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PUMA BIOTECHNOLOGY, INC. : Other Events (form 8-K)

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12/08/2016 | 02:47pm CET
Item 8.01 Other Events.


Managed Access Program

On December 6, 2016, Puma Biotechnology, Inc. (the "Company") announced that it
has initiated a Managed Access Program for PB272 (neratinib). Managed access
programs provide physicians and patients access to medicines when there are
limited or no other therapeutic options available.

The Company's Managed Access Program for neratinib will enable participation
from countries outside the United States, including European Union Member
States, where permitted by applicable rules, procedures and regulatory
authorities. The program will provide access to neratinib for the treatment of
early stage HER2-positive breast cancer (extended adjuvant setting),
HER2-positive metastatic breast cancer and HER2-mutated solid tumors. Patients
must not be able to participate in any ongoing neratinib clinical trial to
qualify for the Company's managed access program. Patients in the managed access
program will be given neratinib and will be instructed to take a prophylaxis
during treatment to manage neratinib-related diarrhea, which the Company expects
will consist of high dose loperamide and budesonide.

The Company has partnered with Caligor Opco LLC, which specializes in early access to medicines, to implement and oversee the Managed Access Program for neratinib.

Presentation of Interim Results of Phase II Trial of PB272 for ERBB2 (HER2) Mutant, HER2 Non-Amplified, Metastatic Breast Cancer at the 2016 San Antonio Breast Cancer Symposium


On December 7, 2016, the Company announced that updated interim results from an
ongoing Phase II clinical trial of PB272 (neratinib), given as monotherapy and
in combination with the anticancer drug fulvestrant, were presented at the 2016
CTRC-AACR San Antonio Breast Cancer Symposium (SABCS). The presentation entitled
"Neratinib plus fulvestrant for ERBB2 mutant, HER2 non-amplified, estrogen
receptor-positive, metastatic breast cancer: Preliminary analysis from the Phase
II SUMMIT trial" was presented as a poster discussion by Dr. David Hyman,
Director, Developmental Therapeutics at Memorial Sloan Kettering Cancer
Center. The poster is available on the Company's website
(www.pumabiotechnology.com) under the Investors - Events & Webcasts tab.

Interim results from this trial were previously presented at the 2015 SABCS and
included patients who were treated with neratinib monotherapy for metastatic
breast cancer and whose tumors have a HER2 mutation. The presentation also
discussed that a bidirectional cross-talk between hormone receptor and HER2
signaling pathways could lead to endocrine resistance due to activated HER2
signaling and ER-mediated tumor proliferation as a potential resistance
mechanism to sustained HER2 inhibition. Preclinical xenograft data has
demonstrated that the combination of an anti-estrogen with neratinib results in
enhanced anti-tumor activity in preclinical models of estrogen receptor
positive/HER2-positive breast tumors. Based on this, the SUMMIT study was
amended to allow for the combination of neratinib plus fulvestrant in eligible
postmenopausal hormone receptor-positive breast cancer patients. The
presentation at SABCS included an update on both the neratinib monotherapy
cohort and the neratinib plus fulvestrant cohort.

In the study, patients with HER2 mutant metastatic breast cancer were enrolled
and received 240 mg of neratinib daily either as monotherapy or in combination
with fulvestrant. All patients received loperamide (16 mg per day initially)
prophylactically for the first cycle of treatment in order to reduce the
neratinib-related diarrhea. For the 25 patients in the group who received
neratinib monotherapy, 23 patients (92%) had HER2-negative disease, 19 patients
(76%) were hormone receptor positive (estrogen receptor or progesterone receptor
positive), and patients had received a median of 4 prior lines of therapy in the
metastatic setting (range 0-8 prior regimens) before entering the trial. For the
17 patients in the trial who received neratinib plus fulvestrant, 15 patients
(88%) had HER2-negative disease, 17 patients (100%) were hormone receptor
positive (estrogen receptor or progesterone receptor positive), and patients had
received a median of 4 prior lines of therapy in the metastatic setting (range
1-7 prior regimens) before entering the trial.

