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Puma Biotechnology
Copyright 2017 Puma Biotechnology
Jefferies 2017 Global Healthcare Conference
June 2017
Copyright 2017 Puma Biotechnology
This presentation contains forward-looking statements within the meaning of the Private Securities
Litigation Reform Act of 1995, including, but not limited to, statements regarding the potential
approval for a drug candidate, pre-commercial activities, 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. These statements are often, but not always, made through the use of words
or phrases such as ``anticipates,'' ``expects,'' ``plans,'' ``believes,'' ``intends,'' and similar words or
phrases. All forward–looking statements included in this presentation 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 statements are based on current
expectations, forecasts and assumptions, and actual outcomes and results could differ materially
from these statements due to a number of factors, which include, but are not limited to, the fact that
we have no product revenue and no products approved for marketing; our dependence on our lead
product candidate PB272, which is still under development and may never receive regulatory
approval; the challenges associated with conducting and enrolling clinical trials; the risk that results
of clinical trials may not support our drug candidate claims; even if approved, the risk that physicians
and patients may not accept or use our products; our reliance on third parties to conduct our clinical
trials and to formulate and manufacture our drug candidates; our dependence on licensed
intellectual property; and the other risk factors disclosed in our periodic reports filed with the
Securities and Exchange Commission from time to time, including our Annual Report on Form 10-K
for the fiscal year ended December 31, 2016. 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 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
HER2-mutant Breast Cancer/Solid Tumors
MetastaticNeratinib (± 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)
EAP/MAP
CONTROL
ExteNET (Phase III HER2+ EBC)
I-SPY 2
NSABP FB-7
3
TBCRC-022
Copyright 2017 Puma Biotechnology
NDA filed 07/16MAA filed 06/16
Copyright 2017 Puma Biotechnology
- HER2 positive breast cancer
- Lymph node negative, positive or
residual invasive disease after
neoadjuvant treatment
Ran
do
miz
e 1
:1
Neratinib (1 year)
2840 patients total
Placebo (1 year)
- Completed 1 year prior adjuvant
treatment 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
4
Copyright 2017 Puma Biotechnology
Kaplan-Meier Estimates of Disease Free Survival
ITT Population
5
Dis
ea
se-f
ree
su
rviv
al (%
)
Months after randomization
100
70
60
50
80
90
0
Neratinib
Placebo
P-value = 0.009
HR (95% CI) = 0.67 (0.50–0.91)
1420
1420
1291
1367
1260
1324
1229
1292
1189
1243
1150
1209
1108
1163
1033
1090
662
704
No. at risk
Neratinib
Placebo
97.8%
93.9%
91.6%95.6%
0 3 6 9 12 15 18 21 24
Copyright 2017 Puma Biotechnology
0 3 6 9 12 15 18 21 24
Dis
ea
se-f
ree
su
rviv
al (%
)
Months after randomization
100
70
60
50
80
90
0
Neratinib
Placebo
741
722
692
706
683
684
672
663
654
641
635
623
610
599
570
561
374
356
No. at risk
Neratinib
Placebo
98.1%
94.9%94.7%
90.6%
Kaplan-Meier Estimates of DFS
Centrally Confirmed HER2 Positive Population
P-value = 0.002
HR (95% CI) = 0.51 (0.33–0.77)
6
Copyright 2012 Puma BiotechnologyCopyright 2014 Puma BiotechnologyCopyright 2017 Puma BiotechnologyCopyright 2017 Puma Biotechnology
Comparator Adjuvant Registration Studies
Study Design
DFS DFS-DCIS
Reduction in
risk of disease
recurrence
