Published Data Support Scientific Basis for Ganaxolone Use in PCDH 19 Female Epilepsy

Print 06 July 2015

RADNOR, Pa., July 6, 2015 (GLOBE NEWSWIRE) -- Marinus Pharmaceuticals, Inc. (Nasdaq:MRNS), a biopharmaceutical company dedicated to the development of innovative neuropsychiatric therapeutics, today announced that Jozef Gecz, Ph.D., Professor of Human Genetics at the Department of Pediatrics, University of Adelaide, published data in the June issue of Human Molecular Genetics, supporting the role for neurosteroids in the pathophysiology of PCDH19 female epilepsy. Marinus is currently conducting a Phase 2 clinical trial in PCDH19 with ganaxolone, a small molecule that is a synthetic analog of the endogenous neurosteroid allopregnanolone, and received orphan designation from the United States Food and Drug Administration for PCDH19 female epilepsy earlier this year.

In his research, Dr. Gecz used primary skin fibroblasts from 12 PCDH19 affected females and three transmitting males, to show that steroid metabolism and neurosteroid metabolism is associated with PCDH19 female epilepsy. Dr. Gecz identified two genes, AKR1C2 and AKR1C3, which code for crucial neurosteroid-metabolizing enzymes and showed that downregulation of the AKR1C3 and AKR1C2 genes leads to allopregnanolone deficiency in the blood of all PCDH19 females tested. Dr. Gecz then studied nine additional PCDH19 females and age-matched control subjects to measure their blood allopregnanolone levels using three alternative assays. While allopregnanolone levels varied with age, all PCDH19 females tested had lower blood allopregnanolone levels than their age-matched controls. In conclusion, the study showed that the deficiency of neurosteroid allopregnanolone, one of the most potent GABA receptor modulators, may contribute to PCDH19 female epilepsy.

"One of the main enzymatic activities of AKR1C3/AKR1C2 is conversation of 5a-DHP to allopregnanolone," commented Dr. Gecz. "Our findings on AKR1C gene dysregulation and subsequent allopregnanolone deficiency suggest that steroids may play an important role in PCDH19 female epilepsy and that supplementation with ganaxolone, a synthetic analog of allopregnanolone, may potentially offer therapeutic benefit."

Marinus is currently enrolling patients in its Phase 2 clinical study in PCDH19. The study is designed to enroll approximately 10 female pediatric patients between the ages of 2 and 10 years old, with a confirmed PCDH19 genetic mutation. After establishing baseline seizure frequency, patients are being treated with ganaxolone, administered as either oral liquid suspension or capsules, for up to 26 weeks. The primary endpoint of the study is percent change in seizure frequency per 28 days relative to baseline. Initial data from the study is anticipated this year with the full data set in 2016. 

About PCDH19 Female Pediatric Epilepsy

PCDH19 female pediatric epilepsy is a serious and rare epileptic syndrome that affects approximately 15,000-30,000 females in the United States. The condition, which is caused by an inherited mutation of the protocadherin 19 (PCDH19) gene, located on the X chromosome, is characterized by early-onset cluster seizures, cognitive and sensory impairment of varying degrees, and behavioral disturbances. The PCDH19 gene encodes a protein, protocadherin 19, which is part of a family of molecules supporting the communication between cells in the central nervous system. In case of mutation, protocadherin 19 may be malformed, reduced in its functions or not produced at all. The abnormal expression of protocadherin 19 is associated with occurrence of seizures beginning in the early years of life, mostly focal clusters of seizures that last from one day to weeks. Often, but not always, the syndrome is also associated with a cognitive impairment of varying nature, and behavioral or social disorders with autistic traits. Currently, there are no approved therapies for PCDH19 female pediatric epilepsy.

About Marinus Pharmaceuticals

Marinus Pharmaceuticals, Inc., is a biopharmaceutical company dedicated to the development of innovative neuropsychiatric therapeutics. The Company's clinical stage drug candidate for the treatment of seizure disorders in adults and children with epilepsy is ganaxolone. Ganaxolone is a novel synthetic analog of the endogenous neurosteroid, allopregnanolone (known for its anticonvulsive and antianxiety effects) and was designed to avoid hormonal side effects associated with endogenous neurosteroids. The Company is currently conducting a multi-national, randomized, placebo-controlled, Phase 3 clinical trial to evaluate ganaxolone as adjunctive treatment of partial-onset seizures in adults. Ganaxolone is also being studied in a Phase 2 proof-of-concept clinical study for the treatment of the rare, genetic disorder, PCDH19 female pediatric epilepsy. To complement the existing formulations and to provide continuity of care, the Company is developing an IV formulation of ganaxolone for use in the hospital setting to control epileptic seizures. In addition, ganaxolone is being evaluated in a Phase 2 proof-of-concept investigator-sponsored clinical trial as a treatment for behaviors in Fragile X Syndrome. For additional information, please visit the Company's website at www.marinuspharma.com.

Forward-Looking Statements

To the extent that statements contained in this press release are not descriptions of historical facts regarding Marinus, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.  Words such as "may", "will", "expect", "anticipate", "estimate", "intend", and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements.  Examples of forward looking statements contained in this press release include, among others, statements regarding our expectations regarding our development plans for our product candidate, including, the clinical trial testing schedule, the ability to complete enrollment in our clinical trials, interpretation of scientific basis for ganaxolone use, timing for availability and release of data, the safety, potential efficacy and therapeutic potential of our product candidate and our expectation regarding the sufficiency of our working capital. Forward-looking statements in this release involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements.  Such risks and uncertainties include, among others, the uncertainties inherent in the conduct of future clinical trials, the timing of the clinical trials, enrollment in clinical trials, availability of data from ongoing clinical trials, expectations for regulatory approvals, and other matters, including the development of formulations of ganaxolone, that could affect the availability or commercial potential of our drug candidates. Marinus undertakes no obligation to update or revise any forward-looking statements.  For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general, see filings Marinus has made with the Securities and Exchange Commission.

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