PCYC corporate presentation 29 August 2014 RE TBdoc.xueqiu.com/148db96d21e2073fea865e21.pdf ·...

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Pharmacyclics®

Corporate PresentationSeptember 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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Pharmacyclics Pipeline

Molecule & Program / Indication Discovery / Preclinical

Phase I

Phase II

Phase III

IMBRUVICA (ibrutinib) : Bruton’s tyrosine kinase (BTK) inhibitor for Oncology *

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Diffuse Large B-cell Lymphoma

Multiple Myeloma

Follicular / Marginal Zone 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

Excipient, Drug Delivery

New BTK inhibitor for Autoimmune Diseases

Autoimmune Disease*Janssen Biotech: global partnership ** Servier: ex-U.S. partnership

APPROVEDAPPROVEDAPPROVEDAPPROVED

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IMBRUVICA (ibrutinib - PCI-32765)

• IMBRUVICA is an oral therapy that targets an importantpathway in B-cell malignancies. Over 3500 patientstreated in company sponsored clinical trials.

• IMBRUVICA is approved for the treatment ofpatients with mantle cell lymphoma and chronic lymphocyticleukemia who have received at least one prior therapy and

for all CLL patients with del17p.

• 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

integrinBTK

ibrutinib

BCRCXCR4CXCR5CCR7

ibrutinib

ibrutinib

CLL LN PB

adhesion + migration survival + proliferation apoptosis

Chronic Lymphocytic Leukemia Cell Lymph Node Peripheral Blood

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B-Cell Development and Origin 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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Phase III

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2

1

1*

1*

1

0

12

IMBRUVICA Trials Across Histologies(Company / Investigator Sponsored Trials as of Q2 2014)

CLL/SLL

MCL

WM

FL

MZL

DLBCL

MM

Total Studies

16

6

1

4

1

6

2

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Phase I/II

7159 Total Patients

Anticipated Enrollment

*FL/MZL is a joint, singular Phase III study

0Other 2

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IMBRUVICA - Key Studies

Histology

CLL/SLL

MCL

WM

FL

MZL

DLBCL

MM

Other

Relapsed/Refractory CombinationTreatment Naive

Relapsed/Refractory

Single-Agent

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CLL Clinical Trial Program

PCYC-1102

Burger-MDACC

RESONATE-17

RESONATE™

RESONATE-2

HELIOS

Key Study

ALLIANCE

CLL-12

ECOG

Watch & Wait Newly Treated Young Fit

Newly Treated Elderly

Relapsed/ Refractory

Combination

Relapsed/ Refractory

Single-Agent

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Targeting 8 Major Hematological Diseases Clinical Program Overview of IMBRUVICA

CLL/SLL

MCL

DLBCL

FL

MM

MZL

STUDY ID DESCRIPTION PHASE 2 PHASE 3WM PCYC‐1127 Rituximab vs. rituximab + ibrutinib

CLL3001 HELIOS (BR vs. BR + ibrutinib)

CLL3002 BRILLIANCE (ibrutinib vs. rituximab)

PCYC‐1112 RESONATETM (ibrutinib vs. ofatumumab)

PCYC‐1103 Single‐agent ibrutinib

PCYC‐1117 RESONATETM‐17 (Single‐agent ibrutinib)

PCYC‐1115 RESONATETM‐2 (ibrutinib vs. chlorambucil)

MCL3001 RAY (ibrutinib vs. temsirolimus)

MCL2001 SPARK (Single‐agent ibrutinib)


MCL3002 SHINE (BR vs. BR + ibrutinib)


PCYC‐1123 ibrutinib + lenalidomide + rituximab vs. ibrutinib + lenalidomide

PCYC‐1124 ibrutinib + lenalidomide + DA‐EPOCH‐R

DBL3001 PHOENIX (R‐CHOP vs. R‐CHOP + ibrutinib)

FLR3001 SELENE (ibrutinib + BR or R‐CHOP)

FLR2002 DAWN (Single‐agent ibrutinib)