Absolute reduction
in risk of disease
recurrence
HR p HR p DFS DFS-
DCIS
DFS DFS-
DCIS
‘Extended’ adjuvant HER2+ BC
ExteNET Local HER2 0.67 0.009 0.63 0.002 33% 37% 2.3%
(24 mo)
2.9%
(24 mo)
Central HER2 0.51 0.002 0.49 <0.001 49% 51% 4.1%
(24 mo)
4.5%
(24 mo)
HERA
2 years
Central HER2 0.99 0.86 ND 2.4%
(24 mo)
Extended adjuvant HR+ EBC post tamoxifen Rx (HER2+ and HER2-)
MA.17 Letrozole
(post 5yrs
tamoxifen)
0.62 <0.001 2.8%
(24 mo)
Adjuvant treatment HR+ EBC (HER2+ and HER2-)
Arimidex 5 yrs Rx 0.83 0.0049 17% 2.8%
(5 yrs)
Aromasin 2-3 yrs
tamoxifen →
Aromasin
0.69 <0.001 31% 3.4%
(5 yrs)
7
Copyright 2012 Puma BiotechnologyCopyright 2014 Puma BiotechnologyCopyright 2017 Puma Biotechnology
0 3 6 9 12 15 18 21 24
Dis
ea
se-f
ree
su
rviv
al (%
)
Months after randomization
100
70
60
50
80
90
0
Neratinib
Placebo
P-value = 0.001
HR (95% CI) = 0.51 (0.33–0.77)
816
815
737
784
721
761
698
741
677
716
653
699
629
669
591
622
380
401
No. at risk
Neratinib
Placebo
97.9%
96.0%95.4%
91.2%
Kaplan-Meier Estimates of DFS
Hormone Receptor Positive Patients ITT Population
8
Copyright 2012 Puma BiotechnologyCopyright 2014 Puma BiotechnologyCopyright 2017 Puma BiotechnologyCopyright 2017 Puma Biotechnology
Crosstalk between ER and HER2 Signaling Pathways:
Rationale for Dual Neratinib and Hormonal Therapy
Source: Prat and Baselga. Nat Clin Practice Onc 2008;5:531–42
*Inhibition of cross talk not seen in extended adjuvant trials of
Herceptin (HERA 2 year) or Tykerb (TEACH)
9
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 12 24 36 48 60
Dis
ea
se-f
ree
su
rviv
al
Months after randomization
Neratinib
Placebo
HR (95% CI): 0.73 (0.57-0.92)
Two-sided P=0.008
At risk
Neratinib 1420 1316 1272 1225 1106 978 965 949 938 920 885
Placebo 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% Δ
92.2%
90.2%
91.2%
89.1%
(Descriptive P value)
90.2%
87.7%
10
0 12 24 36 48 60
Months after randomization
Neratinib
Placebo
HR (95% CI): 0.95 (0.66-1.35)
Two-sided P=0.762
604 559 541 520 464 407 400 391 384 376 362
605 575 548 529 495 448 444 435 427 416 402
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
ea
se
-fre
e s
urv
iva
l
Months after randomization
Neratinib
Placebo
HR (95% CI): 0.60 (0.43-0.83)
Two-sided P=0.002
At risk
Neratinib 816 757 731 705 642 571 565 558 554 544 523
Placebo 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)
Copyright 2017 Puma Biotechnology
ExteNET-HER2+ Extended Adjuvant Breast Cancer
Filed NDA for US FDA approval (July 2016)
Filed MAA for EU approval (June 2016)
Label revised to include patients treated up to one year from
completion of adjuvant Herceptin (March 2017)
Managed Access Program (MAP) launched Q4 16
Expanded Access Program (EAP) launched Q1 17
FDA Oncologic Drugs Advisory Committee voted to recommend approval (May 24, 2017)
Anticipated PDUFA Date (July 2017)
12
Copyright 2017 Puma Biotechnology
Neratinib (PB272)Safety
Over 3,000 patients treated with neratinib prior to Puma licensing
drug
Neratinib - Main Grade 3/4 AE-Diarrhea (previously ~30% Grade
3/4)
Typically a first cycle effect (first 28 days)
Historically treated with antidiarrheal agents (loperamide) after
diarrhea occurs
Treated with dose reductions after diarrhea occurs
Puma introduced diarrhea prophylaxis with loperamide
Given Day 1 with neratinib dose for first cycle
High dose of loperamide initially (8-16mg)
Taper dose during cycle 1
13
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 NeratinibPaclitaxel + 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
04 (57%)
of 71 (50%)
of 21 (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
14Copyright 2017 Puma Biotechnology
