TOKYO, BASKING RIDGE, N.J. & LOS ANGELES--(BUSINESS WIRE)--Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and Puma
Biotechnology, Inc. (Nasdaq: PBYI) have announced a preclinical research
collaboration with Memorial Sloan Kettering Cancer Center (MSK) to
explore the combination of Daiichi Sankyo’s investigational antibody
drug conjugate DS-8201 and Puma Biotechnology’s irreversible pan-HER
tyrosine kinase inhibitor neratinib (NERLYNX®) in HER2-mutated or
HER2-positive solid tumors.
A team of scientists led by Maurizio Scaltriti, PhD, and in
collaboration with a team of clinical investigators led by Bob Li,
MD, will use isogenic models and established patient-derived xenograft
models to assess the susceptibility of HER2-mutated or HER2-positive
cancers to DS-8201, neratinib and other HER2-targeting therapies,
elucidate mechanisms of action and resistance of these various tumor
types, and evaluate the potential for synergistic combinations. Daiichi
Sankyo and Puma Biotechnology will co-sponsor the research.
“Since early clinical data suggest that DS-8201 may have activity beyond
breast and gastric cancers, the archetype HER2-driven tumors, we are
interested in studying this asset on a molecular level as well as in
combination with other HER2-targeting agents,” said Tom Held, Vice
President, Global Head, Antibody Drug Conjugate Task Force, Daiichi
Sankyo. “In this collaboration, we are examining whether combining
DS-8201 and neratinib, with its specific covalent binding to the HER2
receptor and associated increased internalization, is a rational
combination therapy strategy to pursue. We are excited to join forces
with Memorial Sloan Kettering and Puma to advance the understanding of
combining HER2-targeted therapies to potentially treat various forms of
HER2-mutated cancer.”
“We are pleased to enter into this research collaboration with Memorial
Sloan Kettering and Daiichi Sankyo to explore the combination of
neratinib and DS-8201,” said Alan Auerbach, Puma’s Chief Executive
Officer and President. “Combination therapy with agents that address
different and complementary pathways, with neratinib targeting the HER2
kinase and DS-8201 providing an innovative targeted delivery of a potent
cytotoxic, represents an intriguing approach to the treatment of HER2
mutated tumors and helps to maximize the potential for both agents in
treating cancers with a HER2 mutation.”
About DS-8201
DS-8201 is the lead product in the ADC Franchise of the Daiichi Sankyo
Cancer Enterprise. ADCs are targeted cancer medicines that deliver
cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached
to a monoclonal antibody that binds to a specific target expressed on
cancer cells. Designed using Daiichi Sankyo’s proprietary ADC
technology, DS-8201 is a smart chemotherapy comprised of a humanized
HER2 antibody attached to a novel topoisomerase I inhibitor payload by a
tetrapeptide-based linker. It is designed to target and deliver
chemotherapy inside cancer cells and reduce systemic exposure to the
cytotoxic payload (or chemotherapy) compared to the way chemotherapy is
commonly delivered.
DS-8201 is currently in phase 2 clinical development for HER2-positive
unresectable and/or metastatic breast cancer resistant or refractory to
T-DM1 (DESTINY-Breast01),
phase 2 development for HER2-positive advanced gastric resistent or
refractory to trastuzumab (DESTINY-Gastric01)
and phase 1 development for other HER2-expressing advanced/unresectable
or metastatic solid tumors.
DS-8201 has been granted Breakthrough Therapy designation for the
treatment of patients with HER2-positive, locally advanced or metastatic
breast cancer who have been treated with trastuzumab and pertuzumab and
have disease progression after ado-trastuzumab emtansine (T-DM1), and
Fast Track designation for the treatment of HER2-positive unresectable
and/or metastatic breast cancer in patients who have progressed after
prior treatment with HER2-targeted therapies including T-DM1 by the U.S.
Food and Drug Administration (FDA). DS-8201 is an investigational agent
that has not been approved for any indication in any country. Safety and
efficacy have not been established.
About NERLYNX
®
(neratinib)
Neratinib was approved by the 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.
Important Safety Information (ISI)
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, 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.
