-
Muscle biopsy data demonstrate highly efficient tissue
transduction as indicated by vector copy number, robust
myotubularin protein expression as assessed by western blot, and
significant improvement in histology in first three treated
patients at 24-week timepoint
-
Efficacy analysis updated to include week 24 assessments for
Patient 3, demonstrating significant improvements in neuromuscular
and respiratory function and reduction in ventilator
dependence
- No
serious adverse events in any patient since the last data update
provided at ASGCT in May 2018
-
Proceeding with per protocol dose escalation from
1x1014 vector genomes per kilogram (vg/kg) to
3x1014 vg/kg
SAN FRANCISCO, Aug. 7, 2018 /PRNewswire/ -- 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 reported its financial results for the second
quarter ended June 30, 2018 and
provided an update on ASPIRO, the phase 1/2 clinical trial of AT132
in patients with X-Linked Myotubular Myopathy (XLMTM), including
muscle biopsy results from the first three patients treated in the
study and the week 24 efficacy analysis for Patient 3.
"We're very pleased with continued clinical progress in ASPIRO,
and in particular the results of the muscle biopsy data from the
first three ASPIRO patients, which show unprecedented levels of
tissue transduction and protein expression from a systemically
administered gene therapy for a neuromuscular disease," stated Dr.
Suyash Prasad, Senior Vice President
and Chief Medical Officer of Audentes. "The consistency of effect
between the functional measures and histological improvement gives
us further confidence in the emerging profile of AT132 as a therapy
with the potential to bring transformative benefit to patients
living with XLMTM. We look forward to continuing with the per
protocol dose escalation and initiating enrollment of the second
dose cohort at the 3x1014 vg/kg dose in the coming
weeks."
"We anticipate building on the significant momentum of our XLMTM
program with continued progress across our portfolio of product
candidates, including advancing an exciting new research initiative
directed toward a large neuromuscular disease with significant
unmet medical need," stated Matthew R.
Patterson, Chief Executive Officer of Audentes. "Coupled
with further advancements in the commercial readiness of our
manufacturing operations, we believe we are well-positioned as a
leader in the AAV gene therapy field with significant near-term
growth potential."
ASPIRO Update
Today's announcement includes
incremental safety, efficacy and muscle biopsy data updates since
the most recent data disclosure in an oral presentation held on
May 16, 2018 at the American Society
of Gene and Cell Therapy (ASGCT) Annual Meeting.
Safety
There have been no serious adverse events in any patient since the
last update.
Efficacy
The ASGCT oral presentation included week-24 assessments for
Patients 1, 2, and 4 (untreated control) as well as earlier
assessments for Patients 5, 6, and 7 from the Cohort 1 expansion
group. Today's update adds week 24 assessments for Patient 3 to the
available data set, including:
- CHOP-INTEND score: increased from 34 at baseline to 48 at week
24 (41% increase)
- Maximal Inspiratory Pressure (MIP): increased from 26
cmH20 at baseline to 70 cmH20 at week 24
(170% increase)
- Ventilator support: decreased from continuous (24 hours/day)
invasive ventilator support at baseline to night-time only (8
hours/day) ventilator support at week 24
Subsequent to the week 24 assessment, Patient 2 successfully
achieved ventilator independence.
Muscle biopsy
Muscle biopsy samples at the 24-week timepoint show evidence of
highly efficient tissue transduction as indicated by vector copy
number, robust myotubularin protein expression as assessed by
western blot, and significant improvement in histology as assessed
by improved myofiber size, nuclei peripheralization and organelle
localization.
|
Vector
Copy
|
MTM1 Protein
Expression
|
|
Per Diploid
Genome
|
As a Percent of
Normal
|
|
Baseline
|
Week 24
|
Baseline
|
Week 24
|
Patient 1
|
BLOD
|
6.2
|
BLOD
|
~120%
|
Patient 2
|
BLOD
|
7.1
|
5%
|
~250%
|
Patient 3
|
BLOD
|
2.7
|
BLOD
|
~80%
|
BLOD = Below limit
of detection
|
|
|
|
Based on these findings, the independent Data Monitoring
Committee for ASPIRO recommended continuing with dose escalation
per protocol, from 1x1014 vg/kg for Cohort 1 to
3x1014 vg/kg for Cohort 2. Patient screening is
underway, and dosing is expected to commence in the coming
weeks.