The interim efficacy results from the trial showed that for the 24 efficacy
evaluable patients in the neratinib monotherapy cohort, 8 patients (33.3%)
experienced an objective response, which included 3 patients with a complete
response and 5 patients with partial responses. At week 8, 8 patients (33.3%)
achieved an objective

--------------------------------------------------------------------------------
response, with 2 patients achieving a complete response and 6 patients achieving
a partial response. The secondary endpoints of the trial included confirmed
objective response (complete response or partial response), clinical benefit
rate and progression free survival (PFS). The results of the trial showed that 6
patients (25%) had a confirmed objective response, 10 patients (41.7%)
demonstrated clinical benefit and the median progression free survival was 3.5
months.

For the 12 efficacy evaluable patients in the neratinib plus fulvestrant cohort,
7 patients (58.3%) experienced an objective response, which included 2 patients
with a complete response and 5 patients with partial responses. At week 8, 5
patients (41.7%) achieved an objective response, with 2 patients achieving a
complete response and 3 patients achieving a partial response. The secondary
endpoints of the trial included confirmed objective response (complete response
or partial response), clinical benefit rate and progression free survival (PFS).
The results of the trial showed that 3 patients (25%) had a confirmed objective
response, 7 patients (58.3%) demonstrated clinical benefit and the median
progression free survival was 3.7 months. The progression free survival data may
not be mature in the neratinib plus fulvestrant cohort as 4 of the 12 efficacy
evaluable patients are continuing to receive study treatment without disease
progression and an additional 5 patients have not yet had an assessment for
efficacy.

The interim safety results of the study showed that the most frequently observed
adverse event was diarrhea. For the 25 patients enrolled in the neratinib
monotherapy arm, 6 patients (24%) reported grade 3 diarrhea. The median duration
of grade 3 diarrhea for the patients in the neratinib monotherapy cohort was 1
day. No patient in the neratinib monotherapy cohort has permanently discontinued
neratinib due to diarrhea and 5 patients (20%) have temporarily discontinued
neratinib due to diarrhea and then restarted after the diarrhea subsided. For
the 17 patients enrolled in the neratinib plus fulvestrant cohort, 2 of 17
patients (12%) experienced grade 3 diarrhea. The median duration of grade 3
diarrhea was 1 day and typically occurred during the first cycle of treatment.
No patient (0%) in the neratinib plus fulvestrant cohort permanently
discontinued neratinib due to diarrhea and 2 patients (12%) temporarily
discontinued neratinib due to diarrhea and then restarted after the diarrhea
subsided.

Presentation of Results of Biomarker Analysis of Phase II Trial of PB272 in Neoadjuvant Treatment of HER2-Positive Locally Advanced Breast Cancer at the 2016 San Antonio Breast Cancer Symposium


On December 7, 2016, the Company announced that a biomarker analysis of the
NSABP FB-7 Phase II clinical trial of PB272 (neratinib) was presented at the
2016 SABCS. The presentation entitled "An exploratory correlative biomarker
analysis of NSABP FB-7, a phase II randomized trial evaluating neoadjuvant
therapy with weekly paclitaxel (P) plus neratinib (N) or trastuzumab (T) or
neratinib and trastuzumab (N+T) followed by doxorubicin and cyclophosphamide
(AC) with postoperative T in women with locally advanced HER2-positive breast
cancer" was presented as a poster presentation. This trial was sponsored by the
NSABP Foundation, Inc. The poster is available on the Company's website under
the Investors - Events & Webcasts tab.

The FB-7 trial is a randomized Phase II clinical trial for women with
HER2-positive locally advanced stage IIB-IIIC invasive breast cancer. Patients
were randomly assigned to receive trastuzumab (T) or neratinib (N) or the
combination (T+N) with weekly paclitaxel (P) followed by standard doxorubicin
and cyclophosphamide chemotherapy (AC) administered prior to surgery. 126 U.S.,
Canadian, and European patients were randomly assigned to Arm 1 (T+P followed by
AC), Arm 2 (N+P followed by AC) or Arm 3 (T+N+P followed by AC). The primary
endpoint of the trial was pathological complete response rate (pCR) in the
breast and lymph nodes. The clinical safety and efficacy data from this trial
was presented at the 2015 SABCS.