CONTROLStudy Design
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
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)
15Copyright 2017 Puma Biotechnology
CONTROLStudy Flowchart
NeratinibLoperamide prophylaxis
Budesonide
Budesonide cohort n=40 planned(Amendment 3)
Colestipol cohortn=40 planned(Amendment 4)
Investigational cohortn=40 planned(Amendment 4)
Loperamide cohortn~120 planned
(Original protocolAmendment 1 and 2)
Stage 1-3c HER2+ breast cancerTrastuzumab-based adjuvant therapy completed within 1 year
NeratinibLoperamide prophylaxis
NeratinibLoperamide prophylaxis
Colestipol
NeratinibLoperamide prophylaxis
To be decided
Sequential investigational cohorts
Po
pu
lati
on
Co
ho
rtTr
eatm
en
tA
nal
ysis
16Copyright 2017 Puma Biotechnology
Planned enrollmentstart date: 2017
Interim analysis(N=137)
Preliminary analysis(N=64)
Preliminary analysis(N=26)
CONTROL1 ExteNET2
Loperamide prophylaxis
(original + modified)
Loperamide prophylaxis
+ budesonide
Loperamide prophylaxis
+ colestipol
Loperamide
prn
N (at data cut-off) 137 64 26 1408
Any grade 77.4 79.7 57.7 95.4
Grade 1 24.1 26.6 30.8 22.9
Grade 2 22.6 29.7 15.4 32.5
Grade 3 30.7 23.4 11.5 39.8
Grade 4 0 0 0 0.1
Median duration of
neratinib treatment,
months 10.6 5.1 1.7 11.6
Characteristics of treatment-emergent diarrheaCONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea
Loperamide prophylaxis reduces incidence and severity of diarrhea
1. Ibrahim et al. AACR 2017
2. Chan et.al. Lancet Oncol 2016 17Copyright 2017 Puma Biotechnology
CONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea
Significant improvement seen with CONTROL prophylaxis
Ibrahim et al. AACR 2017
18
CONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea
Loperamide prophylaxis reduces diarrhea duration
Median cumulative duration per patient, days
CONTROL 1 ExteNET 2
Loperamide prophylaxis (original + modified)
Loperamide prophylaxis
+ budesonide
Loperamide prophylaxis
+ colestipol
Loperamide
prn
(n=127) (n=64) (n=26) (n=1408)
Any grade 12.0 10.0 8.0 59.0
Grade ≥ 2 4.0 3.0 2.0 10.0
Grade ≥ 3a 3.0 2.0 2.0 5.0
Treatment
duration, months
Median 10.6 5.1 1.7 11.6
19Copyright 2017 Puma Biotechnology
a No grade 4 events in the CONTROL study;
one grade 4 event in the ExteNET study
1. Ibrahim et.al. AACR 2017
2. Chan et.al. Lancet Oncol 2016
Median diarrhea episodes per patient
CONTROL1 ExteNET2
Loperamide
prophylaxis
(original + modified)
Loperamide
prophylaxis +
budesonide
Loperamide
prophylaxis +
colestipol
Loperamide
prn
(n=137) (n=64) (n=26) (n=1408)
Any grade 2 4 3 8
Grade ≥ 2 2 2 2 3
Grade ≥ 3a 1 1 2 2
• Loperamide prophylaxis with or without the addition of budesonide reduces the
number of diarrhea episodes experienced by patients
a No grade 4 events in the CONTROL study;
one grade 4 event in the ExteNET study.
CONTROL vs ExteNET: Neratinib Treatment-Emergent Diarrhea
Loperamide prophylaxis reduces diarrhea episodes
20Copyright 2017 Puma Biotechnology 1. Ibrahim et.al. AACR 2017
2. Chan et.al. Lancet Oncol 2016
Loperamide Prophylaxis in CONTROL Decreases
Neratinib Dose Reductions and Dose Holds
1. Ibrahim et al. AACR 2017
2. Chan et.al. Lancet Oncol 2016
Actions required due to diarrhea, %
CONTROL 1 ExteNET 2
Loperamide
prophylaxis
(original +
modified)
Loperamide
prophylaxis +
budesonide
Loperamide
prophylaxis +
colestipol
Loperamide
prn
(n=137) (n=64) (n=26) (n=1408)
Dose reduction 7.3 1.6 3.8 26.4
Dose hold 14.6 14.1 7.7 33.9
Discontinued treatment 20.4 9.4 0 16.8
Hospitalization 1.5 0 0 1.4
21Copyright 2017 Puma Biotechnology
CONTROLPrior pertuzumab exposure affects diarrhea incidence
Prior pertuzumab exposure
