Enanta Pharmaceuticals, Inc., (NASDAQ: ENTA), a research and
development-focused biotechnology company dedicated to creating small
molecule drugs in the infectious disease field, announced today that new
Phase 2b data related to ABT-450, Enanta's lead HCV protease inhibitor
identified in its ongoing collaboration with AbbVie, as well as new
preclinical data on Enanta's proprietary cyclophilin inhibitor, EDP-546,
will be presented at the International Liver Congress, (ILC), which is
the 48th Annual Meeting of the European Association for the
Study of the Liver (EASL) taking place in Amsterdam April 24-28, 2013.
Results from "Aviator," AbbVie's Phase 2b clinical trial of ABT-450
combined with two of AbbVie's proprietary investigational direct-acting
antivirals (DAAs), for the treatment of hepatitis C virus (HCV)
infection, continue to demonstrate high sustained viral response (SVR)
rates against genotype 1 HCV, across patient types. SVR rates of 96% to
99% after 12 weeks of treatment were achieved in patients new to
treatment (naïve) and 93% in patients who had previously failed
treatment with pegylated interferon and ribavirin (null responders). In
addition, similarly high SVR rates over 90% observed after 24 weeks of
treatment in the Phase 2b trial reinforce the adequacy of the 12-week
treatment duration for the investigational interferon-free, triple DAA
combination. The triple-DAA combination is currently being studied in
Phase 3 clinical trials. Data from the "Aviator" study will be presented
during the official ILC press conference in Amsterdam on Wednesday,
April 24 at 11:00 am CEST and also in an oral presentation on Thursday,
April 25.
About Study M11-652 (Aviator)
The objective of this Phase 2b study was to assess the safety, and
efficacy of ABT-450/r (dosed 100/100 to 200/100mg once daily), ABT-267
(25mg once daily), ABT-333 (400mg twice daily) and ribavirin in
non-cirrhotic, treatment-naïve patients and prior
peg-interferon/ribavirin null responders administered for 8, 12 or 24
weeks. Enrollment was open to GT1-infected patients regardless of IL28B
host genotype, and ribavirin dosing was weight-based.
A summary of key data from the trial is below:
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Treatment-Naïve
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Null Responders
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Duration
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8 weeks
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12 weeks
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24 Weeks
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12 weeks
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24 weeks
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Regimen
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ABT-450/r
ABT-267
ABT-333
RBV
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ABT-450/r
ABT-333
RBV
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ABT-450/r
ABT-267
RBV
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ABT-450/r
ABT-267
ABT-333
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ABT-450/r
ABT-267
ABT-333
RBV
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ABT-450/r
ABT-267
ABT-333
RBV
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ABT-450/r
ABT-267
RBV
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ABT-450/r
ABT-267
ABT-333
RBV
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ABT-450/r
ABT-267
ABT-333
RBV
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Number dosed
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80
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41
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79
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79
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79
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80
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45
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45
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43
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Breakthrough
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0
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1
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1
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1
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0
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0
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0
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3
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1
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Relapse
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10
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4
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8
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5
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1
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2
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5
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0
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0
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SVR12 (ITT)
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89%
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85%
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91%
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90%
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99%
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93%
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89%
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93%
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98%
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SVR24 (ITT)
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88%
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83%
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89%
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87%
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96%
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90%
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89%
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93%
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95%
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For the 12-week triple-DAA regimen with ribavirin that is being studied
in the Phase 3 trials, these Phase 2b Aviator data show:
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99% of treatment-naïve patients achieved SVR12, 96%
achieved SVR24 in this intent-to-treatanalysis
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93% of prior null responders achieved SVR12 and SVR24
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The single relapse with this regimen occurred at post-treatment week
two
With the triple-DAA plus ribavirin regimen, comparable SVR24
response rates were also seen in treatment naïve patients and null
responder patients across HCV subtype, IL28B genotype, baseline HCV-RNA
levels and severity of fibrosis.
SVR24 by patient subtype in the "Aviator"
study
Characteristic
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Treatment Naïve
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Null Responders
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GT1a
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91% (n=108)
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93% (n=55)
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GT1b
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98% (n=50)
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97% (n=33)
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Non-CC IL28B genotype
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95% (n=115)
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94% (n=85)
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CC IL28B genotype
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89% (n=44)
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100% (n=3)
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Viral Load (?7 log)
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89% (n=35)
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91% (n=22)
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Viral load (<7 log)
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94% (n=124)
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96% (n=66)
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Fibrosis Stage (F0-F1)*
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94% (n=113)
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95% (n=41)
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Fibrosis Stage (F2-F3)*
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91% (n=42)
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93% (n=45)
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Male
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92% (n=78)
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93% (n=55)
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Female
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94% (n=81)
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97% (n=33)
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*The fibrosis analysis was post-hoc based on biopsy or non-invasive
testing at screening.
The safety profile seen in this study is consistent with the initial
presentation of results in November 2012. Of the 247 patients included
in this analysis, four patients (1.6 percent) discontinued the study
because of drug-related adverse events. Serious adverse events were
noted in 4 patients (1.6 percent), with one (arthralgia) considered
possibly drug-related. Other events reported in more than 10 percent of
patients included headache, fatigue, nausea, insomnia, and diarrhea.
Grade 3-4 laboratory abnormalities in total bilirubin (six patients) and
ALT (one patient) were noted; all resolved with continued dosing.
