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ACADIA Pharmaceuticals and Neuren Pharmaceuticals Announce Exclusive License Agreement for the North American Development and Commercialization of Trofinetide in Rett Syndrome

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-ACADIA plans to initiate a Phase 3 study of trofinetide for the
treatment of Rett syndrome, a rare neurodevelopmental congenital CNS
disorder, in the second half of 2019

-Neuren retains all rights to trofinetide outside of North America

-Neuren to receive US $10 million upfront plus potential milestones
of up to US $455 million and royalties

ACADIA Pharmaceuticals Inc. (NASDAQ:ACAD) and Neuren Pharmaceuticals
Limited (ASX: NEU) announced today that they have entered into an
exclusive North American License Agreement for the development and
commercialization of trofinetide for Rett syndrome and other
indications. Neuren retains rights to develop and commercialize
trofinetide for all indications outside of North America.

This press release features multimedia. View the full release here:
https://www.businesswire.com/news/home/20180806005653/en/

ACADIA plans to initiate a Phase 3 randomized, double-blind
placebo-controlled study evaluating trofinetide in the second half of
2019 following completion of additional manufacturing activities. This
study will evaluate trofinetide and placebo in approximately 180 girls
with Rett syndrome and will measure the Rett Syndrome Behavior
Questionnaire (RSBQ), a caregiver assessment, and the Clinical Global
Impression of Improvement (CGI-I), a physician assessment, as co-primary
efficacy endpoints.

"A potential treatment for Rett syndrome is a perfect fit with ACADIA's
mission to develop novel therapies to improve the lives of patients with
central nervous system disorders," said Serge Stankovic, M.D., M.S.P.H,
Executive Vice President, Head of Research and Development at ACADIA.
"Today there are no approved treatments for the girls and women
suffering from Rett syndrome. We look forward to initiating a Phase 3
study in the second half of 2019 to further explore the potential
benefits of trofinetide for patients and their caregivers."

Neuren Executive Chairman Dr. Richard Treagus commented, "We are
delighted to be partnering with ACADIA in North America. ACADIA's team
has a proven record in developing and commercializing medicines in
central nervous system disorders with no approved therapies and high
unmet needs. ACADIA's additional capabilities and resources will
immediately make a very significant difference, enabling us to advance
our shared goal of developing this novel treatment option for Rett
syndrome patients."

Steve Kaminsky, Ph.D., Chief Science Officer of Rettsyndrome.org,
commented, "Rettsyndrome.org is grateful to Neuren for their dedication
to the development of trofinetide. ACADIA's commitment to advance
trofinetide to Phase 3 brings us closer to the first potential treatment
for Rett syndrome with a drug designed to address the underlying biology
and improve the lives of those suffering from the condition."

Trofinetide is a novel synthetic analog of the amino‐terminal tripeptide
of IGF-1 designed to treat the core symptoms of Rett syndrome by
reducing neuroinflammation and supporting synaptic function. In the
central nervous system, IGF-1 is produced by both of the major types of
brain cells – neurons and glia. IGF-1 in the brain is critical for both
normal development and for response to injury and disease1,2.
Trofinetide has been granted U.S. Food and Drug Administration (FDA)
Fast Track Status and Orphan Drug Designation in the U.S. and Europe.

Neuren conducted a Phase 2 double-blind placebo-controlled dose ranging
study in girls aged 5 to 15 years with Rett syndrome, in which
statistically significant and clinically meaningful improvement was
demonstrated on the RSBQ and the CGI-I. This followed positive trends
observed in an earlier Phase 2 trial in adolescents and adults aged 16
to 45 years with Rett syndrome3. In addition, Neuren has
completed an exploratory study in Fragile X syndrome.

Dr. Daniel Glaze, Medical Director at the Blue Bird Circle Rett Center,
Texas Children's Hospital commented, "The trofinetide Phase 2 results in
Rett syndrome are very promising in terms of both safety and clinical
benefit. For many families, these improvements would provide meaningful
improvement in their child's quality of life."

Under the terms of the License Agreement, Neuren is eligible to receive
US $10 million upfront plus potential milestone payments of up to US
$455 million. In addition, Neuren is eligible to receive tiered,
escalating, double-digit percentage royalties on net sales of
trofinetide in North America and one third of the market value of any
Rare Pediatric Disease Priority Review Voucher, if awarded by the U.S.
FDA upon approval of a New Drug Application for trofinetide. The
potential milestone payments to Neuren consist of US $105 million
subject to achievement of development milestones in Rett syndrome and
Fragile X syndrome and up to US $350 million subject to achievement of
thresholds of annual net sales of trofinetide in North America. ACADIA
will fund and execute the remaining development for trofinetide in Rett
syndrome in North America, except for the completion by Neuren of
certain in-progress preparatory activities. ACADIA and Neuren will form
a Joint Steering Committee to direct the development of trofinetide in
all indications, including the next clinical trial for Fragile X
syndrome. Any data and regulatory filings generated by ACADIA or Neuren
may be used by either party for the development and commercialization of
trofinetide in their respective territories. ACADIA has a right of first
negotiation to acquire a license to develop and commercialize
trofinetide outside North America. Neuren has an obligation not to
develop a competing product in indications for which ACADIA develops and
commercializes trofinetide.

About Trofinetide
Trofinetide is a novel synthetic analog of
the amino‐terminal tripeptide of IGF-1 designed to treat the core
symptoms of Rett syndrome by reducing neuroinflammation and supporting
synaptic function. In the central nervous system, IGF-1 is produced by
both of the major types of brain cells – neurons and glia. IGF-1 in the
brain is critical for both normal development and for response to injury
and disease1,2. Trofinetide has been granted U.S. FDA Fast
Track Status and Orphan Drug Designation in the U.S. and Europe for both
Rett syndrome and Fragile X syndrome.

