THOUSAND OAKS, Calif.,
Oct. 30, 2019 /PRNewswire/
-- Amgen (NASDAQ: AMGN) today announced a publication in
Nature unveiling the discovery of AMG 510, a small molecule
inhibitor of KRASG12C being investigated as a treatment
for a variety of solid tumors with KRAS G12C mutation. AMG
510 is the first investigational KRASG12C inhibitor to
advance to the clinic and is currently enrolling in a potentially
registrational Phase 2 study.
Experience the interactive Multichannel News Release here:
https://www.multivu.com/players/English/8490257-amgen-nature-amg510-publication/
Titled "The Clinical KRASG12C Inhibitor AMG 510
Drives Anti-Tumor Immunity," the paper highlights novel structural
insights that led to the discovery of AMG 510, the preclinical
evidence of AMG 510 activity, its potential ability to induce
tumor-cell killing as both a monotherapy and in combination
with other therapies, and its impact on the immune system that may
render tumor cells particularly sensitive to immunotherapy. Early
evidence of clinical activity of AMG 510 is also presented in the
paper.
"We are pleased to share how our team of scientists at Amgen
were the first to exploit the previously hidden groove on the
protein surface to finally identify a potential drug against this
important oncogenic protein," said David M.
Reese, M.D., executive vice president of Research and
Development at Amgen. "These scientific insights, coupled with
superb molecular engineering, paved the way for AMG 510 to be first
to clinic, where it has demonstrated early evidence of clinical
activity."
KRAS, identified over 30 years ago as a proto-oncogene,
is one of the most frequently mutated oncogenes in human
cancer.1,2 Amgen researchers first identified the
novel histidine 95 (H95) groove located on an inactive
KRASG12C protein. Through extensive compound
screening and structure-based design, AMG 510 emerged as the top
investigational candidate from the optimization of a series of H95
groove-binding molecules. It is designed to irreversibly bind to
KRASG12C protein and permanently lock it in an
inactive state, leading to inhibition of tumor cell growth in
KRASG12C driven tumors. In preclinical
experiments, AMG 510 demonstrated favorable potency and
selectivity, and induced regression in mice bearing
KRASG12C mutated tumors.
"There is a significant unmet need for tumor-selective therapies
that minimize a negative impact on normal cells, and many patients
diagnosed with KRAS-mutated solid tumors have typically
faced a challenging prognosis with limited targeted treatment
options," said David S. Hong, M.D.,
one of the paper's authors, AMG 510 clinical study investigator and
deputy chair, Department of Investigational Cancer Therapeutics,
Division of Cancer Medicine at University of
Texas MD Anderson Cancer Center, Houston. "This publication shows
investigational AMG 510 has high selectivity in non-clinical
experiments, binding only to KRASG12C out of more
than 6,000 proteins and likely contributing to the absence of
dose-limiting toxicities in the clinical study to date, supporting
the potential for an encouraging safety profile."
The U.S. Food and Drug Administration (FDA) granted Orphan Drug
Designation to AMG 510 for previously treated metastatic non-small
cell lung cancer (NSCLC) and colorectal cancer with KRAS
G12C mutation and Fast Track Designation for previously treated
metastatic NSCLC with KRAS G12C mutation. Additional data
from the ongoing Phase 1 clinical trial evaluating AMG 510 was
recently presented at the 2019 World Conference on Lung Cancer
hosted by the International Association for the Study of Lung
Cancer and at the European Society for Medical Oncology 2019
Congress, both of which were held in Barcelona, Spain.
About KRAS
The subject of more than three
decades of research, the RAS gene family are the most
frequently mutated oncogenes in human cancers.1,2 Within
this family, KRAS is the most prevalent variant and is
particularly common in solid tumors.2 A specific
mutation known as KRAS G12C accounts for approximately 13%
of non-small cell lung cancers, three to five percent of colorectal
cancers and one to two percent of numerous other solid
tumors.3 Approximately 30,000 patients are diagnosed
each year in the United States
with KRAS G12C-driven cancers.4
KRASG12C has been considered "undruggable" due to a
lack of traditional small molecule binding pockets on the protein.
Amgen is exploring the potential of KRASG12C inhibition
across a broad variety of tumor types.
About Amgen Oncology
Amgen Oncology is searching for
and finding answers to incredibly complex questions that will
advance care and improve lives for cancer patients and their
families. Our research drives us to understand the disease in the
context of the patient's life – not just their cancer journey – so
they can take control of their lives.
For the last four decades, we have been dedicated to discovering
the firsts that matter in oncology and to finding ways to reduce
the burden of cancer. Building on our heritage, Amgen continues to
advance the largest pipeline in the Company's history, moving with
great speed to advance those innovations for the patients who need
them.
At Amgen, we are driven by our commitment to transform the lives
of cancer patients and keep them at the center of everything we
do.
For more information, follow us on
www.twitter.com/amgenoncology.
About Amgen
Amgen is committed to unlocking the potential of biology for
patients suffering from serious illnesses by discovering,
developing, manufacturing and delivering innovative human
therapeutics. This approach begins by using tools like advanced
human genetics to unravel the complexities of disease and
understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and
leverages its expertise to strive for solutions that improve health
outcomes and dramatically improve people's lives. A biotechnology
pioneer since 1980, Amgen has grown to be one of the
world's leading independent biotechnology companies, has reached
millions of patients around the world and is developing a pipeline
of medicines with breakaway potential.
For more information, visit www.amgen.com and follow
us on www.twitter.com/amgen.
