1530 TH 1 Puma Biotechnology, Inc - Jefferies Group · Acaria Health. Accredo. CVS. Onco360....
Transcript of 1530 TH 1 Puma Biotechnology, Inc - Jefferies Group · Acaria Health. Accredo. CVS. Onco360....
Puma Biotechnology
Copyright 2019 Puma Biotechnology
Jefferies 2019 Healthcare Conference
June 2019
Copyright 2019 Puma Biotechnology
This presentation contains forward-looking statements, including statementsregarding the benefits of NERLYNX® (neratinib) and neratinib, thecommercialization of NERLYNX, the potential indications of our drugcandidates and the development of our drug candidates, including, but notlimited to, the anticipated timing for the commencement and completion ofvarious clinical trials and announcement of data relative to these trials. Allstatements other than historical facts are forward–looking statements and arebased on our current expectations, forecasts and assumptions. Forward–looking statements involve risks and uncertainties that could cause our actualresults to differ materially from the anticipated results and expectationsexpressed in these forward-looking statements. These risk and uncertaintiesare identified in our Annual Report on Form 10-K for the year ended December31, 2018, and any subsequent documents we file with the SEC. Readers arecautioned not to place undue reliance on these forward-looking statements,which speak only as of the date hereof. We assume no obligation to updatethese forward-looking statements except as required by law.
Forward-Looking Safe Harbor Statement
2
Product PipelineNeratinib across the breast cancer therapy spectrum
Phase I Phase II Phase III Registration Approval
HER2+ Breast Cancer
Extended adjuvantNeratinib monotherapy
MetastaticMonotherapy or combination therapy
Metastatic w/ brain metsMonotherapy or combination therapy
NeoadjuvantCombination with standard therapy
US: 7/17EU: 9/18
HER2-mutant Breast Cancer/Solid TumorsMetastaticNeratinib (± fulvestrant in MBC)
NSABP FB-7
NALA (Phase III 3rd Line HER2+ MBC)
FB-10: T-DM1 + neratinib
NEfERTT (Phase II HER2+MBC)
SUMMIT (Basket Trial)
Phase II trial (WashU)
CONTROL
ExteNET (Phase III HER2+ EBC)
I-SPY 2
NSABP FB-7
TBCRC-022
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EAP/MAP
33
Puma’s Pharmacy and Distributor Network
4
Specialty Distributor Network
Patients
Hub Services
Specialty Pharmacy Network
Acaria HealthAccredo
CVSOnco360DiplomatBiologics
Sites of Care
Academic Hospitals Community Hospitals
Other (VA, DoD)Physician Practices
McKessonASD / Oncology Supply
Cardinal Health
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$45.6 Million Net Revenuein Q1 2019
5
6.1
20.1
36.0
50.8 52.6
61.1
45.6
Q 3 2 0 1 7 Q 4 2 0 1 7 Q 1 2 0 1 8 Q 2 2 0 1 8 Q 3 2 0 1 8 Q 4 2 0 1 8 Q 1 2 0 1 9
QUARTERLY NET REVENUE (IN $MM)
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6
Bottles Sold By Quarter
• SP = Specialty Pharmacy Network, SD = Specialty Distributor Network
675
2,137
3,517
4,799 4,936
5,538
4,449
1,600
Q3-17 Q4 -1 7 Q1 -1 8 Q2-18 Q3-18 Q4-18 Q1 -19 Q2 -19
BOTTLES SOLD BY QUARTER (SP+SD)
April
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Time to First Dispense in Specialty Pharmacy Network
7
74% of patients receive their first dispense within 15 days of a network SP receiving the RX
33%
26%
15%
7% 8%4%
2% 2% 1% 1%
5 O R L E S S 5 T H R O U G H 1 0
1 0 T H R O U G H 1 5
1 5 T H R O U G H 2 0
2 0 T H R O U G H 3 0
3 0 T H R O U G H 4 5
4 5 T H R O U G H 6 0
6 0 T H R O U G H 9 0
9 0 T H R O U G H 1 2 0
1 2 0 A N D G R E A T E R
PERCENT OF PATIENTS TIME TO FIRST DISPENSE
