Copyright 2014 Puma Biotechnology
This presentation contains forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995, including statements regarding 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, 2013.
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
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Copyright 2014 Puma Biotechnology
Company Highlights
In-licensing driven business model – mitigates R&D risk
PB272 (neratinib)- clinical stage candidate targeting multiple oncology indications
HER2+ Metastatic Breast Cancer
HER2+ Metastatic Breast Cancer with Brain Metastases
HER2+ Neoadjuvant Breast Cancer
HER2+ Adjuvant 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 data for PB272 (single agent and in combination with chemotherapy)
Potential for multiple clinical trial readouts during 2014
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Copyright 2014 Puma Biotechnology
Product Pipeline Drug Indication Pre-clinical I II III Registration
PB272
Combination w/
Xeloda
Metastatic
Breast Cancer
PB272
Combination w/
Torisel
Metastatic
Breast Cancer
PB272
Single agent/
combination
Metastatic
Breast Cancer
with Brain Mets
PB272
Combination w/
chemotherapy
Neoadjuvant
Breast Cancer
PB272
Combination w/
Paclitaxel
Metastatic
Breast Cancer
PB272
Single agent Adjuvant
Breast Cancer
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Copyright 2014 Puma Biotechnology
Product Pipeline (cont’d.)
Drug Indication Pre-clinical I II III Registration
PB272 (oral)
Combination and
Single agent
HER2 Mutated
NSCLC
PB272 (oral)
Single agent HER2 Mutated
Breast Cancer
PB272 (oral)
Single agent
HER2 Mutated
Solid Tumors
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Copyright 2014 Puma Biotechnology
Neratinib (PB272) Safety
Over 3,000 patients treated with neratinib
Neratinib - Main Grade 3/4 AE-Diarrhea (~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
High dose of loperamide initially (8-16mg)
Taper dose during cycle 1
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Copyright 2014 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-data expected
2014)
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Copyright 2014 Puma Biotechnology
HER2+ Metastatic Breast Cancer-Tykerb (Lapatinib)
Tykerb-oral, reversible pan-HER tyrosine kinase inhibitor-
dual inhibitor EGFR/HER2
Single agent activity in second-line HER2+ MBC
Response rate: 5-7%
Progression free survival: 8-9 weeks
Activity in combination with Xeloda (capecitabine) in
second/third line HER2+ MBC (FDA approved regimen)
Response rate (n=399)
23.7 % for Tykerb/Xeloda vs. 13.9% for Xeloda alone
Progression free survival
27.1 weeks for Tykerb/Xeloda vs. 18.6 weeks for Xeloda alone
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Copyright 2014 Puma Biotechnology
Neratinib (PB272)
Oral irreversible pan-HER tyrosine kinase inhibitor
In-licensed from Pfizer (August 2011)
Irreversible dual inhibitor of EGFR/HER2
Single agent activity in second line metastatic breast cancer (MBC; n=63)
Response rate: 24%
Progression free survival: 22.3 weeks Journal of Clinical Oncology, March 2010
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Copyright 2014 Puma Biotechnology
Neratinib (PB272) Activity in second-line/third-line HER2+ MBC
Response
Rate
PFS
(weeks)
Tykerb (single agent) 5-7% 8-9
Neratinib (single agent) 24% 22.3
Herceptin plus vinorelbine 25% 22.0
Neratinib plus vinorelbine 57% 44.1
Tykerb plus capecitabine 23.7% 27.1
Neratinib plus capecitabine 64% 40.3
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Copyright 2014 Puma Biotechnology
PB272 Phase III Trial-Third Line HER2+ MBC
(PUMA-NER-1301)
Obtained SPA from FDA and review by EMA in February
2013
Performed in patients with HER2+ Metastatic Breast
Cancer (MBC) who have been treated with two or more
prior treatments (third-line disease)
Trial Design
PB272 plus Xeloda (capecitabine) versus Tykerb plus Xeloda
(N=600, 1:1 randomization)
150 study sites (North America, Europe, Asia-Pacific)
Co-primary endpoint: progression free survival/overall survival
Trial initiated June 2013
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Copyright 2014 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
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Copyright 2014 Puma Biotechnology
Neratinib (PB272) Combination with Torisel
Temsirolimus
Neratinib
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Source: Company
Copyright 2014 Puma Biotechnology
Neratinib (PB272)
