Marinus Pharmaceuticals
MARINUS PHARMACEUTICALS INC (Form: 8-K, Received: 09/11/2017 08:50:20)

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C.  20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

 

Date of Report

(Date of earliest event reported)

 

September 11, 2017

 

MARINUS PHARMACEUTICALS, INC.

(Exact name of registrant as specified in its charter)

 

Delaware
(State or other jurisdiction
of incorporation)

 

001-36576
(Commission File Number)

 

20-0198082
(I.R.S. Employer
Identification No.)

 

Three Radnor Corporate Center
170 N. Radnor Chester Rd., Suite 250
Radnor, PA

(Address of principal executive offices)

 

19087
(Zip Code)

 

Registrant’s telephone number, including area code:  (484) 801-4670

 

N/A

(Former name or former address, if changed since last report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

o                         Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

o                         Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

o                         Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

o                         Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

 

Emerging growth company x

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. x

 

 

 



 

Item 7.01 .                                         Regulation FD Disclosure .

 

On September 11, 2017, Marinus Pharmaceuticals, Inc. (the “Company”) conducted an investor conference call and webcast.  A copy of the slides presented during that call is submitted as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference in this Item 7.01 as though fully set forth herein.

 

Item 8.01 .                                         Other Events .

 

On September 11, 2017, the Company issued a press release announcing top-line results from a Phase 2 open-label study in patients with CDKL5 disorder.  A copy of the press release is filed as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated by reference in this Item 8.01 as though fully set forth herein.

 

Item 9.01 .                                         Financial Statements and Exhibits .

 

Exhibit No.

 

Exhibit Description

 

 

 

99.1

 

Slide Presentation at Investor Conference Call and Webcast on September 11, 2017 at 9:00 a.m. ET

 

 

 

99.2

 

Press Release dated September 11, 2017

 

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SIGNATURE

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

 

MARINUS PHARMACEUTICALS, INC.

 

 

 

 

 

By:

/s/ Edward Smith

 

 

Edward Smith,

 

 

Vice President, Chief Financial Officer,

 

 

Secretary and Treasurer

 

 

Date: September 11, 2017

 

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Exhibit 99.1

Mindful Innovation Phase 2 Clinical Study Evaluating Ganaxolone in Children with CDKL5 Disorder September 11, 2017 Follow @MarinusPharma on Twitter!

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Safe Harbor Statement 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”, “believe”, 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 interpretation of preclinical studies, development plans for our product candidate, including the development of dose forms, the clinical trial testing schedule and milestones, 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, the attainment of clinical trial results that will be supportive of regulatory approvals, and other matters, including the development of formulations of ganaxolone, and the availability or potential availability of alternative products or treatments for conditions targeted by the company 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 Marinus' 10-K dated March 13, 2017 and other filings by the company with the U.S. Securities and Exchange Commission. You may access these documents for free by visiting EDGAR on the SEC web site at www.sec.gov. 1

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Agenda Introduction Christopher M. Cashman, CEO Phase 2 clinical trial design & data Dr. Lorianne Masuoka, CMO Case summaries of patients w/ CDKL5 disorder Dr. Nicola Specchio, Principal Investigator, Ospedale Pediatrico Bambino Gesù, Rome Closing Remarks Christopher M. Cashman, CEO 2

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Marinus’s Development of Ganaxolone 3 Clear efficacy signal in refractory, CDKL5 disorder Need for mechanistically novel, efficacious & safe treatment options Committed to improving lives of patients with refractory epilepsies and psychiatric disorders

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Ganaxolone in children with CDKL5 Disorder Dr. Lorianne Masuoka, CMO

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5 Ganaxolone (GNX) Targets Synaptic and Extrasynaptic GABAA Receptors GNX is a synthetic analog of allopregnanolone GNX is designed to modulate both synaptic and extrasynaptic GABAA receptors to calm over-excited neurons