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74% of Targeted Prescribers Reached
• Reach defined as physician detailed.• Numbers reported for historical quarters may be slightly different from previous statements due to data updates
26%
54%
61%66%
69% 71% 74%
Q 3 - 1 7 Q 4 - 1 7 Q 1 - 1 8 Q 2 - 1 8 Q 3 - 1 8 Q 4 - 1 8 Q 1 - 1 9
CUMULATIVE TARGET WRITER REACH BY QUARTER
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Pierre Fabre License for NERLYNX® in EuropeMarch 2019
• Well established oncology commercial/medical infrastructure in breast cancer throughout Europe, based on Navelbine® (vinorelbine)
• Pierre Fabre has commercial and development rights to neratinib in Europe and parts of North and Western Africa
• First anticipated launch is Germany in 2019, with other countries to follow in 2019/2020
• UK NICE submission complete and under review • Major financial terms of the agreement
– $60M USD upfront upon execution of the license agreement– Additional commercial and regulatory milestones totaling $345M USD– Double digit royalties up to 40% on net sales
9Copyright 2019 Puma Biotechnology
Rest of World Partnerships – Timelines
10
Region Partner Expected Regulatory Approval
Australia / SE Asia • Approved in ITT population –Australia
Israel • Q3 2019
Canada • Q3 2019
Greater China • 1H 2020 – China• Q4 2019 – Hong Kong• 1H 2020 – Taiwan
Latin AmericaSouth America
• 1H 2020 – Mexico• 1H 2020 – Argentina • 1H 2020 – Chile• 1H 2020 – Ecuador• 1H 2020 – Peru• 2H 2020 – Colombia• 1H 2021 – Brazil
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Ustaris et al. Am J Hematol Oncol 2015
No prophylaxis Loperamide prophylaxis
Targetpopulation
HER2+MBC
HER2+ MBC
HER2+MBC
HER2+ EBC
(ExteNET)
HER2+MBC
HER2+MBC
HER2 mutated
NSCLC
HER2 mutated
NSCLC
HER2 mutatedtumors
Protocol-directedtherapy
Paclitaxel + Herceptin
+ Neratinib
Neratinib + Torisel Neratinib Neratinib
Paclitaxel + Herceptin + Neratinib
Neratinib + Torisel
Neratinib + Torisel Neratinib Neratinib
Loperamide prophylaxis None 16 mg → 6 mg during cycle 1
Total patients (N) 15 37 66 1408 6 41 14 13 81
Grade 3 diarrhea 8 (53%) 12 (32%) 20 (30%)1 562 (40%)1 0 7 (17%) 2 (14%) 1 (8%) 10 (12%)
Noncompliantwith Loperamide
0 4 (57%) of 7
1 (50%) of 2 1 (100%)
Duration of TE diarrhea(days)
‒ 14 14 ‒ ‒ 2 2 2 2
Loperamide Prophylaxis Reduces Duration and Incidence of Neratinib-induced Diarrhea
1. Includes 1 grade 4 event
11Copyright 2019 Puma Biotechnology
CONTROLStudy Design
STUDY ENDPOINTSPrimary endpoint: Incidence of grade ≥3 diarrheaSecondary endpoints: Frequency distribution of maximum-grade diarrhea; incidence and severity of diarrhea by loperamide exposure
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• Received up to 1 year of
adjuvant trastuzumab• Stage I–3c• HR (ER/PR) +/–
Neratinib 240 mg/day(endocrine therapy as indicated)
As needed
Cycle 1-2
Loperamideprophylaxis
Day 57 onwardsAnti-inflammatory agent or bile acid sequestrant (Cycle 1)
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NeratinibLoperamide prophylaxisBudesonide
Budesonide cohort Colestipol cohort Colestipol cohortLoperamide cohort(Original protocol)
Stage 1-3c HER2+ breast cancerTrastuzumab-based adjuvant therapy completed within 1 year
NeratinibLoperamide prophylaxis
NeratinibLoperamide prophylaxisColestipol
NeratinibColestipol
prophylaxisLoperamide PRN
Sequential investigational cohorts
Popu
latio
nCo
hort
Trea
tmen
tAn
alys
isCONTROL
Study Flowchart
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Interim analysis(N=137)
