Puma Biotechnology Presents 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

LOS ANGELES–(BUSINESS WIRE)–Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company,
announced that interim results from a Phase II clinical trial of Puma’s
investigational drug PB272 (neratinib) were presented at the 2016
CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) that is currently
taking place in San Antonio, Texas. 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 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





Loperamide cohort




Prophylaxis Original     Modified Loperamide Loperamide + Loperamide
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 ≥2 5.0 4.0 4.0 3.0 10.0
Grade ≥3b 2.0 3.0 3.0 2.5 5.0
Median diarrhea episodes/patient
Any grade 2 2 2 2 8
Grade ≥2 2 1 2 1 3
Grade ≥3b 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


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.


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: Treatment
Emergent Diarrhea, which is attached to this news release.

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


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%

Dr. Carlos H. Barcenas, Assistant Professor, Department of Breast
Oncology and Associate Medical Director, Breast Cancer Survivorship for
the University of Texas MD Anderson Cancer Center, said, “We are pleased
to see the reduction in incidence, severity and duration of
neratinib-associated diarrhea when using the loperamide prophylaxis and
the loperamide plus budesonide prophylaxis. When using either the
loperamide prophylaxis or the loperamide plus budesonide prophylaxis
there appears to be a reduction in the incidence and severity of grade 3
diarrhea with neratinib. Importantly, the severe grade 2 and grade 3
diarrhea, when using the prophylaxis, appears to be acute, self-limiting
and manageable. We look forward to completing the loperamide plus
budesonide cohort and to the testing of additional investigational
agents as well.”

Alan H. Auerbach, Chief Executive Officer and President of Puma
Biotechnology, said, “We are pleased to see the reductions in the
incidence of severe neratinib-related diarrhea in the CONTROL trial when
using the loperamide and/or loperamide plus budesonide combination. We
are further pleased to see the severe diarrhea become more acute,
whereby it does not typically recur after the first month.”

About Puma Biotechnology

Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on
the development and commercialization of innovative products to enhance
cancer care. The Company in-licenses the global development and
commercialization rights to three drug candidates—PB272 (neratinib
(oral)), PB272 (neratinib (intravenous)) and PB357. Neratinib is a
potent irreversible tyrosine kinase inhibitor that blocks signal
transduction through the epidermal growth factor receptors, HER1, HER2
and HER4. Currently, the Company is primarily focused on the development
of the oral version of neratinib, and its most advanced drug candidates
are directed at the treatment of HER2-positive breast cancer. The
Company believes that neratinib has clinical application in the
treatment of several other cancers as well, including non-small cell
lung cancer and other tumor types that over-express or have a mutation
in HER2. Further information about Puma Biotechnology can be found at www.pumabiotechnology.com.

Forward-Looking Statements:

This press release contains forward-looking statements, including
statements regarding the development of the Company’s drug candidates.
All forward-looking statements included in this press release 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.


Puma Biotechnology, Inc.
Alan H. Auerbach or Mariann Ohanesian
David Schull or Darren Chia