-ACADIA plans to initiate a Phase 3 study of trofinetide for thetreatment of Rett syndrome, a rare neurodevelopmental congenital CNSdisorder, 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 milestonesof up to US $455 million and royalties
SAN DIEGO & MELBOURNE, Australia—(BUSINESS WIRE)—Aug. 6, 2018—ACADIA Pharmaceuticals Inc. (NASDAQ: ACAD) and Neuren PharmaceuticalsLimited (ASX: NEU) announced today that they have entered into anexclusive North American License Agreement for the development andcommercialization of trofinetide for Rett syndrome and otherindications. Neuren retains rights to develop and commercializetrofinetide for all indications outside of North America.
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ACADIA plans to initiate a Phase 3 randomized, double-blindplacebo-controlled study evaluating trofinetide in the second half of2019 following completion of additional manufacturing activities. Thisstudy will evaluate trofinetide and placebo in approximately 180 girlswith Rett syndrome and will measure the Rett Syndrome BehaviorQuestionnaire (RSBQ), a caregiver assessment, and the Clinical GlobalImpression of Improvement (CGI-I), a physician assessment, as co-primaryefficacy endpoints.
“A potential treatment for Rett syndrome is a perfect fit with ACADIA’smission to develop novel therapies to improve the lives of patients withcentral 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 womensuffering from Rett syndrome. We look forward to initiating a Phase 3study in the second half of 2019 to further explore the potentialbenefits of trofinetide for patients and their caregivers.”
Neuren Executive Chairman Dr. Richard Treagus commented, “We aredelighted to be partnering with ACADIA in North America. ACADIA’s teamhas a proven record in developing and commercializing medicines incentral nervous system disorders with no approved therapies and highunmet needs. ACADIA’s additional capabilities and resources willimmediately make a very significant difference, enabling us to advanceour shared goal of developing this novel treatment option for Rettsyndrome patients.”
Steve Kaminsky, Ph.D., Chief Science Officer of Rettsyndrome.org,commented, “Rettsyndrome.org is grateful to Neuren for their dedicationto the development of trofinetide. ACADIA’s commitment to advancetrofinetide to Phase 3 brings us closer to the first potential treatmentfor Rett syndrome with a drug designed to address the underlying biologyand improve the lives of those suffering from the condition.”
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 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 rangingstudy in girls aged 5 to 15 years with Rett syndrome, in whichstatistically significant and clinically meaningful improvement wasdemonstrated on the RSBQ and the CGI-I. This followed positive trendsobserved in an earlier Phase 2 trial in adolescents and adults aged 16to 45 years with Rett syndrome3. In addition, Neuren hascompleted 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 inRett syndrome are very promising in terms of both safety and clinicalbenefit. For many families, these improvements would provide meaningfulimprovement in their child’s quality of life.”
Under the terms of the License Agreement, Neuren is eligible to receiveUS $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 oftrofinetide in North America and one third of the market value of anyRare Pediatric Disease Priority Review Voucher, if awarded by the U.S.FDA upon approval of a New Drug Application for trofinetide. Thepotential milestone payments to Neuren consist of US $105 millionsubject to achievement of development milestones in Rett syndrome andFragile X syndrome and up to US $350 million subject to achievement ofthresholds of annual net sales of trofinetide in North America. ACADIAwill fund and execute the remaining development for trofinetide in Rettsyndrome in North America, except for the completion by Neuren ofcertain in-progress preparatory activities. ACADIA and Neuren will forma Joint Steering Committee to direct the development of trofinetide inall indications, including the next clinical trial for Fragile Xsyndrome. Any data and regulatory filings generated by ACADIA or Neurenmay be used by either party for the development and commercialization oftrofinetide in their respective territories. ACADIA has a right of firstnegotiation to acquire a license to develop and commercializetrofinetide outside North America. Neuren has an obligation not todevelop a competing product in indications for which ACADIA develops andcommercializes trofinetide.
About Trofinetide
Trofinetide is a novel synthetic analog ofthe amino‐terminal tripeptide of IGF-1 designed to treat the coresymptoms of Rett syndrome by reducing neuroinflammation and supportingsynaptic function. In the central nervous system, IGF-1 is produced byboth of the major types of brain cells – neurons and glia. IGF-1 in thebrain is critical for both normal development and for response to injuryand disease1,2. Trofinetide has been granted U.S. FDA FastTrack Status and Orphan Drug Designation in the U.S. and Europe for bothRett syndrome and Fragile X syndrome.
About Rett Syndrome
Rett syndrome is a debilitatingneurological disorder that occurs primarily in females followingapparently normal development for the first six months of life. Rettsyndrome has been most often misdiagnosed as autism, cerebral palsy, ornon-specific developmental delay. Rett syndrome is caused by mutationson the X chromosome on a gene called MeCP24. There are morethan 200 different mutations found on the MeCP2 gene that interfere withits ability to generate a normal gene product4. Rett syndromeoccurs worldwide in approximately one of every 10,000 to 15,000 femalebirths5 causing problems in brain function that areresponsible for cognitive, sensory, emotional, motor and autonomicfunction. Typically, between six to eighteen months of age, patientsexperience a period of rapid decline with loss of purposeful hand useand spoken communication and inability to independently conductactivities of daily living5. Symptoms also include seizures,disorganized breathing patterns, an abnormal side-to-side curvature ofthe spine (scoliosis) and sleep disturbances. Currently, there are noapproved medicines approved for the treatment of Rett syndrome1.