Preliminary analysis(N=64)
Preliminary analysis(N=136)
Currently ongoing (N=104)
Dose escalation cohort
Neratinibdose escalation
Currently enrolling
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CONTROL1 ExteNET2
LoperamideLoperamide
+ budesonideLoperamide+ colestipol
Loperamideprn + colestipol
Neratinib dose escalation +
loperamide prn
Loperamideprn
N (at data cut-off) 137 64 136 104 60 1408
Any grade 79.6 85.9 83.1 95.2 95.0 95.4
Grade 1 24.1 25.0 27.9 30.8 43.3 22.9
Grade 2 24.8 32.8 34.6 32.7 40.0 32.5
Grade 3 30.7 28.1 20.6 31.7 11.7 39.8
Grade 4 0 0 0 0 0 0.1Median neratinib treatment duration, months 11.6 12.0 11.9 11.9 5.6 11.6Discontinuation due to diarrhea 20.4% 10.9% 4.4% 6.7% 3.3% 16.8%
Characteristics of treatment-emergent diarrheaCONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea
Loperamide prophylaxis reduces incidence and severity of diarrhea
1. Barcenas et al. ASCO 20192. Chan et al. Lancet Oncol 2016 14Copyright 2019 Puma Biotechnology
Copyright 2019 Puma Biotechnology 15
PB272 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
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Treatment Paradigm for HER2+ Metastatic Breast Cancer
Prior HER2+ MBC Rx
T-DM1(EMILIA)
Tykerb (lapatinib) + Xeloda (capecitabine)
Herceptin + other Chemo Rx
Herceptin + Tykerb
Herceptin (trastuzumab) + Perjeta (pertuzumab)
+docetaxel
Neratinib +Xeloda (capecitabine)
No Prior HER2+ Rx
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Phase III Trial – Third Line HER2+ MBC (NALA): Study Rationale
Therapy Region / Study Response Rate (%)
Median PFS (weeks)
Tykerb (lapatinib) Phase II 5-7 8-9
lapatinib + capecitabine USA (USPI) 24 27.1
lapatinib + capecitabine EMILIA 31 27.8
neratinib Phase II 24 22.3
neratinib + capecitabine Phase II 64 40.3
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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
STUDY OBJECTIVESCo-Primary: PFS (central) and OSSecondary: PFS (local), ORR, DoR, CBR, time to intervention for CNS metastases, safety, health outcomes
HER2+ mBCReceived ≥2 prior
lines of HER2-directed therapy
PD
PD
Neratinib + Capecitabine
Lapatinib + Capecitabine
Follow-up (Survival)
1:1
RAN
DOM
IZAT
ION
1831
n=600
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Phase III Trial – Third Line HER2+ MBC (NALA): Study ResultsCentrally Confirmed PFS (co-primary endpoint)
307 183 113 69 54 35 20 13 9 7 3 2 2314 183 82 39 24 9 8 3 2 2 2 2 1
N+CL+C
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
00 3 6 9 12 15 18 21 24 27 30 33 36
Time since randomization (months)
PFS
prob
abili
ty
No. at risk:
Saura et al. ASCO 2019 Oral Session: Breast Cancer – Metastatic. Abstract 10002. Presented Tuesday, June 4, 2019.
15%
29%38%
47%
7%
16%
Hazard ratio(95% CI)
Log-rank p-value
0.76 (0.63–0.93) 0.0059Neratinib + Capecitabine
Lapatinib + Capecitabine
ASCO 201919
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Phase III Trial – Third Line HER2+ MBC (NALA): Study Results Prespecified restricted means analysis – PFS
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1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
00 3 6 9 12 15 18 21 24 27 30 33 36
Time since randomization (months)
PFS
prob
abili
ty
No. at risk:
Mean PFS(months) p-value
8.80.0003
6.6
Neratinib + Capecitabine
Lapatinib + Capecitabine
Restriction: 24 months
2.2 months
307 183 113 69 54 35 20 13 9 7 3 2 2314 183 82 39 24 9 8 3 2 2 2 2 1
N+CL+C
Saura et al. ASCO 2019 Oral Session: Breast Cancer – Metastatic. Abstract 10002. Presented Tuesday, June 4, 2019.
