SAN FRANCISCO, Oct. 5, 2018 /PRNewswire/ --
Conference call and webcast Friday, October 5, 2018 at 8:30 am ET
Webcast may be accessed via
the Investor and Media page of the Audentes website
Call
may be accessed by dialing (833) 659-8620 (U.S.) or (409) 767-9247
(international) and using conference ID# 8458939
Audentes Therapeutics, Inc. (Nasdaq: BOLD), a biotechnology
company focused on developing and commercializing innovative gene
therapy products for patients living with serious, life-threatening
rare diseases, today announced new positive interim data from
ASPIRO, the Phase 1/2 clinical trial of AT132 for the treatment of
X-linked Myotubular Myopathy (XLMTM). The data will be
presented at the 23rd International Annual Congress of the World
Muscle Society by Nancy Kuntz, MD,
Principal Investigator at Ann & Robert H. Lurie Children's
Hospital of Chicago, Medical
Director of Mazza Foundation Neuromuscular Program and Professor of
Pediatrics and Neurology at Northwestern
University Feinberg School of Medicine. The oral
presentation by Dr. Kuntz will be held during a session on new
therapeutic modalities scheduled to begin at 9:30 a.m. ET on October
5, 2018.
The newly reported data include follow-up assessments ranging
from 4 to 48 weeks for the eight patients enrolled in ASPIRO to
date, including the seven patients enrolled in Cohort 1
(1x1014 vg/kg; six treated and one untreated control)
and one patient enrolled to date in Cohort 2 (3x1014
vg/kg). Key assessments include neuromuscular function as
measured by CHOP INTEND; respiratory function as measured by
maximal inspiratory pressure (MIP) and ventilator dependence; and
vector transduction, transgene expression and histological
improvement as assessed via muscle biopsy. All treated
patients continue to show meaningful improvements in neuromuscular
and respiratory function, with no new treatment-related SAEs
reported since the last scientific update in May 2018.
"The encouraging safety and efficacy trends we've seen
throughout the ASPIRO trial of AT132 are further strengthened by
this latest update, with continued and durable improvements seen in
all treated patients," stated Dr. Kuntz. "The dramatic
reductions in required respiratory support, with three patients
achieving ventilator independence post-treatment, is an
unprecedented outcome in children with a congenital myopathy who
have been ventilated from birth."
"We are thrilled with the continued progress in ASPIRO,
including the promising early data for the Cohort 2 sentinel
patient, and plan to continue enrollment at the 3x1014
vg/kg dose in the coming weeks," stated Matthew R. Patterson, Co-Founder and Chief
Executive Officer of Audentes. "With the recently awarded
RMAT and PRIME designations, we look forward to collaborating
closely with the FDA and EMA to advance AT132 toward our goal of
making AT132 available to patients living with XLMTM as rapidly as
possible."
Data Summary
Safety
AT132 has been well tolerated with a manageable safety profile to
date at doses up to 3x1014 vg/kg. There have
been no treatment-related SAEs reported since the last scientific
update in May 2018.
Efficacy
Today's presentation provides incremental new CHOP INTEND and
ventilator dependence data for all patients; MIP data for Patients
2, 5, 6, 7, and 8; and week 24 biopsy data for Patient 5.
Data continue to show significant improvements in neuromuscular
and respiratory function as assessed via CHOP INTEND and MIP in all
treated patients, including the Cohort 2 sentinel patient.
All treated patients in Cohort 1 have shown significant
reductions in ventilator use, and three patients have now achieved
ventilator independence.
Week 24 muscle biopsies show evidence of highly efficient tissue
transduction as indicated by vector copy number and robust
myotubularin protein expression as assessed by Western blot.
Histological analyses also show significant improvements in
myofiber size, nuclear peripheralization and organelle
localization.
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Summary Table of
Key Baseline and Follow-up Assessments
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Demographics
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Neuromuscular
Assessment
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Respiratory
Assessments
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Biopsy
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Age at
Baseline
(Years)
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CHOP INTEND
at Baseline
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CHOP INTEND
at Last Report
(Max Score=64)
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Δ From
Baseline
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MIP at
Baseline
(cm H2O) 2
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MIP at
Last Report
(cm H2O) 2
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Δ From
Baseline
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Ventilator Status
at Baseline
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Ventilator
Use at
Baseline
(hrs per day)
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Ventilator
Use at Last
Report
(hrs per day)
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Δ From
Baseline
(hrs per day)
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VCN
per diploid genome
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MTM1
expression
vs.