About Fragile X syndrome
Fragile X syndrome is the mostcommon inherited cause of intellectual disability and the most commonknown cause of autism. Fragile X syndrome is caused by a single genedefect on the X chromosome that impacts the FMRP protein, which isresponsible for regulating the synapses of nerve cells. One of every5,000 males and one of every 4,000 to 8,000 females are estimated tohave the full gene mutation6. Generally males are moreseverely affected than females. Clinically, Fragile X syndrome ischaracterized by intellectual disability, hyperactivity and attentionalproblems, autistic symptoms, anxiety, emotional lability and epilepsy.Currently, there are no medicines approved for the treatment of FragileX syndrome.
About ACADIA Pharmaceuticals
ACADIA is a biopharmaceuticalcompany focused on the development and commercialization of innovativemedicines to address unmet medical needs in central nervous systemdisorders. ACADIA has developed and is commercializing the first andonly medicine approved for the treatment of hallucinations and delusionsassociated with Parkinson’s disease psychosis. In addition, ACADIA hasongoing clinical development efforts in additional areas withsignificant unmet need including dementia-related psychosis,schizophrenia inadequate response, schizophrenia-negative symptoms andmajor depressive disorder. This press release and further informationabout ACADIA can be found at: www.acadia-pharm.com.
About Neuren Pharmaceuticals
Neuren Pharmaceuticals Limited(Neuren) is a biopharmaceutical company developing new therapies forbrain injury, neurodevelopmental and neurodegenerative disorders. Neurenhas completed Phase 2 development of trofinetide for Rett syndrome andhas completed a Phase 2 clinical trial in Fragile X syndrome.
About Rettsyndrome.org
Rettsyndrome.orgis one of the leading private funders of Rett syndrome research. Theorganization hosts the largest global gathering of Rett researchers andclinicians to establish research direction for the future. The missionof the organization is to accelerate the full spectrum research to cureRett syndrome and empower families with information, knowledge andconnectivity. Further information about Rettsyndrome.org canbe found at: rettsyndrome.org.
Forward-Looking Statements
Statements in this press releasethat are not strictly historical in nature are forward-lookingstatements. These statements include but are not limited to statementsregarding the timing of the commencement of the Phase 3 clinical trialevaluating trofinetide; the likelihood of success of such clinicaltrial; the prospects for FDA approval of trofinetide for Rett syndromeand other indications; and the success of any efforts to commercializetrofinetide in North America. These statements are only predictionsbased on current information and expectations and involve a number ofrisks and uncertainties. Actual events or results may differ materiallyfrom 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 theseand other factors, please refer to ACADIA’s annual report on Form 10-Kfor the year ended December 31, 2017 as well as ACADIA’s subsequentfilings with the Securities and Exchange Commission. You are cautionednot to place undue reliance on these forward-looking statements, whichspeak only as of the date hereof. This caution is made under the safeharbor provisions of the Private Securities Litigation Reform Act of1995. All forward-looking statements are qualified in their entirety bythis cautionary statement and ACADIA undertakes no obligation to reviseor update this press release to reflect events or circumstances afterthe date hereof, except as required by law.
This ASX-announcement contains forward-looking statements that aresubject to risks and uncertainties. Such statements involve known andunknown risks and important factors that may cause the actual results,performance or achievements of Neuren to be materially different fromthe statements in this announcement.
References
1Tropea, D., et al. (2009). "Partial reversal of RettSyndrome-like symptoms in MeCP2 mutant mice." Proc Natl Acad Sci U S A106(6): 2029-2034.
2Vahdatpour, C., et al. (2016). "Insulin-Like Growth Factor 1and Related Compounds in the Treatment of Childhood-OnsetNeurodevelopmental Disorders." Front Neurosci 10: 450.
3Glaze, D. G., et al. (2017). "A Double-Blind, Randomized,Placebo-Controlled Clinical Study of Trofinetide in the Treatment ofRett Syndrome." Pediatr Neurol 76: 37-46.
4Chahrour, M. and H. Y. Zoghbi (2007). "The story of Rettsyndrome: from clinic to neurobiology." Neuron 56(3): 422-437.
5Ip, J. P. K., et al. (2018). "Rett syndrome: insights intogenetic, molecular and circuit mechanisms." Nat Rev Neurosci 19(6):368-382.
6Hagerman, R.J., et al. (2017). “Fragile X syndrome.” Nat RevDisease Primers 3: 1-19.
Source: ACADIA Pharmaceuticals Inc.
ACADIA Pharmaceuticals Inc.
Investor Contact:
ElenaRidloff, CFA
(858) 558-2871
ir@acadia-pharm.com
or
MediaContact:
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or
NeurenPharmaceuticals Limited
Contact:
Dr. Richard Treagus
ExecutiveChairman
+61 417 520 509
rtreagus@neurenpharma.com