Bob Duggan' Pharmacyclics' Presentation

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1 Pharmacyclics Corporate Presentation March 2014

description

This is a presentation given by the board at Pharamacyclics, where Bob Duggan is the CEO. http://bobduggan.net

Transcript of Bob Duggan' Pharmacyclics' Presentation

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PharmacyclicsCorporate Presentation

March 2014

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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.

Safe Harbor Statement

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Making a difference for the betterment of patients

Our MissionTo 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.

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PCYC Corporate Development Jan 2006 to Dec 2008

$0

$1

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$3

$4

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Share Price

$0.79

$5.07$4.92

$1.45

04/10/06:Assumption of Celera compoundsBTK, FVIIa, HDAC

09/11/08:PCYC Board &ManagementTransition

09/19/07:Bob Dugganjoins PCYCBoard 05/01/08:

Offer to  purchase4M shares at $1.05 /shareby RW Duggan 

10/21/07:FDA Non‐approvableletter for Xcytrin

02/22/07:FDA Refusal to file letter forXcytrin

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PCYC Corporate DevelopmentJan 2009 to Mar 2014

$0

$20

$40

$60

$80

$100

$120

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$160

Share Price

02/12/14:IMBRUVICA approved for CLL pts w/ at least one prior therapy. 

$57.78

$3.14$6.08

$14.828/5/2009Rights Offering22.5M sharessold at $1.28

07/17/11: SecondaryOffering6.5M sharessold at $8.85

11/13/13:IMBRUVICA approved for MCL pts w/ at least one prior therapy. PCYC's first label.

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

07/10/13: PCYC announced its first NDA filing of ibrutinib, for treatment of patients with R/R CLL and R/R MCL.

2/12/13: PCYC receives BreakthroughTherapy Designation from the FDA for MCL and WM. $70.37

12/8/11: PCYC enters intocollaboration agreement with Janssen Biotech, Inc.

6/21/10: PCYC raises $50.8M net proceeds in a registered direct offering.$6.74

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IMBRUVICA Approved November 13, 2013 in MCL and February 12, 2014 in CLL

4.5 years from 1st patient in to NDA filing 4.5 months from filing to first FDA approval

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“[IMBRUVICA] is a revolutionary blood cancer drug.”

Headlines and Highlights….Approval Grabs Attention of Top Tier Media

FDA speedily approves Imbruvica, a treatment

for rare lymphoma

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

Breakthrough Drug

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IMBRUVICA (ibrutinib)Leads Our Oncology Pipeline

Molecule & Program / Indication Discovery / Preclinical

Phase I

Phase II

Phase III

Ibrutinib (PCI-32765): Bruton’s tyrosine kinase (BTK) inhibitor for Oncology *

Chronic lymphocytic leukemia

Mantle cell lymphoma

Diffuse large B-cell lymphoma

Multiple myeloma

Follicular lymphoma

Waldenstrom’s 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

APPROVEDAPPROVED

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IMBRUVICA (Ibrutinib - PCI-32765)

• IMBRUVICA is an oral therapy that targets an importantpathway in B-cell malignancies. Over 2800 patientstreated in company sponsored clinical trials.

• IMBRUVICA was approved for the treatment ofpatients 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 patientso Responses in patients previously treated with

chemotherapy and with aggressive diseaseo Durable responses with many patients still on drug after

prolonged periods of timeo Patient tolerability demonstrated

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BTK Signaling Pathway

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

Mechanism of BTK: IMBRUVICA (ibrutinib – PCI-32765) Blocks Malignant B-cell Growth and Proliferation

Chronic Lymphocytic Leukemia Cell Lymph Node Peripheral Blood

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B-Cell Development andOrigin of B-cell Malignancies

Pre-B ImmatureB

NaïveB

GerminalCenter B

MemoryB

PlasmaCell

Malignant:

Leukemia

Chronic Lymphocytic

Leukemia (CLL)un-mutated Mantle Cell Lymphoma

(MCL)Multiple Myeloma

(MM)

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

Normal :

Immature antibody producing

Chronic Lymphocytic

Leukemia mutated

Follicular Lymphoma (FL)

Diffuse Large B-Cell Lymphoma (DLBCL)

Waldenstrom’sMacroglobulinemia (WM)

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Clinical Program Overview

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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© 2013 DR/Decision Resources, LLC.  All rights reserved.  Reproduction, distribution, transmission or publication is prohibited. Reprinted with permission. For the CLL  diagnosed incidence the US National Cancer Institute estimations were used2 IMS patient claims estimates for July 2012‐June 2013. Note: This information is an estimate derived from the use of information under license from the following IMS Health Incorporated information service: IMS Oncology Tracking Reports for the period July 2012 to June 2013. IMS expressly reserves all rights, including rights of copying, distribution and republication.