20ASCO 2019
Phase III Trial – Third Line HER2+ MBC (NALA): Study Results OS (co-primary endpoint)
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Saura et al. ASCO 2019 Oral Session: Breast Cancer – Metastatic. Abstract 10002. Presented Tuesday, June 4, 2019.
307 294 275 244 220 182 142 112 82 13 6 2 1314 303 273 240 208 170 132 107 84 12 8 3 1
6467
4747
1822
1517
44
3436
2827
OS
prob
abili
ty
No. at risk:N+CL+C
Restriction: 48 months
3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57
1.7 months
Neratinib + Capecitabine
Lapatinib + Capecitabine
Mean OS(months)
Hazard ratio(95% CI)
Log-rank p-value
24.00.88 (0.72–1.07) 0.2086
22.2
21ASCO 2019
Time since randomization (months)
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
00
Phase III Trial – Third Line HER2+ MBC (NALA): Study Results Time to intervention for CNS metastases
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Saura et al. ASCO 2019 Oral Session: Breast Cancer – Metastatic. Abstract 10002. Presented Tuesday, June 4, 2019.
22ASCO 2019
100
90
80
70
60
50
40
30
20
10
00 6 12 18 24 30 36 42 48 54 60
Time since randomization (months)
Neratinib + Capecitabine
Lapatinib + Capecitabine
Overall cumulative incidence (Gray’s test): 22.8% vs 29.2%; p=0.043
InterventionNeratinib + Capecitabine
(n=55/307)Lapatinib + Capecitabine
(n=75/314)
Radiation therapy 11% 15%
Surgery/procedure 2% 3%
Anticancer medication 1% 1%
Cum
ulat
ive
inci
denc
e (%
)
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PB272 Third-Line HER2+ MBCMarket 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
Tykerb 2017 US sales - $68 M ($118M ex US) Approved in combination with Xeloda In US, Herceptin often substituted for Tykerb in combination with
Xeloda
Opportunity to gain market share from both Xeloda-Tykerb patients and Xeloda-Herceptin patients
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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 (Perjeta naïve): 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
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FB-10 - Phase I/II trial of Kadcyla (T-DM1) plus Neratinib
25
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)
HER2+ MBC
Must have received prior anti-HER2-based
therapy with pertuzumab for mBC
No prior T-DM1 or HER2 TKI allowed
Neratinib Dose level 1: 120 mg/d Dose level 2: 160 mg/d Dose level 3: 200 mg/d Dose level 4: 240 mg/d
T-DM13.6 mg/kg IV d1 Q3W
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FB-10 - Phase I/II Trial of Kadcyla (T-DM1) plus Neratinib
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0 100 200 300 400 500 600 700 800
120120120120120160160160160160160160160200200200200200240240
Days on Treatment
Dos
e m
g/d
+
CRPRSDPD
*
*
*
*
*
*Off TX, AE/withdrawn + On treatment
ORR (CR/PR): 12 of 20 (60%)
ASCO 2018
DS-8201: Rationale of Neratinib Combo*
Research collaboration with Puma and Memorial Sloan Kettering Cancer Center (Dec 2017)
HER2-ADC
HER2
Degradation
Endosome
InternalizationEndolysosome
HER2 positive Cancer CellLysosome
Drug release
DS-8201Neratinib
ADC
Will confirm synergetic effect hypothesis in non-clinical study HER2 dual blockage by combination of DS-8201 and neratinib Increase of internalization rate of DS-8201 by neratinib (increase uptake rate of DS-8201 into tumor)
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HER2 Signal Cell proliferationCell survival
NeratinibTyrosine kinase inhibitorIrreversibly inhibit HER2,
EGFR, HER4 and suppress cell proliferation
HER2-TKI
* Daiichi Sankyo FY2017 Q3 Financial Results Presentation Material
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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) in MBC patients with CNS metastases (n=242)
6% response rate in CNS metastases (Tykerb naïve)
Phase II extension trial of Tykerb (lapatinib) plus Xeloda in MBC patients with CNS metastases (n=50) 20% response rate in CNS metastases
