-Successful Phase 1 Clinical Trial Garners
Late-Breaking ADA Presentation and Supports Advancement to Phase 2
Development-
Zafgen, Inc. (Nasdaq:ZFGN) today announced the presentation of new
data for ZGN-1061, the Company's second-generation MetAP2
inhibitor, in two late-breaking posters at the American Diabetes
Association's 77th Annual Scientific Sessions (ADA). The data show
that ZGN-1061 treatment causes improvements across multiple
metabolic measures consistent with MetAP2 inhibition, demonstrates
rapid drug absorption and clearance, and has a favorable safety
profile with no evidence of prothrombotic effects. The poster
presentations, numbers 143-LB and 144-LB, are available on the
“Events & Presentations” section of the Zafgen website.
“The results presented at ADA highlight the favorable safety and
pharmacokinetic profile of ZGN-1061 and demonstrate its potential
to positively impact glycemic control, weight loss and other
metabolic parameters,” stated Thomas Hughes, Ph.D., President and
Chief Executive Officer of Zafgen. “Based on the data generated to
date, as well as our deep experience with MetAP2 inhibition, we
believe ZGN-1061 offers a novel opportunity to address the unmet
medical need of patients failing other therapies and who are at the
challenging interface of type 2 diabetes and obesity.”
Phase 1 Clinical Trial Data
Poster 144-LB, “Single and Multiple Dose Evaluation of a Novel
MetAP2 Inhibitor: Results of a Randomized, Double-Blind,
Placebo-Controlled Clinical Trial,” details the full results from
the Phase 1 clinical trial of ZGN-1061, including new efficacy data
related to secondary endpoints. The multiple ascending dose (MAD)
phase evaluated twice-weekly administration of ZGN-1061 in
overweight or obese patients (ZGN-1061 N=22, placebo N=7; average
BMI of 33 kg/m2). Patients in the MAD phase were domiciled while
receiving treatment and were subjected to inpatient safety
monitoring for most of the clinical trial's 28-day
duration. Data from the clinical trial are highlighted
below:
- As previously reported, on average, patients treated with
ZGN-1061 for four weeks lost weight relative to placebo-treated
patients (-4.6 lbs, -2.2 lbs, and -3.8 lbs for 0.2 mg, 0.6 mg, and
1.8 mg, respectively vs. -0.51 lbs for placebo).
- Body weight loss was steady and progressive during treatment
with ZGN-1061 and rebounded post-treatment, supporting a drug
effect.
- ZGN-1061 produced improvements in waist circumference relative
to placebo. In addition, treatment with ZGN-1061 resulted in a
trend for reduced food intake relative to placebo.
- The clinical trial demonstrated trends for reductions in
LDL-cholesterol, and high-sensitivity C-reactive protein (hsCRP).
Notably, there were greater reductions in mean LDL-cholesterol and
hsCRP in ZGN-1061-treated subjects with abnormally elevated LDL or
hsCRP at baseline.
- The clinical trial also showed a trend for reductions in leptin
and increases in adiponectin with ZGN-1061 compared to placebo,
reflective of favorable changes in adipose function and
signaling.
- ZGN-1061 is rapidly metabolized and cleared following
administration, with a much shorter half-life than beloranib,
minimizing exposure to the compound while driving desired metabolic
effects.
- Single and repeat doses of ZGN-1061 were generally safe and
well tolerated. There were no severe adverse events (AEs), no
serious AEs (SAEs), and no AEs leading to early withdrawal from the
clinical trial.
- As previously reported, there was no prothrombotic effect
observed with ZGN-1061. No treatment emergent venous
thromboembolisms (VTEs), no clinically meaningful D-dimer
elevations indicative of thrombosis and no elevations in mean
D-dimer levels were observed in the dosing groups compared to
baseline or placebo. There were no clinically significant
changes in coagulation laboratory parameters or other key
biomarkers of interest, including von Willebrand factor and soluble
thrombomodulin.
“The data emerging from our ZGN-1061 program are quite
encouraging, and reinforce our confidence in the candidate as we
advance toward initiating our Phase 2 clinical trial in patients
with type 2 diabetes who are obese, in the second half of 2017,”
said Dennis Kim, M.D., Chief Medical Officer of Zafgen. “We are
particularly impressed with the optimized safety profile of
ZGN-1061, as well as new preclinical data supporting the potential
to impact both glycemic control and insulin resistance, consistent
with MetAP2 inhibition.”
Preclinical Efficacy and Safety Differentiation
Data
Preclinical data presented at the meeting demonstrated that
ZGN-1061 showed similar effects on diabetes, obesity, and other
metabolic endpoints, but with a greatly improved safety profile in
comparison to the Company’s prior development compound, beloranib.
In poster 143-LB, “The MetAP2 Inhibitor ZGN-1061 Improves Glycemia
and has Weight Loss Efficacy with an Improved Safety Profile in
Preclinical Models,” Zafgen presented results from a study
comparing ZGN-1061, beloranib and vehicle in a mouse model of
obesity and insulin resistance, as well as in vitro and in vivo
data demonstrating the impact of ZGN-1061 versus beloranib on
multiple thrombotic markers. Highlights of the data include:
- ZGN-1061 showed statistically significant improvements in
glycemic control, insulin sensitivity, body weight, body fat,
lipids and cardiometabolic biomarkers compared to vehicle, and
these improvements were comparable to those seen for
beloranib.