Loperamide prophylaxis Loperamide prophylaxis + budesonide
Yes(n=55)
No(n=82)
Yes(n=39)
No(n=25)
Grade 3 diarrhea, % 38.2 25.6 10.3 36.0
22
• Prior pertuzumab may result in a higher incidence of grade 3 diarrhea that is not prevented/reduced with loperamide prophylaxis alone
• Adding budesonide may reduce grade 3 diarrhea
Ibrahim et.al. AACR 2017Copyright 2017 Puma Biotechnology
Antidiarrheal Prophylaxis Reduces the Incidence and Severity of DiarrheaExteNET and CONTROL (Updated May 2017)
22%
24%23%
31%
5%
23%
32%
40%
None
Grade 1
Grade 2
Grade 3
25%
28%27%
20%
ExteNET
n=1408
Loperamide
n=137
Loperamide + budesonide
n=64
46%
26%
20%
8%
Colestipol + loperamide
n=39
23
Copyright 2012 Puma BiotechnologyCopyright 2017 Puma Biotechnology
Commercial Launch Initiatives
2016 Q1 2017 Q2 2017 Q3 2017
Market Research (Physician & Patient)
Commercial Operations (3PL, Distribution, Specialty Pharmacy, Reimbursement Hub)
Patient Advocacy Partnerships; Oncology Congress Presence
Marketing : Message and Market Development
Market Access : Payer Education, AMCP Dossier, NCCN
Field Team Sizing
Disease Awareness Campaigns
Key examples (not full list of initiatives)
Sales Force
EU : Physician & Payer Research
L
A
U
N
C
H
Pricing
Managed Access, Global Value Dossiers
24
Copyright 2017 Puma Biotechnology 25
PB272 Extended Adjuvant HER2+ Breast
Cancer Market Size
Approximately 36,000 patients (US) with early stage HER2+
breast cancer
Approximately 34,000 patients (EU) with early stage HER2+
breast cancer
Treatment duration: 12 months
Estimated 2015 WW Herceptin adjuvant revenue (year 1) :
$4.5-$5.0 billion
Neratinib would be used in year 2 after adjuvant Herceptin
Copyright 2017 Puma Biotechnology
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)Neratinib + Torisel
No Prior HER2+ Rx
T-DM1 +/- Perjeta
(MARIANNE-trial did not
achieve primary endpoint
December 2014)
26
Phase III Trial – Third Line HER2+ MBC (NALA):
Study Rationale
Therapy Region / StudyResponse 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
27Copyright 2017 Puma Biotechnology
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 OBJECTIVES
Co-Primary: PFS (central) and OS
Secondary: 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
RA
ND
OM
IZA
TIO
N
2831
n=600
28Copyright 2017 Puma Biotechnology
Copyright 2017 Puma Biotechnology
PB272 Third-Line HER2+ MBC
Market Size
Approximately 5,000-6,000 patients (US) with third-line
HER2+ metastatic breast cancer
Tykerb 2013 WW sales - ~$325 M (~$86 M US, ~$239M
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
29
NEfERTT Trial – First-Line HER2 Positive
Metastatic Breast Cancer
30
Primary endpoint: Progression free survival (PFS)
Secondary endpoints: Overall response rate, clinical benefit rate, safety, time to
CNS mets
No loperamide prophylaxis used to prevent neratinib related diarrhea
Awada et al. JAMA Oncol 2016
Previously untreated HER2+ locally recurrent or mBC• No evidence of primary disease
refractory to trastuzumab or paclitaxel
• No prior therapy for locally recurrent or mBC
Trastuzumab +Paclitaxel
Neratinib + Paclitaxel
PD
PD
1:1
RA
ND
OM
IZA
TIO
N
n=479
Copyright 2017 Puma Biotechnology
Copyright 2017 Puma Biotechnology
PB272 First-Line HER2+
Metastatic Breast Cancer Trial (NEfERTT)
Progression Free Survival:
Paclitaxel-Neratinib: 12.9 months
Paclitaxel-Herceptin: 12.9 months (p=0.89)
Objective Response Rate:
Paclitaxel-Neratinib: 74.8%
Paclitaxel-Herceptin: 77.6% (p=0.52)
Incidence of CNS Metastases:
Paclitaxel-Neratinib: 8.3%
Paclitaxel-Herceptin: 17.3% (p=0.002)
31
CNS ProgressionNeratinib-Paclitaxel Delayed Onset of CNS Metastases