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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
29Copyright 2019 Puma Biotechnology
HER2+ mBC
w/ Brain Mets
Neratinib (240 mg/day)
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
(Tre
at u
ntil
PD o
r tox
icity
; if n
on-C
NS
PD, t
rast
uzum
ab m
ay b
e ad
ded)
Cohort 1 (n = 40 pts)
Neratinib (240 mg/day) X 1 cycle, Surgical resection, then Neratinib (240 mg/day)
Cohort 2 (n = 5 pts)
Cohort 3a (n = 39 pts)Neratinib (240 mg/day)
Capecitabine (1500 mg/m2, d1-14, q3w)Cohort 3b (n = 12 pts)
Progressive brain mets
Craniotomy candidates
Progressive brain mets:
3a: No prior lapatinib3b: Prior lapatinib
4a: Untreated CNS disease; no prior T-
DM14b: Progressive CNS disease; no prior T-
DM14c: Progressive CNS disease; prior T-DM1
Cohort 4a (n = 20 pts)
Cohort 4b (n = 20 pts)Cohort 4c (n = 23 pts)
Neratinib (160 mg/day) T-DM1 (3.6 mg/kg IV q21d)
TBCRC-022 Cohort 3a– CNS Response %
redu
ctio
n in
vol
ume
of C
NS
lesi
ons
* ASCO 2017
-100
-80
-60
-40
-20
0
20
40
60
80
100
Best Volumetric Response (n=31)*
CNS ORR = 49% (95% CI 32-66%)
18 responses
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Neratinib Recently Included as a Treatment Option for Recurrent Breast Cancer CNS Metastases By NCCN® Guidelines1
1. NCCN Guidelines v 1.2018. Central Nervous System Cancers.2. Freedman RA, et al. Presented at ASCO Annual Meeting, 2017. Abstract 10053. Awada A, et al. Poster Presentation at ASCO Annual Meeting, 2015. #610.4. Awada A, et al. JAMA Oncol. 2016;2:1557-1564.
Category 2B: Neratinib + Capecitabine
Category 2B: Neratinib + Paclitaxel
Guidelines updated March 20, 2018
TBCRC 0222 NEfERT-T3,4
A Phase II Trial of Neratinib and Capecitabine for Patients with
HER2+ Breast Cancer Brain Metastases (NCT01494662)
Randomized, Multi-Center, International Study of
HER2-Directed Therapy in 1st-line mBC (NCT00915018)
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NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers V.1.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed [March 20, 2018]. To view the most recent and complete version of the guideline, go online to NCCN.org
SUMMIT Study Design
EGFR, HER2 or HER4 mutations(documented by local testing)
Primary endpoint• Objective response rate at first post-baseline
tumor assessment (ORRfirst)
Secondary endpoints• ORR (confirmed)• Clinical benefit rate (CBR)• Progression-free survival (PFS)• Safety• Biomarkers
Simon 2-stage design• If ≥1 response in first evaluable 7 patients,
expand cohort to Stage 2 (N=18)• 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
Breast HRc-positive*
Breast HRc-negative
Lung
Colorectal (KRAS/NRAS/BRAF wild-type)
HER2-mutanttumors
Neratinib monotherapy
Biliary tract
Cervical
Salivary
Solid tumors (NOS)
Neratinib* + Trastuzumab#
*plus fulvestrant (in ER+ breast)#biosimilar may be used if available
Bladder Neratinib + Paclitaxel
Lung Neratinibmonotherapy
Solid tumors (NOS) NeratinibmonotherapyHER4-mutant
tumors
EGFR exon18-mutant tumors
32Copyright 2019 Puma Biotechnology
Cohorts expanded based on above stated criteria
Neratinib Monotherapy Efficacy in HER2-mutant Patients by Tumor Type
33* no target lesion measurement
Hyman et.al. AACR 2017Hyman et al, Nature 2018
Somatic Mutations in HER2 (ERBB2) Are a New Class of Oncogenic Drivers in Breast Cancer and Other Solid Tumors
1TCGA; 2 Ma et al, ASCO 2016; 3Wagle et al, ASCO 2016; 4Desmedt et al, JCO 2016, 5Deniziaut et al, Oncotargets 2016; 6Bose et al, Cancer Disc. 2013
• Incidence:- 1.6%, newly diagnosed breast cancer1
- 2.4%, heavily pre-treated MBC2
- 7-9%, pre-treated ER+ MBC3
- 5-15%, invasive lobular carcinomas4,5
• Tumor characteristics:- usually mutually exclusive to HER2 amplifications- predominantly in ER-positive disease (85-90%)- enriched in invasive lobular subtype
• Preclinical evidence of oncogenic activity:- constitutive activation of intracellular kinase and
