Puma Biotechnology Inc · NASDAQ:PBYI
Puma Biotechnology — J.P. Morgan 2020 Healthcare Conference
64 slides from Puma Biotechnology's conference presentation, Jan 13, 2020
Slide 1: Puma Biotechnology J.P. Morgan 2020 Healthcare Conference
Puma Biotechnology J.P. Morgan 2020 Healthcare Conference January 2020 Copyright 2020 Puma Biotechnology
Slide 2: Forward-Looking Safe Harbor Statement
Forward-Looking Safe Harbor Statement This presentation contains forward-looking statements, including statements regarding the benefits of NERLYNX® (neratinib) and neratinib, the commercialization of NERLYNX, the potential indications of our drug candidates and the development of our drug candidate
Slide 3: Product Pipeline: Neratinib across the breast cancer therapy spectrum
Product Pipeline Neratinib across the breast cancer therapy spectrum Phase I Phase II Phase III Registration Approval HER2+ Breast Cancer US:7/17 CONTROL EC:8/18 Extended adjuvant EAP/MAP Neratinib monotherapy ExteNET (Phase III HER2+ EBC) Australia: 3/19 Canada: 7/19 FB-10: T-DM1 + neratinib Argent
Slide 4: Puma's Pharmacy and Distributor Network
Puma’s Pharmacy and Distributor Network Hub Services Specialty Pharmacy Network Acaria Health Patients Accredo CVS Onco360 Diplomat Sites of Care Biologics Academic Hospitals Community Hospitals Specialty Distributor Network Physician Practices Other (VA, DoD) McKesson ASD / Oncology Supply Cardinal
Slide 5: $53.5 Million Net Revenue in Q3 2019
$53.5 Million Net Revenue in Q3 2019 QUARTERLY NET REVENUE (IN $MM) 61.1 53.8 53.5 52.6 50.8 45.6 36.0 20.1 6.1 Q3 2017 Q4 2017 Q1 2018 Q2 2018 Q3 2018 Q4 2018 Q1 2019 Q2 2019 Q3 2019 Copyright 2020 Puma Biotechnology 5
Slide 6: From CONTROL Poster Presented at ASCO 2019
From CONTROL Poster Presented at ASCO 2019 6
Slide 7: 29% of Patients in Q4 Started NERLYNX at a Reduced Dose
29% of Patients in Q4 Started NERLYNX at a Reduced Dose PERCENT OF PATIENT STARTS AT REDUCED DOSE 35% 30% 29% 25% 20% 18% 15% 11% 10% 9% 6% 6% 5% 2% 2% 3% 3% 0% Q3-17 Q4-17 Q1-18 Q2-18 Q3-18 Q4-18 Q1-19 Q2-19 Q3-19 Q4-19 (est) Reduced Dose defined as fewer than 6 pills per day Copyright 2020 Puma Bi
Slide 8: Bottles Sold By Quarter
Bottles Sold By Quarter BOTTLES SOLD BY QUARTER (SP+SD) 6,000 5,538 4,936 4,900 5,000 4,799 4,791 4,696 4,452 4,000 3,517 3,000 2,137 2,000 1,000 675—Q3-17 Q4-17 Q1-18 Q2-18 Q3-18 Q4-18 Q1-19 Q2-19 Q3-19 Q4-19 (est) SP = Specialty Pharmacy Network, SD = Specialty Distributor Network Copyright 2020 P
Slide 9: Rest of World Partnerships – Timelines
Rest of World Partnerships –Timelines Region Partner Expected Regulatory Approval Australia / SE Asia March 2019 –Approved in Australia Israel Q1 2020 Canada July 2019–Approved Greater China November 2019 –Approved in Hong Kong 1H 2020 –China 1H 2020 –Taiwan Latin America September 2019 –Approved in
Slide 10: CONTROL Study Design
CONTROL Study Design Phase 2 trial to characterize the incidence and severity of diarrhea in patients with HER2+ early breast cancer treated with neratinib and loperamide prophylaxis +/-an investigational agent 1 year of therapy HER2+ early BC Neratinib 240 mg/day Received up to 1 year of (endocrine
Slide 11: CONTROL Study Flowchart
