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European Commission Grants Marketing Authorisation for Puma Biotechnology's NERLYNX® (neratinib) for Extended Adjuvant Treatment of Hormone Receptor Positive HER2-Positive Early Stage Breast Cancer

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  • Neratinib becomes the first anti-HER2 treatment to be EC-approved
    as extended adjuvant therapy for early stage hormone receptor positive
    HER2-positive breast cancer following adjuvant trastuzumab-based
    therapy
  • Treatment with neratinib in the approved European indication
    resulted in a 51% reduction in the risk of invasive disease recurrence
    or death versus placebo after patients completed one year of therapy
    following a trastuzumab-based regimen
  • Neratinib addresses an unmet medical need, as up to 25% of
    HER2-positive early stage breast cancer patients treated with
    trastuzumab-based adjuvant treatment experience a recurrence

Puma Biotechnology, Inc. (NASDAQ:PBYI) announced that the European
Commission (EC), has granted marketing authorisation for NERLYNX®
(neratinib) for the extended adjuvant treatment of adult patients with
early stage hormone receptor positive HER2-overexpressed/amplified
breast cancer and who are less than one year from the completion of
prior adjuvant trastuzumab based therapy.

EC approval was based on the Phase III ExteNET trial, a multicenter,
randomized, double-blind, placebo-controlled trial of neratinib
following adjuvant trastuzumab treatment. Patients (n=2,840) with early
stage HER2-positive breast cancer and within two years of completing
adjuvant trastuzumab were randomized to receive either neratinib
(n=1420) or placebo (n=1420) for one year.

The results of the ExteNET trial demonstrated that after two years of
follow-up, for patients with hormone receptor positive, HER2-positive
early stage breast cancer patients who were treated within one year
after the completion of trastuzumab based adjuvant therapy, invasive
disease-free survival (iDFS) was 95.3% in the patients treated with
neratinib compared with 90.8% in those receiving placebo (hazard ratio =
0.49; 95% CI: (0.30, 0.78); p=0.002)

The most common adverse reactions (>5%) were diarrhea, nausea, abdominal
pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle
spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin,
abdominal distention, weight loss, and urinary tract infection. The most
common adverse reaction leading to discontinuation was diarrhea, which
was observed in 16.8% of neratinib-treated patients. Hepatotoxicity or
increases in liver transaminases led to drug discontinuation in 1.7% of
neratinib-treated patients.

"Reducing the risk of disease recurrence remains a need for patients,
despite advances in the treatment of early stage HER2-positive breast
cancer," said Puma Biotechnology CEO and President Alan H. Auerbach. "We
are pleased to bring this new medicine to patients in Europe and would
like to express our appreciation to the patients, caregivers and
physicians who contributed to the neratinib clinical development program
and, more specifically, the ExteNET trial. We are committed to
continuing to expand NERLYNX accessibility to patients worldwide. We
expect NERLYNX to be commercially available in Europe in 2019, beginning
with our launch in Germany during the first half of 2019 and followed by
additional countries throughout Europe in the second half of 2019."

The approval of NERLYNX by the European Commission follows the positive
opinion issued by the Committee for Medicinal Products for Human Use of
the European Medicines Agency in June 2018.

Neratinib was approved by the U.S. Food and Drug Administration (FDA) in
July 2017 for the extended adjuvant treatment of adult patients with
early stage HER2-positive breast cancer following adjuvant
trastuzumab-based therapy, and is marketed in the United States as
NERLYNX® (neratinib) tablets.

About HER2-Positive Breast Cancer

Approximately 20 to 25 percent of breast cancer tumors over-express the
HER2 protein. HER2-positive breast cancer is often more aggressive than
other types of breast cancer, increasing the risk of disease progression
and death. Although research has shown that trastuzumab can reduce the
risk of early stage HER2-positive breast cancer returning after surgery,
up to 25% of patients treated with trastuzumab experience recurrence.

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. Puma in-licenses the global development and
commercialization rights to three drug candidates — PB272 (neratinib,
oral), PB272 (neratinib, intravenous) and PB357. Neratinib, oral was
approved by the U.S. Food and Drug Administration in July 2017 for the
extended adjuvant treatment of adult patients with early stage
HER2-overexpressed/amplified breast cancer, following adjuvant
trastuzumab-based therapy, and is marketed in the United States as
NERLYNX® (neratinib) tablets. NERLYNX is a registered
trademark of Puma Biotechnology, Inc.