downstream signaling pathways6
- increased cell proliferation and tumor growth6
- Cross-talk occurs between ER and HER2 mutation (modified clinical trial to add fulvestrant to ER positive patients)
HER2 somatic mutations
P PP P P
MAPK PathwayPI3K PathwayRAS
RAF
MEK
ERK
PI3K
AKT
mTOR
Nucleus↑ Cell cycle control and proliferation↑ Cell survival and decreased apoptosis↑ Cellular migration and metastasis↑ Angiogenesis
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Neratinib + Fulvestrant for HER2-mutant HR+ Metastatic Breast Cancers: Updated Results from SUMMIT Trial
L. Smyth et al SABCS 2018 Abstract PD3-06
Chan
ge fr
om b
aseli
ne (%
) 50
0
–50
–100
100
* * * * * *
= PET responses*
Prior CDK4/6 inhibitor
Prior fulvestrant
Not shown: 5 patients in whom no % change in tumor size could be calculated (n=1 died before first post-baseline assessment; n=1 ended treatment due to AEs before first post-baseline assessment; n=3 non-target lesions only)
–30%
HER2 mutation typeKinase domain hotspotExtracellular domain hotspotTransmembrane hotspotNon-hotspot
− + + + + +− − − + + − − − − − − + − + − − + − − + − − + − − + + + − − − − − − +−− + + +− + + − + + − − +− − +−− + − − + − − − − +− − + + + ++ + + + − − + + +
Histology
HistologyDuctalLobularOther/unknown
− + + + + +− − − + + − − − − − − + − + − − + − − + − − + − − + + + − − − − − − +−
Objective responseCR or PRSD ≥24 weeksPD
= Treatment ongoing= (duration on N+F)/(duration on prior CDK4/6 inhibitor or fulvestrant) ≥1= (duration on N+F)/(duration on prior CDK4/6 inhibitor or fulvestrant) <1= no prior CDK4/6 inhibitor or no prior fulvestrant
− + + +− + + − + + − − +− − +−− + − − + − − − − +− − + + + ++ + + + − − + + +Objective response − + + + + +− − − + + − − − − − − + − + − − + − − + − − + − − + + + − − − − − − +−4.5 9.2 3.9 7.3 14.8 9.0 5.4 11.2 9.2 11.0 16.6 7.2 7.4 9.3 Duration of PRs and CRs (months)
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Puma - Expected Milestones Present data from Phase III trial in third-line MBC patients (Q2 19)
Report additional data from Phase II CONTROL trial (Q2 19)
File NDA for neratinib based on results of the Phase III trial in third-line metastatic breast cancer (Q3 19)
Meet with FDA to discuss clinical development and regulatory strategy for SUMMIT trial (Q3 19)
Regulatory decision on neratinib for extended adjuvant HER2 positive early stage breast cancer indication in other countries (H2 19)
Report Phase II data from the SUMMIT basket trial of neratinib in patients with HER2 mutations (H2 19)
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Copyright 2019 Puma Biotechnology
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 2030)
Composition of specific salt of neratinib (recently issued)
Additional use patents filed
37
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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 irreversible EGFR inhibitor for use in treating cancer having a T790M mutation
Claims for the pharmaceutical composition for use in the treatment of cancer including lung cancer and non-small cell lung cancer
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Copyright 2019 Puma Biotechnology
Experienced Management TeamAlan H. AuerbachChairman, Chief Executive Officer, President, Founder
- Chief Executive Officer, President, Founder, Cougar Biotechnology
Steven LoChief Commercial Officer
- Corcept Therapeutics, Genentech
Richard Bryce, MDChief Medical and Scientific Officer
- Onyx, Roche, ICON Clinical Research
Maximo F. NouguesChief Financial Officer
- Getinge AB, Boston Scientific, The Clorox Company
Douglas HuntSenior Vice President, Regulatory Affairs
- ArmaGen, Baxter Healthcare, Amgen
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Board of DirectorsAlan H. AuerbachChairman, Chief Executive Officer, President, FounderPuma Biotechnology, Inc.