CONTROL Study Flowchart Population Stage 1-3c HER2+ breast cancer Trastuzumab-based adjuvant therapy completed within 1 year Sequential investigational cohorts Cohort Loperamidecohort Budesonide cohort Colestipol cohort Colestipol cohort Dose escalation (Original protocol) cohort Treatment Neratinib
Slide 12: CONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea
CONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea Characteristics of Loperamide prophylaxis reduces treatment-emergent diarrhea incidence and severity of diarrhea CONTROL1 ExteNET2 Neratinib dose Budesonide Colestipol Colestipol + escalation + Loperamide Loperamide + loperamide + loperamide
Slide 13: NERLYNX Extended Adjuvant HER2+ Breast Cancer Market Size
NERLYNX® Extended Adjuvant HER2+ Breast Cancer Market Size Approximately 28,300 patients (US) with early stage HER2+ breast cancer treated with adjuvant treatment1 Approximately 37,000 patients (EU) with early stage HER2+ breast cancer treated with adjuvant treatment1 – Approximately 65–70% of patie
Slide 14: Treatment Paradigm for HER2+ Metastatic Breast Cancer
Treatment Paradigm for HER2+ Metastatic Breast Cancer No Prior HER2+ Rx Prior HER2+ MBC Rx Herceptin (trastuzumab) T-DM1 Tykerb (lapatinib) + Herceptin + other Chemo + Perjeta (pertuzumab) (EMILIA) Xeloda (capecitabine) Rx +docetaxel Herceptin + Tykerb Neratinib+ Xeloda(capecitabine) Copyright 2020
Slide 15: Phase III Trial – Third-Line HER2+ MBC (NALA) Study Design
Phase III Trial –Third-Line HER2+ MBC (NALA) Study Design 3rd-or later-line therapy for patients with HER2+ mBC Patients with asymptomatic CNS metastatic disease are eligible Obtained SPA from FDA and review by EMA in February 2013 RANDOMIZATION Neratinib+ Capecitabine PD HER2+ mBC Received ³ 2 prio
Slide 16: NALA Study Results: Centrally Confirmed PFS
Phase III Trial –Third Line HER2+ MBC (NALA): Study Results Centrally Confirmed PFS (co-primary endpoint) 1.0 0.9 Hazard ratio Log-rank (95% CI) p-value 0.8 Neratinib + Capecitabine 0.76 (0.63 –0.93) 0.0059 0.7 Lapatinib + Capecitabine probability 0.6 0.5 47% PFS 0.4 38% 0.3 29% 0.2 16% 0.1 15% 7% 0
Slide 17: NALA Study Results: Restricted Means Analysis PFS
Phase III Trial –Third Line HER2+ MBC (NALA): Study Results Prespecifiedrestricted means analysis –PFS 1.0 0.9 Mean PFS (months) p-value 0.8 Neratinib + Capecitabine 8.8 0.0003 0.7 Lapatinib + Capecitabine 6.6 probability 0.6 Restriction: 24 months 0.5 PFS 0.4 0.3 0.2 2.2 months 0.1 0 0 3 6 9 12 Tim
Slide 18: NALA Study Results: OS
Phase III Trial –Third Line HER2+ MBC (NALA): Study Results OS (co-primary endpoint) 1.0 0.9 Mean OS Hazard ratio Log-rank (months) (95% CI) p-value 0.8 Neratinib + Capecitabine 24.0 0.88 (0.72 –1.07) 0.2086 0.7 Lapatinib + Capecitabine 22.2 probability 0.6 Restriction: 48 months 0.5 OS 0.4 0.3 0.2
Slide 19: NALA Study Results: Time to Intervention for CNS Metastases
Phase III Trial –Third Line HER2+ MBC (NALA): Study Results Time to intervention for CNS metastases 100 Neratinib + Capecitabine Lapatinib + Capecitabine Intervention (n=55/307) (n=75/314) 90 Radiation therapy 11% 15% (%) 80 Surgery/procedure 2% 3% incidence Anticancer medication 1% 1% 70 60 Cumulat
Slide 20: Third-Line HER2+ MBC Market Size
Third-Line HER2+ MBC Market Size Approximately 6,400 patients (US) with third-line HER2+ metastatic breast cancer and 4,700 patients (US) with fourth line HER2 positive metastatic breast cancer1 Tykerb2017 US sales -$68 M ($118M ex US) Approved in combination with Xeloda In US, Herceptin often subst
