NGM Bio Announces New Clinical Data from Ongoing Trial of NGM707 in Advanced Solid Tumors and Outlines Evolved Strategy for Aldafermin and NGM120 to Focus on Rare Conditions with Significant Unmet Need
10 January 2024 - 12:00AM
NGM Biopharmaceuticals, Inc. (NGM Bio) (Nasdaq: NGM), a
biotechnology company focused on discovering and developing
transformative therapeutics for patients, today announced
encouraging new data from an ongoing Phase 1 Part 1b study
evaluating NGM707, a dual ILT2/ILT4 antagonist antibody product
candidate, in combination with KEYTRUDA® (pembrolizumab). NGM Bio
also outlined its strategy to evolve clinical development of its
product candidates aldafermin and NGM120 to focus on rare
conditions characterized by significant unmet need.
“Our priorities for 2024 center on directing our efforts and
investing our resources as efficiently and effectively as possible
toward select development activities that we believe have the
greatest potential to deliver nearer-term impact and value creation
while being fully aligned with our mission to deliver life-changing
medicines for patients with significant unmet needs,” said David J.
Woodhouse, PhD, Chief Executive Officer at NGM Bio.
Dr. Woodhouse continued, “Our focus on the combination of NGM707
and pembrolizumab stems from encouraging responses observed in
heavily pretreated patients with very advanced disease, including
MSS CRC, that has been largely unresponsive to anti-PD-1/L1
monotherapy. Our interest and efforts in aldafermin in PSC are
based on data that we believe supports aldafermin’s differentiated
potential as an engineered FGF19 analog to address the bile acid
dysregulation underpinning this rare liver disease, including our
prior Phase 2 study in PSC, as well as our positive clinical study
in NASH F4 patients and data from other PSC trials supporting the
use of biomarkers of fibrosis, such as ELF, to predict clinical
outcomes. Finally, our potential exploration of NGM120, a
GDF15/GFRAL antagonist, in a proof-of-concept study for the
treatment of hyperemesis gravidarum is rooted in our decade-long
efforts advancing the understanding of GDF15 biology and exploring
its therapeutic application in a number of disease areas. Recent
landmark genetic research confirmed the link between this rare,
devastating condition experienced during pregnancy to higher levels
of GDF15. Given our deep expertise in GDF15 biology, we believe we
are well positioned to potentially pursue this indication for
NGM120. As we concurrently pursue these important development
efforts, exploring partnering opportunities across our full product
candidate and research portfolio, all wholly owned by NGM, remains
an important priority for us in 2024.”
Key Pipeline Updates
NGM707 in Advanced Solid Tumors
- Announced encouraging new findings from the Phase 1 Part 1b
dose escalation cohort of the ongoing Phase 1/2 trial evaluating
NGM707 in combination with pembrolizumab for the treatment of
patients with advanced or metastatic solid tumors. The combination
of NGM707 and pembrolizumab was generally well tolerated at all
four dose levels of NGM707. The maximum tolerated dose was not
reached.
- The Phase 1 Part 1b cohort enrolled 46 patients as of a
November 6, 2023 data-cutoff. Of 37 response-evaluable patients
(those completing at least one on-treatment scan), there were four
confirmed partial responses (PRs) across multiple indications,
including one pathological complete response (CR), and 12 stable
disease (SD) (11% overall response rate [ORR] and 43% disease
control rate [DCR]). The pathological CR patient had significant
target lesion reduction that allowed subsequent surgical resection
of all gross residual disease, resulting in a confirmed
pathological CR with no active tumor cells and ctDNA below
detection. Three of the four responders had active liver metastases
at baseline; patients with liver metastases, which are associated
with immune suppression and lower survival rates, tend to have a
reduced response to immunotherapy.
- Eight of the 37 response-evaluable patients had MSS CRC; two of
these MSS CRC patients were among the confirmed PRs, including the
patient with a pathological CR, and two had SD (25% ORR and 50%
DCR). Anti-PD-1/L1 monotherapies have shown low or no benefit in
MSS CRC patients.