3 Major markets include: US, UK, Spain, Germany, France, Italy, and Japan   4 WM Foundation estimate Pharmacyclics, Inc. makes no representation with respect to the accuracy or reliability of this information. Investors are advised to independently verify this informationbefore using it to make investment decisions.

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CLL/SLL & MCL US Patient Estimates

CLL/SLL MCLDiagnosed 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

*Other 2 (All these patients are between lines of therapy; 1/3 received maintenance, 2/3 were not on therapy in observation period)

25,300 3,300

1 © 2013 DR/Decision Resources, LLC.  All rights reserved.  Reproduction, distribution, transmission or publication is prohibited. Reprinted with permission. For the CLL  diagnosed incidence the US National Cancer Institute estimations were used.2 IMS patient claims estimates for July 2012‐June 2013. Note: This information is an estimate derived from the use of information under license from the following IMS Health Incorporated information service: IMS Oncology Tracking Reports for the period July 2012 to June 2013. IMS expressly reserves all rights, including rights of copying, distribution and republication.Pharmacyclics, Inc. makes no representation with respect to the accuracy or reliability of this information. Investors are advised to independently verifythis information before using it to make investment decisions. 

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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 MCLand 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 2013o Waldenstrom’s Macroglobulinemia (WM) Feb 2013o Chronic Lymphocytic Leukemia (CLL) with deletion 17p Mar 2013

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Clinical Development Plan: Select Studies of IMBRUVICA in CLL/SLL PatientsPCYC/JNJ/ISTs Phase Study ID Status Line of 

Therapy# of 

PatientsTrial 1stReleased Study Design

CLL

I PCYC‐1108 compl RR 33 Feb‐11 i+FCR; i+BR

II

PCYC‐1103 active RR 200 Jun‐10 Roll Over Study

PCYC‐1117RESONATE‐17 active RR 111 Jan‐13 Monotherapy in 17p

PCYC‐1102 compl TN/RR 133 May‐10 Monotherapy

Burger‐MDACC active RR 40 Feb‐12 i+R in high risk pts

Burger‐MDACC recruit RR 208 Dec‐13 i vs iR

III

PCYC‐1112RESONATE active RR 350 Jun‐12 i vs Ofa

(Cross‐over added 8/13/13)

PCYC‐1115RESONATE‐2 active TN 272 Jan‐13 i vs Chlorambucil in Elderly

HELIOS recruit RR 580 Sept‐12 i+BR

CLL3002 not yet RR 150 Oct‐13 i vs R (in China)

Woyach not yet TN 523 Jun‐13 i vs iR vs BR in Elderly

CLL‐12 not yet TN 302 ASH ’13 i vs Placebo; Watch & Wait (German Study Group)

ECOG not yet TN 519 ASH ’13 iR vs. FCR; Young Fit

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The Bruton’s 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 (O’Brien, ASH 2013)

• A total of 148 patients TN or R/R CLL/SLL received ibrutinibmonotherapy 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 ibrutinibmonotherapy

• Median Duration of Response (DOR) was not reached for either Treatment Naïve (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.

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The Bruton’s 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 (O’Brien, 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.

• 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.

Response Rate

n (%)

TN ≥ 65 years (n = 31)

R/R(n = 117)

Total(N = 148)

ORR 25 (80.6%) 98 (83.8%) 123 (83.1%)

ORR + PR‐L27 (87.1%) 104 (88.9%) 131 (88.5%)

Safety: Treatment-Emergent Related AE’s Grade ≥ 3 With Incidence ≥ 2%

Efficacy: Best Overall Response (ORR)

(Partial Response with Lymphocytosis)

AEs Grade 3 = Severe    Grade 4 = Life Threatening

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Single Agent Ibrutinib Achieves Equal Responses in CLL Patients With and Without Deletion 17p (Farooqui, ASH 2013)

Patient Population: 53 Total Patients• 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

Non-Heme Toxicity

Responses Progression Free Survival

(Median Follow‐up: 14 mos)

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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)

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• 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).