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CDKL5 Disorder – Rare, serious epileptic condition 6 Cause Mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome Symptoms Early-onset, difficult-to-control seizures, & severe neuro-developmental impairment Most can’t walk, talk or care for themselves Suffer from scoliosis, visual impairment, gastrointestinal difficulties & sleeping disorders Prevalence Affects <1000 children WW Predominantly females Genetic testing available Orphan Drug designation Treatments No approved treatments Mechanistic Rationale Potential GABAA dysfunction

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Phase 2 Study in CDKL5 Disorder Trial Design: 2 sites in US; 1 site in Italy Oral ganaxolone - up to 1,800 mg/day + existing treatment regimen 6 females, 1 male; ages 2-16 Enrollment criteria: Confirmed CDKL5 mutation, stable background treatment, >4 seizures per 28-day period in baseline Endpoints: Primary: % change in seizure frequency per 28 days relative to baseline Secondary: % increase in seizure-free days from baseline, safety and tolerability, CGI 7 12 weeks Baseline Treatment Period 26 weeks 52 weeks 1-year extension

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CDKL5 Disorder - Phase 2 Efficacy Data (as of Sept 11, 2017) 8 One-Year Extension Enrollees N=3* Median Seizure reduction 70% Median increase in seizure-free days 75% ITT Analysis N=7 Median seizure reduction from baseline 43% Median increase in seizure-free days 78% *One high responder is still undergoing the 26-week treatment period Efficacy of existing AEDs and the ketogenic diet in patients with the CDKL5 mutation is low and the durability of effect is short1 1Müller, A. et al. Retrospective evaluation of long-term efficacy of antiepileptic drugs and ketogenic diet in 39 patients with CDKL5-related epilepsy, European Journal of Paediatric Neurology, Volume 20 (2016), 147-151. Patients with Improved Control of Epilepsy N=5 Median Seizure Reduction 65% (range 24% - 85%)

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CDKL5 Disorder - Phase 2 Safety Profile (as of Sept 11, 2017) Generally safe and well-tolerated No serious adverse events No reports of somnolence or dizziness (the most frequently reported AE in prior studies) Two patients discontinued prior to completing the 26-week treatment due to lack of efficacy 9

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Case summaries Dr. Nicola Specchio Principal Investigator, Ospedale Pediatrico Bambino Gesù in Rome

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8-Year Old Female Pre-ganaxolone treatment Post-ganaxolone treatment % Change Seizures daily spasms and tonic spasms spasms almost disappeared; improvement in attention and interaction; child shows affection Seizure frequency (per 28 days) 155 23 85% decrease in seizures Seizure-free days 9 16 >50% seizure-free days 11 Prior treatment meds: lamotrigine, carbamezapine, vigabatrin Patient continues treatment with ganaxolone CGI-I and CGI-P – “much improved”

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11-Year Old Female Pre-ganaxolone treatment Post-ganaxolone treatment % Change Seizures multiple absences and spasms per day; severe behavior disturbance; frequent respiratory infections reduction of seizure frequency and intensity; improved quality of life; relieved by burden of epilepsy Seizure frequency (per 28 days) 116 41 65% decrease in seizures Seizure-free days 3 14 400% increase in seizure-free days 12 Prior treatment meds: valproate, acetazolamide, lorazepam & clobazam Patient continues treatment with ganaxolone CGI-I and CGI-P – “much improved”

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Why Ganaxolone in CDKL5 Disorder? 13 Remarkable response in efficacy, safety and behavior with ganaxolone in this extremely rare, refractory patient population that has little success in controlling their seizures with existing treatment regimens Magnitude of Effect The children with improved seizure control continued improvement beyond the 6 months of treatment Durability of Effect Ganaxolone has a clean safety profile; it was generally safe and well-tolerated with no SAEs Safety

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Thank you Follow @MarinusPharma on Twitter!

