Full Press Release Details
Puma Biotechnology J.P. Morgan 2020 Healthcare Conference January 2020 Copyright 2020 Puma Biotechnology
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 candidates, including, but not limited to, the
anticipated timing for the commencement and completion of various clinical trials and announcement of data relative to these trials. All statements other than historical facts are forward looking statements and are based on our current
expectations, forecasts and assumptions. Forward looking statements involve risks and uncertainties that could cause our actual results to differ materially from the anticipated results and expectations expressed in these forward-looking
statements. These risk and uncertainties are identified in our Annual Report on Form 10-K for the year ended December 31, 2018, and any subsequent documents we file with the SEC. Readers are cautioned not
to place undue reliance on these forward-looking statements, which speak only as of the date hereof. We assume no obligation to update these forward-looking statements exceptasrequiredbylaw. Copyright 2020 Puma Biotechnology 2
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 Argentina: 8/19 Metastatic 10/19 NEfERTT (Phase II HER2+MBC) Hong Kong: Monotherapy or combo therapy Singapore: 11/19 NALA (Phase III 3rd Line HER2+ MBC) sNDA: 6/19 Metastatic w/ brain mets TBCRC-022 Monotherapy or combo therapy HER2-mutant Breast Cancer/Solid Tumors SUMMIT- Breast HRC+ SUMMIT Cervical Metastatic Neratinib ( fulvestrantin MBC) SUMMIT (Basket Trial) Phase II Trial (WashU)
Copyright 2020 Puma Biotechnology 33
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 Health Copyright 2020 Puma Biotechnology 4
$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
From CONTROL Poster Presented at ASCO 2019 6
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 Biotechnology 7
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 Puma Biotechnology 8
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 Argentina South
America 1H 2020 Chile, Peru 2H 2020 Mexico 2H 2020 Colombia, Brazil, Ecuador Europe Launch Timelines Q4 2019 Germany-Launched Q4 2019 United Kingdom-Launched Q4 2019 Austria-Launched 2020-2022 Rest of Europe
Copyright 2019 Puma Biotechnology 9
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 therapy as
indicated) adjuvant trastuzumab Stage I 3c Loperamide HR (ER/PR) +/ prophylaxis As needed Anti-inflammatory agent or bile acid sequestrant (Cycle 1) Day 57 onwards Cycle 1-2 STUDY ENDPOINTS Primary
endpoint: Incidence of grade 3 diarrhea Secondary endpoints: Frequency distribution of maximum-grade diarrhea; incidence and severity of diarrhea by loperamide exposure Copyright 2020 Puma Biotechnology
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 Neratinib
Neratinib Neratinib Neratinib Loperamide Loperamide Loperamide Colestipol dose escalation prophylaxis prophylaxis prophylaxis prophylaxis Budesonide Colestipol Loperamide PRN Analysis Interim analysis Preliminary analysis Preliminary analysis
Currently ongoing Currently enrolling (N=137) (N=64) (N=136) (N=104) Copyright 2020 Puma Biotechnology 11
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 loperamide prn loperamide prn prn (n = 137) (n = 64) (n =
136) (n = 104) (n = 60) (n = 1408) Treatment-emergent diarrhea incidence (%) No diarrhea 20.4 14.1 16.9 4.8 3.3 4.6 Grade 1 24.1 25.0 27.9 31.7 40.0 22.9 Grade 2 24.8 32.8 34.6 29.8 41.7 32.5 Grade 3 30.7 28.1 20.6 33.7 15.0 39.8 Grade 4 0 0 0 0 0
0.1 Diarrhea leading to 20.4 10.9 3.7 7.7 3.3 16.8 discontinuation Hospitalization (due 1.5 0 0 0 0 1.4 to diarrhea) Discontinuation of 44.5 20.3 28.7 27.9 20.0 38.9 neratinib (any cause) Copyright 2020 Puma Biotechnology 1. Chan et al. SABCS 2019
2. Chan et al. Lancet Oncol 2016 12
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 patients have
HR-positive disease 1Roche epidemiology slides 09/18 Copyright 2020 Puma Biotechnology 13
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 Puma
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 2 prior Follow-up lines of HER2- (Survival) directed therapy 1:1 Lapatinib + Capecitabine PD n=600 STUDY OBJECTIVES Co-Primary:
PFS (central) and OS Secondary: PFS (local), ORR, DoR, CBR, time to intervention for CNS metastases, safety, health outcomes 15 Copyright 2020 Puma Biotechnology 31 15
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 0 3 6 9 12 Time 15 since randomization (months) 18 21 24 27 30 33 36 No. at risk: N+C 307 183 113 69 54 35 20 13 9 7 3 2 2 L+C 314 183 82 39 24 9 8 3 2 2 2 2 1
Sauraet al. ASCO 2019 Oral Session: Breast Cancer Metastatic. Abstract 10002. Presented Tuesday, June 4, 2019. ASCO 2019 Copyright 2020 Puma Biotechnology 16
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 Time
15 since randomization (months) 18 21 24 27 30 33 36 No. at risk: N+C 307 183 113 69 54 35 20 13 9 7 3 2 2 L+C 314 183 82 39 24 9 8 3 2 2 2 2 1 Sauraet al. ASCO 2019 Oral Session: Breast Cancer Metastatic. Abstract 10002. Presented Tuesday,
June 4, 2019. ASCO 2019 Copyright 2020 Puma Biotechnology 17
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 1.7 months 0.1 0 0 3 6 9 12 15 18 21Time 24 since 27 randomization (months) 30 33 36 39 42 45 48 51 54 57 No. at risk: N+C 307 294
275 244 220 182 142 112 82 64 47 34 28 18 15 13 6 4 2 1 L+C 314 303 273 240 208 170 132 107 84 67 47 36 27 22 17 12 8 4 3 1 Sauraet al. ASCO 2019 Oral Session: Breast Cancer Metastatic. Abstract 10002. Presented Tuesday, June 4, 2019.