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• 31 treatment naïve pts treated with ibrutinibmonotherapy.

• 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)

Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma:anopen-label, multicentre, phase 1b/2 trial (O’Brien, Lancet 2013)

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• Toxicity was mainly of mild-to-moderate severity (grade 1–2). 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.

Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma:anopen-label, multicentre, phase 1b/2 trial (O’Brien, Lancet 2013)

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Clinical Development Plan: Select Studies of IMBRUVICA in MCL patients

PCYC/JNJ/ISTs Phase Study ID Status Line of 

Therapy# of 

PatientsTrial 1stReleased Study Design

MCL

II

PCYC‐1104 active RR 115 Feb‐11 Monotherapy

SPARK active RR 120 Aug‐12 Monotherapy; Failed BR

Wang‐MDACC recruit RR 50 Jul‐13 i+R

IIIRAY recruit RR 280 Dec‐12 Monotherapy vs. Temsirol

SHINE recruit TN 520 May‐13 i+BR in elderly

IV MCL4001 recruit RR 250 Apr‐13 Monotherapy

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Highlights EHA 2013: Phase II Monotherapy Trial in Relapsed/Refractory MCL Patients-Long Term Follow Up (Rule, EHA 2013)

PATIENT CHARACTERISTICS FOR ALL TREATED POPULATIONBortezomib‐Naïve

(N = 63)Bortezomib‐Exposed

(N = 48)Total

(N = 111)

Median Age, yrs (Range) 66 (46‐83) 69 (40–84) 68 (40–84)

Gender:  Male 46 (73%)  39 (81%) 85 (77%)

ECOG Status:  0 ‐ 12> 2

53 (84%)9 (14%)1 (2%)

46 (96%)2 (4%) 0 (0%)

99 (89%)11 (10%)1 (1%)

Prior Regimens:Median (Range)≥ 3 regimens

2 (1‐5)31 (49%)

3 (1‐5)30 (63%)

3 (1‐5)61 (55%)

Median Months Since Diagnosis (Range) 29 (3‐213) 48 (7‐223) 42 (3‐223)

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Hematological AE

Bleeding events ≥ grade 3 occurred in 5% of patients

Non‐Hematological AE

.

0% 10% 20% 30% 40% 50% 60%

NeutropeniaThrombocytopenia

Anemia

0% 10% 20% 30% 40% 50% 60%

DiarrheaFatigueNausea

Oedema peripheralDyspnea

ConstipationUpper respiratory tract infection

VomitingDecreased appetite

CoughPyrexia

Abdominal painContusion

Rash

Grade 1Grade 2Grade 3Grade 4Grade 5

Highlights EHA 2013: Treatment Related and Unrelated AEs Occurring in >15% of MCL Patients (Rule, EHA 2013)

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Highlights EHA 2013: Phase II Monotherapy Trial in Relapsed/Refractory MCL – PFS and Duration of Response (Rule, EHA 2013)

100

0

80

20

40

60

240 4 128 16 20

Progression‐Free

 Survival, %

Months From First Dose

AllBortezomib‐ExposedBortezomib‐NaïveCensored

111 81 57 33 22 048 37 29 14 10 063 44 28 19 12 0

220

100

0

80

20

40

60

200 4 128 16Months From First Response

75 56 40 24 6 032 26 17 9 3 043 30 23 15 3 0

AllBortezomib‐ExposedBortezomib‐NaïveCensored

Patie

nts A

live With

out P

rogression

, %

Est. median PFS = 13.9 mos

Est. median DOR = 17.5 mos

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Best Response

19 23 21

49 44 47

0

20

40

60

80

100

Bortezomib‐Naïve(n = 63)

Bortezomib‐Exposed(n = 48)

Total(n = 111)