Time (months)
242237
191196
141144
10296
7370
5753
4544
3835
00
3533
3227
2223
1414
106
33
GroupNeratinib + paclitaxel
Trastuzumab + paclitaxel
N242237
Event2041
Median (95% CI)Not estimableNot estimable
Hazard ratio (95% CI) = 0.48 (0.29, 0.79)Log-rank test P-value = 0.002
0 4 8 12 16 20 24 28 5632 36 40 44 48 52
Free
of
CN
S p
rogr
essi
on
(%
)1.0
0.6
0.5
0.8
0.9
0.0
0.7
0.2
0.1
0.4
0.3
Neratinib + paclitaxel
Trastuzumab + paclitaxel
No. at riskNeratinib + paclitaxelTrastuzumab + paclitaxel
323Awada et al. JAMA Oncol 201632Copyright 2017 Puma Biotechnology
Copyright 2017 Puma Biotechnology
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
33
FB-10 - Phase I/II trial of Kadcyla (T-DM1) plus
Neratinib
34
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
Copyright 2017 Puma Biotechnology
-100%
-80%
-60%
-40%
-20%
0%
20%
40%
60%
80%
100%
FB-10-Phase I/II trial of Kadcyla (T-DM1) plus
Neratinib
PD
SD
CR/PR
ORR (CR/PR): 9 of 16 (56%)
Abraham et.al. AACR 2017
35
Copyright 2017 Puma Biotechnology
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
36
Ongoing Neratinib Studies Investigating
CNS Metastases
TBCRC -022
37
Cohort 1 (neratinib monotherapy): 7.5% ORR in CNS (ASCO 2014)-85% Tykerb refractory
Cohort 3: Results anticipated Q2 17
Copyright 2017 Puma Biotechnology
TBCRC-022 Cohort 3a– CNS Response %
re
du
cti
on
in
vo
lum
e o
f C
NS
le
sio
ns
* ASCO 2017
-100
-80
-60
-40
-20
0
20
40
60
80
100
Best Volumetric CNS response (n=31 evaluable pts)Best Volumetric Response (n=31)*
CNS ORR = 49% (95% CI 32-66%)
18 responses
Open-label, multinational, phase 2 study of neratinib as monotherapy or in combination in patients with tumors harboring ERBB2 mutations
Primary endpoint: ORR
Secondary endpoints: ORR (confirmed), CBR, PFS, safety, biomarkers
Simon 2-stage design: If threshold response rate hit in first evaluable 7 patients expand cohort
HER
2m
uta
nt*
M
on
oth
era
py
Breast cancer HR (–)
Biliary tract
Endometrial
Gastro-esophageal
Ovarian
Solid tumors (Other)
HER
2m
uta
nt*
C
om
bin
ati
on Breast cancer HR (+)
Neratinib + fulvestrant
Bladder/urinary tractNeratinib + paclitaxel
*Documented mutations based on local testing
PD
NeratinibMonotherapy or
combination therapy in HER2-mutant bladder or
HR+ breast cohort*
3939
Phase II HER2 Mutation Basket Trial (SUMMIT)
Study Design
Copyright 2017 Puma Biotechnology
Neratinib Monotherapy Efficacy in HER2-mutant Patients by Tumor Type
40* no target lesion measurement
Hyman et.al. AACR 2017
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 Pathway
RAS
RAF
MEK
ERK
PI3K
AKT
mTOR
Nucleus
↑ Cell cycle control and proliferation
↑ Cell survival and decreased apoptosis
↑ Cellular migration and metastasis
↑ Angiogenesis
Copyright 2017 Puma Biotechnology
Best Change in Tumor Burden: Neratinib Monotherapy (n=25)
SABCS 2016
Still on treatment
Objective
response
rate: 33%
Best Change in Tumor Burden: Neratinib + Fulvestrant
(n=17)
SABCS 2016
Objective
response
rate: 58.3%
Copyright 2017 Puma Biotechnology
Phase II HER2 mutant MBC: Investigator Sponsored
Study
Neratinib 240mg daily
STUDY OBJECTIVES:
1o endpoint: Clinical Benefit Rate (CR + PR + SD ≥ 6 months)
2o endpoints: Correlate HER2 mutations with histology, Grade, Stage, PFS
PD
HER2 mutant,
non-HER2
amplified
Stage IV MBC w/ documented
ERBB2 mutation
44
Copyright 2017 Puma Biotechnology
Phase II HER2 mutant MBC: Investigator Sponsored
Study
Interim data presented at 2016 ASCO Annual Meeting
Neratinib monotherapy (n=14)
Clinical benefit rate: 36% (1 CR, 1 PR, 3 stable disease> 6 months)
PFS: 5.0 months
94% of patients were HR positive
Preclinical data shows cross talk between HER2 mutation and ER
