
A Phase 3 trial of R-CHOP ibrutinib is ongoing in de novo non-GCB pts.

31

Clinical Development Plan: Select Studies of

IMBRUVICA in Other NHL patients
PCYC/JNJ/
ISTs

Phase

Study ID

Status

Line of
Therapy

#of
Patients

Trial 1st
Released

UjjaniNCI

recruit

TN

33

Apr13

i+R+Len;FL

BlumOSU

recruit

RR

48

Dec11

i+BR;MZL,FL,WM,DLBCL,MCL

Christian
OSU

recruit

RR

34

Oct13

i+Len;MZL,FL,WM,DLBCL,
MCL

PCYC1125

Notyet

TN

80

Dec13

i+R;FL

PCYC1121

Notyet

RR

60

Oct13

Monotherapy;MZL

FLR2002

recruit

RR

110

Apr13

Monotherapy;FL

BartlettNCI

recruit

RR

40

Apr13

Monotherapy;FL

FLR3001

Notyet

RR

400

Oct13

i+BR ori+RCHOP;FL,MZL

StudyDesign

NHL
II

III

32

Highlights ASH 2012: Phase I Monotherapy Trial Subset

of Relapsed/Refractory Follicular Lymphoma Patients
(Fowler, ASH 2012)
Background:
Prior chemoimmunotherapy
Median of 3 prior therapies (1-5)

Results:
16 subjects enrolled: ORR=44%
Trend for dose response
o 9 patients >5.0 mg/kg with ORR: 56% (3 CRs and 2 PRs) and median
estimated Progression Free Survival = 19.6 months

Study initiated by Janssen:

Single arm monotherapy IMBRUVICA Phase II trial in relapsed / refractory
follicular patients
Primary endpoint Overall Response Rate

33

Clinical Development Plan:

IMBRUVICA in Waldenstrom patients
IST
WM

Phase

II

Study ID

Status

Line of
Therapy

#of
Patients

Trial 1st
Released

TreonDFCI

active

RR

60

May12

StudyDesign

Monotherapy

Background:
Phase I trial, PCYC 04753, PR in 3 out of 4 WM patients
Phase II collaboration with the Dana-Farber Cancer Institute
Phase II trial:
Safety and efficacy of IMBRUVICA monotherapy in relapsed or refractory
WM patients (2 median priors)
420 mg q day until PD; 30 planned patients
Trial expanded from 35 patients to 63 patients.
Updates:
Breakthrough Therapy Designation February 2013
PCYC to discuss further development with the FDA
34

Phase II Monotherapy Investigator sponsored Trial in

Relapsed/Refractory Waldenstroms Macroglobulinemia
Patients (Treon, ASH 2013)
IgM andHemoglobinlevelsimprovedpostibrutinib treatment

35

Phase II Monotherapy Investigator sponsored Trial in

Relapsed/Refractory Waldenstroms Macroglobulinemia
Patients (Treon, ASH 2013)
Efficacy Response:
83% ORR after a median of 9
cycles

Safety Response:
87.3% (55) patients continued on
therapy after a median of 9 cycles
Serious AEs (Grade 3) Events
Thrombocytopenia:
7
Neutropenia:
9
Anemia:
1
Pneumonic Infection:
1

36

Clinical Development Plan: Select Studies of

IMBRUVICA in Multiple Myeloma patients
PCYC/JNJ

Study ID

Status

Line of
Therapy

#of
Patients

Trial 1st
Released

PCYC1119

Notyet

RR

176

Dec13

i+Carfilzomib

II

PCYC1111

recruit

RR

164

Mar12

Monotherapy ori+Dex

Phase

MM

StudyDesign

Highlights ASH 2012: Phase II Monotherapy Trial in Relapsed/Refractory MM Patients

(Vij, ASH 2012)