Normal 4
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Cohort
1
(1x1014vg/kg)
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Patient
1
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0.8
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29
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56 (Wk 48)
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+27 (93%)
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33
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89 (Wk
24)3
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+56 (170%)
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BiPAP
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12 hrs.
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0 (Wk 48)
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-12 hrs.
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6.2 (Wk
24)
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~120%
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Patient
2
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4.1
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45
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64 (Wk 48)
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+19 (42%)
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44
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112 (Wk
48)
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+68 (155%)
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Invasive
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22 hrs.
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6 (Wk 48)
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-16 hrs.
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7.1 (Wk
24)
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~250%
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Patient
3
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2.6
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34
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34 (Wk 36)
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0
(0%)1
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26
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70 (Wk 24)
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+44 (170%)
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Invasive
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24 hrs.
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0 (Wk 40)
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-24 hrs.
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2.7 (Wk
24)
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~80%
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P. 4
(Control)
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4.0
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49
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47 (Wk 36)
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-2 (-4%)
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58
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46 (Wk 24)
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-12 (-21%)
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BiPAP
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12 hrs.
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12 (Wk 36)
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0 hrs.
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NA
5
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NA
5
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Cohort
1
Expansion
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Patient
5
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1.0
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36
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53 (Wk 24)
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+17 (47%)
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14
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78 (Wk 24)
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+64 (457%)
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Invasive
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24 hrs.
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12 (Wk 24)
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-12 hrs.
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2.2 (Wk
24)
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~52%
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Patient
6
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0.8
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39
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52 (Wk 16)
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+13 (33%)
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35
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87 (Wk 12)
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+52 (149%)
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Invasive
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24 hrs.
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0 (Wk 20)
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-24 hrs.
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NA
6
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NA
6
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Patient
7
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0.8
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43
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53 (Wk 16)
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+10 (23%)
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29
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68 (Wk 12)
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+39 (134%)
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Invasive
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23.5 hrs.
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10 (Wk 20)
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-13.5 hrs.
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NA
6
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NA
6
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Cohort
2
(3x1014vg/kg)
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Patient
8
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1.2
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36
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55 (Wk 4)
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+19 (53%)
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31
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67 (Wk 4)
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+36 (116%)
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Invasive
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22.5 hrs.
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23.3 (Wk
4)
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+0.8 hrs.
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NA
6
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NA
6
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MIP = Maximal
Inspiratory Pressure; Ventilator Use = Ventilator Dependence Over
Prior 24 hours; VCN = Vector Copy Number
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1. Patient 3 was
fitted with a temporary halo traction device for treatment of
preexisting scoliosis at the time of his week 36 visit, impeding
his ability to complete the
full CHOP INTEND assessment. As of the 24-week assessment, Patient
3 had achieved a 41% improvement in CHOP INTEND from
baseline.
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2. >80 cmH20 is
considered in the normal range for healthy children less than five
years of age.
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3. Unable to
collect data at week 48 due to lack of cooperation by the
patient.
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4. Protein
expression numbers may change in future presentations as Audentes
is currently titrating the standard and extending the linear range
of the assay.
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5. Control
patients are not treated until the optimal dose has been selected.
Once treated, biopsies are conducted at baseline, week 24 and week
48 post treatment.
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6. The longest
duration of follow-up for Patients 6, 7 and 8 is 16 weeks. Post
treatment biopsies will be conducted at week 24 and week
48.
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The independent Data Monitoring Committee (DMC) has reviewed the
preliminary safety and efficacy data from the Cohort 2 sentinel
patient and has recommended continuing with enrollment of the
remaining three patients in Cohort 2, which is expected to commence
in the coming weeks. In addition, with the goal of gaining
alignment with the U.S. Food and Drug Administration (FDA) and the
European Medicines Agency (EMA) on the potential registration
pathway for AT132 under its Regenerative Medicine Advanced Therapy
(RMAT) and Priority Medicines (PRIME) designations, Audentes plans
to hold initial discussions with both regulatory bodies beginning
in the fourth quarter of 2018.
