Positive Phase 2 Study Results of Trofinetide in Pediatric Rett Syndrome Published in Neurology, the Medical Journal of the American Academy of Neurology

—Statistically Significant Improvement Indicates Trofinetide’sPotential for Treating Rett Syndrome

—Trofinetidefor Rett Syndrome has Fast Track Status and Orphan Drug Designation inthe U.S. and Orphan Drug Designation in Europe

SAN DIEGO & CINCINNATI & MELBOURNE, Australia—(BUSINESS WIRE)—Mar. 27, 2019—ACADIA Pharmaceuticals Inc. (NASDAQ: ACAD), Neuren PharmaceuticalsLimited (ASX: NEU), and Rettsyndrome.org (RSO) announced today that thepositive results from a Phase 2 study conducted by Neuren, whichevaluated the safety and efficacy of trofinetide in females with Rettsyndrome (RTT), have been published in Neurology^®,the medical journal of the American Academy of Neurology.

This press release features multimedia. View the full release here:https://www.businesswire.com/news/home/20190327005774/en/

The study, “Double-Blind,Randomized, Placebo-Controlled Study of Trofinetide in Pediatric RettSyndrome” has been published online and will appear in the April 16,2019 issue of Neurology. The study evaluated 82 females with Rettsyndrome aged 5 to 15 years and found at the highest dose (200 mg/kgtwice daily or BID) trofinetide achieved statistically significantimprovement compared with placebo on three of five syndrome-specificefficacy measures: the Rett Syndrome Behaviour Questionnaire (RSBQ), acaregiver assessment (p=0.042), the Clinical Global ImpressionScale-Improvement (CGI-I), a clinician assessment of the improvement ofRett syndrome (p=0.029), and the RTT-Clinician Domain SpecificConcerns-Visual Analog Scale (RTT-DSC), a clinician assessment(p=0.025). Results of the study also showed trofinetide waswell-tolerated at all dose levels (50 mg/kg BID, 100 mg/kg BID, and 200mg/kg BID).

“Disease burden is severe for Rett patients and their families, and theimpact of the disorder is life-long,” said Daniel Glaze, M.D., studyauthor, Baylor College of Medicine, Department of Pediatrics andNeurology and Director at the Blue Bird Circle Rett Center, TexasChildren’s Hospital. “The data reported in this study show that femalestreated with trofinetide experienced lessened neurobehavioralimpairments including social communication deficits, anxiety-likebehavior, and mood dysregulation. These are very promising data for theRett community that is currently without any U.S. FDA-approved treatmentoption.”

In 2018, ACADIA entered into an exclusive North American licenseagreement with Neuren for the development and commercialization oftrofinetide for Rett syndrome and other indications.

“Rett syndrome is a condition that leads to severe neurologicalimpairments and is not only debilitating for the person with thedisease, but also very hard on the families and caregivers of thechildren, mostly females, who are often unable to speak, walk, eat, andeven breathe normally,” said Steve Kaminsky, Ph.D., Chief ScienceOfficer of RSO. “These results are very encouraging because they providestrong evidence that trofinetide may be a potential treatment for Rettsyndrome.”

ACADIA plans to initiate a 12-week Phase 3 double-blind, randomized,placebo-controlled study evaluating trofinetide in the second half of2019 following completion of additional manufacturing scale-upactivities. This study will evaluate efficacy and safety of trofinetideand placebo in approximately 180 females ages 5 to 20 years with Rettsyndrome. Half of the study participants will receive trofinetide andhalf will receive placebo. The study will use the RSBQ and the CGI-Isyndrome specific efficacy measures as co-primary efficacy endpoints.The Phase 3 study will be followed by a nine month open label extensionstudy in which all participants, including those on placebo in the Phase3 study, will be eligible to receive trofinetide. In the open labelextension study, all participants will be followed to evaluate long termtolerability and safety of trofinetide.

“Neuren has successfully led the clinical development of trofinetide todate, which allows us to further evaluate trofinetide as a potentiallyimportant treatment option for Rett syndrome,” said Serge Stankovic,M.D., M.S.P.H., ACADIA’s President. “In addition to achieving successfuloutcomes from early-stage clinical research with trofinetide for Rettsyndrome, Neuren has fostered strong and enduring relationships with theRett community. We will build on these efforts as we continue to studytrofinetide for this unmet medical need.”

Phase 2 Study Design

In the Phase 2 study, 82 females were enrolled and randomized to receiveliquid trofinetide or placebo orally or via gastrostomy tube for sixweeks: 24 subjects to placebo BID, 15 subjects to 50 mg/kg oftrofinetide BID, 16 subjects to 100 mg/kg of trofinetide BID, and 27subjects to 200 mg/kg of trofinetide BID. Safety and tolerabilityassessments included adverse events (AEs), clinical laboratory tests,physical examinations, and concomitant medications.

The five core efficacy endpoints included three clinician-completedmeasures and two caregiver-completed measures.

