Exhibit 99.1
Marinus Pharmaceuticals Provides Business
Update and Reports First Quarter 2020 Financial Results
Constructive
End of Phase 2 Meeting with FDA for Status Epilepticus Completed in March; Pivotal Phase 3 Clinical Trial Expected
to Begin Next Quarter
Topline Data on Track for Q3 2020 from
Pivotal Phase 3 Marigold Study in CDKL5 Deficiency Disorder and Preparations Continue for Potential NDA Filing
First Patients to be Screened this Quarter
for Phase 2 Tuberous Sclerosis Complex Clinical Trial
RADNOR,
PA, May 4, 2020 -- Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS), a pharmaceutical company dedicated to the development
of innovative therapeutics to treat rare seizure disorders, today provided an update on its clinical development activities and
reported its financial results for the first quarter ended March 31, 2020.
“We
are proud to have made real progress across all of our clinical programs prior to and during the unprecedented and challenging
global impact of the COVID-19 pandemic,” said Scott Braunstein, M.D., Chief Executive Officer of Marinus. “We
remain confident that our key milestones are still on track, including the topline data from our pivotal Phase 3 clinical trial
in CDKL5 deficiency disorder in Q3 2020. With positive topline data, we intend to continue preparations for both our first NDA
submission and the commercial launch of ganaxolone.”
Dr.
Braunstein added, “We had a highly constructive end-of-Phase 2 meeting with the FDA for our status epilepticus program and
anticipate enrolling the first patient in the Phase 3 trial later this year. In addition, we have made significant headway in expanding
our biomarker-informed trial for tuberous sclerosis complex, as our first site has been activated for patient enrollment.
This will be a year of noteworthy milestones for the organization, and we are confident that we are just beginning to unlock ganaxolone’s
potential to improve the lives of patients and families affected by rare and severe epilepsies.”
Pipeline Update:
Status Epilepticus (SE)
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Marinus is moving forward with plans for its Phase 3 pivotal clinical trial in SE after a constructive end-of-Phase 2
meeting with the FDA. Based upon feedback from the FDA, the Company anticipates the following trial design and timeline:
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Co-primary endpoints that focus on status cessation within 30-minutes and suppression of status for at least 24 hours.
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Ganaxolone administered intravenously for 48 hours, the first 12 hours of which is expected to target a 500 ng/ml serum concentration.
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Enrollment of approximately 125 patients; providing greater than 90 percent power to detect a 30 percent efficacy difference
between ganaxolone and placebo.
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Patients enrolled will have previously failed a benzodiazepine and at least two second-line antiepileptic drugs.
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Patient enrollment to begin in Q3 2020 and trial sites have already identified and are in process of being readying.
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Topline data expected in the first half of 2022.
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CDKL5 Deficiency Disorder (CDD)
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Enrollment has been completed in the pivotal Phase 3 Marigold Study, which is evaluating the use of oral ganaxolone in
children and young adults with CDD. The global, double-blind, placebo-controlled, clinical trial has enrolled 101 patients between
the ages of 2 and 21 with a confirmed disease-related CDKL5 gene variant.
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Patients randomized to ganaxolone receive up to 600 mg (oral liquid suspension) three times a day.
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The primary endpoint of the trial is percent change in 28-day seizure frequency. The discontinuation rate in this trial is
in-line with expectations (less than 10 percent), and enrollment in the open label extension part of the trial continues to be
high.
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Marinus remains on-track to report top-line data from the trial in Q3 2020 with no expected material delays due to COVID-19.
The Company has begun preparations for a potential NDA filing and the development of its commercial strategy.
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Phase 1 supportive clinical trials have experienced delays in enrollment due to COVID-19, which, as of today, are not expected
to impact timing for a potential NDA filing.
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Tuberous Sclerosis Complex (TSC)
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Marinus is conducting a Phase 2 open-label trial to evaluate the safety and tolerability of adjunctive ganaxolone treatment
in patients with TSC. The trial is expected to enroll approximately 30 patients ages 2 to 65.
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Patients will undergo a four-week baseline period followed by a 12-week treatment period where they will receive up to 600
mg of ganaxolone (oral liquid suspension) three times a day. Patients who meet eligibility criteria may continue ganaxolone treatment
in a 24-week extension to the trial.
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The primary endpoint for the trial is percent change in 28-day primary seizure frequency for the treatment period relative
to baseline. The Company plans to analyze allopregnanolone sulfate levels as part of the trial efficacy analysis.
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Marinus intends to start screening patients this quarter. As of today, the Company does not anticipate COVID-19 will have a
material impact on enrollment or trial progress and expects to report top line data in Q1 2021.