Slide 21: NALA sNDA Filing and Anticipated PDUFA Date
NALA -HER2+ MBC Phase III Trial Neratinib + capecitabine in third-line patients FiledsNDAfor U.S. FDA approval (June 2019) sNDAaccepted by U.S. FDA (September 2019) Anticipated PDUFA Date (April 2020) 21
Slide 22: NSABP FB-10 Phase I/II Trial: Kadcyla plus Neratinib
NSABP FB-10 Phase I/II Trial Kadcyla(T-DM1) plus Neratinib Kadcyla (T-DM1) Current second line standard of care in second line HER2 positive metastatic breast cancer Phase III EMILIA Trial (Perjetanaïve): Objective Response Rate: 43.6% Median Progression Free Survival: 9.6 months JCO 2016: Patients
Slide 23: FB-10 Phase I/II Trial Design
FB-10 -Phase I/II trial of Kadcyla (T-DM1) plus Neratinib HER2+ MBC Neratinib Dose level 1: 120 mg/d Must have received Dose level 2: 160 mg/d prior anti-HER2-based Dose level 3: 200 mg/d therapy with Dose level 4: 240 mg/d pertuzumabfor mBC No prior T-DM1 or HER2 T-DM1 TKI allowed 3.6 mg/kg IV d1 Q
Slide 24: FB-10 Phase I/II Trial Results
FB-10 -Phase I/II Trial of Kadcyla (T-DM1) plus Neratinib 240 * 240 *Off TX, AE/withdrawn 200 + On treatment 200 200 200 * 200 ORR (CR/PR): 12 of 20 (60%) 160 160 CR 160 PR Dose mg/d 160 SD 160 160 PD 160 * 160 + 120 * 120 120 120 * 120 0 100 200 300 400 500 600 700 800 Days on Treatment ASCO 2018 C
Slide 25: Neratinib HER2+ MBC with Brain Metastases
Neratinib(PB272) HER2+ MBC with Brain Metastases 33% of HER2+ advanced metastatic breast cancer patients develop brain metastases Phase II trial of Tykerb (lapatinib) in MBC patients with CNS metastases (n=39) 2.6% response rate in CNS metastases (Tykerb naïve) Phase II trial of Tykerb (lapatinib) i
Slide 26: TBCRC 022: Neratinib and Capecitabine in Brain Metastases
TBCRC 022: A Phase II Trial of HKI-272 (Neratinib) and Capecitabine for Patients with Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer and Brain Metastases Primary endpoint: ORR in CNS: Cohort 1 >5 pts (12.5%), Cohort 3a >9 pts (25.7%), Cohort 3b >2 pts (8%); Cohort 2: PFS Seco
Slide 27: TBCRC-022 Cohort 3a CNS Response
TBCRC-022 Cohort 3a– CNS Response Best Volumetric Response (n=31)* 100 80 CNS ORR = 49% (95% CI 32-66%) lesions 60 CNS 40 of volume 20 in 0 reduction -20 -40 % -60 -80 18 responses -100 Copyright 2020 Puma Biotechnology * ASCO 2017 27
Slide 28: Neratinib Included in NCCN Guidelines for CNS Metastases
Neratinib Recently Included as a Treatment Option for Recurrent Breast Cancer CNS Metastases By NCCN® Guidelines1 Guidelines updated March 20, 2018 Category 2B: Category 2B: Neratinib + Capecitabine Neratinib + Paclitaxel TBCRC 0222 NEfERT-T3,4 A Phase II Trial of Neratinib and Randomized, Multi-Cen
Slide 29: Current SUMMIT Basket Trial: Study Design
Current SUMMIT ‘Basket’ Trial: Study Design EGFR exon18-mutant tumors Lung Cervical Salivary gland Solid tumors (NOS) HER2-mutant tumors Bladder Breast HRc-positive* Breast HRc-negative HER4-mutant Solid tumors (NOS) tumors Key Inclusion Criteria Histologically confirmed cancers for which no curativ
Slide 30: SUMMIT Hormone Receptor Positive Breast Cancer Cohort
SUMMIT Hormone Receptor Positive Breast Cancer Cohort Copyright 2020 Puma Biotechnology 30
Slide 31: Somatic Mutations in HER2 in Hormone Receptor Positive Breast Cancer