1. The RSBQ, a rating scale in which the subject’s caregiver rates thefrequency of symptoms.
2. The CGI-I, in which the clinician rates how much the subject’s overallillness has improved or worsened, relative to baseline.
3. The RTT-DSC, in which the clinician assesses - on a visual analogscale - the severity of concerns identified for each subject on anindividual basis.
4. The Motor Behavioral Assessment, a rating scale in which the clinicianrates the subject’s current level of function.
5. The Caregiver Top 3 Concerns, in which the subject’s caregiverassesses - on a visual analog scale - the severity of concernsidentified for each subject on an individual basis.

About Trofinetide

Trofinetide is a novel synthetic analog of the amino‐terminal tripeptideof IGF-1 designed to treat the core symptoms of Rett syndrome byreducing neuroinflammation and supporting synaptic function. In thecentral nervous system, IGF-1 is produced by both of the major types ofbrain cells – neurons and glia. IGF-1 in the brain is critical for bothnormal development and for response to injury and disease. Trofinetidehas been granted Fast Track Status and Orphan Drug Designation in theU.S. and Orphan Drug Designation in Europe for both Rett syndrome andFragile X syndrome.

About Rett Syndrome

Rett syndrome is a debilitating neurological disorder that occursprimarily in females following apparently normal development for thefirst six months of life. Rett syndrome has been most often misdiagnosedas autism, cerebral palsy, or non-specific developmental delay. Rettsyndrome is caused by mutations on the X chromosome on a gene calledMeCP2. There are more than 200 different mutations found on the MeCP2gene that interfere with its ability to generate a normal gene product.Rett syndrome occurs worldwide in approximately one of every 10,000 to15,000 female births causing problems in brain function that areresponsible for cognitive, sensory, emotional, motor and autonomicfunction. Typically, between six to 18 months of age, patientsexperience a period of rapid decline with loss of purposeful hand useand spoken communication and inability to independently conductactivities of daily living. Symptoms also include seizures, disorganizedbreathing patterns, an abnormal side-to-side curvature of the spine(scoliosis), and sleep disturbances. Currently, there are no approvedmedicines for the treatment of Rett syndrome.

About ACADIA Pharmaceuticals

ACADIA is a biopharmaceutical company focused on the development andcommercialization of innovative medicines to address unmet medical needsin central nervous system disorders. ACADIA has developed and iscommercializing the first and only medicine approved for the treatmentof hallucinations and delusions associated with Parkinson’s diseasepsychosis. In addition, ACADIA has ongoing clinical development effortsin additional areas with significant unmet need, includingdementia-related psychosis, schizophrenia inadequate response,schizophrenia-negative symptoms, major depressive disorder, and Rettsyndrome. This press release and further information about ACADIA can befound at: www.acadia-pharm.com.

About Neuren Pharmaceuticals

Neuren Pharmaceuticals Limited (Neuren) is a biopharmaceutical companydeveloping new therapies for brain injury, neurodevelopmental andneurodegenerative disorders. Neuren has completed Phase 2 development oftrofinetide for Rett syndrome and has completed a Phase 2 clinical trialof trofinetide in Fragile X syndrome. In addition, Neuren is advancingthe pre-clinical development of its second drug candidate NNZ-2591.Further information about Neuren can be found at: www.neurenpharma.com.

About Rettsyndrome.org

Rettsyndrome.org (RSO) is one of the leading private funders of Rettsyndrome research, investing over $46 million to date. The mission ofthe organization is to accelerate full spectrum research to cure Rettsyndrome and empower families with information, knowledge andconnectivity. Rettsyndrome.org recently earned Charity Navigator’sprestigious 4-star rating for its strong financial health and commitmentto accountability and transparency. Further information aboutRettsyndrome.org can be found at: www.rettsyndrome.org.

Forward-Looking Statements

Statements in this press release that are not strictly historical innature are forward-looking statements. These statements include but arenot limited to statements regarding the timing of the commencement ofthe Phase 3 clinical trial evaluating trofinetide; the likelihood ofsuccess of such clinical trial; the prospects for FDA approval oftrofinetide for Rett syndrome and other indications; and the success ofany efforts to commercialize trofinetide in North America. Thesestatements are only predictions based on current information andexpectations and involve a number of risks and uncertainties. Actualevents or results may differ materially from those projected in any ofsuch statements due to various factors, including the risks anduncertainties inherent in drug discovery, development, approval andcommercialization. For a discussion of these and other factors, pleaserefer to ACADIA’s annual report on Form 10-K for the year ended December31, 2018 as well as ACADIA’s subsequent filings with the Securities andExchange Commission. You are cautioned not to place undue reliance onthese forward-looking statements, which speak only as of the datehereof. This caution is made under the safe harbor provisions of thePrivate Securities Litigation Reform Act of 1995. All forward-lookingstatements are qualified in their entirety by this cautionary statementand ACADIA undertakes no obligation to revise or update this pressrelease to reflect events or circumstances after the date hereof, exceptas required by law.

Source: ACADIA Pharmaceuticals Inc.

ACADIA Pharmaceuticals Inc.
Investor Contact:
MarkJohnson, CFA
(858) 261-2771
ir@acadia-pharm.com

Media Contact:
Maurissa Messier
(858) 768-6068
media@acadia-pharm.com

Neuren Pharmaceuticals
Contact:
Jon Pilcher,Chief Financial Officer
+61 438 422 271
jpilcher@neurenpharma.com