CORRECTING and REPLACING GRAPHIC Puma Biotechnology Presents Interim Results of Phase II CONTROL Trial of Neratinib in Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer at the ASCO 2019 Annual Meeting

LOS ANGELES–(BUSINESS WIRE)–In the release dated June 2, 2019, please replace the PDF file with the
accompanying corrected file.

The release reads:

PUMA BIOTECHNOLOGY PRESENTS INTERIM RESULTS OF PHASE II CONTROL TRIAL
OF NERATINIB IN EXTENDED ADJUVANT TREATMENT OF HER2-POSITIVE
EARLY STAGE BREAST CANCER AT THE ASCO 2019 ANNUAL MEETING

Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company,
will present updated interim results from a Phase II clinical trial of
Puma’s drug neratinib at the American Society of Clinical Oncology
(ASCO) 2019 Annual Meeting in Chicago. The presentation entitled,
“Effect of prophylaxis on neratinib-associated diarrhea and tolerability
in patients with HER2+ early-stage breast cancer: Phase II CONTROL
trial,” will be presented at a poster session on June 2 at 8:00 a.m. CT.
A full copy of the poster is available on the Puma Biotechnology website.

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.

The main adverse event 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, prophylactic use of anti-diarrheal medications
was not mandatory. In the trial, 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 median
cumulative duration of grade 3 diarrhea in the ExteNET trial was 5 days
and 16.8% of patients who received neratinib in the ExteNET trial
discontinued the drug due to diarrhea.

The CONTROL trial is an international, open-label, Phase II study
investigating the use of antidiarrheal prophylaxis or dose escalation in
the reduction of neratinib-associated diarrhea that has a primary
endpoint of the incidence of grade 3 diarrhea.

In the CONTROL 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. The trial initially tested
high dose loperamide prophylaxis given for the first 2 cycles (56 days)
of treatment (12 mg on days 1-14, 8 mg on days 15-56 and as needed
thereafter). The CONTROL trial was then expanded to include four
additional cohorts. One cohort received the combination of loperamide
and budesonide, the second cohort received the combination of loperamide
plus colestipol, the third cohort received colestipol plus loperamide as
needed and the fourth cohort did not use any antidiarrheal drugs as
mandatory prophylaxis but instead used a dose escalation during the
first month of neratinib treatment. Budesonide is a locally acting
corticosteroid that Puma believes targets the inflammation identified in
a preclinical model of neratinib-induced diarrhea and colestipol is a
bile acid sequestrant that Puma believes targets potential bile acid
malabsorption that could result from such inflammation. The dose
escalation involved treating with neratinib at 120 mg per day for the
first week, 160 mg per week for the second week and 240 mg per week
starting at week 3 and until the end of treatment.

The interim analysis of the CONTROL trial presented in the poster
included a total of 137 patients who received neratinib plus loperamide
prophylaxis, 64 patients who received neratinib plus loperamide
prophylaxis for 2 cycles and budesonide for 1 cycle, 136 patients who
received neratinib plus loperamide prophylaxis for 1 cycle and
colestipol for 1 cycle, 104 patients who received colestipol for 1 cycle
and loperamide as needed and 60 patients who received the dose
escalation regimen of neratinib.

The results of the trial showed that the incidence of grade 3 diarrhea
for the 137 patients who received the loperamide prophylaxis was 30.7%
and that for the 137 patients in this cohort, 20.4% discontinued
neratinib due to diarrhea. The median cumulative duration of grade 3
diarrhea was 3 days.

For the 64 patients who received the combination of loperamide plus
budesonide, the results of the trial showed that the incidence of grade
3 diarrhea was 28.1% and that for the 64 patients in this cohort, 10.9%
discontinued neratinib due to diarrhea. The median cumulative duration
of grade 3 diarrhea was 2.5 days.

For the 136 patients who received the combination of loperamide plus
colestipol, the results of the trial showed that the incidence of grade
3 diarrhea was 20.6% and that for the 136 patients in this cohort, 4.4%
discontinued neratinib due to diarrhea. The median cumulative duration
of grade 3 diarrhea was 3.5 days.