Somatic Mutations in HER2 (ERBB2) in Hormone Receptor Positive Breast Cancer Incidence:—7-9%, pre-treated ER+ MBC1 Tumor characteristics:—usually mutually exclusive to HER2 amplifications Preclinical evidence of oncogenic activity:—constitutive activation of intracellular kinase and downstream signa
Slide 32: HR positive HER2 Mutated Breast
HR positive HER2 Mutated Breast Copyright 2020 Puma Biotechnology 32
Slide 33: HR positive HER2 Mutated Breast
HR positive HER2 Mutated Breast Copyright 2020 Puma Biotechnology 33
Slide 34: HR positive HER2 Mutated Breast
HR positive HER2 Mutated Breast 0 Copyright 2020 Puma Biotechnology 34
Slide 35: Proposed Amendment to Breast Cancer Cohort in SUMMIT
Proposed Amendment to Breast Cancer Cohort in SUMMIT for HR positive/HER2-negative, HER2mut MBC Cohort to Support Accelerated Approval HER2 mutations (documented by local testing) Primary endpoint Objective response rate Secondary endpoints fulvestrant DOR fulvestrant+ trastuzumab Randomized 1:1:1 S
Slide 36: SUMMIT Cervical Cancer Cohort
SUMMIT Cervical Cancer Cohort Copyright 2020 Puma Biotechnology 36
Slide 37: Characteristics of HER2 Mutant Cervical Cancer
Characteristics of HER2 Mutant Cervical Cancer Incidence Histology Genomics 5%—Metastatic cervical Enriched in adenocarcinomas Most common HER2mut is cancers High occurrence in HPV+ S310 extracellular domain May be negatively prognostic tumors hotspot mutation for survival Usually exclusive to HER2
Slide 38: Neratinib Monotherapy Results Presented at SGO Meeting
Neratinib Monotherapy Results Presented at SGO Meeting Copyright 2020 Puma Biotechnology 38
Slide 39: Neratinib Monotherapy Results Presented at SGO Meeting
Neratinib Monotherapy Results Presented at SGO Meeting Copyright 2020 Puma Biotechnology 39
Slide 40: Path Forward
Path Forward SUMMIT study to enroll additional patients with HER2 mutated cervical cancer Monotherapy data can be used to file for accelerated approval Overall response rate Duration of response Puma to schedule pre-NDA meeting with FDA (anticipated Q4 2020-Q2 2021) 40
Slide 41: HER-Seq (PUMA-NER-9501): HER2 mutation screening protocol
HER-Seq (PUMA-NER-9501): HER2 mutation screening protocol
Slide 42: HER-Seq: blood-based screening protocol for HER2 mutant patients
HER-Seq: a convenient, minimally-invasive blood-based screening protocol to identify HER2 mutant patients for neratinib clinical trials Simple, non-invasive blood-based screening protocol for identifying HER2 mutations from plasma cfDNA HER-SeqNGS assay is analytically- validated, CE-marked, and ISO
Slide 43: HER-Seq (PUMA-NER-9501) Study Protocol
HER-Seq (PUMA-NER-9501) Study Protocol HER-Seq: A Blood-based Screening Study to Identify Patients with HER2 Mutations for Enrollment into SUMMIT (initiated December 2018) Metastatic breast or consented Patient cancer patient cervical PRIMARY OBJECTIVE: To identify who may be eligible for patients w
Slide 44: HER-Seq Trial
HER-SeqTrial Currently open at ~15 sites Being expanded to other SUMMIT sites Utilizes proprietary next generation sequencing assay for HER2 mutations Screening Goals: Breast cancer: Screen 2500 patients Cervical cancer: Screen 1200 patients Patients with HER2 mutations identified through HER-Seq wi
Slide 45: SUMMIT Trial Proposed Registration Pathway