Copyright 2020 Puma Biotechnology ASCO 2019 18
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 Cumulative Overall cumulative incidence (Gray s test):
22.8% vs 29.2%; p=0.043 50 40 30 20 Neratinib + Capecitabine 10 Lapatinib + Capecitabine 0 0 6 12 18 24 30 36 42 48 54 60 Time since randomization (months) Sauraet al. ASCO 2019 Oral Session: Breast Cancer Metastatic. Abstract 10002. Presented
Tuesday, June 4, 2019. ASCO 2019 Copyright 2020 Puma Biotechnology 19
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 substituted for Tykerbin combination with Xeloda Opportunity
to gain market share from both Xeloda-Tykerbpatients and Xeloda-Herceptin patients 1Roche epidemiology slides 09/18 Copyright 2020 Puma Biotechnology 20
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
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
(Perjetana ve): Objective Response Rate: 43.6% Median Progression Free Survival: 9.6 months JCO 2016: Patients previously treated with Perjeta ORR (second line): 23.1% Median duration of therapy: 4.0 months Copyright 2020 Puma Biotechnology 22
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 Q3W Primary endpoint: Phase I:Recommended dose of neratinib when given with
T-DM1; Phase 2: Objective response rate (CR/PR) Secondary endpoint: Clinical benefit rate (CR/PR/SD), PFS, PK, tumor biopsy for PDX model (optional) Copyright 2020 Puma Biotechnology 23
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 Copyright 2020 Puma Biotechnology 24
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 na ve) Phase II trial of Tykerb (lapatinib) in MBC patients with CNS metastases (n=242) 6%
response rate in CNS metastases (Tykerb na ve) Phase II extension trial of Tykerb (lapatinib) plus Xeloda in MBC patients with CNS metastases (n=50) 20% response rate in CNS metastases Copyright 2020 Puma Biotechnology 25
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 Secondary
endpoints: ORR in non-CNS, PFS, OS Progressive brain mets Craniotomy HER2+ candidates mBC Progressive brain mets: w/ Brain 3a: No prior lapatinib Mets 3b: Prior lapatinib 4a: Untreated CNS disease; no prior T-DM1 4b: Progressive CNS disease; no prior T-DM1 4c: Progressive CNS disease; prior T-DM1 Cohort 1 (n = 40 pts) Cohort 2 (n = 5 pts)
Cohort 3a (n = 39 pts) Cohort 3b (n = 12 pts) Cohort 4a (n = 20 pts) Cohort 4b (n = 20 pts) Cohort 4c (n = 23 pts) Neratinib (240 mg/day) added) Neratinib (240 mg/day) X 1 cycle, Surgical resection, then if
non-CNS Neratinib (240 mg/day) be toxicity; may Neratinib (240 mg/day) trastuzumab Capecitabine (1500 mg/m2, d1-14, q3w) PD or Neratinib (160 mg/day) T-DM1 (3.6 mg/kg IV q21d) (Treat untilPD, Copyright 2020 Puma Biotechnology 26
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
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-Center,
Capecitabine for Patients with International Study of HER2+ Breast Cancer Brain HER2-Directed Therapy in Metastases (NCT01494662) 1st-line mBC (NCT00915018) NCCN makes no warranties of any kind whatsoever
regarding their content, use or application and disclaims any responsibility fortheir application or use in any way. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) for Central Nervous System
Nervous System Cancers. 2. Freedman RA, et al. Presented at ASCO Annual Meeting, 2017. Abstract 1005 3. Awada A, et al. Poster Presentation at ASCO Annual Meeting, 2015. #610. 28 4. Awada A, et al. JAMA Oncol. 2016;2:1557-1564.
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 curative therapy exists Documented EGFR exon 18, HER2 or HER4 mutation ECOG status of 0 to 2 RECIST 1.1 non-measurable, evaluable evaluable disease by other (measurable accepted
criteria or non-measurable disease): if RECIST Clinical Trials.gov Identifier NCT01953926 Neratinib monotherapy Neratinib monotherapy Neratinib+ Paclitaxel Neratinib* + Trastuzumab# *plus fulvestrant (in ER+
breast) #biosimilar may be used if available Neratinib monotherapy EGFR, HER2 or HER4 mutations (documented by local testing) Primary endpoint tumor assessment Objective response rate at first )first post-baseline (ORR Secondary endpoints ORR
(confirmed) Clinical benefit rate (CBR) Progression-free survival (PFS) Safety Biomarkers Simon 2-stage design If expand cohort 1 response in to Stage 2 first
evaluable (N=18) 7 patients, If 4 responses in Stage 2, expand or breakout Tumor assessments RECIST v1.1 (primary criteria) PET response criteria (RECIST
non-evaluable) Statistical methods ORRfirst, ORR, CBR: associated 95% CI Median PFS: Kaplan-Meier estimate with 95% CI Key Exclusion Criteria Prior treatment with any