89bio, Inc. (Nasdaq: ETNB) today announced positive topline results
from its Phase 1b/2a trial with BIO89-100, an investigational FGF21
analog, in patients with nonalcoholic steatohepatitis (NASH). All
dose groups demonstrated significant reductions in liver fat at
week 13, with relative reductions up to 60% versus baseline and up
to 70% versus placebo, as measured by magnetic resonance imaging –
proton density fat factor (MRI-PDFF). A significant proportion of
subjects responded to therapy with up to 88% and 71% of subjects
achieving a ≥30% or a ≥50% reduction in liver fat versus baseline,
respectively. Treatment with BIO89-100 also resulted in significant
improvements in liver transaminases, with a 35 U/L decrease in ALT
from baseline in subjects with elevated baseline levels, and
reductions in ProC3, a marker of fibrosis. Importantly, BIO89-100
is the first FGF21 analog to show benefit in subjects with NASH
with every two-week dosing. BIO89-100 was well tolerated at
all doses with low incidence of adverse events that occurred in
≥10% of subjects and very low frequency of gastrointestinal (GI)
events relative to placebo.
The MRI-PDFF results are summarized in the table below:
|
|
BIO89-100 (once-weekly) |
BIO89-100 (once every two weeks) |
Measure |
Placebo (n= 19) |
3mg (n= 6) |
9mg (n= 12) |
18mg (n= 11) |
27mg (n= 10) |
18 mg (n= 14) |
36 mg (n= 9) |
Relative reduction/increase in liver fat vs. baseline |
+10% |
-37%** |
-50%** |
-36%** |
-60%** |
-43%** |
-50%** |
Relative reduction in liver fat vs. placebo |
|
-47%** |
-59%** |
-46%** |
-70%** |
-53%** |
-60%** |
Proportion of subjects with ≥30% relative reduction in liver
fat |
0% |
60%* |
82%** |
60%** |
86%** |
69%** |
88%** |
Absolute change in liver fat vs. baseline |
+1.4 |
-7.5%* |
-10%** |
-7.5%** |
-13.5%** |
-9.0%** |
-9.7%** |
*p<0.01; **p<0.001 vs. placebo. n based on subjects
randomized. Least square mean based on MRI analysis set (N=75) and
responder analysis based on subjects with MRI at Week 13. Levels of
liver fat in the BIO89-100 and placebo groups at baseline were
21.2% (on a pooled basis) and 21.8%, respectively. Baseline liver
fat levels and changes in liver fat were similar in
biopsy-confirmed NASH and phenotypical NASH subjects. “The robust
reductions in liver fat and key liver markers add to a growing body
of evidence demonstrating the promise of BIO89-100 for the
treatment of NASH and cardio-metabolic diseases,” 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 magnitude of ≥30% relative reduction in liver fat
has been shown in the literature to translate into higher odds of
histologic response and potential to deliver clinically meaningful
benefit to patients with NASH.”
BIO89-100 had a favorable safety and tolerability profile with
no deaths or serious adverse events related to treatment. The
frequency of GI events compared favorably to placebo with diarrhea
(BIO89-100 12.7% vs. placebo 22.2%) and nausea (BIO89-100 7.9% vs.
placebo 16.7%) being the only GI events occurring in ≥5% of
BIO89-100-treated subjects. The only treatment-related adverse
event that occurred in ≥10% of all BIO89-100-treated subjects was
mild, increased appetite (15.9%) consistent with other
investigational FGF21 analogs. No adverse effects on heart rate or
blood pressure were observed.
Treatment with BIO89-100 resulted in significant reductions in
triglycerides (up to 28%; p <0.05), non-HDL (up to 16%;
p<0.01) and LDL-C (up to 16%; p<0.05). Triglycerides were
reduced to a greater extent in subjects with elevated triglycerides
at baseline (TG≥200 mg/mL), and 53% of the BIO89-100 subjects in
this group normalized triglyceride levels versus 0% in the placebo
group. BIO89-100 also demonstrated significant increases in the
insulin-sensitizing hormone adiponectin (up to 61%; p<0.001).
This study was a randomized, double-blind, placebo-controlled,
multiple ascending dose-ranging trial in biopsy-proven NASH or
phenotypical NASH (PNASH) subjects. A total of 81 subjects were
randomized to receive weekly or every two-week dosing of BIO89-100
or placebo for up to 12 weeks. Key endpoints assessed were safety,
tolerability, and PK of BIO89-100 as well as change in liver fat
measured by MRI-PDFF and other metabolic markers.
“The favorable safety and tolerability profile of BIO89-100
together with potential best-in-class dosing regimen could be
important considerations for a NASH therapeutic given the chronic
and generally asymptomatic nature of the disease,” said Hank
Mansbach, MD, Chief Medical Officer, 89bio. “These factors,
combined with improvements in liver fat and metabolic markers,
unequivocally support advancing the clinical development of
BIO89-100 in NASH and reinforce our confidence in the severe
hypertriglyceridemia program. We plan to initiate our next trial in
NASH in the first half of 2021.”
“We are pleased with this data that highlight BIO89-100’s
promising clinical profile and its potential to be a leading FGF21
analog in a class with the potential to become a backbone treatment
approach for NASH,” said Rohan Palekar, Chief Executive
Officer, 89bio. “I would like to sincerely thank all of our
investigators, clinical sites, subjects, and employees who
supported the trial, especially amid a pandemic that has severely
impacted the global healthcare system in an unprecedented manner.”