PCYC‐1125 ibrutinib + rituximab

PCYC‐1111 Ibrutinib ± dexamethasone

PCYC‐1119 ibrutinib + carfilzomib


Active, Not Recruiting


Active, Recruiting


Active, Rollover Protocol



OUS Only Active, Not Recruiting


Closed, Not Recruiting

Active, Recruiting


Active, Recruiting

US Only ‐ Active, Recruiting

Active, Recruiting

Active, Recruiting


Active, Recruiting

Active, Recruiting

Active, Recruiting

Active, Recruiting

RELAPSED OR REFRACTORY


TREATMENT NAïVE


TREATMENT NAïVE


TREATMENT NAïVE


TREATMENT NAïVE



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IMBRUVICA Clinical Development Program

714% Growth

50 Total Clinical Trials (as of Q2, 2014)

12 Phase III Trials

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Clinical Development Plan: Select Studies of IMBRUVICA in CLL/SLL Patients

PCYC/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 active RR 580 Sept‐12 i+BR

CLL3002 recruit RR 150 Oct‐13 i vs R (in China)

Woyach recruit TN 523 Jun‐13 i vs iR vs BR in Elderly

CLL‐12 recuit TN 302 ASH ’13 i vs Placebo; Watch & Wait (German Study Group)

ECOG recruit TN 519 ASH ’13 iR vs. FCR; Young Fit

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Randomized Comparison of Ibrutinib Versus Ofatumumab in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Results From the Phase III RESONATETM Trial (Hillmen, EHA 2014)

• A total of 195 previously treated CLL/SLL patients were assigned to receive ibrutinib monotherapy until PD or unacceptable toxicity.

• Trial was stopped due to statistically significant improvement in Progression Free Survival and Overall Survival versus Ofatumumab.

• Median time on study was 9.4 mosat interim analysis.

• Investigator Assessment of ORR was 85% for ibrutinib (2%CR, 68%PR,15%PR-L) vs. 23% for Ofa. IRC assessment of ORR was 63% for ibrutinib (43% PR, 20% PR-L) vs. 4% for Ofa.

(57 pts on Ofa arm crossed over after confirmed PD)

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Randomized Comparison of Ibrutinib Versus Ofatumumab in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Results From the Phase III RESONATE Trial (Hilmen, EHA 2014)

• Safety: Adverse Events (≥15%) Regardless of Attributiona

• The most commonly occurring adverse events independent of Grade (AEs in 20% or more of patients) were diarrhea (48% vs.18%), fatigue (28% vs. 30%), pyrexia (fever; 24% vs. 15%), nausea (26% vs.18%), anemia (23% vs. 17%) and neutropenia (22% vs. 15%).

• Patients receiving IMBRUVICA showed a discontinuation rate due to progressive disease, adverse events or death of 13% (vs. Ofa 28%), with 86% of patients continuing on ibrutinibmonotherapy.

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• A total of 132 patients TN or R/R CLL/SLL received ibrutinibmonotherapy in a phase 1b/2 continuous-dosing study (PCYC-1102),4 and were continued on a long-term extension study (PCYC-1103) for a 3-year follow-up for safety and efficacy.

• 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 32.1 and 26.6 months. 64% of total patients remain on therapy.

Independent Evaluation of Ibrutinib Efficacy 3 Years Post-Initiation ofMonotherapy in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Including Deletion 17p Disease (O’Brien, ASCO 2014)

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• Any Grade ≥3 AEs (severe) were61% for treatment naïve (TN) and 82% for relapsed/refractory (R/R) patients. Any Grade ≥3 serious AEs (life threatening) were 29% for TN patients and 66% for R/R patients. 3 (10%) of TN patients and 11 (11%) of R/R patients discontinued due to AEs after a median time of 32.1 mos and 26.6 mos repectively.

• AEs leading to ibrutinib discontinuation occurred in 8% (10/132) of patients within the first year of treatment and declined to 2%(2/103) of patients after the first year of and 3%(2/68) after the second year of treatment.

Response

Rate n (%)

TN ≥ 65 years (n = 31)

R/R(n = 101)

Total(N = 148)

ORR 81% 86% 84%

ORR + PR‐L87% 90% 89%

Safety: Grade ≥ 3 Adverse Events by Time to Event Onset*

Efficacy: Best Overall Response (ORR)

(Partial Response with Lymphocytosis)

Independent Evaluation of Ibrutinib Efficacy 3 Years Post-Initiation ofMonotherapy in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Including Deletion 17p Disease (O’Brien, ASCO 2014)

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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)

• 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).

