NGM Discloses Third Oncology Development Candidate, NGM438, a Novel Antagonist Antibody Inhibiting LAIR1 for the Treatment of...
December 09 2020 - 4:05PM
NGM Biopharmaceuticals, Inc. (NGM) (Nasdaq: NGM), a biotechnology
company focused on discovering and developing transformative
therapeutics for patients, today disclosed its third oncology
development candidate, NGM438, a novel antagonist antibody that
inhibits Leukocyte-associated immunoglobulin-like receptor 1
(LAIR1). NGM438 was featured earlier today during NGM’s first
R&D Day. The event highlighted the company’s diverse portfolio
of therapeutic candidates for liver and metabolic disease, retinal
diseases and cancer. All presentations from the R&D Day can be
found in the Investors & Media section of NGM’s website here.
LAIR1 is a collagen-binding inhibitory receptor expressed on
immune cells1-2 that is implicated in immune suppression. LAIR1 and
collagens are upregulated in multiple cancer types3-7 where
collagens are produced by activated stromal cells. These
stromal-derived suppressive factors are associated with poor
responses to checkpoint inhibitors. For such tumors, formation of
the LAIR1-collagen complex may act as a stromal checkpoint to both
physically exclude immune cells from the tumor and impose
signaling-based immune suppression8-9. Consequently, inhibiting
this stromal checkpoint represents a potentially promising new
therapeutic strategy to treat cancer by promoting the remodeling of
the tumor architecture that restricts T cell infiltration of the
tumor cell mass and reversing immune suppression in the tumor
microenvironment.
Designed to inhibit LAIR1 interactions with stromal-derived
collagens, NGM438 has the potential to block this stromal
checkpoint and restore anti-tumor immune responses. In preclinical
studies, NGM438 demonstrated the ability to reprogram
collagen-suppressed myeloid cells to a stimulatory phenotype,
induce inflammatory cytokine production by myeloid and T cells, and
relieve collagen-based suppression of T cell proliferation.
Reinvigoration of collagen-suppressed immune cells may address a
key resistance mechanism that limits responses to current
immunotherapies.
“At NGM’s inaugural R&D Day today, we were excited to
showcase NGM’s powerful in-house drug discovery engine. NGM438, a
novel immuno-oncology candidate, is yet another example of our
team’s biology-driven approach and expertise in tailoring
highly-specialized antibodies,” said David J. Woodhouse, Ph.D.,
Chief Executive Officer at NGM. “NGM438, which inhibits LAIR1, and
NGM707, our dual antagonist antibody that inhibits ILT2 and ILT4,
are both examples of our strategy to broaden and deepen anti-tumor
immune responses for patients through myeloid reprogramming by
addressing key resistance mechanisms and reversing stromal and
myeloid checkpoints.”
NGM438 joins NGM707 as the second myeloid reprogramming product
candidate in the NGM oncology portfolio. NGM707 is a novel dual
antagonist antibody that inhibits Immunoglobulin-like transcript 2
(ILT2) and Immunoglobulin-like transcript 4 (ILT4). First-in-human
testing for NGM707 is expected to begin in mid-2021. NGM’s third
oncology candidate is NGM120, a first-in-class antagonistic
antibody that binds glial cell-derived neurotrophic factor receptor
alpha-like (GFRAL) and inhibits growth differentiation factor 15
(GDF15) signaling. NGM120 is in an ongoing Phase 1a/1b trial in
patients with cancer and cancer anorexia/cachexia syndrome
(CACS).
NGM438, NGM707 and NGM120 were discovered by NGM under
its strategic collaboration with
Merck.
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 cancer. 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 “may,”
“plans,” “implicate,” “potentially,” “promising,” “designed to,”
“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
therapeutic potential, potential benefits and design of NGM438,
including NGM438’s potential to impede anti-tumor immunity by
its inhibiting LAIR1; the planned first in-human testing
of NGM438 and NGM707 and the anticipated timing thereof;
implications of the potential therapeutic advantages of
inhibiting a stromal checkpoint to both physically exclude immune
cells from the tumor and impose signaling-based immune
suppression; the potential for reinvigoration of
collagen-suppressed immune cells to address a key resistance
mechanism that limits responses to current immunotherapies;
NGM’s strategy to broaden and deepen anti-tumor immune responses
for patients through myeloid reprogramming by addressing key
resistance mechanisms and reversing stromal and myeloid
checkpoints; and other statements that are not historical fact.
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 initiating, enrolling
or completing clinical studies; the risk that NGM’s ongoing or
future clinical studies in humans may show that NGM438, and/or
NGM707 are not tolerable and effective treatments for cancer or
that the effects of inhibiting LAIR1 interactions with
stromal-derived collagens are otherwise different than
anticipated; the ongoing COVID-19 pandemic, which has
adversely affected, and could materially and adversely affect
in the future, NGM’s business and operations, including NGM’s
ability to timely supply, initiate, enroll and complete its
ongoing and future clinical studies; the time-consuming and
uncertain regulatory approval process; NGM’s reliance on
third-party manufacturers for NGM438 and NGM707 and its
other product candidates; 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 “Risk Factors” and “Management’s
Discussion and Analysis of Financial Condition and Results of
Operations” in NGM’s quarterly report on Form 10-Q for the
quarter ended September 30, 2020 and future filings and
reports that NGM makes from time to time with the United
States Securities and Exchange Commission. 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 |
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1. Meyaard, Immunity, 19972. Guo, Trans Med, 20203. Cao, 2015,
Biochem Biophys Res Commun4. Wang, Exp Ther Med, 20165. Wu, CP
Cancer, 20186. Yang, Head & Neck, 20187. Jingushi, Onc.
Reports, 20188. Peng, Nat Comm, 20209. Lijun, Oncoimmunology,
2020
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