- NGM Bio is completing enrollment in the Phase 1 Part 1b cohort
and anticipates providing an update in mid-2024 on the completed
cohort and subsequent next steps, including the potential for
additional cohorts, which may include MSS CRC patients.
Aldafermin in Primary Sclerosing Cholangitis (PSC)
- Announced planned further development of aldafermin for the
treatment of PSC, a rare liver disease that irreparably damages the
bile ducts, leading to bile acid dysregulation, which, ultimately,
results in serious liver damage. There are currently no
FDA-approved therapies for PSC. NGM Bio recently met with the FDA
regarding the design of a potential registrational trial, including
the utilization of proposed surrogate primary endpoints. NGM Bio
plans to continue working with the FDA to reach agreement on a
trial design in the coming months, with the goal of initiating
trial enrollment by the end of 2024, contingent upon reaching
agreement with the FDA on trial design and additional capital
availability.
- NGM Bio’s decision to pursue the potential further clinical
development of aldafermin as a treatment for PSC was informed by a
large body of clinical data. Over 800 patients across multiple
indications have been treated with aldafermin, which has repeatedly
demonstrated powerful bile acid suppression in patients with PSC
and NASH, and thus, NGM Bio believes aldafermin has the
differentiated potential to directly address the underlying biology
of PSC. NGM Bio previously reported data from a randomized,
double-blind, placebo-controlled Phase 2 study of aldafermin for
the treatment of PSC. While that Phase 2 study did not meet its
primary endpoint of statistically significant change in alkaline
phosphatase, an exploratory biomarker of PSC disease progression,
from baseline to week 12, aldafermin demonstrated both
statistically significant improvements in biomarkers of hepatic
injury and fibrosis, as well as statistically significant
reductions in biomarkers of bile acid synthesis and serum bile
acids, consistent with past studies of aldafermin in other liver
diseases. The Phase 2 study met the secondary endpoints and was
generally well tolerated by patients.
NGM120 in Hyperemesis Gravidarum
- Announced potential development of NGM120 for the treatment of
hyperemesis gravidarum (referred to colloquially as hyperemesis),
subject to the outcome of ongoing discussions with the FDA.
Hyperemesis, a rare, serious condition that affects approximately
100,000 – 150,000 women in the United States each year during
pregnancy, is characterized by intractable nausea and vomiting,
which then results in dehydration, weight loss and malnutrition.
Hyperemesis has a significant physical and psychosocial impact on
patients and leads to overall higher rates of fetal loss,
preeclampsia, preterm birth, low birth weight and fetal
malnutrition. Hyperemesis is the second leading cause of
hospitalization in pregnancy (second to preterm labor) and
typically recurs in subsequent pregnancies. There are currently no
FDA-approved therapies for this condition.
- Research published by an international team that included
Marlena Fejzo, Ph.D., Clinical Assistant Professor of Population
and Public Health Sciences in the Center for Genetic Epidemiology
at the University of Southern California, and Sir Stephen
O'Rahilly, M.D. FRS FMedSci, Professor of Clinical
Biochemistry and Medicine at the University of Cambridge, found
that GDF15 levels increase steadily in early pregnancy and are
higher in women who experience nausea and vomiting in pregnancy and
hyperemesis. The research uncovered that women with GDF15 genetic
variants associated with lower levels of GDF15 in a non-pregnant
state are predisposed to hyperemesis. NGM120, a GFRAL antagonist
antibody, is designed to block GDF15 signaling and, thereby, may
have therapeutic benefit for treating patients suffering from
hyperemesis. Dr. Fejzo, who experienced hyperemesis in her own
pregnancies and subsequently dedicated her professional life to
uncovering the biology underpinning the condition, is serving as an
advisor to NGM Bio.
Key 2023 Highlights
Solid Tumor Oncology
- Continued enrollment in a Phase 1 Part 1b cohort of the ongoing
Phase 1/2 trial evaluating NGM707 in combination with pembrolizumab
for the treatment of patients with advanced or metastatic solid
tumors. This cohort is anticipated to complete enrollment in the
first half of 2024.