SUMMIT Trial Proposed Registration Pathway Meet with FDA to discuss registration pathway in HR-positive, HER2 negative HER2 mutated breast cancer and HER2 mutated cervical cancer Modify SUMMIT trial to expand HER2 mutated breast cancer cohort Continue to enroll HER2 mutated cervical cancer cohort Ex
Slide 46: IST Landscape – Other Cancers
IST Landscape –Other Cancers ISTs FC-7 (NSABP) Quad Wild-Type mCRCw/ prior cetuximabor panitumumab, dose finding for N + Cetuximab FC-11 (NSABP) Quad Wild-Type mCRC, HER2+ w/ prior EGFR theror HER2-mutated: N+T, HER2+ w/o prior EGFR therapy: N+Cetuximab ACOMPLI (INSERM) HER2+ or HER2-mutated mCRC, N
Slide 47: Puma - Expected Milestones
Puma -Expected Milestones Modify SUMMIT trial to expand HER2 mutated breast cancer cohort (Q1 20) FDA decision on sNDAin third-line HER2 positive MBC (Q2 20) Potential pre NDA meeting to discuss clinical data for SUMMIT trial (Q4 20) Report Phase II data from HR positive breast and cervical cohorts
Slide 48: Intellectual Property
Intellectual Property Composition of matter patent issued (expires 2025) Can be extended w/ Hatch/Waxman Use in the treatment of cancer issued (expires 2025) Two polymorph patents issued (both expire 2028) Combination with capecitabine (expires 2031) Use in extended adjuvant breast cancer (expires 2
Slide 49: Intellectual Property on EGFR T790M Mutations
Intellectual Property on EGFR T790M Mutations Issued claims in Europe, Asia, Australia (expires 2026) Possibility to extend up to 5 years Pending claims in United States Patent claims upheld after European Opposition Hearing (February 2014) Claims for the pharmaceutical composition comprising an irr
Slide 50: Experienced Management Team
Experienced Management Team Alan H. Auerbach Chairman, Chief Executive Officer, President, Founder -Chief Executive Officer, President, Founder, Cougar Biotechnology Richard Bryce, MD Chief Medical and Scientific Officer—Onyx, Roche, ICON Clinical Research Maximo F. Nougues Chief Financial Officer—G
Slide 51: Board of Directors
Board of Directors Alan H. Auerbach Chairman, Chief Executive Officer, President, Founder, Puma Biotechnology, Inc. Ann Miller, M.D. Former VP, Marketing, Global Marketing, Sanofi S.A.; Eisai; Amgen; Merck Michael Miller EVP U.S. Commercial, Jazz Pharmaceuticals; Former VP, Sales & Marketing, Genent
Slide 52: Puma Biotechnology - Financial
Puma Biotechnology -Financial Currently trading on NASDAQ: PBYI Cash, cash equivalents and marketable securities at September 30, 2019: $110 million Cash burn in Q3 2019: ~$7 million Amended term loan agreement (June 2019) New term loan of $100 million replaces loan of $155 million $100 million draw
Slide 53: Company Highlights
Company Highlights NERLYNX® -First HER2 directed drug approved by FDA for extended adjuvant treatment of early stage HER2-positive breast cancer in patients who have received prior trastuzumab Additional potential indications HER2+ Metastatic Breast Cancer HER2+ Metastatic Breast Cancer with Brain M
Slide 54: Puma Biotechnology J.P. Morgan 2020 Healthcare Conference
Puma Biotechnology J.P. Morgan 2020 Healthcare Conference January 2020 Copyright 2020 Puma Biotechnology 54
Slide 55: Appendix
Puma Biotechnology J.P. Morgan 2020 Healthcare Conference APPENDIX January 2020 Copyright 2020 Puma Biotechnology 55