About Rett Syndrome
Rett syndrome is a debilitating
neurological disorder that occurs primarily in females following
apparently normal development for the first six months of life. Rett
syndrome has been most often misdiagnosed as autism, cerebral palsy, or
non-specific developmental delay. Rett syndrome is caused by mutations
on the X chromosome on a gene called MeCP24. There are more
than 200 different mutations found on the MeCP2 gene that interfere with
its ability to generate a normal gene product4. Rett syndrome
occurs worldwide in approximately one of every 10,000 to 15,000 female
births5 causing problems in brain function that are
responsible for cognitive, sensory, emotional, motor and autonomic
function. Typically, between six to eighteen months of age, patients
experience a period of rapid decline with loss of purposeful hand use
and spoken communication and inability to independently conduct
activities of daily living5. Symptoms also include seizures,
disorganized breathing patterns, an abnormal side-to-side curvature of
the spine (scoliosis) and sleep disturbances. Currently, there are no
approved medicines approved for the treatment of Rett syndrome1.

About Fragile X syndrome
Fragile X syndrome is the most
common inherited cause of intellectual disability and the most common
known cause of autism. Fragile X syndrome is caused by a single gene
defect on the X chromosome that impacts the FMRP protein, which is
responsible for regulating the synapses of nerve cells. One of every
5,000 males and one of every 4,000 to 8,000 females are estimated to
have the full gene mutation6. Generally males are more
severely affected than females. Clinically, Fragile X syndrome is
characterized by intellectual disability, hyperactivity and attentional
problems, autistic symptoms, anxiety, emotional lability and epilepsy.
Currently, there are no medicines approved for the treatment of Fragile
X syndrome.

About ACADIA Pharmaceuticals
ACADIA is a biopharmaceutical
company focused on the development and commercialization of innovative
medicines to address unmet medical needs in central nervous system
disorders. ACADIA has developed and is commercializing the first and
only medicine approved for the treatment of hallucinations and delusions
associated with Parkinson's disease psychosis. In addition, ACADIA has
ongoing clinical development efforts in additional areas with
significant unmet need including dementia-related psychosis,
schizophrenia inadequate response, schizophrenia-negative symptoms and
major depressive disorder. This press release and further information
about ACADIA can be found at: www.acadia-pharm.com.

About Neuren Pharmaceuticals
Neuren Pharmaceuticals Limited
(Neuren) is a biopharmaceutical company developing new therapies for
brain injury, neurodevelopmental and neurodegenerative disorders. Neuren
has completed Phase 2 development of trofinetide for Rett syndrome and
has completed a Phase 2 clinical trial in Fragile X syndrome.

About Rettsyndrome.org
Rettsyndrome.org
is one of the leading private funders of Rett syndrome research. The
organization hosts the largest global gathering of Rett researchers and
clinicians to establish research direction for the future. The mission
of the organization is to accelerate the full spectrum research to cure
Rett syndrome and empower families with information, knowledge and
connectivity. Further information about Rettsyndrome.org can
be found at: rettsyndrome.org.

Forward-Looking Statements
Statements in this press release
that are not strictly historical in nature are forward-looking
statements. These statements include but are not limited to statements
regarding the timing of the commencement of the Phase 3 clinical trial
evaluating trofinetide; the likelihood of success of such clinical
trial; the prospects for FDA approval of trofinetide for Rett syndrome
and other indications; and the success of any efforts to commercialize
trofinetide in North America. These statements are only predictions
based on current information and expectations and involve a number of
risks and uncertainties. Actual events or results may differ materially
from those projected in any of such statements due to various factors,
including the risks and uncertainties inherent in drug discovery,
development, approval and commercialization. For a discussion of these
and other factors, please refer to ACADIA's annual report on Form 10-K
for the year ended December 31, 2017 as well as ACADIA's subsequent
filings with the Securities and Exchange Commission. You are cautioned
not to place undue reliance on these forward-looking statements, which
speak only as of the date hereof. This caution is made under the safe
harbor provisions of the Private Securities Litigation Reform Act of
1995. All forward-looking statements are qualified in their entirety by
this cautionary statement and ACADIA undertakes no obligation to revise
or update this press release to reflect events or circumstances after
the date hereof, except as required by law.

This ASX-announcement contains forward-looking statements that are
subject to risks and uncertainties. Such statements involve known and
unknown risks and important factors that may cause the actual results,
performance or achievements of Neuren to be materially different from
the statements in this announcement.

References

1Tropea, D., et al. (2009). "Partial reversal of Rett
Syndrome-like symptoms in MeCP2 mutant mice." Proc Natl Acad Sci U S A
106(6): 2029-2034.

2Vahdatpour, C., et al. (2016). "Insulin-Like Growth Factor 1
and Related Compounds in the Treatment of Childhood-Onset
Neurodevelopmental Disorders." Front Neurosci 10: 450.

3Glaze, D. G., et al. (2017). "A Double-Blind, Randomized,
Placebo-Controlled Clinical Study of Trofinetide in the Treatment of
Rett Syndrome." Pediatr Neurol 76: 37-46.

4Chahrour, M. and H. Y. Zoghbi (2007). "The story of Rett
syndrome: from clinic to neurobiology." Neuron 56(3): 422-437.

5Ip, J. P. K., et al. (2018). "Rett syndrome: insights into
genetic, molecular and circuit mechanisms." Nat Rev Neurosci 19(6):
368-382.

6Hagerman, R.J., et al. (2017). "Fragile X syndrome." Nat Rev
Disease Primers 3: 1-19.

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