Recent Achievements & Upcoming Key Events
- AT132 for XLMTM:
-
- Presented positive interim data from ASPIRO during an oral
presentation at the ASGCT Annual Meeting in May 2018.
- The ASPIRO data set now includes safety and efficacy results
through week 24 for patients 1-4 of Cohort 1, and up to week 4 data
for the Cohort 1 expansion patients (patients 5-7), as well as week
24 muscle biopsy data for patients 1-3. To date, all patients show
clinically meaningful improvements in neuromuscular and respiratory
function. Patients 1-3 show significant reductions in ventilator
dependence, with Patient 1 achieving ventilator independence by
week 24.
- Awarded PRIME designation by the European Medicines Agency
- Next data update anticipated at the 23rd
International Congress of the World Muscle Society, October 2–6,
2018
- AT342 for Crigler-Najjar Syndrome:
-
- Presented initial proof of concept at a dose of
1.5x1012 vg/kg at the Annual Congress of the
51st Annual Meeting of the European Society for
Paediatric Gastroenterology, Hepatology and Nutrition in
May 2018
- AT342 has been well-tolerated with no significant
treatment-related safety signals
- Dose escalating to 6x1012 vg/kg and plan to provide
the next interim data update from VALENS in the fourth quarter of
2018
- AT982 for Pompe Disease:
-
- Presented preclinical data from AT982 in a Pompe mouse model at
the ASGCT Annual Meeting in May
2018
- Conducting preclinical program in support of IND submission to
evaluate AT982 in both infantile and late onset Pompe disease
patients
- Plan to submit the AT982 IND in 2019
- Plan to initiate INQUIRO, a prospective natural history run-in
study in both infantile and late onset Pompe disease patients in
the first half of 2019
- AT307 for CASQ2-CPVT:
-
- IND application is active
- Received Fast Track designation from the FDA
- Continuing patient identification activities to better
characterize CASQ2-CPVT prevalence. Results from these efforts will
inform clinical plans as they relate to the timing of a potential
phase 1/2 clinical trial.
- Pipeline expansion:
-
- Research initiative underway focused on the design and
development of a novel AAV-based therapeutic targeting a large
neuromuscular disease with significant unmet medical need
- Manufacturing:
-
- Commenced BLA preparation and validation efforts for our
internal cGMP manufacturing facility, AT132 process and analytical
methods. Since program inception, clinical material has been
manufactured utilizing substantially the same process, scale, and
facility intended to supply the commercial market.
- Current facility and scale provide sufficient capacity for the
expected global commercial needs of XLMTM and Crigler-Najjar
markets, and ongoing clinical supply for current pipeline
programs.
Second Quarter 2018 Financial Results
- Cash Position: At June 30,
2018, Audentes had cash, cash equivalents, and short-term
investments of $314.4 million.
Current cash, cash equivalents and short-term investments are
expected to fund operations into the second half of 2020.
- Research and Development Expense: Research and
development expense was $26.3 million
for the second quarter of 2018 compared to $18.8 million for the same period in 2017, an
increase of $7.5 million. The
increase in research and development expense was primarily
attributable to an increase in development costs related to our
AT982 program, increased headcount and related facility costs,
increased internal manufacturing costs and higher stock
compensation expense. Research and development expense for the
second quarter includes $2.3 million
of non-cash stock-based compensation expense. For the six months
ended June 30, 2018, research and
development expense was $46.2 million
compared to $33.4 million for the
same period in 2017.