Slide 56: ExteNET Trial - HER2 Positive Extended Adjuvant Breast Cancer
ExteNETTrial -HER2 Positive Extended Adjuvant Breast Cancer -HER2 positive breast cancer Neratinib (1 year) -Completed 1 year prior adjuvant 1:1 treatment with trastuzumab prior to Randomize randomization 2840 patients total -Lymph node negative, positive or residual invasive disease after neoadjuva
Slide 57: Kaplan-Meier Estimates of Disease Free Survival
Kaplan-Meier Estimates of Disease Free Survival ITT Population 100 97.8% 93.9% 95.6% 90 91.6% (%) survival 80 70 P-value = 0.009 -free HR (95% CI) = 0.67 (0.50 –0.91) Disease 60 50 Neratinib Placebo 0 18 21 24 0 3 6 9 12 15 Months after randomization No. at risk Neratinib 1420 1291 1260 1229 1189 11
Slide 58: Kaplan-Meier Estimates of DFS Hormone Receptor Positive Patients
Kaplan-Meier Estimates of DFS Hormone Receptor Positive Patients ITT Population 100 97.9% 95.4% 96.0% 90 91.2% (%) 80 survival 70 P-value = 0.001 -free HR (95% CI) = 0.51 (0.33 –0.77) Disease 60 50 Neratinib Placebo 0 0 3 6 9 12 15 18 21 24 Months after randomization No. at risk Neratinib 816 737 72
Slide 59: Rationale for efficacy in HR+ subgroup
Rationale for efficacy in HR+ subgroup HER2 signalling decreases HER2 inhibition upregulates Inhibition of HER2 and ER is required for ER-regulated gene transcription ER-regulated gene transcription effective blockage in HER2+/HR+ tumors HER2 HER1/2/3 HER2 HER1/2/3 HER2 HER1/2/3 em ane em ane em ane
Slide 60: 5-year Analysis Shows Durable iDFS Benefit
5-year Analysis Shows Durable iDFS Benefit ITT Population 1.0 97.9% 94.3% 92.2% 91.2% 90.2% 95.5% 0.9 91.7% 2.5% survival 90.2% 89.1% 87.7% 0.8 -free 0.7 Disease 0.6 HR (95% CI): 0.73 (0.57 -0.92) Two-sided P=0.008 Neratinib 0.5 Placebo (Descriptive P value) 0 12 24 36 48 60 At risk Months after ran
Slide 61: iDFS by Hormone Receptor Status 5-Year Analysis
iDFS by Hormone Receptor Status 5-Year Analysis Hormone receptor positive Hormone receptor negative 1.0 98.1% 97.5% 95.4% 96.1% 93.6% 92.6% 92.8% 91.2% 94.7% 90.8% 0.9 89.9% 88.9% 91.7% 4.4% Ä 91.8% 90.4% 89.8% 88.5% 86.8% 89.3% 88.8% survival 0.8 -free 0.7 Disease 0.6 HR (95% CI): 0.60 (0.43 -0.83)
Slide 62: iDFS for HR+ patients completing prior trastuzumab
iDFS for HR+ patients completing prior trastuzumab £ 1 year from randomization (2-year and 5-year Analyses) EC Approved Indication 2-year (primary) analysis 5-year analysis 51% relative reduction 42% relative reduction in risk of recurrence in risk of recurrence GnantM, et al. SABCS 2018, poster #P2
Slide 63: DDFS for HR+ patients completing prior trastuzumab
DDFS for HR+ patients completing prior trastuzumab £ 1 year from randomization (2-year and 5-year Analyses) EC Approved Indication 2-year (primary) analysis 5-year analysis 47% relative reduction in risk of recurrence 43% relative reduction in risk of recurrence GnantM, et al. SABCS 2018, poster #P2
Slide 64: iDFS for HR+ patients with prior neoadjuvant therapy and no pCR
iDFS for HR+ patients completing prior trastuzumab £ 1 year from randomization (2-year and 5-year Analyses) who had prior neoadjuvant therapy with no pCR 2-year (primary) analysis 5-year analysis 36% relative reduction in risk of recurrence 40% relative reduction in risk of recurrence GnantM, et al.
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