NGM Biopharmaceuticals, Inc. (Nasdaq: NGM), a biotechnology company
focused on discovering and developing transformative therapeutics
for patients, today announced it has dosed the first patient in an
expansion of its ongoing Phase 1b proof-of-concept study of NGM120
in patients with metastatic pancreatic cancer. NGM120 is an
antagonistic antibody that binds glial cell-derived neurotrophic
factor receptor alpha-like (GFRAL) and inhibits growth
differentiation factor 15 (GDF15) signaling. This
placebo-controlled study will evaluate the effect of NGM120 on both
cancer and cancer-related cachexia. Cachexia is the uncontrolled
wasting of both skeletal muscle and fat linked to many cancers. It
is estimated to affect 60% to 80% of advanced cancer patients and
to be responsible for approximately 30% of all cancer deaths1. This
proof-of-concept expansion represents a pre-planned progression of
an ongoing Phase 1a/1b dose-finding clinical trial NGM is
conducting in patients with select advanced solid tumors and
metastatic pancreatic cancer.
NGM is a leader in research elucidating the central role of the
GDF15/GFRAL pathway in promoting tumor-associated appetite
regulation, metabolic regulation and immune modulation. Through
systematic screening of human secreted factors in preclinical
models, NGM identified that GDF15 expression has the ability to
promote an outsized effect in weight loss. Evidence has also shown
that serum levels of GDF15 are elevated in patients with a number
of tumor types, including non-small cell lung cancer, melanoma,
pancreatic, prostate, colorectal, gastric, esophageal and ovarian
cancer, and are associated with a worse prognosis in multiple
cancers.
As published in Nature, NGM was the first to identify GDF15’s
cognate receptor, GFRAL, and the associated signaling pathway2.
This discovery enabled the development of NGM120, a proprietary
inhibitory antibody binding to GFRAL that is designed to block the
effects of elevated GDF15 levels. In preclinical studies, NGM has
demonstrated that blocking the interaction between GDF15 and GFRAL
both reduces tumor-associated weight loss and slows tumor growth.
In a murine pancreatic tumor model, treatment with NGM120s, an
anti-GFRAL antibody similar to NGM120, resulted in greater tumor
shrinkage as well as improved survival versus the control arm. In a
murine cancer cachexia model, NGM120s rapidly reversed
tumor-induced weight loss. In addition, in a murine model of
chemotherapy-induced weight loss, administration of NGM120s
preserved lean mass and muscle function in animals treated with
cisplatin, while treatment with cisplatin alone resulted in greater
than 20% weight loss.
“We are pleased to advance NGM120 into a placebo-controlled,
Phase 1b expansion in patients with metastatic pancreatic cancer.
Patients with this aggressive disease are in particularly dire need
of therapeutic solutions to fight their disease and enhance their
quality of life,” said Alex DePaoli, M.D., Senior Vice President,
Chief Translational Officer at NGM. “Our approach of targeting the
GDF15 receptor, GFRAL, gives NGM120 a novel profile in the GDF15
inhibition space and enables us to evaluate NGM120 as a potential
treatment for both cancer-related cachexia and the underlying
cancer.”
About the Design of the NGM120 Phase 1b
Expansion
In February 2020, NGM initiated a Phase 1a/1b multi-site,
open-label, dose-escalation clinical study to evaluate the safety,
tolerability and pharmacokinetics of NGM120 as a monotherapy in
patients with select advanced solid tumors (Cohort 1) and in
combination with gemcitabine and Abraxane® (paclitaxel protein
bound) in patients with metastatic pancreatic cancer (Cohort 2).
Entry criteria included elevated serum levels of GDF15. Cohorts 1
and 2 are fully enrolled.
The Phase 1b expansion portion of the study will evaluate the
safety, tolerability and efficacy of NGM120 as a first-line
treatment in 60 patients with metastatic pancreatic cancer. Entry
criteria includes elevated serum GDF15 levels. The study is a
randomized, single-blind (sponsor unblinded), placebo-controlled,
multi-center trial. Patients will be randomized 1:1 to receive
either NGM120 or placebo monthly in combination with the first-line
standard of care, gemcitabine and Abraxane. The study will have
both cancer and cachexia endpoints, including overall response rate
(ORR), progression-free survival (PFS), overall survival (OS), body
weight change, lean body mass change, patient reported outcomes and
functional status changes.