"Results from treatment utilizing ABT-450 in combination with other
antiviral agents in AbbVie's portfolio continue to generate high SVR
rates across multiple HCV patient types," stated Jay R. Luly, Ph.D.,
President and Chief Executive Officer. "These results are especially
promising for those who have failed previous therapy and for those with
more advanced disease."
The focus of ABT-450 development is to study the compound in combination
with other antiviral agents in AbbVie's portfolio. The three direct
acting antivirals, or triple DAA cocktail, studied in the Phase 2b
interferon-free Aviator trial included ritonavir-boosted protease
inhibitor ABT-450/r, non-nucleoside polymerase inhibitor ABT-333, and
NS5A inhibitor ABT-267.
Abstracts for the three presentations can be viewed at the EASL website
at www.easl.eu
ABT-450 containing data presentations are as follows:
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Oral Presentation - Kris V. Kowdley, et al., Thursday, April
25 from 1:30 - 3:30 p.m. CEST
"Safety and Efficacy
of Interferon-Free Regimens of ABT-450/r, ABT-267, ABT-333 ± ribavirin
in Patients with Chronic HCV GT1 Infection: Results from the
Aviator Study"
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Poster # 1190 - Michael Epstein, et al., Saturday,
April 27 from 12:30 - 1:30 p.m. CEST
"Study of ABT-267
2-Day Monotherapy Followed by 12-Week Combination Therapy in Treatment
Naïve Patients with Chronic HCV Genotype 1 Infection"
Enanta's proprietary cyclophilin inhibitor data presentation:
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Poster #1213 - C.M. Owens, et al., Saturday, April 27 from
9:00 a.m. - 6:00 p.m. CEST
"Cyclophilin Inhibitor EDP-546
is a Potential Cornerstone Drug for Use in Combination with NS5A and
Protease Inhibitors Due to Its High Barrier to Resistance"
"We continue to advance our lead cyclophilin candidates in preclinical
studies and are continuing to generate and characterize a number of
additional candidates," commented Yat Sun Or, Ph.D., Senior Vice
President and Chief Scientific Officer. "We expect to select a
preclinical candidate to advance during 2013."
About Hepatitis C Virus (HCV)
Hepatitis C is a liver disease affecting over 170 million people
worldwide. The virus is typically spread through direct contact with the
blood of an infected person. Hepatitis C increases a person's risk of
developing chronic liver disease, cirrhosis, liver cancer and death.
There is an acute need for new HCV therapies that are safer and more
effective for many variants of the virus.
Collaboration with AbbVie (formerly the research-based pharmaceutical
business of Abbott Labs)
In December 2006, Enanta and Abbott announced a worldwide agreement to
collaborate on the discovery, development and commercialization of HCV
NS3 and NS3/4A protease inhibitors and HCV protease inhibitor-containing
drug combinations. Under the agreement, AbbVie is responsible for all
development and commercialization activities for ABT-450, the program's
lead compound. Enanta received a $57 million upfront payment upon
signing the collaboration agreement and is eligible to receive
additional pre-commercial milestones, as well as double-digit royalties
on any revenue allocable to the collaboration's protease inhibitors.
Also, for any additional collaborative HCV protease inhibitor product
candidate developed under the agreement, Enanta holds an option to fund
40 percent of U.S. development costs and U.S. commercialization efforts
(sales and promotion costs) in exchange for 40 percent of any U.S.
profits ultimately achieved after regulatory approval.
About Enanta
Enanta Pharmaceuticals is a research and development-focused
biotechnology company that uses its robust chemistry-driven approach and
drug discovery capabilities to create small molecule drugs in the
infectious disease field. Enanta is discovering and developing novel
inhibitors designed for use against the hepatitis C virus (HCV). These
inhibitors include members of the direct acting antiviral (DAA)
inhibitor classes - protease (partnered with AbbVie), NS5A (partnered
with Novartis) and nucleotide polymerase - as well as a host-targeted
antiviral (HTA) inhibitor class targeted against cyclophilin.
Additionally, Enanta has created a new class of antibiotics, called
Bicyclolides, for the treatment of multi-drug resistant bacteria, with a
current focus on developing an intravenous and oral treatment for
hospital and community MRSA (methicillin-resistant Staphylococcus
aureus) infections.
Forward Looking Statement
This press release contains forward-looking statements, including with
respect to our expectation that we will select a preclinical cyclophilin
inhibitor candidate to advance to clinical trials during 2013 and
expectations regarding the successful completion of clinical development
of ABT-450. Statements that are not historical facts are based on our
management's current expectations, estimates, forecasts and projections
about our business and the industry in which we operate and our
management's beliefs and assumptions. The statements contained in this
release are not guarantees of future performance and involve certain
risks, uncertainties and assumptions, which are difficult to predict.
Therefore, actual outcomes and results may differ materially from what
is expressed in such forward-looking statements. Important factors that
may affect actual results include our ability to successfully identify
appropriate candidates for clinical development of our future product
candidates, the development efforts of our collaborators, regulatory
actions affecting clinical development and clinical development of
competitive product candidates. Enanta cautions investors not to place
undue reliance on the forward-looking statements contained in this
release. These statements speak only as of the date of this release, and
Enanta undertakes no obligation to update or revise these statements,
except as may be required by law.

Investor Contact
Enanta Pharmaceuticals, Inc.
Carol
Miceli, 617-607-0710
[email protected]
or
Media
Contact
MacDougall Biomedical Communications
Kari Watson
or Charles Liles, 781-235-3060
[email protected]
or [email protected]