Michael MillerEVP U.S. Commercial, Jazz Pharmaceuticals; Former SVP & Chief Commercial Officer, Vivus; VP, Sales & Marketing, Genentech; Connetics; Alza; Syntex
Jay MoyesFormer CFO, Myriad Genetics
Adrian Senderowicz, M.D.SVP & Chief Medical Officer, Constellation Pharmaceuticals; Former Chief Medical Officer, Cerulean; Chief Medical Officer & SVP, Clinical and Regulatory, Ignyta; Sanofi, Astrazeneca; FDA (Division of Oncology Drug Products)
Troy Wilson, PhD, JDCEO, Kura Oncology; CEO, Wellspring Biosciences; CEO Avidity Nanomedicines;Former CEO, President, Intellikine
Frank ZavrlFormer Partner, Adage Capital Management
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Copyright 2019 Puma Biotechnology
Currently trading on NASDAQ: PBYI
Cash, cash equivalents and marketable securities at March 31, 2019: $150 million
Cash burn in Q1 2019: ~$15 million
Amended term loan agreement (May 2018) New term loan of $155 million replaces loan of $100 million $125 million drawn down Silicon Valley Bank and Oxford Finance
Shares issued and outstanding: 38.6 million
Puma Biotechnology - Financial
41
Copyright 2019 Puma Biotechnology
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 Metastases HER2+ Neoadjuvant Breast Cancer HER2 Mutated Non-Small Cell Lung Cancer HER2 Mutated Breast Cancer HER2 Mutated Solid Tumors
Retain full U.S. commercial rights to NERLYNX®
Large initial market opportunity with additional label expansion potential
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Puma Biotechnology
Copyright 2019 Puma Biotechnology
Jefferies 2019 Healthcare Conference
June 2019
Puma Biotechnology
Copyright 2019 Puma Biotechnology
Jefferies 2019 Healthcare ConferenceAPPENDIXJune 2019
Copyright 2019 Puma Biotechnology
- HER2 positive breast cancer
- Lymph node negative, positive or residual invasive disease after
neoadjuvant treatment
Ran
dom
ize
1:1
Neratinib (1 year)
2840 patients total
Placebo (1 year)
- Completed 1 year prior adjuvanttreatment with trastuzumab prior to
randomization
Primary endpoint: Invasive Disease Free Survival (IDFS)
Secondary endpoints: Disease Free Survival Including Ductal Carcinoma in Situ (DFS-DCIS), Time to Distant Recurrence, Incidence of CNS recurrence, Overall Survival
No loperamide prophylaxis used to prevent neratinib related diarrhea
ExteNET Trial - HER2 Positive Extended Adjuvant Breast Cancer
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Copyright 2019 Puma Biotechnology
Kaplan-Meier Estimates of Disease Free SurvivalITT Population
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Dis
ease
-free
sur
viva
l (%
)
Months after randomization
100
70
60
50
80
90
0
NeratinibPlacebo
P-value = 0.009HR (95% CI) = 0.67 (0.50–0.91)
14201420
12911367
12601324
12291292
11891243
11501209
11081163
10331090
662704
No. at riskNeratinibPlacebo
97.8%
93.9%
91.6%95.6%
0 3 6 9 12 15 18 21 24
Copyright 2012 Puma BiotechnologyCopyright 2014 Puma BiotechnologyCopyright 2019 Puma Biotechnology
0 3 6 9 12 15 18 21 24
Dis
ease
-free
sur
viva
l (%
)
Months after randomization
100
70
60
50
80
90
0
NeratinibPlacebo
P-value = 0.001HR (95% CI) = 0.51 (0.33–0.77)
