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 reported positive
top-line results from the Phase 2a LIFT clinical trial of TERN-101,
a liver-distributed farnesoid X receptor (FXR) agonist for the
treatment of patients with NASH.
The LIFT study is a multicenter, randomized, double-blind,
placebo-controlled, parallel-group, Phase 2a clinical trial to
evaluate the safety, tolerability, efficacy, and pharmacokinetics
of orally-administered TERN-101 tablets at doses of 5 mg, 10 mg and
15 mg in 100 adult patients with presumed non-cirrhotic
non-alcoholic steatohepatitis (NASH). The primary objective of the
clinical trial was to evaluate the safety and tolerability of
TERN-101 over 12 weeks of treatment plus a four-week post-treatment
follow-up period. Secondary endpoints included percent change from
baseline in ALT levels and plasma pharmacokinetics of TERN-101.
Exploratory efficacy endpoints included changes in liver
fibro-inflammation measured by MRI corrected T1 (cT1), liver fat
content by MRI proton density fat fraction (MRI-PDFF),
pharmacodynamic parameters, and serum NASH biomarkers.
In the LIFT trial, TERN-101 was generally well tolerated with a
similar incidence of adverse events (AEs) across treatment groups.
All treatment-related adverse events were mild/moderate with no
apparent dose relationship. There were no treatment-related serious
adverse events, and no patient discontinued TERN-101 due to any
adverse event including pruritus. The most frequent
treatment-emergent adverse events included pruritus, headache,
constipation, diarrhea, decreased appetite and dizziness. Pruritus
was reported in four patients (16%) in the 5 mg TERN-101 arm, three
patients (11.5%) in the 10 mg TERN-101 arm, four patients (17.4%)
in the 15 mg TERN-101 arm and no patients in the placebo group.
Three pruritus cases were Grade 2 (widespread and intermittent);
the rest were Grade 1 (mild or localized). Notably, there were no
Grade 3 (widespread and constant) pruritus events and no
discontinuations due to pruritus. Most pruritus cases resolved
during continued TERN-101 treatment.
No change in LDL cholesterol was observed in patients in the 5
mg and 10 mg TERN-101 arms as compared to placebo (Week 12 mean
change: 4.8% for placebo, 6.7% for 5 mg TERN-101, 3.2% for 10 mg
TERN-101, not significant). Statistically significant LDL changes
were observed only in the 15 mg arm (Week 12 mean change: 15.9%,
p<0.05). Significant decreases in HDL cholesterol were observed
in all TERN-101 dose groups at Week 4 and Week 8 but returned
toward baseline in the 5 mg and 10 mg dose groups without
differences from placebo at Week 12. Decreases in HDL were
significantly different from placebo for the 15 mg group at all
observed timepoints through Week 12.
Multiple efficacy biomarkers of NASH, including corrected T1
(cT1), MRI-PDFF and ALT, were evaluated in the LIFT Study:
- Mean changes in cT1 at Week 12 were
-0.8 msec for placebo, -38.0 msec (p=0.033) for the 5 mg arm, -57.7
msec (p=0.002) for the 10 mg arm, and -74.0 msec (p<0.001) for
the 15 mg arm. Improvements of at least 80 msec in cT1 were
observed in a significant proportion of patients in the 5 mg and 10
mg groups at Week 12 (as compared to placebo). Significant
decreases in cT1 were also observed at Week 6 for all dose groups.
cT1 is a magnetic resonance-based imaging test measuring free-water
content in liver tissue, which has shown a strong correlation with
inflammation and fibrosis histology and clinical outcomes in
patients with liver disease.
- Mean relative changes in MRI-PDFF
were -8.4% (placebo), -15.1% (5 mg), -19.7% (10 mg), and -12.9% (15
mg) at Week 12. Mean relative changes in MRI-PDFF were significant
at Week 6 for the 10 mg and 15 mg dose groups compared to placebo,
although these changes were not statistically significant at Week
12. MRI-PDFF is an imaging marker that measures liver fat
content.
- Mean percent changes in ALT at Week
12 were -5.3% (placebo), -2.6% (5 mg), -18% (10 mg), and -13.2% (15
mg).
- No discernable trends were observed
in initial analyses of the enhanced liver fibrosis (ELF) score,
CK-18 and Pro-C3.