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Exhibit 99.2

 

MARINUS ANNOUNCES SUCCESSFUL CLINICAL TRIAL RESULTS AND

DECLARES CDKL5 DISORDER ITS LEAD PEDIATRIC

ORPHAN EPILEPSY PROGRAM FOR GANAXOLONE

 

Substantial and Durable Anti-Seizure Efficacy Shown in Patients Suffering From Severe,

Rare Genetic Epilepsy

 

Marinus to Host Conference Call and Webcast Today at 9:00 am EDT

 

RADNOR, PA, September 11, 2017 (Globe Newswire) — Marinus Pharmaceuticals, Inc. (Nasdaq:MRNS), today announced that top-line data from the Phase 2 open-label study in patients with CDKL5 disorder support advancing ganaxolone into a definitive late-stage clinical trial. Oral ganaxolone, in addition to baseline treatment, showed a sizable and durable seizure-frequency reduction in the majority of patients, with some achieving an increase in the number of seizure-free days and reporting behavioral benefits. CDKL5 disorder is a severe, rare genetic epilepsy that results in early-onset, treatment-refractory seizures, pervasive neuro-developmental delay and disabling behavioral issues. There are no approved or effective available treatment options. Marinus plans to meet with regulatory agencies to obtain agreement on the clinical development plan that would be needed for approval of ganaxolone for CDKL5 disorder.

 

O rrin Devinsky, MD, Director of the NYU Langone Medical Center’s Comprehensive Epilepsy Center and Principal Investigator in the current study, commented, “I am impressed with the magnitude of seizure reduction and gain in seizure-free days seen with ganaxolone treatment in children with this highly refractory epilepsy. The durable anti-epileptic effect seen in several children distinguishes ganaxolone’s efficacy from the more than 20 currently available anti-epileptic drugs that provide limited seizure control lasting a few weeks to months. When treating children with the severest forms of epilepsy such as CDKL5 disorder, there is a desperate need for new drugs that are well-tolerated, efficacious and easy to administer with no need for special monitoring. With no other treatment showing this degree of promise, I am excited to lead the effort to advance ganaxolone into potentially the first, late-stage clinical trial in children with CDKL5 disorder.”

 

Top-line Data:

 

·                   The median change in 28-day seizure frequency from baseline in the ITT (intent-to-treat) population (primary endpoint) was a decrease of 43% (n=7).

·                   The median change from baseline in seizure-free days in the ITT population (key secondary endpoint) was an increase of 78% (n=5; two subjects cannot be calculated due to 0 baseline seizure-free days).

 



 

·                   Five of the seven children experienced a meaningful seizure reduction compared to baseline; median reduction of 65% (range 24% - 85%).

·                   Three children have so far met the criteria to enter the one year study extension (completed 26-weeks of treatment with excellent seizure control) and continue to experience a median seizure reduction of 70% and median increase in seizure-free days of 75%.

·                   The Clinical Global Impression Scale rated by Investigators (CGI-I) and Caregivers (CGI-P) were consistent with seizure control for all the children. Children with a 43% or higher seizure reduction were rated as “much improved” or “very much improved” by the Investigators and Caregivers.

·                   Investigators and Caregivers reported improvements in attention, mood, behavior and sleep via investigator narratives.

·                   Ganaxolone was generally safe and well-tolerated with no serious adverse events. To date, there have been no adverse event reports of somnolence or dizziness.

·                   One child has not yet reached the 26-week visit and two children discontinued prior to completing the 26-week treatment due to lack of efficacy.

 

Nicola Specchio, MD, PhD, Principal Investigator at the Ospedale Pediatrico Bambino Gesù in Rome, commented, “I am very impressed with the improvement my patients experienced while on ganaxolone. They showed a sizeable decrease in seizure frequency and increase in attention associated with a calmer demeanor, which exceeded my expectations. Ganaxolone’s safety profile and effect on seizure and non-seizure related comorbidities, common in children with CDKL5 disorder, makes it an exciting potential therapeutic for this rare patient population that critically needs an effective and lasting treatment option.”

 

Marinus is planning to submit the full CDKL5 disorder data set for publication or presentation at a medical conference.  Earlier this year, Marinus received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) to develop ganaxolone for the treatment of CDKL5 Disorder.

 

“We believe that the efficacy and safety profile of ganaxolone in this study provide compelling evidence that a definitive study in patients with CDKL5 disorder should be undertaken as soon as possible,” commented Dr. Lorianne Masuoka, Chief Medical Officer of Marinus Pharmaceuticals.  “The tolerability and complete lack of dose regimen-limiting safety concerns, as compared to the most widely used anti-epileptic drugs for this condition, could make ganaxolone an exceptional option for patients with CDKL5 disorder.”