Protocol amended to treat with combination of neratinib
plus fulvestrant
Additional data anticipated 2017
45
Copyright 2017 Puma Biotechnology
Puma-Expected Milestones
Report additional data from Phase II CONTROL trial (loperamide +
budesonide prophylaxis (Q2 17)
Report Interim Phase I/II data from neratinib plus Kadcyla (T-DM1) in
HER2-positive metastatic breast cancer trial (Q2 17)
Report Phase II data from SUMMIT basket trial of neratinib in patients
with HER2 mutations (Q2 17)
Report Phase II trial in MBC patients with brain metastases (Q2 17)
Report final 5-year DFS data from ExteNET (Q2 17)
Report Phase III trial in third-line MBC patients (Q2 17)
Regulatory decision in US/EU on neratinib in extended adjuvant HER2
positive early stage breast cancer (Q3 17)
46
Copyright 2017 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
47
Copyright 2017 Puma Biotechnology
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
48
Copyright 2017 Puma Biotechnology
Experienced Management Team
Alan H. Auerbach
Chairman, Chief Executive Officer, President, Founder
-Chief Executive Officer, President, Founder, Cougar Biotechnology
Richard Bryce, MD
Senior Vice President Clinical Research and Development
-Onyx, Roche, ICON Clinical Research
Charles R. Eyler
Senior Vice President, Finance and Treasurer
-Cougar Biotechnology, Hayes Medical
Steven LoChief Commercial Officer
-Corcept Therapeutics, Genentech
49
Copyright 2017 Puma Biotechnology
Board of Directors
Alan H. Auerbach
Chairman, Chief Executive Officer, President, Founder
Puma Biotechnology, Inc.
Jay Moyes
Former CFO, Myriad Genetics
Adrian Senderowicz, M.D.
Chief Medical Officer, Cerulean; Former Chief Medical Officer and SVP, Clinical and Regulatory, Ignyta, Inc.; Sanofi, Astrazeneca; FDA (Division of Oncology Drug Products)
Troy Wilson, PhD, JD
CEO, Kura Oncology; CEO, Wellspring Biosciences; CEO Avidity
Nanomedicines; Former CEO, President, Intellikine
Frank Zavrl
Former Partner, Adage Capital Management
50
Copyright 2017 Puma Biotechnology
Currently Trading on NASDAQ: PBYI
Cash position at March 31, 2017: $194.0 million
Net cash used in operating activities (burn) in Q1 2017: $36.0 million
Completed $172.5 million Public Offering (October 2016)
Issued 4,312,500 shares at $40.00 per share
Shares issued and outstanding: 37.0 million
Puma Biotechnology-Financial
51
Copyright 2017 Puma Biotechnology
Company Highlights In licensing driven business model – mitigates R&D risk
PB272 (neratinib) - clinical stage candidate targeting multiple oncology indications
HER2+ Extended Adjuvant Breast Cancer
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
Retained commercial rights to PB272
Strong Phase II and Phase III data for PB272 (single agent and in combination with chemotherapy)
Potential for multiple clinical and regulatory milestones over next 6-12 months
52
Puma Biotechnology
Copyright 2017 Puma Biotechnology
Jefferies 2017 Global Healthcare Conference
June 2017
Puma Biotechnology
Copyright 2017 Puma Biotechnology
Jefferies 2017 Global Healthcare Conference
APPENDIX
June 2017
Neratinib / Placebo treatment
0 3 6 9 12 15 18 21 24
Dis
ease
-fre
e su
rviv
al (
%)
Months after randomization
11521145
10471100
10231063
10021035
971997
936964
899929
833865
No. at riskNeratinibPlacebo
100
60
50
80
90
0
70Two sided P-value = 0.006HR (95% CI) = 0.63 (0.45–0.88)
97.9%
95.2%93.8%
90.9%
Neratinib
Placebo
Intention-to-treat population
DFS in patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab
55
526554
* p-value descriptive
Copyright 2017 Puma Biotechnology
