Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Bob Duggan' Pharmacyclics' Presentation

3,400 views

Published on

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

  • Be the first to comment

Bob Duggan' Pharmacyclics' Presentation

  1. 1. 1 Pharmacyclics Corporate Presentation March 2014
  2. 2. 2 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
  3. 3. 3 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.
  4. 4. 4 PCYC Corporate Development Jan 2006 to Dec 2008 $0 $1 $2 $3 $4 $5 $6 Share Price $0.79 $5.07 $4.92 $1.45 04/10/06: Assumption of  Celera compounds BTK, FVIIa, HDAC 09/11/08: PCYC Board & Management Transition 09/19/07: Bob Duggan joins PCYC Board 05/01/08: Offer to  purchase 4M shares at  $1.05 /share by RW Duggan  10/21/07: FDA Non‐ approvable letter for Xcytrin 02/22/07: FDA Refusal to  file letter for Xcytrin
  5. 5. 5 PCYC Corporate Development Jan 2009 to Mar 2014 $0 $20 $40 $60 $80 $100 $120 $140 $160 Share Price 02/12/14: IMBRUVICA  approved for CLL  pts w/ at least one  prior therapy.  $57.78 $3.14 $6.08 $14.828/5/2009 Rights Offering 22.5M shares sold at $1.28 07/17/11:  Secondary Offering 6.5M shares sold at $8.85 11/13/13: IMBRUVICA  approved for MCL  pts w/ at least one  prior therapy.  PCYC's first label. 12/31/08 Price: $0.79 Employees:  47 Mkt Cap: $20M W.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 Breakthrough Therapy Designation from the FDA for MCL  and WM. $70.37 12/8/11: PCYC  enters into collaboration  agreement with  Janssen Biotech,  Inc. 6/21/10: PCYC  raises $50.8M  net proceeds in a  registered direct  offering. $6.74
  6. 6. 6 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
  7. 7. 7 “[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
  8. 8. 8 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 APPROVED APPROVED
  9. 9. 9 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
  10. 10. 10 BTK Signaling Pathway
  11. 11. 11 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
  12. 12. 12 B-Cell Development and Origin of B-cell Malignancies Pre-B Immature B Naïve B Germinal Center B Memory B Plasma Cell Malignant: Leukemia Chronic Lymphocytic Leukemia (CLL) un-mutated Mantle Cell Lymphoma (MCL) Multiple Myeloma (MM) Adopted from: 2012 Pan Pacific Lymphoma Conference J Rubenstein, M.D., Ph.D. Normal : Immature antibody producing Chronic Lymphocytic Leukemia mutated Follicular Lymphoma (FL) Diffuse Large B-Cell Lymphoma (DLBCL) Waldenstrom’s Macroglobulinemia (WM)
  13. 13. 13 Clinical Program Overview
  14. 14. 14 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 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. 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 information before using it to make investment decisions.
  15. 15. 15 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 *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 verify this information before using it to make investment decisions. 
  16. 16. 16 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 Waldenstrom’s Macroglobulinemia (WM) Feb 2013 o Chronic Lymphocytic Leukemia (CLL) with deletion 17p Mar 2013
  17. 17. 17 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 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‐1117 RESONATE‐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‐1112 RESONATE active RR 350 Jun‐12 i vs Ofa (Cross‐over added 8/13/13) PCYC‐1115 RESONATE‐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
  18. 18. 18 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 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 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.
  19. 19. 19 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‐L 27 (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
  20. 20. 20 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)
  21. 21. 21 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) 21 • 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).
  22. 22. 22 • 31 treatment naïve 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) 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)
  23. 23. 23 • 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)
  24. 24. 24 Clinical Development Plan: Select Studies of IMBRUVICA in MCL patients PCYC/JNJ /ISTs Phase Study ID Status Line of  Therapy # of  Patients Trial 1st Released 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 III RAY 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
  25. 25. 25 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 ‐ 1 2 > 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)
  26. 26. 26 Hematological AE Bleeding events ≥ grade 3 occurred in 5% of patients Non‐Hematological AE . 0% 10% 20% 30% 40% 50% 60% Neutropenia Thrombocytopenia Anemia 0% 10% 20% 30% 40% 50% 60% Diarrhea Fatigue Nausea Oedema peripheral Dyspnea Constipation Upper respiratory tract infection Vomiting Decreased appetite Cough Pyrexia Abdominal pain Contusion Rash Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Highlights EHA 2013: Treatment Related and Unrelated AEs Occurring in >15% of MCL Patients (Rule, EHA 2013)
  27. 27. 27 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 All Bortezomib‐Exposed Bortezomib‐Naïve Censored 111 81 57 33 22 0 48 37 29 14 10 0 63 44 28 19 12 0 2 2 0 100 0 80 20 40 60 200 4 128 16 Months From First Response 75 56 40 24 6 0 32 26 17 9 3 0 43 30 23 15 3 0 All Bortezomib‐Exposed Bortezomib‐Naïve Censored Patients Alive Without Progression, % Est. median PFS = 13.9 mos Est. median DOR = 17.5 mos
  28. 28. 28 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 CR PR Patients, % 48.7 53.2 50.5 47.8 46.0 47.3 0 20 40 60 80 100 2 4 6 9 12 15 Response Rate, % Time, months 66.7 68 52.3 62.2 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
  29. 29. 29 Clinical Development Plan: Select Studies of IMBRUVICA in DLBCL patients PCYC/JNJ Phase Study ID Status Line of  Therapy # of  Patients Trial 1st Released Study Design DLBCL II 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
  30. 30. 30 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
  31. 31. 31 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.
  32. 32. 32 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 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
  33. 33. 33 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
  34. 34. 34 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 1st Released Study Design WM II Treon‐DFCI active RR 60 May‐12 Monotherapy
  35. 35. 35 Phase II Monotherapy Investigator sponsored Trial in Relapsed/Refractory Waldenstrom’s Macroglobulinemia Patients (Treon, ASH 2013) IgM and Hemoglobin levels improved post ibrutinib treatment
  36. 36. 36 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) Events Thrombocytopenia: 7 Neutropenia: 9 Anemia: 1 Pneumonic Infection: 1
  37. 37. 37 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. Clinical Development Plan: Select Studies of IMBRUVICA in Multiple Myeloma patients PCYC/JNJ Phase Study ID Status Line of  Therapy # of  Patients Trial 1st Released Study Design MM I PCYC‐1119 Not yet RR 176 Dec‐13 i+Carfilzomib II PCYC‐1111 recruit RR 164 Mar‐12 Monotherapy or i+Dex
  38. 38. 38 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.
  39. 39. 39 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
  40. 40. 40 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
  41. 41. 41 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
  42. 42. 42 Key Corporate Data GENERAL Current - Founded - Location - Employees as of 12/31/2013 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.
  43. 43. 43 Pharmacyclics Making a difference for the  betterment of patients

×