A key secondary endpoint of the FB-7 trial was to evaluate molecular and genetic
markers for correlation with response. Pre-treatment core biopsy samples (n=59)
and post treatment surgical samples (n=17) were obtained from a subset of
patients treated in the FB-7 trial. pCR data were available for 51 patients from
the biomarker cohort. After excluding low tumor content non-evaluable samples,
correlative biomarker analysis was performed in 42 patients.

Expression levels and the activation status of EGFR/HER2 signaling proteins were
investigated. The results of the phosphorylated HER2 (phosphoHER2) showed that
median levels of phosphoHER2 were higher in the patients who achieved a pCR with
neratinib (n=7) than in the patients who did not achieve a pCR who received
either trastuzumab (n=8, p=0.07) or the combination of trastuzumab plus
neratinib (n=4, p=0.035). There was not a significant difference in the median
levels of phosphoHER2 in the patients who achieved a pCR with neratinib (n=7),
trastuzumab (n=8, p=0.16) or the combination of trastuzumab plus neratinib (n=4,
p=0.10).

--------------------------------------------------------------------------------
The truncated form of HER2 known as p95HER2 was measured by the proprietary
assay of Pierian Bioscience. p95HER2 represents a truncated form of the HER2
receptor that lacks the extracellular trastuzumab binding domain. It is believed
to represent a mechanism of trastuzumab resistance. Median p95HER2 levels were
higher in samples from patients who achieved a pCR with neratinib than in the
patients who did not achieve a pCR who received either trastuzumab (p=0.027) or
the combination of trastuzumab plus neratinib (p=0.009). There was not a
significant difference in the median levels of p95HER2 in the patients who
achieved a pCR with neratinib (n=7), trastuzumab (n=8, p=0.16) or the
combination of trastuzumab plus neratinib (n=4, p=0.35).

The MammaPrint assay was performed on 59 samples to determine if there was any
imbalance between arms. This assay is a genomic test that analyzes the activity
of 70 genes and then calculates a recurrence score that is either low risk or
high risk. The results of the MammaPrint showed that the patients in all three
arms of the FB-7 trial were balanced with the median MammaPrint risk score being
similar across arms. There were only three patients with a MammaPrint low score.

Presentation of Interim Results of Phase II CONTROL Trial of PB272 in Extended
Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer at the 2016 San
Antonio Breast Cancer Symposium

On December 8, 2016, the Company announced that interim results from a Phase II
clinical trial of PB272 (neratinib) were presented at the 2016 SABCS. The
presentation entitled "Incidence and severity of diarrhea with neratinib plus
intensive loperamide prophylaxis in patients with HER2-positive early-stage
breast cancer (EBC): Interim analysis from the multicenter, open-label, phase II
CONTROL trial" was presented as a poster presentation. The poster is available
on the Company's website under the Investors - Events & Webcasts tab.

The main adverse event that has been seen to date in clinical trials of
neratinib is diarrhea and more specifically grade 3 diarrhea. In the Phase III
ExteNET trial of neratinib as extended adjuvant treatment of HER2-positive early
stage breast cancer that has previously been treated with adjuvant Herceptin,
95.4% of the patients experienced all grade diarrhea and 39.8% of the patients
experienced grade 3 or higher diarrhea (there was one event of grade 4
diarrhea). The CONTROL trial is an international, open-label, phase II study
investigating the use of loperamide prophylaxis with or without other agents in
the prevention and reduction of neratinib-associated diarrhea and more
specifically grade 3 diarrhea.

In the trial, patients with HER2-positive early-stage breast cancer who had
completed trastuzumab-based adjuvant therapy received neratinib daily for a
period of one year. High dose loperamide prophylaxis was given for the first 2
cycles (56 days) of treatment. Initially, the loperamide dosing used was 16 mg
on day 1, then 12 mg on days 2 and 3 and then 6-8 mg on days 4-56 (original
dosing). The protocol was later amended to simplify the regimen such that
patients took 12 mg on days 1-14 and 8 mg on days 15-56 (modified dosing). The
CONTROL trial has recently been expanded to include prophylaxis with the
combination of loperamide and budesonide, a locally acting corticosteroid that
the Company believes targets the inflammation identified in a preclinical model
of neratinib-induced diarrhea.