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. NERLYNX®
(neratinib) is approved for commercial use by prescription in the United
States as extended adjuvant therapy for early stage HER2-positive breast
cancer following adjuvant trastuzumab-based therapy and is marketed as
NERLYNX. Neratinib is a potent irreversible tyrosine kinase inhibitor
that blocks signal transduction through the epidermal growth factor
receptors, HER1, HER2 and HER4. Currently, Puma is primarily focused on
the commercialization of NERLYNX and the continued development of its
other advanced drug candidates directed at the treatment of
HER2-positive breast cancer. Puma believes that NERLYNX has clinical
application in the potential treatment of several other cancers that
over-express or have a mutation in HER2. Further information about
Puma Biotechnology can be found at
www.pumabiotechnology.com
About Daiichi Sankyo Cancer Enterprise
The vision of Daiichi Sankyo Cancer Enterprise is to leverage our
world-class, innovative science and push beyond traditional thinking in
order to create meaningful treatments for patients with cancer. We are
dedicated to transforming science into value for patients, and this
sense of obligation informs everything we do. Anchored by our Antibody
Drug Conjugate (ADC) and Acute Myeloid Leukemia (AML) Franchises, our
cancer pipeline includes more than 20 small molecules, monoclonal
antibodies and ADCs stemming from our powerful research engines: our two
laboratories for biologic/immuno-oncology and small molecules in Japan,
and Plexxikon Inc., our small molecule structure-guided R&D center in
Berkeley, CA. Compounds in development include: quizartinib, an oral
FLT3 inhibitor, for newly-diagnosed and relapsed or refractory AML with
FLT3-ITD mutations; DS-8201, an ADC for HER2-expressing breast and
gastric cancer, and other HER2-expressing solid tumors; and
pexidartinib, an oral CSF-1R inhibitor, for tenosynovial giant cell
tumor (TGCT), which is also being explored in a range of solid tumors in
combination with the anti-PD1 immunotherapy pembrolizumab. For more
information, please visit: www.DSCancerEnterprise.com.
About Daiichi Sankyo
Daiichi Sankyo Group is dedicated to the creation and supply of
innovative pharmaceutical products to address diversified, unmet medical
needs of patients in both mature and emerging markets. With over 100
years of scientific expertise and a presence in more than 20 countries,
Daiichi Sankyo and its 15,000 employees around the world draw upon a
rich legacy of innovation and a robust pipeline of promising new
medicines to help people. In addition to a strong portfolio of medicines
for hypertension and thrombotic disorders, under the Group’s 2025 Vision
to become a “Global Pharma Innovator with Competitive Advantage in
Oncology,” Daiichi Sankyo research and development is primarily focused
on bringing forth novel therapies in oncology, including
immuno-oncology, with additional focus on new horizon areas, such as
pain management, neurodegenerative diseases, heart and kidney diseases,
and other rare diseases. For more information, please visit: www.daiichisankyo.com.
Daiichi Sankyo, Inc., headquartered in Basking Ridge, New Jersey, is a
member of the Daiichi Sankyo Group. For more information on Daiichi
Sankyo, Inc., please visit: www.dsi.com.
Forward-Looking Statements
This press release contains forward-looking statements, including
statements regarding the benefits of a research collaboration with
Memorial Sloan Kettering and Daiichi Sankyo, including whether a
combination of neratinib and DS-8201 will be successful or beneficial,
the benefits of NERLYNX® and neratinib, Puma’s clinical trials and the
announcement of data relative to those trials. All forward-looking
statements included in this press release involve risks and
uncertainties that could cause Puma’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 Puma has
only recently commenced commercialization and shipment of its only FDA
approved product; Puma’s dependence upon the commercial success of
NERLYNX (neratinib); Puma’s history of operating losses and its
expectation that it will continue to incur losses for the foreseeable
future; risks and uncertainties related to Puma’s ability to achieve or
sustain profitability; Puma’s ability to predict its future prospects
and forecast its financial performance and growth; failure to obtain
sufficient capital to fund Puma’s operations; the effectiveness of sales
and marketing efforts; Puma’s ability to obtain FDA approval or other
regulatory approvals in the United States or elsewhere for other
indications for neratinib or other product candidates; the challenges
associated with conducting and enrolling clinical trials; the risk that
the results of clinical trials may not support Puma’s drug candidate
claims; even if approved, the risk that physicians and patients may not
accept or use Puma’s products; Puma’s reliance on third parties to
conduct its clinical trials and to formulate and manufacture its drug
candidates; risks pertaining to securities class action, derivative and
defamation lawsuits; Puma’s dependence on licensed intellectual
property; and the other risk factors disclosed in the periodic and
current reports filed by Puma with the Securities and Exchange
Commission from time to time, including Puma’s Quarterly Report on Form
10-Q for the quarter ended September 30, 2017. Readers are cautioned not
to place undue reliance on these forward-looking statements, which speak
only as of the date hereof. Puma assumes no obligation to update these
forward-looking statements, except as required by law.
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