• 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: an open-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:an open-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


MCL

II

PCYC‐1104 compl RR 115 Feb‐11 Monotherapy

SPARK active RR 120 Aug‐12 Monotherapy; Failed Bz

Wang‐MDACC recruit RR 50 Jul‐13 i+R

IIIRAY active 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 POPULATION

Bortezomib‐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

rogressio

n, %

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 active RR 125 May‐11 Monotherapy

PCYC‐1123 recruit RR 110 ASH ’13 i+R+Len vs. i+Len

PCYC‐1124 recruit 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 NHL Patients

PCYC/JNJ/ ISTs Phase Study ID Status Line of

Therapy# of


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 recruit TN 80 Dec‐13 i+R; FL

PCYC‐1121 recruit RR 60 Oct‐13 Monotherapy; MZL

FLR2002 active RR 110 Apr‐13 Monotherapy; FL

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

Schiffer‐NCI recruit TN/RR 44 Apr‐13 Montherapy; Hairy Cell

Burger‐NCI recruit RR 20 Apr‐14 Monotherapy ‐ ALL

III FLR3001 recruit 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/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: Select Studies of IMBRUVICA in Waldenstrom’s Patients

IST Phase Study ID Status Line of Therapy

# of Patients


WMII Treon‐DFCI active RR 60 May‐12 Monotherapy

III PCYC‐1127 recruit RR 180 ASCO ‘14 i vs. i+R vs. placebo +R

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Phase II Monotherapy Investigator sponsored Trial in Relapsed/Refractory Waldenstrom’s Macroglobulinemia Patients (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 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 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 observed

Ongoing Study• Cohorts 1-3 were not expanded (420mg, 560 mg with dex, 840mg) as they did not achieve desired

results.• A pre-specified boundary of response was met with cohort 4, a 840 mg dose of IMBRUVICA in

combination with dexamethasone. The Company has expanded the fourth and final dosing cohort to 43 patients (840mg with dexamethasone) as it crossed a minimum pre-defined boundary of efficacy.

Clinical Development Plan: Select Studies of IMBRUVICA in Multiple Myeloma Patients


# of Patients


MMI PCYC‐1119 recruit RR 176 Dec‐13 i+Carfilzomib

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

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Clinical Development Plan: IMBRUVICA in Graft vs. Host Disease Patients


# of Patients


GvHD I PCYC-1129 recruit RR 39 Jul-14 Monotherapy

Background• Graft-versus-host disease (GvHD) develops in patients who have undergone allogeneic (donor) stem cell or

bone marrow transplant. Because the tissue or cells come from a donor, they recognize the patient’s cells as foreign and attack the patients body through an immune response. The probability of GvHD occurring depends on the match between the patient and the donor. Approximately 35-50% of the 10,000 allogeneic transplants in the U.S. develop chronic graft-versus-host disease.

PCYC-1129Primary Outcome Measures• Phase Ib: Number of dose-limiting toxicities as a measure of safety profile to determine recommended dose

of ibrutinib [ Time Frame: 28 treatment days after last subject enrolled in Phase 1 dose level(s).]• Phase II (Efficacy): Overall cGVHD response rate defined as the proportion of evaluable subjects who

achieve a NIH-defined Complete Response (CR) and Partial Response (PR) over all subjects who were treated with recommended phase 2 dose [ Time Frame: When the last subject completes 6 months of treatment.]

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Breakthrough Therapy Designations and Regulatory Progress

• IMBRUVICA received Full (regular) Approval on July 28, 2014 for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, and for the treatment of all CLL patients with deletion of the short arm of chromosome 17 (del 17p CLL).

• European Medicines Agency recommended Full Approval on July 25, 2014 for the treatment of adult patients with CLL who have received at least one prior therapy and with relapsed/refractory MCL. A positive opinion was also received for the treatment of adult CLL patients with del17p or TP53 mutation who are treatment naïve.

• IMBRUVICA received accelerated approval on November 13, 2013 for the treatment of patients with MCL who have received at least one prior therapy.