For the 104 patients who received colestipol and loperamide as needed,
the results of the trial showed that the incidence of grade 3 diarrhea
was 31.7% and that for the 104 patients in this cohort, 6.7%
discontinued neratinib due to diarrhea. The median cumulative duration
of grade 3 diarrhea was 3 days.

For the 60 patients who received no antidiarrheal drugs as mandatory
prophylaxis and dose escalation of neratinib in the first month, the
results of the trial showed that the incidence of grade 3 diarrhea was
11.7% and that for the 60 patients in this cohort, 3.3% discontinued
neratinib due to diarrhea. The median cumulative duration of grade 3
diarrhea was 2 days.

Further information is provided in Table 1 below:

Table 1: Characteristics of Treatment-Emergent Diarrhea
											Neratinib dose
					Loperamide +		Loperamide +		Loperamide		escalation +
			Loperamide	budesonide			colestipol		prn + colestipol		loperamide prn
			(n=137)		(n=64)		(n=136)		(n=104)		(n=60)
	Diarrhea, %
	Any grade		79.6		85.9		83.1		95.2		95.0
	Grade 1		24.1		25.0		27.9		30.8		43.3
	Grade 2		24.8		32.8		34.6		32.7		40.0
	Grade 3		30.7		28.1		20.6		31.7		11.7
	Diarrhea leading to discontinuation, %		20.4		10.9		4.4		6.7		3.3
	Hospitalization (due to diarrhea), %		1.5		0		0		0		0
	Discontinuation of study (any cause), %		44.6		20.3		28.7		26.0		13.6
	Note: Each patient was counted only once in the highest grade category.
	No Grade 4 events reported in the CONTROL study.

Carlos H. Barcenas, MD, MS, Assistant Professor in the Department of
Breast Medical Oncology of The University of Texas MD Anderson Cancer
Center, said, “We are pleased to see the maturation of the data
supporting observations of a reduction in incidence, severity and
duration of neratinib-associated diarrhea with loperamide prophylaxis,
loperamide plus budesonide prophylaxis or the loperamide plus colestipol
prophylaxis. We are pleased to see the initial results of the dose
escalation regimen. Along with the continued reduction in the incidence
and severity of grade 3 diarrhea with neratinib, diarrhea appears to be
early onset, acute, self-limiting and manageable. Not only does the
addition of budesonide or colestipol to loperamide prophylaxis appear to
greatly improve the tolerability of neratinib, the dose escalation
regimen appears as another promising option since there is no mandatory
prophylaxis. We look forward to the completion of the dose escalation
cohort.”

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 antidiarrheal regimens and the dose escalation. The reduction
in the discontinuations due to diarrhea are encouraging and appear to
represent a marked improvement in tolerability over what was seen in the
ExteNET trial.”

About HER2-Positive Breast Cancer

Approximately 20% to 25% 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.

IMPORTANT SAFETY INFORMATION

NERLYNX® (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated
for the extended adjuvant treatment of adult patients with early-stage
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 in
  patients 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, 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. When patients require gastric acid reducing agents, use an
  H2-receptor antagonist or antacid. Separate NERLYNX by at least 3
  hours with antacids. Separate NERLYNX by at least 2 hours before or 10
  hours after H2-receptor antagonists.
• 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.

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.

To help ensure patients have access to NERLYNX, Puma has implemented the
Puma Patient Lynx support program to assist patients and healthcare
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.

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 was granted marketing
authorization by the European Commission in September 2018 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 completion of prior adjuvant trastuzumab-based
therapy. NERLYNX is a registered trademark of Puma Biotechnology, Inc.

Further information about Puma Biotechnology can be found at www.pumabiotechnology.com.

Contacts

Alan H. Auerbach or Mariann Ohanesian, Puma Biotechnology, Inc., +1 424
248 6500
[email protected]
[email protected]

David Schull or Juliette Gorson, Russo Partners, +1-212-845-4271 /
+1-212-845-4235
[email protected]
[email protected]