Interim 5-year DFS in patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab
0 6 12 18 24 36 42 48 6030 54
Dis
ease
-fre
e su
rviv
al (
%)
Months after randomization
11521145
10541080
10171034
976982
855894
728770
717753
684724
No. at riskNeratinibPlacebo
301321
615644
465504
100
60
50
80
90
0
70
97.8%
95.2% 89.9%
86.8%
Neratinib
Placebo
93.8%
91.0%
92.0%
89.5%
90.8%
88.3%
Two sided P-value = 0.014HR (95% CI) = 0.72 (0.55–0.94)
Neratinib /Placebo
treatment
Intention-to-treat population
56
* p-value descriptive
Copyright 2017 Puma Biotechnology
Neratinib / Placebo treatment
0 3 6 9 12 15 18 21 24
Dis
ease
-fre
e su
rviv
al (
%)
Months after randomization
670664
605638
593619
577602
559580
538563
516541
485501
No. at riskNeratinibPlacebo
100
60
50
80
90
0
70Two sided P-value = 0.002HR (95% CI) = 0.49 (0.30–0.78)
98.1%
96.0%95.3%
90.8%
Neratinib
Placebo
HR+ patients
DFS in HR+ patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab
57
307326
* p-value descriptive
Copyright 2017 Puma Biotechnology
0 6 12 18 24 36 42 48 6030 54
Dis
ease
-fre
e su
rviv
al (
%)
Months after randomization
670664
614630
589604
567575
501520
436447
432434
416417
No. at riskNeratinibPlacebo
181171
375370
283284
100
60
50
80
90
0
70
98.0%
96.1% 91.4%
85.9%
Neratinib
Placebo
94.9%
91.3%
93.5%
89.3%
92.6%
87.8%
Two sided P-value = 0.002HR (95% CI) = 0.57 (0.39–0.82)
Neratinib /Placebo
treatment
HR+ patients
58
* p-value descriptive
Copyright 2017 Puma Biotechnology
Interim 5-year DFS in HR+ patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab
Neratinib / Placebo treatment
0 3 6 9 12 15 18 21 24
Dis
ease
-fre
e su
rviv
al (
%)
Months after randomization
482481
442462
430444
425433
412417
398401
383388
348364
No. at riskNeratinibPlacebo
100
60
50
80
90
0
70Two sided P-value = 0.419HR (95% CI) = 0.83 (0.52–1.31)
97.7%
94.1%91.7%91.1%
Neratinib
Placebo
HR– patients
DFS in HR– patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab
59
219228
* p-value descriptive
Copyright 2017 Puma Biotechnology
0 6 12 18 24 36 42 48 6030 54
Dis
ease
-fre
e su
rviv
al (
%)
Months after randomization
482481
440450
428430
409407
354374
292323
285319
268307
No. at riskNeratinibPlacebo
120150
240274
182220
100
60
50
80
90
0
70
97.5%
94.0% 87.9%87.8%
Neratinib
Placebo
92.3%
90.6% 89.8%
89.9%
88.2%
88.9%
Two sided P-value = 0.756HR (95% CI) = 0.94 (0.63–1.39)
Neratinib /Placebo
treatment
HR– patients
60
* p-value descriptive
Copyright 2017 Puma Biotechnology
Interim 5-year DFS in HR– patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab
DFS in centrally confirmed HER2+ (ccHER2+) patients initiating neratinib treatment less than 1 year after completing adjuvant trastuzumab
61
Neratinib / Placebo treatment
0 3 6 9 12 15 18 21 24
Dis
ease
-fre
e su
rviv
al (
%)
Months after randomization
743703
697684
685658
675638
658617
635596
609574
557536
No. at riskNeratinibPlacebo
100
60
50
80
90
0
70Two sided P-value <0.001HR (95% CI) = 0.49 (0.32–0.74)
98.1%
94.1%94.5%
89.9%
Neratinib
Placebo
ccHER2+ patients
352336
* p-value descriptive
Copyright 2017 Puma Biotechnology
Interim 5-year DFS in ccHER2+ patients initiating neratinibtreatment less than 1 year after completing adjuvant trastuzumab
0 6 12 18 24 36 42 48 6030 54
Dis
ease
-fre
e su
rviv
al (
%)
Months after randomization
743703
698667
683638
660606
583554
493481
484472
459451
No. at riskNeratinibPlacebo
195196
410397
312315
100
60
50
80
90
0
70
97.9%
94.1%90.6%
86.7%
Neratinib
Placebo
94.3%
90.0%
92.2%
89.0%
91.1%
87.5%
Two sided P-value = 0.01HR (95% CI) = 0.65 (0.46–0.90)
Neratinib /Placebo
treatment
ccHER2+ patients
62
* p-value descriptive
Copyright 2017 Puma Biotechnology