XLMTM is a rare monogenic disease characterized by extreme
muscle weakness, respiratory failure and early death. The
XLMTM patient population may be larger than previously reported,
potentially increasing the future market opportunity for
AT132. A recent publication by Vandersmissen et al. in
Neuromuscular Disorders indicated that incidence of XLMTM
may be up to 1 in 40,000 live male births, a 20 percent increase
over earlier reports. The Vandersmissen publication confirms
previous literature estimates of two-year mortality of
approximately 50 percent but shows that for boys who survive this
critical period, subsequent 10-year survival is between 75 and 80
percent. A recent mortality analysis of the RECENSUS
retrospective chart review corroborates this finding, suggesting
that while severely functionally impaired, there exists a larger
prevalent population of older boys who may benefit from treatment
with AT132.
Conference Call
At 8:30 a.m.
Eastern Time today, October 5,
2018, Audentes management will host a conference call and a
simultaneous webcast to discuss the new interim data from ASPIRO
that will be presented at the 23rd International Annual Congress of
the World Muscle Society. To access a live webcast of the
conference call, please visit the Investor and Media page of the
Audentes website at www.audentestx.com. Alternatively, please
call (833) 659-8620 (U.S.) or (409) 767-9247 (international) and
dial the conference ID# 8458939 to access the call. A replay
of the webcast will be available on the Audentes website for
approximately 30 days.
About AT132 for X-linked Myotubular Myopathy
AT132 is
the Audentes product candidate being developed to treat XLMTM, a
disease caused by mutations in the MTM1 gene, which encodes the
protein myotubularin. Myotubularin plays an important role in
the development, maintenance and function of skeletal muscle
cells. AT132 is comprised of an AAV8 vector containing a
functional copy of the MTM1 gene. Over the course of 2018,
Audentes has reported promising safety, efficacy and muscle biopsy
data from ASPIRO, a multicenter, ascending dose
Phase 1/2 clinical study to evaluate the safety and
preliminary efficacy of AT132 in approximately 12 XLMTM patients
less than five years of age. The preclinical development of
AT132 was conducted in collaboration with Genethon
(www.genethon.fr).
AT132 has been granted Regenerative Medicine Advanced Therapy
(RMAT), Rare Pediatric Disease, Fast Track and Orphan Drug
designations by the FDA, and Priority Medicines (PRIME) and
Orphan Drug designations by the European Medicines Agency
(EMA).
About Audentes Therapeutics, Inc.
Audentes
Therapeutics (Nasdaq: BOLD) is a biotechnology company focused
on developing and commercializing innovative gene therapy products
for patients living with serious, life-threatening rare
diseases. We are currently conducting
Phase 1/2 clinical studies of our lead product
candidates, AT132 for the treatment of X-linked Myotubular Myopathy
(XLMTM), and AT342 for the treatment of Crigler-Najjar
syndrome. We have two additional product candidates in
development, including AT982 for the treatment of Pompe disease,
and AT307 for the treatment of the CASQ2 subtype of
catecholaminergic polymorphic ventricular tachycardia
(CASQ2-CPVT). We are a focused, experienced and passionate
team committed to forging strong, global relationships with the
patient, research and medical communities.
For more information regarding Audentes, please
visit www.audentestx.com.
Forward Looking Statements
This press release contains
forward-looking statements within the meaning of the "safe harbor"
provisions of the Private Securities Litigation Reform Act of 1995,
including, but not limited to, anticipated clinical milestones, the
timing and nature of clinical development activities, the nature of
the results of clinical data, the timing of regulatory filings, the
potential market size and market opportunity for AT132 and the
expected benefits of the company's product candidates. All
statements other than statements of historical fact are statements
that could be deemed forward-looking statements. Although the
company believes that the expectations reflected in such
forward-looking statements are reasonable, the company cannot
guarantee future events, results, actions, levels of activity,
performance or achievements, and the timing and results of
biotechnology development and potential regulatory approval is
inherently uncertain. Forward-looking statements are subject
to risks and uncertainties that may cause the company's actual
activities or results to differ significantly from those expressed
in any forward-looking statement, including risks and uncertainties
related to the company's ability to advance its product candidates,
obtain regulatory approval of and ultimately commercial its product
candidates, the timing and results of preclinical and clinical
trials, the company's ability to fund development activities and
achieve development goals, the company's ability to protect
intellectual property and other risks and uncertainties described
under the heading "Risk Factors" in documents the company files
from time to time with the Securities and Exchange
Commission. These forward-looking statements speak only as of
the date of this press release, and the company undertakes no
obligation to revise or update any forward-looking statements to
reflect events or circumstances after the date hereof.
Audentes Contacts:
Investor Contact:
Andrew Chang
415.818.1033
achang@audentestx.com
Media Contact:
Katie Hogan
415.951.3398
khogan@audentestx.com
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