Phase II Trial in Combination with Torisel
Neratinib (240 mg) in combination with Torisel (8 mg/wk)
Fourth-Line (and Later) HER2+ Metastatic Breast
Cancer
13 of 27 patients showed clinical benefit
12 patients with PR (44%) and 1 patient with
stable disease > 6 months
Enrollment continuing in 2013 (n=34)
Benefit seen in patients previously treated with
Herceptin, Perjeta, Tykerb, TDM-1
Additional data anticipated in H2 2014
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San Antonio Breast Cancer Symposium 2012
Copyright 2014 Puma Biotechnology
Neratinib (PB272)
Phase II Trial in Combination with Torisel
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Maxim
um
Chan
ge I
n S
ize
of T
arg
et
Lesio
n
-100%
-80%
-60%
-40%
-20%
0%
20%
40%
60%
PR
PR
PR
PR
PR
PR
PR
PR
PR
PR
PR
PR
SD
SD
SD
SD
SD
SD
SD
SD
SD
SD
PO
D
PO
D
Copyright 2014 Puma Biotechnology
Neratinib (PB272)
HER 2+ 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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Copyright 2014 Puma Biotechnology
Neratinib (PB272)
HER2+ MBC with Brain Metastases
Phase II trial of neratinib in MBC patients with brain metastases (Initiated January 2012)
Conducted by Dana Farber Translational Breast Cancer Research Consortium
Patients have been previously treated with Tykerb
Two cohorts of patients:
Single agent neratinib (n=40)
85% of patients are Tykerb refractory
7.5% response rate in CNS metastases (ASCO, 2014)
Xeloda plus neratinib (n=40)
Patients must be Tykerb naïve
Potential for results over next 6-12 months
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Copyright 2014 Puma Biotechnology
Neratinib (PB272)
Neoadjuvant Studies in HER2+ MBC
Neo-ALTTO trial (neoadjuvant Tykerb (lapatinib)) Randomized trial of Taxol, Herceptin, Tykerb in neoadjuvant setting
Results presented San Antonio Breast Cancer Symposium (December 2010)
Pathological complete response rate (breast and axillary lymph nodes)
Taxol plus Herceptin – 27.6%
Taxol plus Tykerb (lapatinib) – 20.0%
Taxol plus Herceptin plus Tykerb – 46.8%
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Copyright 2014 Puma Biotechnology
Neratinib - Neoadjuvant Trials Comparison
pCR rate
(breast & lymph)
NeoALTTO
Taxol + Herceptin 27.6%
Taxol plus Tykerb 20.0%
Taxol plus Herceptin plus Tykerb 46.8%
NeoSphere
Taxotere plus Herceptin 21.5%
Taxotere plus Perjeta 17.7%
Taxotere plus Herceptin plus Perjeta 39.3%
-No doublet (Tax plus single HER2 agent) outperformed Tax plus Herceptin
-Herceptin added ~22-27% to pCR rate for Tax plus single HER2 agent doublet
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Copyright 2014 Puma Biotechnology
Neratinib (PB272)-Neoadjuvant HER2+ Breast Cancer
I-SPY2 Trial (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2)
NIH Funded Trial (n=20 (min) - 120 (max) per arm)
Enrolls patients with higher risk of recurrence (MammaPrint 70 gene signature assay)
Adaptive trial design using Bayesian predictive probability
Taxol plus Herceptin
Taxol plus Neratinib
Extensive Biomarker analysis (signatures) being performed
Endpoint: pathological complete response (path CR) rate (probability of improving path CR for biomarker signature)
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Copyright 2014 Puma Biotechnology
Neratinib-Neoadjuvant HER2+ Breast Cancer I-SPY2 Trial
Neratinib eligible for I-SPY3 (Phase III neoadjuvant trial)
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Patient
Population
pCR
Taxol/
neratinib
pCR
Taxol/
Herceptin
p
Prob of
superiority
to control
Prob of
superiority
in a 300 pt
Phase III
HER2
positive/HR
negative
55.6%
32.6%
0.051
94.9%
79.1%
HER2 positive
(HR negative
and HR positive)
39.4%
22.8%
0.046
95.4%
72.7%
Copyright 2014 Puma Biotechnology
Neratinib-Neoadjuvant HER2+ Breast Cancer I-SPY2 Trial
MammaPrint UltraHigh patients represented those patients with MammaPrint scores above the median from previous I-SPY1 trial
Additional biomarker analyses ongoing
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Patient
Population
pCR
Taxol/
neratinib
pCR
Taxol
(alone or w
Herceptin)
p
Prob of
superiority
to control
Prob of
superiority
in a 300 pt
Phase III
MammaPrint
UltraHigh (MP+)*
47.5%
29.4%
0.067
93.3%
71.8%
*80.5% of MammaPrint UltraHigh patients were HER2 negative
Copyright 2014 Puma Biotechnology
Neratinib (PB272)
Neoadjuvant Studies in HER2+ Breast Cancer
NSABP Trial (FB-7) - Neoadjuvant randomized trial of
neratinib, Taxol, Herceptin
Funded by NSABP (National Surgical Adjuvant Breast and Bowel Project)