Background:
Median of 4 prior treatments
Prior bortezomib and lenalidomide
Results:
Signals of biologic and clinical activity
5/13 patients had a reduction in paraprotein , 1 PR in combo with dexamethasone
Decreases in biomarkers of bone metabolism, angiogenesis and chemotaxis were
observed
Ongoing Study:
Cohorts 1 (Monotherapy, 420mg) and 2 (560 mg with dex) did not achieve desired
results, expansion of these cohorts is not planned.
Expansion to explore IMBRUVICA administration to a 840 mg monotherapy dose and
a 840 mg dose in combination with dexamethasone (Cohorts 3&4) is continuing.
37

Histone Deacetylase Inhibitor: Abexinostat

Abexinostat is optimized for halflife, oral bioavailability, and
potency and synergizes with
DNA-damaging agents
Partnered ex-US with Servier, in
Phase I/II program in Europe
Phase 2 PCYC study in
lymphoma completed and
presented at ASH 2012, further
updates presented at ICML in
Lugano, June 2013
Combination therapies between
HDAC and IMBRUVICA are being
investigated.
38

Factor VIIa Inhibitor: PCI-27483

First small-molecule FVII-specific
inhibitor targeting the tissue factor
(TF) pathway
Tissue factor is upregulated in
certain tumors. TF:VIIa complex
induce signaling pathways that lead
to increase in cancer cell migration
and invasion
Phase II pancreatic cancer trial
completed, results provided at
ASCO, June 2013
Further usage of PCI-27483 are
currently being investigated
39

Collaboration with Janssen Biotech

to Develop and Commercialize IMBRUVICA
Worldwide collaboration to broaden and accelerate the development
of IMBRUVICA in oncology, signed in December 2011

$150M upfront; milestones $250M for continued development progress (of

which $200M were earned as of May 1, 2013), $225M for regulatory progress
and $350M for approval.

Global development plan defined, each company leading the development for
specific indications. Development costs shared 40% Pharmacyclics and 60%
Janssen for multiple phase III trials

50/50 profit split. Pharmacyclics will book sales and lead commercialization
strategy in the US; Janssen will be responsible for the same outside the US

Development and commercialization activities managed through a shared

governance structure

40

Strong Patent Portfolio

BROAD PATENT COVERAGE:
Our lead product candidates have issued US and European
composition of matter patents and are covered by various
issued/pending patent applications in other major markets
BTK Inhibitor, IMBRUVICA (ibrutinib - PCI-32765) covered by
issued/pending patents projected until 2026* (composition of matter;
genus around composition of matter; method of treatment; method of
manufacture; inhibition of Btk via specific, irreversible inhibitor)
Factor VIIa Inhibitor, PCI-27483 covered by issued/pending patents
projected until 2023*
HDAC Inhibitor, PCI-24781 covered by issued/pending patents projected
until 2025*
* which does not include projected patent term extensions in the US
41

Key Corporate Data

GENERAL
- Founded
- Location
- Employees as of 12/31/2013

Current
1991
Sunnyvale, CA
484

SELECT FINANCIAL INFORMATION

- Revenue Q4/2013 as of 12/31/2013

$123.6 M

- Non-GAAP Op. Ex Q4/2013 as of 12/31/2013

$28.5 M*

- Cash & Cash Equivalents as of 12/31/2013

$635.6 M**

- Basic Shares Outstanding as of 12/31/2013

74.2 M

Janssen Biotech, Inc. contractual milestones remaining:

Development Progress
$ 50 million
Regulatory Progress
$ 100 million
Approval
$ 230 million
$ 380 million
(earned as of 02/27: upfront $150M, $200M in development
milestones, $125M in Regulatory Progress, $120M Approval)

* Non GAAP Expenses do not include

$9.6M in stock-based compensation
expense and also $50.2M in Excess
Amounts paid by Janssen.
** Cash does not include $52.0M due to
Company by Janssen under the
collaboration agreement.
42

Pharmacyclics
Makingadifferenceforthe
bettermentofpatients
43