Conference Call/Webcast Details89bio will host
a conference call and webcast with slides at 8:30am ET (5:30am PT)
this morning, September 14. Details for the live conference call
are as follows: Domestic – (833) 570-1145; International – (914)
987-7092; and Passcode - 5064866. To access the live webcast and
slides, please visit “Events and Presentations” under the
“Investors” section of 89bio’s website at
https://ir.89bio.com/events-and-presentations. Following the live
audio webcast, a replay will be available on the company’s website
for 90 days.
About NASH NASH is the most advanced stage of
nonalcoholic fatty liver disease (NAFLD). It is a complex metabolic
disorder that causes fat buildup in the liver, as well as
inflammation and eventually fibrosis, and it can worsen to
cirrhosis and liver failure. NASH affects more than 16 million
adults in the United States, and by 2030 its prevalence is
predicted to increase by 63 percent. The exact cause of NASH is
unknown, but it is commonly found in people with obesity and type 2
diabetes. While there are currently no approved treatments, the
biopharmaceutical industry is actively involved in addressing this
unmet medical need.
About the Phase 1b/2a Study This clinical study
was a multicenter, randomized, double-blind, placebo-controlled,
multiple ascending dose-ranging trial. It was designed to assess
the safety, tolerability, and PK properties of BIO89-100 as well as
change in liver fat measured by MRI-PDFF and key biomarker
assessments in subjects with biopsy-proven NASH with fibrosis or
patients with phenotypical NASH (PNASH). PNASH was defined as
patients with steatosis greater than 10% who have central obesity
and Type 2 diabetes or central obesity and evidence of liver
injury. Both populations that were enrolled had similar disease
characteristics at baseline. A total of 81 subjects were randomized
to receive weekly or every two weeks subcutaneous dosing of
BIO89-100 or placebo for up to 12 weeks. About
BIO89-100 BIO89-100 is a glycoPEGylated analog of FGF21
being developed for the treatment of NASH. 89bio has optimally
engineered BIO89-100 using a proprietary glycoPEGylation technology
to balance efficacy and longer dosing interval. Recent Phase 1b/2a
data show BIO89-100 demonstrated a favorable safety and
tolerability profile and robust reductions in liver fat and key
lipid markers when dosed weekly or once every two weeks. BIO89-100
is also being developed for the treatment of severe
hypertriglyceridemia (SHTG) and is currently in a Phase 2
trial.
About 89bio 89bio is a clinical-stage
biopharmaceutical company focused on the development and
commercialization of innovative therapies for the treatment of
liver and cardio-metabolic diseases. The company's lead product
candidate is BIO89-100, is a specifically engineered glycoPEGylated
analog of FGF21. BIO89-100 is being developed for the treatment of
NASH and severe hypertriglyceridemia (SHTG). 89bio is headquartered
in San Francisco with operations in Herzliya, Israel. For more
information, visit www.89bio.com.
Forward-looking StatementsCertain statements in
this press release may constitute "forward-looking statements"
within the meaning of the federal securities laws, including, but
not limited to, 89bio’s expectations and guidance regarding its
business plans and objectives for BIO89-100, including the
therapeutic potential and clinical benefits thereof, as well as the
safety and tolerability of BIO89-100 and future clinical
development plans; 89bio’s statements regarding the Phase 1b/2a
Trial of BIO89-100; and the potential impact of COVID-19 on patient
retention, strategy, future operations and clinical trials,
including the anticipated timing of the next trial in NASH. Words
such as "may," "might," "will," "objective," "intend," "should,"
"could," "can," "would," "expect," "believe," "design," "estimate,"
"predict," "potential," "develop," "plan" or the negative of these
terms, and similar expressions, or statements regarding intent,
belief, or current expectations, are forward looking statements.
While 89bio believes these forward-looking statements are
reasonable, undue reliance should not be placed on any such
forward-looking statements, which are based on information
available to us on the date of this release. These forward-looking
statements are based upon current estimates and assumptions and are
subject to various risks and uncertainties (including, without
limitation, those set forth in 89bio's filings with the SEC), many
of which are beyond 89bio's control and subject to change. Actual
results could be materially different. Risks and uncertainties
include: expectations regarding the timing and outcome of 89bio’s
initiation of the next trial in NASH; 89bio’s ability to execute on
its strategy; positive results from a clinical study may not
necessarily be predictive of the results of future or ongoing
clinical studies; regulatory developments in the United States; the
effect of the COVID-19 pandemic on 89bio’s clinical trials and
business operations, and the impact of general economic, health,
industrial or political conditions in the United States or
internationally; and other risks and uncertainties identified in
89bio's Annual Report on Form 10-K for the year ended December 31,
2019 and its Quarterly Report on Form 10-Q for the quarter ended
June 30, 2020 and other subsequent disclosure documents filed with
the SEC. 89bio claims the protection of the Safe Harbor contained
in the Private Securities Litigation Reform Act of 1995 for
forward-looking statements. 89bio expressly disclaims any
obligation to update or alter any statements whether as a result of
new information, future events or otherwise, except as required by
law.
Investor Contact: Ryan Martins Chief Financial Officer
investors@89bio.com
Media Contact: Lori Rosen LDR Communications 917-553-6808
lori@ldrcommunications.com
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