Taxol plus Herceptin (n=43)
Taxol plus Neratinib (n=43)
Taxol plus Herceptin plus Neratinib (n=43)
Endpoint: pathological complete response (path CR) rate (breast and axillary lymph nodes)
Results anticipated H1 2014
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Copyright 2014 Puma Biotechnology
PB272 Neoadjuvant HER2+ Breast Cancer
Market Size
Approximately 36,000 patients (US) with newly diagnosed
HER2+ breast cancer
Approximately 34,000 patients (EU) with newly diagnosed
HER2+ breast cancer
Treatment duration: 3 months
Market opportunity: $1.0 - 2.0 billion
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Copyright 2014 Puma Biotechnology
-No Prior Treatment for
Metastatic Disease
-Prior taxane/trastuzumab
in adjuvant setting Ra
nd
om
ize 1
:1 Paclitaxel plus Neratinib
Paclitaxel plus Trastuzumab
Primary endpoint: Progression free survival (PFS)
Secondary endpoints: Overall response rate, clinical benefit rate,
safety, time to CNS mets
Results anticipated H1 2014 •
480 patients total
First Line HER2 Positive
Metastatic Breast Cancer
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Copyright 2014 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)
2800 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
Results anticipated H1 2014
HER2 Positive Adjuvant
Breast Cancer
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Copyright 2014 Puma Biotechnology
HER2 Mutated Non-Small Cell Lung Cancer
(NSCLC)
Approximately 2-4% of NSCLC have HER2 kinase domain
mutation at exon 20 (~4,500-9,000 patients US)
Most common in adenocarcinoma, non-smokers
Mutation narrows ATP binding cleft resulting in increased
tyrosine kinase activity
HER2 mutation also results in increased PI3K/mTOR
activation
Data suggests patients with HER2 mutated NSCLC do not
respond to platinum based chemotherapy or EGFR inhibitors
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Copyright 2014 Puma Biotechnology
HER2 Mutated Non-Small Cell Lung
Cancer (NSCLC)
Phase I dose ranging study of neratinib plus Torisel (3X3
design, 12 dose combinations, n=59)
Enrolled patients with multiple solid tumors
7 patients with HER2 mutated NSCLC were enrolled
Patients had received a median of 3 prior treatments
Data presented ASCO 2011 and International Association
for Study of Lung Cancer (IASLC) 2012
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Copyright 2014 Puma Biotechnology
Phase I Dose Ranging Trial of Neratinib Plus
Torisel-HER2 Mutated NSCLC Cohort
-80
-60
-40
-20
0
20
40
% c
ha
nge
fro
m b
ase
lin
e
160 mg neratinib (N)/ 75 mg torisel (T) 160 N/ 50 T
200 N/ 15 T 120 N/ 75 T
240 N/ 15 T 200 N/ 25 T
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Copyright 2014 Puma Biotechnology 31
Time on Study
*still on study
* SD
SD
PR
PD
SD
PR
NE
Phase I Dose Ranging Trial of Neratinib Plus
Torisel-HER2 Mutated NSCLC Cohort
Time on Study
PR=partial response SD=stable disease
PD=progressive disease NE=not evaluable
Copyright 2014 Puma Biotechnology
Phase II HER2 mutant NSCLC: Study Schema
Prior 1st or
subsequent
line Stage
IIIb/IV NSCLC w/ documented
ERBB2 mutation
Enroll n = 13 each arm
-expand one arm to 39
total
Neratinib 240mg daily
Neratinib 240mg daily +
Temsirolimus 8mg iv weekly
STUDY OBJECTIVES:
1o endpoint: Objective Response Rate (ORR)
2o endpoints: Clinical Benefit Rate, Duration of Response, PFS, OS
Results anticipated in 2014
1:1
PD
PD
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Copyright 2014 Puma Biotechnology
HER2 Negative Breast Cancer with
HER2 Mutation
Approximately 2% of all breast cancer patients have
mutation in HER2 kinase (~4000-5000 patients US)
Identified in patients with HER2 negative disease
Mutation results in increased HER2 kinase activity
Data first presented at 2012 San Antonio Breast Cancer
Symposium and published in Cancer Discovery (December
2012)
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Copyright 2014 Puma Biotechnology
Cell Growth Inhibition by Neratinib and
Lapatinib
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IC50 (nM)
Neratinib Lapatinib
MCF10A - Her2 WT <2 400 ± 60
G309A <2 470 ± 50
V777L <2 1,040 ± 570
D769H <2 980 ± 950
V842I <2 650 ± 210
Del755-759 2.1 ± 0.2 660 ± 90
L755S 15 ± 6 > 10,000
BT474 cells <2 31 ± 2
MCF7 cells > 3,000 > 10,000
Copyright 2014 Puma Biotechnology
Phase II HER2 mutant MBC: Study Schema
Enroll up to 29 patients
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
Results anticipated in 2014
PD
HER2 mutant,
non-HER2
amplified
Stage IV MBC w/ documented