Forward-Looking Statements
This news release contains
forward-looking statements that are based on the current
expectations and beliefs of Amgen. All statements, other than
statements of historical fact, are statements that could be deemed
forward-looking statements, including any statements on the
outcome, benefits and synergies of the acquisition of Otezla®
(apremilast), including anticipated Otezla sales growth and the
timing of non-GAAP EPS accretion, as well as estimates of revenues,
operating margins, capital expenditures, cash, other financial
metrics, expected legal, arbitration, political, regulatory or
clinical results or practices, customer and prescriber patterns or
practices, reimbursement activities and outcomes and other such
estimates and results. Forward-looking statements involve
significant risks and uncertainties, including those discussed
below and more fully described in the Securities and Exchange
Commission reports filed by Amgen, including our most recent annual
report on Form 10-K and any subsequent periodic reports on Form
10-Q and current reports on Form 8-K. Unless otherwise noted,
Amgen is providing this information as of the date of this news
release and does not undertake any obligation to update any
forward-looking statements contained in this document as a result
of new information, future events or otherwise.
No forward-looking statement can be guaranteed and actual
results may differ materially from those we project.
Discovery or identification of new product candidates or
development of new indications for existing products cannot be
guaranteed and movement from concept to product is uncertain;
consequently, there can be no guarantee that any particular product
candidate or development of a new indication for an existing
product will be successful and become a commercial product.
Further, preclinical results do not guarantee safe and effective
performance of product candidates in humans. The complexity of the
human body cannot be perfectly, or sometimes, even adequately
modeled by computer or cell culture systems or animal models. The
length of time that it takes for us to complete clinical trials and
obtain regulatory approval for product marketing has in the past
varied and we expect similar variability in the future. Even when
clinical trials are successful, regulatory authorities may question
the sufficiency for approval of the trial endpoints we have
selected. We develop product candidates internally and through
licensing collaborations, partnerships and joint ventures. Product
candidates that are derived from relationships may be subject to
disputes between the parties or may prove to be not as effective or
as safe as we may have believed at the time of entering into such
relationship. Also, we or others could identify safety, side
effects or manufacturing problems with our products, including our
devices, after they are on the market.
Our results may be affected by our ability to successfully
market both new and existing products domestically and
internationally, clinical and regulatory developments involving
current and future products, sales growth of recently launched
products, competition from other products including biosimilars,
difficulties or delays in manufacturing our products and global
economic conditions. In addition, sales of our products are
affected by pricing pressure, political and public scrutiny and
reimbursement policies imposed by third-party payers, including
governments, private insurance plans and managed care providers and
may be affected by regulatory, clinical and guideline developments
and domestic and international trends toward managed care and
healthcare cost containment. Furthermore, our research, testing,
pricing, marketing and other operations are subject to extensive
regulation by domestic and foreign government regulatory
authorities. Our business may be impacted by government
investigations, litigation and product liability claims. In
addition, our business may be impacted by the adoption of new tax
legislation or exposure to additional tax liabilities. If we fail
to meet the compliance obligations in the corporate integrity
agreement between us and the U.S. government, we could become
subject to significant sanctions. Further, while we routinely
obtain patents for our products and technology, the protection
offered by our patents and patent applications may be challenged,
invalidated or circumvented by our competitors, or we may fail to
prevail in present and future intellectual property litigation. We
perform a substantial amount of our commercial manufacturing
activities at a few key facilities, including in Puerto Rico, and also depend on third parties
for a portion of our manufacturing activities, and limits on supply
may constrain sales of certain of our current products and product
candidate development. In addition, we compete with other companies
with respect to many of our marketed products as well as for the
discovery and development of new products. Further, some raw
materials, medical devices and component parts for our products are
supplied by sole third-party suppliers. Certain of our
distributors, customers and payers have substantial purchasing
leverage in their dealings with us. The discovery of significant
problems with a product similar to one of our products that
implicate an entire class of products could have a material adverse
effect on sales of the affected products and on our business and
results of operations. Our efforts to acquire other companies or
products and to integrate the operations of companies we have
acquired may not be successful. A breakdown, cyberattack or
information security breach could compromise the confidentiality,
integrity and availability of our systems and our data. Our stock
price is volatile and may be affected by a number of events. Our
business performance could affect or limit the ability of our Board
of Directors to declare a dividend or our ability to pay a dividend
or repurchase our common stock. We may not be able to access the
capital and credit markets on terms that are favorable to us, or at
all.
The scientific information discussed in this news release
related to Amgen's product candidates is preliminary and
investigative. Such product candidates are not approved by the U.S.
Food and Drug Administration, and no conclusions can or should be
drawn regarding the safety or effectiveness of the product
candidates.
CONTACT: Amgen, Thousand
Oaks
Trish Hawkins, 805-447-5631
(Media)
Jessica Akopyan, 805-447-0974
(Media)
Arvind Sood, 805-447-1060
(Investors)
- Cox A, et al. Drugging the undruggable RAS: Mission
possible? Nat Rev Drug Discov. 2014
Nov;13(11):828-51.
- Fernandez-Medarde A, Santos E. Ras in cancer and
developmental diseases. Genes Cancer. 2011
Mar;2(3):344-58.
- Lipford, JR. Pre-clinical development of AMG 510: the first
inhibitor of KRASG12C in clinical testing. Oral presentation at
AACR 2019, Atlanta, GA. March 29-April
3, 2019.
- Stephen AG, et al. Dragging ras back in the ring. Cancer
Cell. 2014 Mar 17;25(3):272-81.
View original
content:http://www.prnewswire.com/news-releases/the-discovery-of-amgens-novel-investigational-krasg12c-inhibitor-amg-510-published-in-nature-300948664.html
SOURCE Amgen