- General and Administrative Expense: General and
administrative expense was $6.3
million for the second quarter of 2018 compared to
$4.1 million for the same period in
2017, an increase of $2.2 million.
The increase in general and administrative expense was primarily
attributable to increases in headcount and related facility costs,
professional service fees, stock compensation expense and public
company regulatory compliance costs. General and administrative
expense for the second quarter includes $1.8
million of non-cash stock-based compensation expense. For
the six months ended June 30, 2018,
general and administrative expense was $12.8
million compared to $7.7
million for the same period in 2017.
- Net Loss: Net loss was $31.4
million for the second quarter of 2018 compared to
$22.7 million for the same period in
2017. For the six months ended June 30,
2018, net loss was $56.9
million as compared to $40.9
million for the same period in 2017.
Conference Call
At 8:00 a.m. Eastern
Time today, Audentes management will host a conference call
and a simultaneous webcast to discuss its second quarter 2018
financial results and provide an update on ASPIRO, the phase 1/2
clinical trial of AT132 in Patients with X-Linked Myotubular
Myopathy. To access a live webcast of the conference call,
please visit the Events & Presentations page within the
Investors + Media section of the Audentes website at
www.audentestx.com. Alternatively, please call 1-833-659-8620
(U.S.) or 1-409-767-9247 (international) and dial the conference ID
2572579 to access the call.
A replay of the webcast will be available on the Audentes
website for approximately 30 days.
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 trials 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, potential pipeline
expansion, the timing and nature of clinical development
activities, the timing of the release of data from ongoing clinical
trials, the timing of regulatory filings, the expected benefits of
the company's product candidates, the expected capacity of the
company's internal manufacturing facility, and the use and adequacy
of cash reserves. 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 commercialize its product candidates, the timing and
results of preclinical and clinical trials, the company's ability
to fund development activities and achieve development goals,
establish and scale-up manufacturing processes that comply with
regulatory requirements, 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.
Selected Financial
Information
|
|
Operating
Results:
|
(amounts in
thousands, except share and per share data)
|
|
|
Three months ended
June 30,
|
|
Six months ended June
30,
|
|
2018
|
|
2017
|
|
2018
|
|
2017
|
|
Unaudited
|
|
|
|
|
|
|
|
|
Operating
expenses:
|
|
|
|
|
|
|
|
Research and
development
|
$
26,348
|
|
$
18,776
|
|
$
46,239
|
|
$
33,363
|
General and
administrative
|
6,281
|
|
4,065
|
|
12,800
|
|
7,723
|
Total operating
expenses
|
32,629
|
|
22,841
|
|
59,039
|
|
41,086
|
Loss from
operations
|
(32,629)
|
|
(22,841)
|
|
(59,039)
|
|
(41,086)
|
Interest income,
net
|
1,294
|
|
115
|
|
2,153
|
|
262
|
Other expense,
net
|
(32)
|
|
(13)
|
|
(52)
|
|
(30)
|
Net loss
|
$
(31,367)
|
|
$
(22,739)
|
|
$
(56,938)
|
|
$
(40,854)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Net loss per share,
basic and diluted
|
$
(0.85)
|
|
$
(0.87)
|
|
$
(1.59)
|
|
$
(1.70)
|
Shares used in
computing net loss per share, basic and diluted
|
36,935,940
|
|
26,212,614
|
|
35,765,506
|
|
23,996,187
|
Selected Balance
Sheet Information:
|
(amounts in
thousands)
|
|
|
June 30,
|
|
December
31,
|
|
2018
|
|
2017
|
|
Unaudited
|
|
|
|
|
|
|
|
|
|
|
Cash, cash
equivalents and short-term investments
|
$
314,434
|
|
$
133,605
|
Total
assets
|
$
366,051
|
|
$
178,662
|
Total
liabilities
|
$
25,087
|
|
$
22,064
|
Total stockholders'
equity
|
$
340,964
|
|
$
156,598
|
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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SOURCE Audentes Therapeutics, Inc.