Important EU NERLYNX® (neratinib)
Safety Information

All suspected adverse reactions should be reported in accordance with
the national reporting system.

The adverse reactions described in this section were identified in the
randomized Phase 3 clinical trial (n=2840). The most common adverse
reactions of any grade were diarrhoea (93.6%), nausea (42.5%), fatigue
(27.3%), vomiting (26.8%), abdominal pain (22.7%), rash (15.4%),
decreased appetite (13.7%), abdominal pain upper (13.2%), stomatitis
(11.2%), and muscle spasms (10.0%).

The most common Grade 3-4 adverse reactions were diarrhoea (Grade 3,
36.9% and Grade 4, 0.2%) and vomiting (Grade 3, 3.4% and Grade 4, 0.1%).

Adverse reactions reported as serious included diarrhoea (1.9%),
vomiting (1.3%), dehydration (1.1%), nausea (0.5%), alanine
aminotransferase increased (0.4%), aspartate aminotransferase increased
(0.4%), abdominal pain (0.3%), fatigue (0.3%) and decreased appetite
(0.2%).

For full European prescribing information, please refer to the
NERLYNX (neratinib) Summary of Product Characteristics on the European
Medicines Agency website (
http://www.ema.europa.eu/ema/).

Important Safety Information Regarding NERLYNX® (neratinib)
U.S. Indication

NERLYNX® (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated
for the extended adjuvant treatment of adult patients with HER2
overexpressed/amplified breast cancer, to follow adjuvant
trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

Diarrhea: Aggressively manage diarrhea occurring despite
recommended prophylaxis with additional antidiarrheals, fluids, and
electrolytes as clinically indicated. Withhold NERLYNX in patients
experiencing severe and/or persistent diarrhea. Permanently discontinue
NERLYNX in patients experiencing Grade 4 diarrhea or Grade≥ 2 diarrhea
that occurs after maximal dose reduction.

• Hepatotoxicity: Monitor liver function tests monthly for the
first 3 months of treatment, then every 3 months while on treatment and
as clinically indicated. Withhold NERLYNX in patients experiencing Grade
3 liver abnormalities and permanently discontinue NERLYNX inpatients
experiencing Grade 4 liver abnormalities.

• Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise
patients of potential risk to a fetus and to use effective contraception.

ADVERSE REACTIONS: The most common adverse reactions (≥ 5%) were
diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis,
decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail
disorder, dry skin, abdominal distention, epistaxis, weight decreased
and urinary tract infection.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology,
Inc. at 1-844-NERLYNX (1-844-637-5969) and
www.NERLYNX.com
or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.

DRUG INTERACTIONS:

  • Gastric acid reducing agents: Avoid concomitant use with proton pump
    inhibitors (PPI) and H2-receptor antagonists. Separate NERLYNX by 3
    hours after antacid dosing.
  • Strong or moderate CYP3A4 inhibitors: Avoid concomitant use.
  • Strong or moderate CYP3A4 inducers: Avoid concomitant use.
  • P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of
    narrow therapeutic agents that are P-gp substrates when used
    concomitantly with NERLYNX.

USE IN SPECIFIC POPULATIONS:

•Lactation: Advise women not to breastfeed.

Please see Full
Prescribing Information
for additional safety information.

To help ensure patients have access to NERLYNX, Puma has implemented the
Puma Patient Lynx support program to assist patients and health care
providers with reimbursement support and referrals to resources that can
help with financial assistance. More information on the Puma Patient
Lynx program can be found at www.NERLYNX.com
or 1-855-816-5421.

The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given
orally once daily with food, continuously for one year. Antidiarrheal
prophylaxis should be initiated with the first dose of NERLYNX and
continued during the first 2 months (56 days) of treatment and as needed
thereafter.

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 worldwide expansion of NERLYNX. All
forward-looking statements 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 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, 2017 and its
Quarterly Report on Form 10-Q for the quarter ended June 30, 2018.
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.

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