About NGM120
NGM120 is an antagonistic antibody that binds glial cell-derived
neurotrophic factor receptor alpha-like (GFRAL) and inhibits growth
differentiation factor 15 (GDF15) signaling. NGM scientists have
made several important discoveries related to GDF15, including
identification of its cognate receptor, GFRAL. GFRAL is expressed
in a specific region of the hindbrain, partially outside the blood
brain barrier, and is believed to initiate signaling through
multiple pathways, including the autonomic nervous system. NGM120
binds with high affinity to GFRAL to prevent the formation of the
GDF15 co-receptor complex and its mediated signaling.
About Cachexia
Cachexia is a wasting syndrome common in cancer patients, and a
frequent co-morbidity of the disease. Cachexia is associated
with increased hospitalization and shortened survival compared to
cancer patients who do not exhibit the syndrome. While cachexia can
occur in all types of cancer, particularly high incidence rates are
observed in pancreatic, gastric, colorectal and esophageal cancers,
as well as non-small cell lung cancer. There are no FDA-approved
therapies for cachexia.
About NGM Biopharmaceuticals, Inc.
NGM is a biopharmaceutical company focused on discovering and
developing novel therapeutics based on scientific understanding of
key biological pathways underlying liver and metabolic diseases,
retinal diseases and oncology. We leverage our biology-centric drug
discovery approach to uncover novel mechanisms of action and
generate proprietary insights that enable us to move rapidly into
proof-of-concept studies and deliver potential first-in-class
medicines to patients. At NGM, we aspire to operate one of the most
productive research and development engines in the
biopharmaceutical industry, with multiple programs in clinical
development. Visit us at www.ngmbio.com for more information.
Forward Looking Statements
Statements contained in this press release regarding matters
that are not historical facts are “forward-looking statements”
within the meaning of the Private Securities Litigation Reform Act
of 1995. Words such as “build,” “plans,” “designed to,” “continue,”
“potential” and similar expressions (as well as other words or
expressions referencing future events, conditions or circumstances)
are intended to identify forward-looking statements. These
statements include those related to the design, timing, enrollment
and potential results of NGM’s Phase 1a/1b clinical trial of
NGM120, including the Phase 1b expansion in patients with
metastatic pancreatic cancer; the potential of NGM120 as a novel
treatment for cachexia and the underlying cancer, as well as its
potential to enhance patient quality of life; and the therapeutic
effects and benefits of NGM120 and the role of the GDF15/GFRAL
pathway. Because such statements deal with future events and are
based on NGM’s current expectations, they are subject to various
risks and uncertainties, and actual results, performance or
achievements of NGM could differ materially from those described in
or implied by the statements in this press release. These
forward-looking statements are subject to risks and uncertainties,
including, without limitation, risks and uncertainties associated
with the costly and time-consuming pharmaceutical product
development process and the uncertainty of clinical success,
including risks related to failure or delays in successfully
enrolling or completing clinical studies, the risk that the results
obtained to date in NGM’s clinical trials may not be indicative of
results obtained in subsequent pivotal or other late-stage trials,
and the risk that NGM’s ongoing or future clinical studies in
humans may show that NGM120 is not a tolerable and effective
treatment for cachexia and underlying cancers; the ongoing COVID-19
pandemic, which has adversely affected, and could materially and
adversely affect in the future, our business and operations; the
time-consuming and uncertain regulatory approval process; NGM’s
reliance on third-party manufacturers; the sufficiency of NGM’s
cash, cash equivalents and short-term marketable securities and
need for additional capital; and other risks and uncertainties
affecting NGM and its development programs, as well as those
discussed in the sections titled “Management’s Discussion and
Analysis of Financial Condition and Results of Operations” and
“Risk Factors” in our quarterly report on Form 10-Q for the quarter
ended September 30, 2020, the section titled “Risk Factors” in
exhibit 99.1 to our current report on Form 8-K filed with the
United States Securities and Exchange Commission (SEC) on January
6, 2021 and future filings and reports that NGM makes from time to
time with the SEC. Except as required by law, NGM assumes no
obligation to update these forward-looking statements, or to update
the reasons if actual results differ materially from those
anticipated in the forward-looking statements.
Investor
Contact:Alex Schwartzir@ngmbio.com |
Media
Contact:Liz Melonemedia@ngmbio.com |
1 = Haehlinget al, J. Cachexia Sarcopenia Muscle, 20102 = Hsu
et. al., Nature 2017
NGM Biopharmaceuticals (NASDAQ:NGM)
Historical Stock Chart
From Jun 2024 to Jul 2024
NGM Biopharmaceuticals (NASDAQ:NGM)
Historical Stock Chart
From Jul 2023 to Jul 2024