- Completed enrollment in Phase 1 Part 1b cohorts of Phase 1/1b
trials evaluating NGM831 and NGM438, respectively, in combination
with pembrolizumab in patients with solid tumors. NGM831 is an ILT3
antagonist antibody product candidate, and NGM438 is a LAIR1
antagonist antibody product candidate.
- Initiated an ongoing Phase 1 Part 1c dose finding cohort
evaluating the triplet combination of NGM831, NGM438 and
pembrolizumab. This cohort is anticipated to complete enrollment in
the first half of 2024.
- Completed a Phase 2 randomized, single-blind
(investigator-blinded), placebo-controlled, multi-center expansion
trial of NGM120 in combination with gemcitabine and Nab-paclitaxel
as a first-line treatment in patients with metastatic pancreatic
cancer (referred to as the PINNACLES trial). NGM120 was well
tolerated in the trial. A clear signal of response was not
detected, and further development of NGM120 in oncology has been
paused.
Liver and Metabolic Diseases
- Presented positive, comprehensive results from the Phase 2b
ALPINE 4 trial of aldafermin in patients with compensated cirrhosis
(liver fibrosis stage 4 or F4) due to NASH at AASLD The Liver
Meeting® in November 2023. ALPINE 4 met its primary endpoint, with
aldafermin 3 mg demonstrating a statistically significant reduction
in ELF score compared to placebo at 48 weeks of treatment. Although
ALPINE 4 was not statistically powered for the secondary endpoint
of histological fibrosis improvement of ≥1-stage (NASH Clinical
Research Network, or CRN, criteria), a dose-dependent trend in
fibrosis improvement was observed.
- Announced positive data from a Phase 2 investigator-sponsored
trial of aldafermin for the treatment of patients with
diarrhea-predominant irritable bowel syndrome (IBS-D) and bile acid
malabsorption (BAM) in May 2023 at Digestive Disease Week 2023.
Aldafermin demonstrated statistically significant reductions in
serum 7αC4 (a marker of bile acid synthesis) and fecal bile acids
versus placebo in patients with idiopathic BAM with IBS-D.
Key 2024 Priorities and Anticipated
Milestones
- Complete enrollment in the Phase 1 Part 1b cohort evaluating
the combination of NGM707 and pembrolizumab; provide an update in
mid-2024.
- Continue discussions with the FDA on the design of a potential
registrational trial of aldafermin for the treatment of PSC and
provide an update in the first half of 2024; plan to initiate
enrollment by the end of 2024, contingent upon reaching agreement
with the FDA on trial design and additional capital
availability.
- Plan to initiate a reproductive toxicology study of NGM120 for
the treatment of hyperemesis in 2024, subject to ongoing
discussions with the FDA.
- Continue exploring partnering opportunities across the full NGM
Bio product candidate and research portfolio. NGM Bio may further
develop other product candidates in its pipeline, pending
partnering and/or the availability of additional capital.
NGM Bio plans to post an updated corporate presentation on the
Investor Relations section of NGM Bio’s website
at www.ir.ngmbio.com.
About NGM Bio
NGM Bio is focused on discovering and developing novel,
life-changing medicines for people whose health and lives have been
disrupted by disease. NGM Bio’s biology-centric drug discovery
approach aims to seamlessly integrate interrogation of complex
disease-associated biology and protein engineering expertise to
unlock proprietary insights that are leveraged to generate
promising product candidates and enable their rapid advancement
into proof-of-concept studies. All therapeutic candidates in the
NGM Bio pipeline have been generated by its in-house discovery
engine, always led by biology and motivated by unmet patient need.