68 67 68

Efficacy Population n = 111, Estimated Median Follow‐up 15.3 months

CRPR

Patie

nts, %

48.753.2 50.5 47.8 46.0 47.3

0

20

40

60

80

100

2 4 6 9 12 15

Respon

se Rate, %

Time, months

66.7 68

52.362.2 64 64.9

Improvement of Complete and Overall Response Rates Over Time

Highlights EHA 2013: Phase II Monotherapy Trial in Relapsed/Refractory MCL Patients-Long Term Follow Up (Rule, EHA 2013)

3.6 9.0 13.5 17.1 20.7 20.7

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Clinical Development Plan: Select Studies of IMBRUVICA in DLBCL patients

PCYC/JNJ Phase Study ID Status Line of Therapy

# of Patients

Trial 1stReleased Study Design

DLBCLII

DLB1002 active TN 32 Jun‐12 i+RCHOP; DLBCL, MCL, FL

PCYC‐1106 recruit RR 125 May‐11 Monotherapy

PCYC‐1123 Not yet RR 110 ASH ’13 i+R+Len vs. i+Len

PCYC‐1124 Not yet RR 56 ASH ’13 i+Len+DA‐EPOCH‐R

III DBL3001 recruit TN 800 Sept‐13 i+RCHOP vs. RCHOP

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Highlights EHA 2013: Phase II Monotherapy Trial in Relapsed/Refractory DLBCL Patients(Vos, EHA 2013)

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)

Molecular Subtype Predicts Outcome with R‐CHOP

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Combining Ibrutinib With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP): Updated Results From a Phase 1b Study in Treatment-Naïve Patients With CD20-Positive B-cell Non-Hodgkin’s 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.

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Clinical Development Plan: Select Studies of IMBRUVICA in Other NHL patients

PCYC/JNJ/ ISTs Phase Study ID Status Line of 

Therapy# of 

PatientsTrial 1stReleased Study Design

NHL

I

Ujjani‐NCI recruit TN 33 Apr‐13 i+R+Len; FL

Blum‐OSU recruit RR 48 Dec‐11 i+BR; MZL, FL, WM, DLBCL, MCL 

Christian‐OSU recruit RR 34 Oct‐13 i+Len; MZL, FL, WM, DLBCL, 

MCL 

II

PCYC‐1125 Not yet TN 80 Dec‐13 i+R; FL

PCYC‐1121 Not yet RR 60 Oct‐13 Monotherapy;  MZL

FLR2002 recruit RR 110 Apr‐13 Monotherapy;  FL

Bartlett‐NCI recruit RR 40 Apr‐13 Monotherapy; FL

III FLR3001 Not yet RR 400 Oct‐13 i+BR or i+RCHOP;  FL, MZL

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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

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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

Clinical Development Plan: IMBRUVICA in Waldenstrom patients

IST Phase Study ID Status Line of Therapy

# of Patients

Trial 1stReleased Study Design

WM II Treon‐DFCI active RR 60 May‐12 Monotherapy

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Phase II Monotherapy Investigator sponsored Trial in Relapsed/Refractory Waldenstrom’s MacroglobulinemiaPatients (Treon, ASH 2013)

IgM and Hemoglobin levels improved post ibrutinib treatment

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Phase II Monotherapy Investigator sponsored Trial in Relapsed/Refractory Waldenstrom’s MacroglobulinemiaPatients (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 AE’s (Grade ≥ 3) EventsThrombocytopenia: 7Neutropenia: 9Anemia: 1Pneumonic Infection: 1

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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

observedOngoing 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.

Clinical Development Plan: Select Studies ofIMBRUVICA in Multiple Myeloma patients

PCYC/JNJ Phase Study ID Status Line of Therapy

# of Patients

Trial 1stReleased Study Design

MMI PCYC‐1119 Not yet RR 176 Dec‐13 i+Carfilzomib

II PCYC‐1111 recruit RR 164 Mar‐12 Monotherapy or i+Dex

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Histone Deacetylase Inhibitor: Abexinostat

• Abexinostat is optimized for half-life, 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.

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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

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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

Collaboration with Janssen Biotech to Develop and Commercialize IMBRUVICA

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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*

Strong Patent Portfolio

* which does not include projected patent term extensions in the US

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Key Corporate Data

GENERAL Current

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

1991Sunnyvale, 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 millionApproval $ 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.

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PharmacyclicsMaking a difference for the 

betterment of patients