816815
737784
721761
698741
677716
653699
629669
591622
380401
No. at riskNeratinibPlacebo
97.9%
96.0% 95.4%91.2%
Kaplan-Meier Estimates of DFSHormone Receptor Positive Patients ITT Population
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Rationale for efficacy in HR+ subgroup
membrane
HER2 HER1/2/3
ERE
nucleus
Cytoplasm
ER-regulatedgenetranscription
ER ER X
FOXO3a
MEK
ErK1/2
PI3-K
AKT
RAS
FOXO3a
HER2 signalling decreasesER-regulated gene transcription
Cytoplasm
membrane
HER2 HER1/2/3
ERE
RAS
nucleus ER-regulatedgenetranscription
ER ER
Neratinib
MEK
ErK1/2
PI3-K
AKT
RAS
FOXO3a
XX
HER2 inhibition upregulates ER-regulated gene transcription
ER ER
membrane
HER2 HER1/2/3
ERE
RAS
nucleus
Cytoplasm
ER-regulatedgenetranscription
ER ER
Neratinib
MEK
ErK1/2
PI3-K
AKT
RAS
FOXO3a
XX
Inhibition of HER2 and ER is required for effective blockage in HER2+/HR+ tumors
X
Endocrine therapy
ER ERER
Adapted from: Paplomata et al. Cancer 2015
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0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 12 24 36 48 60
Dis
ease
-free
sur
viva
l
Months after randomization
Neratinib Placebo
HR (95% CI): 0.73 (0.57-0.92)Two-sided P=0.008
At riskNeratinib 1420 1316 1272 1225 1106 978 965 949 938 920 885Placebo 1420 1354 1298 1248 1142 1029 1011 991 978 958 927
5-year Analysis Shows Durable iDFS BenefitITT Population
97.9%
95.5%94.3%
91.7% 2.5% Δ92.2%
90.2%91.2%
89.1%
(Descriptive P value)
90.2%
87.7%
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0 12 24 36 48 60Months after randomization
Neratinib Placebo
HR (95% CI): 0.95 (0.66-1.35)Two-sided P=0.762
604 559 541 520 464 407 400 391 384 376 362605 575 548 529 495 448 444 435 427 416 402
97.5%
94.7% 92.8%
91.8%90.8%90.4%
89.9%89.3% 88.8%
88.9%
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 12 24 36 48 60
Dis
ease
-free
sur
viva
l
Months after randomization
Neratinib Placebo
HR (95% CI): 0.60 (0.43-0.83)Two-sided P=0.002
At riskNeratinib 816 757 731 705 642 571 565 558 554 544 523Placebo 815 779 750 719 647 581 567 556 551 542 525
iDFS by Hormone Receptor Status5-Year Analysis
98.1%
96.1%95.4%
91.7% 4.4% Δ
93.6%
89.8%
92.6%
88.5%
91.2%
86.8%
Hormone receptor positive Hormone receptor negative
(Descriptive P value)
iDFS for HR+ patients completing prior trastuzumab ≤1 year from randomization (2-year and 5-year Analyses)
EC Approved Indication
51% relative reduction in risk of recurrence
42% relative reduction in risk of recurrence
Gnant M, et al. SABCS 2018, poster #P2-13-01 51
2-year (primary) analysis 5-year analysis
DDFS for HR+ patients completing prior trastuzumab ≤1 year from randomization (2-year and 5-year Analyses)
EC Approved Indication
47% relative reduction in risk of recurrence
43% relative reduction in risk of recurrence
Gnant M, et al. SABCS 2018, poster #P2-13-01 52
2-year (primary) analysis 5-year analysis
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
36% relative reduction in risk of recurrence
40% relative reduction in risk of recurrence
Gnant M, et al. SABCS 2018, poster #P2-13-01 53
2-year (primary) analysis 5-year analysis