 

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The study enrolled seven children between the ages of 2 and 16 at three sites within the U.S. and Italy.  Following screening and baseline evaluations, children received up to 1,800 mg/day of oral ganaxolone in addition to their current treatment regimen for up to 26-weeks. The primary efficacy measure was percent change from baseline in the 28-day seizure frequency over 26-weeks. The key secondary outcome measure was percent change from baseline in seizure-free days. Safety and tolerability were secondary objectives of the study. Patients responding to therapy were given the option to enroll into a 52-week extension program.

 

In addition to the CDKL5 disorder cohort of patients, Marinus evaluated a cohort of Lennox-Gastaut syndrome (LGS) patients.  Based upon these robust CDKL5 disorder clinical results and etiologic fit with ganaxolone’s mechanism of action, Marinus has prioritized CDKL5 disorder as its lead pediatric orphan program for advancement into later stage clinical development.

 

Conference Call and Webcast Details

Marinus will host a conference call today at 9:00 a.m. EDT. Stockholders and other interested parties may participate in the call by dialing 844-277-9448 (domestic) or 336-525-7135 (international) and referencing conference ID number 79335646. The live webcast can be accessed on the investor page of Marinus’ website at http://ir.marinuspharma.com/events.cfm. A replay will be available on Marinus’ website approximately two hours after completion of the event and will be archived for up to 30 days.

 

About CDKL5 Disorder

 

CDKL5 disorder is a serious and rare genetic disorder that is caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome. It predominantly affects girls and is characterized by early-onset, difficult-to-control seizures and severe neuro-developmental impairment. The CDKL5 gene encodes a protein essential for normal brain function.  Most children affected by CDKL5 cannot walk, talk, or care for themselves. Many also suffer from scoliosis, visual impairment, gastrointestinal difficulties, and sleeping disorders. CDKL5 disorder is among the epileptic encephalopathies that are most refractory to treatment.  Currently, there are no approved therapies for CDKL5 Disorder.

 

About Ganaxolone

 

Ganaxolone, a positive allosteric modulator of GABA A , is being developed in three different dose forms (intravenous, capsule, and liquid) intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Unlike benzodiazepines, ganaxolone exhibits anti-seizure and anti-anxiety activity via its effects on synaptic and extrasynaptic GABA A  receptors.  Ganaxolone has been studied in more than 1,500 subjects, both pediatric and adult, at therapeutically relevant dose levels and treatment regimens for up to two years. In these studies, ganaxolone was generally safe and well-tolerated. The most commonly reported adverse events were somnolence, dizziness and fatigue.

 

About Marinus Pharmaceuticals

 

Marinus Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to the development of ganaxolone, which offers a new mechanism of action, demonstrated efficacy and safety, and

 

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convenient dosing to improve the lives of patients suffering from epilepsy and neuropsychiatric disorders. Ganaxolone is a positive allosteric modulator of GABA A  that acts on a well-characterized target in the brain known to have both anti-seizure and anti-anxiety effects. Ganaxolone is being developed in three different dose forms (IV, capsule and liquid) intended to maximize therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. Marinus is currently evaluating ganaxolone in women with postpartum depression and in orphan pediatric indications for the treatment of genetic seizure and behavior disorders, and preparing to initiate a Phase 2 study in status epilepticus, an orphan indication. For more information visit www.marinuspharma.com. Please follow us on Twitter: @MarinusPharma.

 

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”, “believe”, 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 interpretation of preclinical studies, development plans for our product candidate, including the development of dose forms, the clinical trial testing schedule and milestones, 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, the attainment of clinical trial results that will be supportive of regulatory approvals, and other matters, including the development of formulations of ganaxolone, and the availability or potential availability of alternative products or treatments for conditions targeted by the company 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.

 

CONTACT:

 

Lisa M. Caperelli

Executive Director, Investor & Strategic Relations

Marinus Pharmaceuticals, Inc.

484-801-4674

lcaperelli@marinuspharma.com

 

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