ERBB2 mutation
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Copyright 2014 Puma Biotechnology
HER2 Mutation Phase II Basket Study
Approximately 2-10% of solid tumors have mutation in
HER2 kinase
Bladder: ~7,000-7,500 patients (US)
Colorectal: 4,000-4,500 patients (US)
Glioblastoma: ~1,500-2,000 patients (US)
Melanoma: ~1,000 patients (US)
Prostate: ~4,000-5,000 patients (US)
Stomach: ~1,000 patients (US)
Uterine: ~1,000-2000 patients (US)
Phase II “basket” trial of neratinib in patients with solid
tumors that have a HER2 kinase mutation initiated Q4 2013
Potential to present initial data in 2014
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Copyright 2014 Puma Biotechnology
Phase II Basket Trial: Study Schema
STUDY OBJECTIVES:
1o endpoint: Objective Response Rate (ORR)
2o endpoints: Clinical Benefit Rate, PFS, Duration of Response
For each cohort:
• Enroll n=7 per cohort
• If threshold response rate hit
then expand cohort
Bladder & GU carcinoma
Colorectal carcinoma
Gastro-Esoph carcinoma
Ovarian carcinoma
Endometrial carcinoma
Other tumor types
Neratinib
240mg daily PD
ERBB2
mutations
Primary brain tumors EGFR mutation*
All tumor types ERBB3 mutation*
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* Planned expansion in H1 2014
Copyright 2014 Puma Biotechnology
Phase II Basket Study-Breast Cohort
Expansion
Expanded cohort that included HER2 negative breast
cancer with HER2 mutations (May 2014)
Enrolled in “other tumor” basket
Basket expanded to 18 patients
Anticipate announcing additional cohort expansions during
2014
Potential to present initial data in 2014
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Copyright 2014 Puma Biotechnology
Puma-Expected Milestones
Initiate Phase III neratinib plus Xeloda randomized trials in third line
MBC (Q2 2013)
Initiate Phase II trial of neratinib in HER2 mutated NSCLC (Q1
2013)
Initiate Phase II trial of neratinib in HER2 negative mutated MBC
(Q1 2013)
Potential to report data from 1) Phase II neoadjuvant studies (I-
SPY2 and NSABP); 2) Phase II trial in MBC patients with brain
metastases; 3) Phase II HER 2 mutated NSCLC trial; 4) Phase II
HER2 mutated MBC trial; 5) Phase II mutation basket trial; 6) Phase
II first line HER2 positive MBC trial; and 7) Phase III HER2 positive
adjuvant trial during 2014
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Copyright 2014 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)
Formulation patent allowed (expires 2030)
Additional use patents filed
Covers entire family of in-licensed candidates
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Copyright 2014 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
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Copyright 2014 Puma Biotechnology
Experienced Management Team
Alan H. Auerbach
Chairman, Chief Executive Officer, President, Founder
-Chief Executive Officer, President, Founder, Cougar Biotechnology, Inc.
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
Richard B. Phillips, Ph.D.
Senior VP Regulatory Affairs, Quality Assurance, Pharmacovigilance
-Cougar Biotechnology, Johnson & Johnson
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Copyright 2014 Puma Biotechnology
Board of Directors
Alan H. Auerbach
Chairman, Chief Executive Officer, President, Founder
Puma Biotechnology, Inc.
Tom Malley
Portfolio Manager (retired)
Janus Global Life Sciences Fund
Jay Moyes
Former CFO
Myriad Genetics
Troy Wilson, PhD, JD
CEO, Wellspring Biosciences, CEO Avidity Nanomedicines
Former CEO, President, Intellikine
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Copyright 2014 Puma Biotechnology
Currently Trading on NYSE: PBYI
Cash position at March 31, 2014: ~$196.1 million
Payment due from licensor in Q2 2014: ~$13.3 million
Net loss Q1 2014 (non-GAAP): ~$14.6 million
Completed $138.0 million Public Offering (February 2014)
Issued 1,126,530 shares at $122.50 per share
Shares issued and outstanding: 30,117,819
Puma Biotechnology-Financial
45
Copyright 2014 Puma Biotechnology
Company Highlights
In licensing driven business model – mitigates R&D risk
PB272 (neratinib)- clinical stage candidate targeting multiple oncology indications
HER2+ Metastatic Breast Cancer
HER2+ Metastatic Breast Cancer with Brain Metastases
HER2+ Neoadjuvant Breast Cancer
HER2+ Adjuvant 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 data for PB272 (single agent and in combination with chemotherapy)
Potential for multiple clinical trial readouts during 2014
46