The interim analysis of the trial presented in the poster included a total of
135 patients who received neratinib plus loperamide prophylaxis (28 patients
taking the original dosing and 107 patients taking the modified dosing) and 40
patients who received neratinib plus loperamide prophylaxis for 2 cycles and
budesonide for 1 cycle.

The results of the trial showed that the incidence of grade 3 diarrhea for the
total 135 patients who received the loperamide prophylaxis was 28.1%. For the 28
patients who received loperamide using the original dosing regimen the grade 3
diarrhea rate was 25.0% and for the 107 patients who received the modified
loperamide dosing regimen the grade 3 diarrhea rate was 29.0%. For the patients
in the original dosing group, 71% of the patients who experienced grade 3
diarrhea were known to be non-compliant with the loperamide regimen and for the
patients in the modified loperamide dosing regimen, 35% of the patients were
known to be non-compliant with their loperamide dosing regimen. For the 135
patients who received the loperamide prophylaxis, the median number of grade 3
diarrhea episodes per patient was 1 and the median cumulative duration of grade
3 diarrhea was 3 days. For the 135 patients who received loperamide prophylaxis,
18.5% discontinued neratinib due to diarrhea.

--------------------------------------------------------------------------------
For the 40 patients who received the combination of loperamide plus budesonide,
the results of the trial showed that the incidence of grade 3 diarrhea was
15.0%. None of the patients who experienced grade 3 diarrhea were non-compliant
with the loperamide plus budesonide regimen. The median number of grade 3
diarrhea episodes per patient was 1 and the median cumulative duration of grade
3 diarrhea was 2.5 days. For the 40 patients who received loperamide plus
budesonide prophylaxis, 5.0% discontinued neratinib due to diarrhea. Further
information is provided in Table 1 below:

            Table 1: Characteristics of Treatment-Emergent Diarrhea



Study                                                            CONTROL                                      ExteNET
                                                                                         Budesonide          Neratinib
                                                  Loperamide cohort                        cohort               arm
                                     Original         Modified        Loperamide        Loperamide +        Loperamide
Prophylaxis                          schedule         schedule           total           budesonide             prn
                                      (n=28)          (n=107)           (N=135)            (N=40)            (N=1408)
Diarrhea, %
Any grade                                 82.1             73.8              75.6                65.0              95.4
Grade 1                                   35.7             21.5              24.4                32.5              22.9
Grade 2                                   21.4             23.4              23.0                17.5              32.5
Grade 3a                                  25.0             29.0              28.1                15.0              39.8
Grade 4                                      0                0                 0                   0               0.1
Median cumulative duration,
days
Grade ³2                                   5.0              4.0               4.0                 3.0              10.0
Grade ³3b                                  2.0              3.0               3.0                 2.5               5.0
Median diarrhea
episodes/patient
Any grade                                    2                2                 2                   2                 8
Grade ³2                                     2                1                 2                   1                 3
Grade ³3b                                    1                1                 1                   1                 2
Action taken, %
Dose hold                                  7.1             12.1              11.1                 7.5              33.9
Dose reduction                            10.7              7.5               8.1                 5.0              26.4
Discontinuation                           28.6             15.9              18.5                 5.0              16.8
Hospitalization                              0              1.9               1.5                   0               1.4
Duration of neratinib
treatment, months
Median                                     9.7              7.4               7.5                 1.8              11.6
Range                                 0.1-13.1         0.1-12.8          0.1-13.1            0.1-6.3          0.03-13.3



a Non-compliance with loperamide prophylaxis in patients with grade 3 diarrhea

was 71% with the original loperamide schedule, 35% with the modified

loperamide schedule, and 0% with loperamide prophylaxis plus budesonide.

b No grade 4 events in the CONTROL study; one grade 4 event in the ExteNET

study.