• 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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IMBRUVICA®

Received Full Approval for two CLL indications on July 28, 2014 and Accelerated Approval for one MCL indication on November 13, 2013.

Label includes: Statistically Significant Improvement in Overall Survival (HR=0.22, p<0.0001) and Progression Free Survival (HR=0.43, p<0.05) for Previously Treated CLL Patients vs. Ofatumumab

Indications: CLL and MCL Patients who have received at least one prior therapyCLL Patients with Del 17P (all lines)

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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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Q4 2013 Q1 2014 Q2 2014First Approval –

November 13, 2013Second Approval –February 12, 2014

13,372

6,889

1,572

9,427

3,945

3,953

2,936615957

Bottles of IMBRUVICA Shipped 21,833 Total Bottles Shipped Since Launch

IMBRUVICA 90‐pillIMBRUVICA 120‐pill

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Patient Populations (G7) in Major Hematological Malignancies

US All Major Markets3

Incidence Prevalence Incidence Prevalence

CLL/SLL 20,6001 121,2002 41,0001 267,0001

MCL 2,9001 11,3002 6,5001 38,2001

WM 1,5004 12,0002 6,0004 23,0004

DLBCL 25,0001 112,0002 54,1001 367,0001

FL 13,7001 63,0002 28,5001 245,0001

MM 20,0001 77,0001 48,0001 183,0001

TOTAL 83,700 396,5002 184,100 1,123,2001

1 © 2014 DR/Decision Resources, LLC. All rights reserved. Reproduction, distribution, transmission or publication is prohibited.2 IMS patient claims estimates for July 2013‐June 2014. 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 2013 to June 2014. 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 Prevalence Patient Estimates

CLL/SLL MCL

Diagnosed Incidence 1 20,600 2,900

Prevalence 2 121,200 13,300

No Therapy 2 54,700 2,400

1L Therapy 2 23,300 4,800

2L Therapy 2 10,300 1,400

3L+ Therapy 2 7,000 1,000

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

25,900 3,700

1 © 2014 DR/Decision Resources, LLC. All rights reserved. Reproduction, distribution, transmission or publication is prohibited. Reprinted with permission. 2 IMS patient claims estimates for July 2013‐June 2014. 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 2013 to June 2014. 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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Histone Deacetylase Inhibitor: Abexinostat

• Abexinostat is optimized for half-life, oral bioavailability, and potency and synergizes with DNA-damaging agents. A new formulation has been developed and recently patented.

• 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 other agents 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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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 Dec 2026 – with a potential patent term extension to Nov. 2027. (Pharmacyclics also owns pending patent applications in the U.S. and internationally covering specifically crystalline and polymorph forms of IMBRUVICA as well as the use of IMBRUVICA for the treatment of various types of cancer).

• Factor VIIa Inhibitor, PCI-27483 covered by issued/pending patents projected until2023

• HDAC Inhibitor, PCI-24781 with new formulation covered by issued/pending patents projected until 2035

Strong Patent Portfolio

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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, $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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Key Corporate Data

GENERAL

- Founded- Location- Employees as of 06/30/2014

1991Sunnyvale, CA

557

SELECT FINANCIAL INFORMATION

- Net Product Sales Q2/2014 $109.5 M

- Non-GAAP Total Costs and Expenses Q2/2014 $132.9 M*

- Cash & Cash Equivalents as of 06/30/2014 $678.0 M**

- Basic Shares Outstanding as of 06/30/2014 75.3 M

Janssen Biotech, Inc. contractual milestones remaining:Development Progress $ 50 million Regulatory Progress $ 70 millionApproval $ 200 million

$ 320 million (earned as of 08/05/14: upfront $150M, $200M in development milestones, $155M in Regulatory Progress, $150M Approval)

•Non GAAP Expenses do not include $17.2M in stock-based compensation expense.

** Cash does not include net $24.7M payment due to Janssen under the collaboration agreement.

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PharmacyclicsMaking a difference for the

betterment of patients

PCYC corporate presentation 29 August 2014 RE TBdoc.xueqiu.com/148db96d21e2073fea865e21.pdf ·...

Documents

Transcript of PCYC corporate presentation 29 August 2014 RE TBdoc.xueqiu.com/148db96d21e2073fea865e21.pdf ·...