- ZGN-1061 is rapidly metabolized and cleared following
administration, with a much shorter half-life than beloranib,
minimizing exposure to the compound while driving desired metabolic
effects.
- ZGN-1061 displays a reduced impact on endothelial cells
compared to beloranib, and on several thrombotic markers, including
P21, thrombomodulin, and plasminogen activator inhibitor-1 (PAI-1),
in vitro, as well as thrombin time and D-dimer in vivo.
- ZGN-1061 has improved safety margins for morbidity and
coagulopathy, with a 200-fold margin for ZGN-1061 compared to
approximately 4-fold for a clinically equivalent dose of
beloranib.
About ZGN-1061
ZGN-1061 is a fumagillin-class, injectable small molecule second
generation MetAP2 inhibitor that was advanced into development due
to its unique properties that maximize impact on metabolic
parameters relevant to the treatment of type 2 diabetes and other
related metabolic disorders. In preclinical studies, ZGN-1061 has
demonstrated promising efficacy in animal models of type 2 diabetes
and obesity, with an improved pharmacokinetic profile and safety
margin relative to previous molecules in the MetAP2 class. As
demonstrated clinically for MetAP2 inhibitors, ZGN-1061 is
anticipated to improve glycemic control while also helping to
restore balance to fat metabolism, enabling calories to once again
be used as a productive energy source, leading to improved
metabolic control and long-term weight loss. Zafgen recently
completed its first Phase 1 clinical trial of ZGN-1061, and is
planning to advance the compound to Phase 2 clinical testing in
patients with type 2 diabetes who are overweight or
obese. Zafgen holds exclusive worldwide rights for the
development and commercialization of ZGN-1061.
About Zafgen
Zafgen (Nasdaq:ZFGN) is a biopharmaceutical company dedicated to
significantly improving the health and well-being of patients
affected by metabolic diseases including type 2 diabetes and
obesity. Zafgen is focused on developing novel therapeutics that
treat the underlying biological mechanisms of metabolic diseases
through the MetAP2 pathway. Zafgen has pioneered the study of
MetAP2 inhibitors in both common and rare forms of obesity, and in
patients affected by type 2 diabetes. Zafgen's lead product
candidate is ZGN-1061, which is a novel, first-in-class,
subcutaneous injection. Zafgen aspires to improve the lives of
patients through targeted treatments and has assembled a team
accomplished in bringing therapies to patients affected by
metabolic diseases.
Safe Harbor Statement
Various statements in this release concerning Zafgen's future
expectations, plans and prospects, including without limitation,
Zafgen's expectations regarding the use of ZGN-1061 and other
MetAP2 inhibitors as treatments for metabolic diseases including
type 2 diabetes and obesity, ZGN-1061's improved safety margin,
including as it relates to pro-thrombotic characteristics, compared
to first generation MetAP2 inhibitors, such as over beloranib, and
Zafgen's expectations with respect to the timing and success of its
preclinical studies and clinical trials of ZGN-1061 and its other
product candidates, may constitute forward-looking statements for
the purposes of the safe harbor provisions under The Private
Securities Litigation Reform Act of 1995 and other federal
securities laws. Forward-looking statements can be identified by
terminology such as "anticipate," "believe,\" "could," "could
increase the likelihood," "estimate," "expect," "intend," "is
planned," "may," "should," "will," "will enable," "would be
expected," "look forward," "may provide," "would" or similar terms,
variations of such terms or the negative of those terms. Actual
results may differ materially from those indicated by these
forward-looking statements as a result of various important
factors, including, without limitation, Zafgen's ability to
successfully demonstrate the efficacy and safety of ZGN-1061 and
its other product candidates and to differentiate ZGN-1061 and its
other product candidates from first generation MetAP2 inhibitors,
such as beloranib, the preclinical and clinical results for
ZGN-1061 and its other product candidates, which may not support
further development and marketing approval, actions of regulatory
agencies, which may affect the initiation, timing and progress of
preclinical studies and clinical trials of its product candidates,
Zafgen's ability to obtain, maintain and protect its intellectual
property, Zafgen's ability to enforce its patents against
infringers and defend its patent portfolio against challenges from
third parties, competition from others developing products for
similar uses, Zafgen's ability to manage operating expenses,
Zafgen's ability to obtain additional funding to support its
business activities and establish and maintain strategic business
alliances and new business initiatives when needed, Zafgen's
dependence on third parties for development, manufacture,
marketing, sales and distribution of product candidates, the
outcome of litigation, and unexpected expenditures, as well as
those risks more fully discussed in the section entitled "Risk
Factors" in Zafgen's most recent Quarterly Report on Form 10-Q
filed with the Securities and Exchange Commission, as well as
discussions of potential risks, uncertainties, and other important
factors in Zafgen's subsequent filings with the Securities and
Exchange Commission. In addition, any forward-looking statements
represent Zafgen's views only as of today and should not be relied
upon as representing its views as of any subsequent date. Zafgen
explicitly disclaims any obligation to update any forward-looking
statements, whether as a result of new information, future events
or otherwise.
Media/Investor Relations Contact:
Zafgen, Inc.
Patricia Allen
Chief Financial Officer
617-648-9792
Argot Partners
Investor Relations
Laura Perry
212-600-1902
laura@argotpartners.com
Spectrum Science
Media Relations
Michelle Strier
202-587-2582
mstrier@spectrumscience.com
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