Terns Announces Initiation of Dosing in Phase 1 Clinical Trial of TERN-501, its THR-Beta Agonist in Development for the Treat...
March 22 2021 - 6:35AM
Terns Pharmaceuticals, Inc. (“Terns” or the “Company”) (Nasdaq:
TERN), a clinical-stage biopharmaceutical company developing a
portfolio of small-molecule single-agent and combination therapy
candidates for the treatment of non-alcoholic steatohepatitis
(NASH) and other chronic liver diseases, today announced the
initiation of dosing in a Phase 1 clinical trial evaluating
TERN-501, a selective thyroid hormone receptor beta (THR-β) agonist
with high metabolic stability, enhanced liver distribution and
greater selectivity for THR-β when compared with other THR-β
agonists in development. Terns expects to report initial top-line
data from the trial in the second half of 2021.
“We are excited to initiate the first-in-human study of TERN-501
and are proud of the hard work our team has done to advance three
NASH programs of different therapeutic classes into clinical
development. We believe each of our single-agent programs has
improved upon a validated mechanism of action for the treatment of
NASH,” said Erin Quirk, M.D., President and Chief Medical Officer
of Terns. “It has always been our goal to rapidly advance
monotherapy candidates with high potential to be used in
combination regimens. Furthermore, initiating first-in-human dosing
of TERN-501 advances Terns closer to our goal of starting a Phase
2a clinical proof-of-concept trial evaluating a combination of
TERN-101, our liver-distributed farnesoid X receptor agonist
currently in Phase 2a development, and TERN-501 in the first half
of 2022.”
This Phase 1 clinical trial is being conducted in the United
States and is expected to enroll approximately 90 healthy
participants. The trial is designed to incorporate both single
ascending dose and multiple ascending dose cohorts in which the
safety, tolerability and pharmacokinetics of TERN-501 will be
assessed, as well as pharmacodynamic biomarkers such as sex hormone
binding globulin and serum lipid levels that could serve as an
early marker of THR-β target engagement.
About TERN-501TERN-501 is a thyroid hormone
receptor beta (THR-β) agonist with high metabolic stability,
enhanced liver distribution and greater selectivity for THR-β
compared to other THR-β agonists in development. Agonism of THR-β
increases fatty acid metabolism via mitochondrial oxidation and
affects cholesterol synthesis and metabolism. As a result, THR-β
stimulation has the ability to reduce hepatic steatosis and improve
serum lipid parameters including LDL cholesterol and triglycerides.
In vivo NASH studies in a rodent model have demonstrated that
low-doses of TERN-501 achieved complete resolution of steatosis and
reductions in serum lipids, hepatic inflammation and fibrosis.
TERN-501 has high liver distribution and is 23-fold more selective
for THR-β than for THR-α activation in a cell free assay, thereby
minimizing the risk of cardiotoxicity and other off-target effects
associated with non-selective THR stimulation. Finally, TERN-501
has been designed to be metabolically stable and is therefore
expected to have little pharmacokinetic variability and a low
clinical dose, making it an attractive candidate for use in
fixed-dose combinations for NASH treatment.
About TERN-101 TERN-101 is a
liver-distributed, non-bile acid FXR agonist that has demonstrated
a differentiated tolerability profile and improved target
engagement, likely due to its sustained FXR activation in the liver
but only transient FXR activation in the intestine. FXR is a
nuclear receptor primarily expressed in the liver, intestine and
kidneys. FXR regulates hepatic expression of various genes involved
in lipid metabolism, inflammation and fibrosis. Studies have
demonstrated that there is minimal overlap between liver and
intestine FXR binding sites, indicating potentially a high degree
of tissue-specific FXR function. Clinical studies of other FXR
agonists have demonstrated significant histological NASH
improvements but have also resulted in pruritus and adverse lipid
changes. These tolerability issues have generally been observed in
Phase 1 clinical trials of other FXR agonists in development and
have been regarded as dose-limiting toxicities, which are
suboptimal for patients and can lead to treatment discontinuation.
However, in all four Phase 1 clinical trials of TERN-101, none of
the 119 subjects who received TERN-101 reported pruritus, and the
serum lipid profiles among TERN-101 recipients were similar to
placebo recipients even at high doses.
About Terns PharmaceuticalsTerns
Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company
developing a portfolio of small-molecule single-agent and
combination therapy candidates for the treatment of non-alcoholic
steatohepatitis, or NASH, and other chronic liver diseases. Terns’
programs are based on clinically validated and complementary
mechanisms of action to address the multiple hepatic disease
processes of NASH in order to drive meaningful clinical benefits
for patients. For more information, please visit
www.ternspharma.com.
Cautionary Note Regarding Forward-Looking
Statements
This press release contains forward-looking statements about
Terns Pharmaceuticals, Inc. (the “Company,” “we,” “us,” or “our”)
within the meaning of the federal securities laws, including those
related to the Company’s expectations of timing and potential
results of the Company’s clinical trials and other development
activities and the potential utility and progress of the Company’s
product candidates in NASH. All statements other than statements of
historical facts contained in this press release, including
statements regarding the Company’s strategy, future financial
condition, future operations, projected costs, prospects, plans,
objectives of management and expected market growth, are
forward-looking statements. In some cases, you can identify
forward-looking statements by terminology such as “aim,”
“anticipate,” “assume,” “believe,” “contemplate,” “continue,”
“could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,”
“may,” “objective,” “plan,” “positioned,” “potential,” “predict,”
“seek,” “should,” “target,” “will,” “would” and other similar
expressions that are predictions of or indicate future events and
future trends, or the negative of these terms or other comparable
terminology. The Company has based these forward-looking statements
largely on its current expectations, estimates, forecasts and
projections about future events and financial trends that it
believes may affect its financial condition, results of operations,
business strategy and financial needs. In light of the significant
uncertainties in these forward-looking statements, you should not
rely upon forward-looking statements as predictions of future
events. These statements are subject to risks and uncertainties
that could cause the actual results and the implementation of the
Company’s plans to vary materially, including the risks associated
with the initiation, cost, timing, progress and results of the
Company’s current and future research and development activities
and preclinical studies and clinical trials. In particular, the
impact of the COVID-19 pandemic on the Company’s ability to
progress with its research, development, manufacturing and
regulatory efforts, including the Company’s clinical trials for its
product candidates, will depend on future developments that are
highly uncertain and cannot be predicted with confidence at this
time, such as the ultimate duration of the pandemic, travel
restrictions, quarantines, social distancing and business closure
requirements in the United States and in other countries,
and the effectiveness of actions taken globally to contain and
treat the disease. These risks are not exhaustive. For a detailed
discussion of the risk factors that could affect the Company’s
actual results, please refer to the risk factors identified in the
Company’s SEC reports, including but not limited to its prospectus
dated February 4, 2021. Except as required by law, the Company
undertakes no obligation to update publicly any forward-looking
statements for any reason.
US Media Contact:Investor Relations
Contact:Mark Vignola investors@ternspharma.com
Media Contact: Cory
Tromblee media@ternspharma.com
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