“NASH is a complex multifaceted condition, making it difficult
to use just one target to treat the disease. The LIFT data are
exciting because we see improvement in key non-invasive tests
associated with disease severity along with an attractive safety
profile with no discontinuations due to side effects,” said Rohit
Loomba, MD, MHSc, director of the UC San Diego NAFLD Research
Center and director of Hepatology at UC San Diego School of
Medicine. “The results add to the growing body of evidence showing
the promise of TERN-101 as a multi-modal therapy to treat the
multiple facets of this disease.”
Summary of Week 12 Analysis
|
|
TERN-101 tablet formulation(once-daily) |
Mean change (baseline to week 12) |
PlaceboN=26 |
5 mgN=25 |
10 mgN=26 |
15 mgN=23 |
LDL-c (%) |
4.8% |
6.7% |
3.2% |
15.9%* |
HDL-c (%) |
2.4% |
-2.6% |
-0.5% |
-8.2%* |
ALT (%) |
-5.3% |
-2.6% |
-18.0% |
-13.2% |
AST (%) |
0.3% |
1.4% |
-12.9% |
-4.2% |
GGT (%) |
8.1% |
-15.6%* |
-34.2% *** |
-17.6%* |
ALP (%) |
0.2% |
2.5% |
9.4% |
24.4%*** |
cT1 (msec)+ |
-0.8 |
-38.0* |
-57.7** |
-74.0*** |
MRI-PDFF relative change (%) |
-8.4% |
-15.1% |
-19.7% |
-12.9% |
*p<0.05, **p<0.01, ***p<0.001 versus placebo+ cT1 was
conducted only at available sites (n=22, 24, 20 and 18 for placebo,
5 mg, 10 mg and 15 mg groups, respectively).
“We are encouraged by the positive effects of well tolerated
doses of TERN-101 on cT1 relaxation time, a biomarker correlated
with improved clinical outcomes. LIFT is the first controlled NASH
trial to show significant cT1 improvement as early as Week 6.
TERN-101 has the potential to be an effective component of a NASH
treatment regimen. We look forward to advancing this program in our
planned combination therapy trial,” said Erin Quirk, MD, president,
chief medical officer and head of research and development at
Terns. “I would like to thank all those who have helped us rapidly
advance the LIFT Study, including our outstanding team of
investigators and clinical sites, the members of the Terns team,
and the patients who participated in the study.”
Terns plans to submit data from the LIFT Study to an upcoming
scientific conference. Based on these positive results, Terns
continues to plan a combination trial of TERN-101 together with
TERN-501, the Company’s thyroid hormone receptor beta agonist
(THR-β) also in development for the treatment of NASH. The multiple
ascending dose portion of the TERN-501 Phase 1 trial started in
June 2021, and top-line data from the trial is expected in the
second half of 2021. The combination trial of TERN-101 and TERN-501
is expected to start in the first half of 2022.
Investor Conference Call
Terns will host an update call for investors today, June 14,
2021, beginning at 8:30 a.m. ET. The webcast of the conference call
will be made available at
https://edge.media-server.com/mmc/p/2gsxxmta. To access the call
via dial-in, please dial 1-833-665-0612 (U.S./Canada toll-free) or
1-929-517-0403 (international) using the conference code 7587739. A
replay of the call will also be available on the investor page of
the Terns website for 30 days.
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. Clinical
studies of other FXR agonists have demonstrated significant
histological NASH improvements but have also resulted in pruritus,
adverse lipid changes and discontinuations.
About Terns Pharmaceuticals
Terns 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 therapeutic potential of TERN-101; the
potential utility and progress of the Company’s product candidates
in NASH, including the clinical utility of the data from and the
endpoints used in the Phase 2a LIFT Study of TERN-101; expectations
of timing and potential results of the Company’s clinical trials;
the Company’s clinical development plans and activities, including
the development plans for TERN-101 in combination with TERN-501 and
potentially other product candidates; the Company’s expectations
regarding the profile of its product candidates, including
tolerability, safety, metabolic stability and pharmacokinetic
profile; the Company’s ability to continue to execute on its
clinical strategy and plans; and the sufficiency of our cash on
hand to fund our operating expenses and capital expenditures. 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, future
trial results, 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 Annual Report on Form
10-K for the year ended December 31, 2020 and Quarterly Report on
form 10-Q for the three months ended March 31, 2021. Except as
required by law, the Company undertakes no obligation to update
publicly any forward-looking statements for any reason.
Contacts for Terns
Investors Justin
Ng investors@ternspharma.com
Media Jenna UrbanBerry & Company
Public Relationsmedia@ternspharma.com
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