--------------------------------------------------------------------------------

In the ExteNET trial, higher grade (grade 2 and grade 3) diarrhea occurred early
and persisted throughout the duration of the 12-month treatment period. In the
CONTROL trial, in both the loperamide prophylaxis and loperamide plus budesonide
prophylaxis arms, the results showed that higher grade diarrhea (grade 2 and 3)
occurred early but did not typically recur. This is shown in more detail in
Figure 1 below:



                            [[Image Removed: LOGO]]

The grade 3 diarrhea rates seen in the loperamide cohort have increased over
what was previously reported in December 2015 (n=50, grade 3 diarrhea rate
16%). During the course of the CONTROL trial there has been an increase in the
proportion of patients previously treated with pertuzumab (mainly in the
neoadjuvant setting). More specifically in the data reported in December 2015,
18% (9 of 50 patients) had previously received pertuzumab. In the current data
set 40% (54 of 135 patients) of the patients in the combined loperamide
prophylaxis arms received prior pertuzumab and 55% (22 of 40 patients) received
prior pertuzumab in the budesonide arm.

For the 54 patients in the loperamide prophylaxis cohort who received prior
pertuzumab, the grade 3 diarrhea rate was 35.2% (Table 2). For the 81 patients
who did not receive prior pertuzumab, the grade 3 diarrhea rate was 23.5%. For
the 22 patients in the budesonide cohort who received prior pertuzumab, the
grade 3 diarrhea rate was 13.6%. For the 18 patients in the budesonide cohort
who did not receive prior pertuzumab, the grade 3 diarrhea rate was 16.7%. This
analysis suggests that prior pertuzumab exposure may have led to a higher rate
of grade 3 diarrhea in CONTROL that was not effectively managed by loperamide
prophylaxis alone but was more effectively managed by loperamide plus
budesonide.

Table 2: Incidence of Grade 3 Diarrhea in CONTROL by Prior Pertuzumab Treatment



                               Loperamide Cohort               Budesonide Cohort
                              Yes              No             Yes              No
                           (n = 54)         (n = 81)       (n = 22)         (n = 18)
        Grade 3 Diarrhea        35.2 %           23.5 %         13.6 %           16.7 %

Forward-Looking Statements:

This Current Report on Form 8-K contains forward-looking statements, including statements regarding development of the Company's drug candidates and the Managed Access Program for PB272 (neratinib) for the treatment of early

--------------------------------------------------------------------------------

stage HER2-positive breast cancer (extended adjuvant setting), HER2-positive
metastatic breast cancer and HER2-mutated solid tumors. All forward-looking
statements included in this Current Report on Form 8-K involve risks and
uncertainties that could cause the Company's 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 the Company has no product revenue and no products approved for
marketing, the Company's dependence on PB272, which is still under development
and may never receive regulatory approval, the challenges associated with
conducting and enrolling clinical trials, the risk that the results of clinical
trials may not support the Company's drug candidate claims, even if approved,
the risk that physicians and patients may not accept or use the Company's
products, the Company's reliance on third parties to conduct its clinical trials
and to formulate and manufacture its drug candidates, the Company's dependence
on licensed intellectual property, and the other risk factors disclosed in the
periodic and current reports filed by the Company with the Securities and
Exchange Commission from time to time, including the Company's Annual Report on
Form 10-K for the year ended December 31, 2015. Readers are cautioned not to
place undue reliance on these forward-looking statements, which speak only as of
the date hereof. The Company assumes no obligation to update these
forward-looking statements, except as required by law.

--------------------------------------------------------------------------------

© Edgar Online, source Glimpses

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Financials ($)
Sales 2016 -
EBIT 2016 -272 M
Net income 2016 -272 M
Finance 2016 224 M
Yield 2016 -
P/E ratio 2016 -
P/E ratio 2017
EV / Sales 2016 0
EV / Sales 2017 16,8x
Capitalization 1 465 M
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Number of Analysts 7
Average target price 87,0 $
Spread / Average Target 119%
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NameTitle
Alan H. Auerbach Chairman, President, CEO & Secretary
Charles R. Eyler Treasurer & Senior VP-Finance & Administration
Richard Paul Bryce Senior VP-Clinical Research & Development
Jay M. Moyes Independent Director
Troy E. Wilson Independent Director
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