Visit us at www.ngmbio.com for more information.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme
Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA
Abbreviations (in Alphabetical Order)
F4=Fibrosis stage 4; ILT2=Immunoglobin-Like Transcript 2;
ILT3=Immunoglobin-Like Transcript 3; ILT4=Immunoglobin-Like
Transcript 4; LAIR1=Leukocyte-Associated Immunoglobulin-Like
Receptor 1; MSS=Microsatellite stable; NASH=nonalcoholic
steatohepatitis
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 “support”, “aims,” “anticipates,” “believe,”
“may,” “plans,” “potential,” “promising,” “proposed” 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: NGM Bio’s evolved strategy for aldafermin and NGM120
and focus on rare conditions with unmet needs, and NGM Bio’s belief
that this strategy has the greatest potential to deliver
nearer-term impact and value creation; discussions with the FDA
regarding the design of a potential registrational trial of
aldafermin in PSC, including the proposed use of surrogate
endpoints for potential accelerated approval; NGM Bio’s belief that
the large body of clinical data supports aldafermin’s
differentiated potential to address the bile acid dysregulation
underpinning PSC; the potential of aldafermin as an engineered
FGF19 analog to address the bile acid dysregulation underpinning
PSC; the potential of biomarkers of fibrosis, like ELF, to predict
clinical outcome in patients with PSC; the potential of NGM120 to
treat hyperemesis; NGM Bio’s potential exploration of NGM120 in a
planned proof-of-concept study for the treatment of hyperemesis,
including ongoing discussions with the FDA on an acceptable
toxicology package; the therapeutic potential of, potential
indications for and/or planned and continued development of the
product candidates in NGM Bio’s pipeline, including NGM707,
aldafermin, NGM120, NGM831 and NGM438; the planned timing of
initiation, enrollment, data readouts and results of NGM Bio’s
clinical trials; NGM Bio’s continued pipeline development,
including identification and engagement of third-party partners for
potential future business development arrangements (“BD
Arrangements”) to determine further development of programs across
the full NGM Bio product candidate and research portfolio; and
other statements that are not historical fact. Because such
statements deal with future events and are based on NGM Bio’s
current expectations, they are subject to various risks and
uncertainties, and actual results, performance or achievements of
NGM Bio 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
shift in NGM Bio’s strategy and investor perception thereof; the
costly and time-consuming pharmaceutical product development
process and the uncertainty of clinical success; risks related to
failure or delays in successfully initiating, enrolling, reporting
data from or completing clinical studies, as well as the risks that
results obtained in preclinical or clinical trials to date may not
be indicative of results obtained in future trials and that interim
topline and preliminary results of clinical trials may change as
more participant data becomes available and are subject to audit
and verification procedures, which could result in material changes
in the final data and such interim topline and preliminary results
may not be predictive of final results or results obtained in
future trials; the lack of regulatory clarity regarding acceptable
surrogate endpoints for PSC and related development uncertainty;
the vulnerable patient population experiencing hyperemesis and
risks associated with clinical trials on such patient population;
uncertainties inherent in the preclinical development process of
NGM120 in hyperemesis, including that NGM120 in hyperemesis may
never reach clinical development; NGM Bio’s ability to identify,
attract and engage third-party partners for BD Arrangements; the
time-consuming and uncertain regulatory approval process; NGM Bio’s
reliance on third-party manufacturers for its product candidates
and the risks inherent in manufacturing and testing pharmaceutical
products; the sufficiency of NGM Bio’s cash resources and
anticipated cash runway, including the risk that NGM Bio could
utilize its available capital resources sooner than it currently
expects, and its need for additional capital to pursue further
development of its product candidates, including the additional
capital necessary for NGM Bio to pursue further development of
aldafermin in PSC and NGM120 in hyperemesis; macroeconomic
conditions (such as the impacts of global geopolitical conflict,
global economic slowdown, increased inflation, high interest rates
and recent and potential future bank failures); and other risks and
uncertainties affecting NGM Bio and its development programs,
including those discussed in the section titled “Risk Factors” in
NGM Bio’s Quarterly Report on Form 10-Q for the quarter ended
September 30, 2023 filed with the United States Securities and
Exchange Commission (“SEC”) on November 2, 2023 and future filings
and reports that NGM Bio makes from time to time with the SEC.
Except as required by law, NGM Bio 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: |
Media
Contact: |
ir@ngmbio.com |
media@ngmbio.com |
NGM Biopharmaceuticals (NASDAQ:NGM)
Historical Stock Chart
From Nov 2024 to Dec 2024
NGM Biopharmaceuticals (NASDAQ:NGM)
Historical Stock Chart
From Dec 2023 to Dec 2024