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PCDH19 Related Epilepsy (PCDH19-RE)
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After careful consideration, Marinus will transition the ongoing Phase 3 Violet Study to a proof-of-concept (POC) trial evaluating
allopregnanolone sulfate as a biomarker in the patients currently enrolled with a confirmed PCDH19 mutation. Marinus has decided
to limit trial enrollment due to several factors, including the significant requirements needed to enroll a global trial (including
COVID-19 impact), the episodic nature of seizures in PCDH19 patients, and potential commercial challenges. The Company now expects
to complete the double-blind portion of the trial with approximately 15-20 patients and announce results of this POC trial in the
first half of 2021.
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The scale down to a POC trial is part of the Company’s strategic plan to focus capital resources on indications with
high unmet needs and a meaningful percentage of patients being underserved by available treatment options.
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Marinus plans to continue to evaluate if the allopregnanolone sulfate biomarker hypothesis could have broader utility in other
targeted indications.
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The POC biomarker trial will stratify patients into one of two biomarker groups based on baseline allopregnanolone sulfate
levels and randomized (ganaxolone or placebo) within each stratum. The trial will consist of a 12-week prospective baseline period
to collect seizure data, followed by a 17-week double-blind treatment phase. Patients randomized to ganaxolone will titrate over
four weeks to a dose of up to 600 mg of ganaxolone (oral liquid suspension) three times a day and maintain that dose for the following
13-weeks.
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Marinus intends to provide access to ganaxolone for PCDH19-RE patients who saw benefits in the Violet Study.
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Corporate Update:
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In April, the Company announced the formation of Scientific Advisory Board with six globally recognized seizure disorder experts.
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In March, Sasha Damouni Ellis was appointed Vice President, Investor Relations and Corporate Communications.
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Financial
Update:
On March 31, 2020, the Company had cash and cash equivalents and investments
totaling $77.8 million compared to $91.7 million on December 31, 2019. Marinus believes that its cash, cash equivalents and investments
as of March 31, 2020 will enable the Company to fund operating expenses and capital expenditure requirements into the third quarter
of 2021.
Research
and development expenses increased to $15.0 million for the three months ended March 31, 2020, as compared to $8.9 million for
the three months ended March 31, 2019. The primary drivers for the increase to our research and development expenditures
are clinical and manufacturing activities in support of our Phase 3 trial in CDD and preparations for a Phase 3 trial in SE, partially
offset by decreased costs for non-seizure disorder indications.
General
and administrative expenses were $3.9 million for the three months ended March 31, 2020 as compared to $3.7 million in the prior
year. The primary drivers of the increase were professional fees and other costs associated with an increased scale
of operations.
The
Company reported a net loss of $18.7 million for the three months ended March 31, 2020, compared to $12.5 million for the three
months ended March 31, 2019. Cash used in operating activities increased to $14.0 million for the three months ended March
31, 2020 compared to $11.7 million for the three months ended March 31, 2019.
Readers
are referred to, and encouraged to read in its entirety, the Company’s Quarterly Report on Form 10-Q for the quarter ended
March 31, 2020 to be filed with the Securities and Exchange Commission, which includes further detail on the Company’s business
plans, operations, financial condition and results of operations.
Marinus
Pharmaceuticals, Inc.
Selected Financial Data (in thousands, except share and per share amounts)
(unaudited)
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March 31,
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December
31,
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2020
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2019
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Assets:
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Cash and cash equivalents
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$
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70,326
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$
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90,943
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Investments
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7,460
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739
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Other assets
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6,772
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7,160
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Total assets
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$
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84,558
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$
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98,842
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Liabilities and stockholders’ equity:
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Accounts payable and accrued expenses
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$
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10,325
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$
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8,031
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Other liabilities
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2,921
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3,042
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Total liabilities
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13,245
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11,073
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Series A preferred stock
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28,200
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28,200
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Total stockholders’ equity
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43,113
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59,569
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Total liabilities and stockholders’ equity
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$
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84,558
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$
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98,842
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Three Months Ended March
31,
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2020
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2019
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Expenses:
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Research and development
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$
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15,004
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$
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8,872
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General and administrative
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3,850
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3,667
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Loss from operations
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(18,854
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)
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(12,539
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)
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Interest income
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222
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|
|
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96
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Other expense
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(40
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)
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(40
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)
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Net loss
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(18,672
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)
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(12,483
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)
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Deemed dividends on convertible preferred stock
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(8,880
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)
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—
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Net loss applicable to common shareholders
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$
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(27,552
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)
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$
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(12,483
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)
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Per share information:
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Net loss per share of common stock—basic and diluted
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$
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(0.32
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)
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$
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(0.24
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)
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Basic and diluted weighted average shares outstanding
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86,661,845
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52,465,207
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About Marinus Pharmaceuticals
Marinus Pharmaceuticals, Inc. is a pharmaceutical company dedicated
to the development of innovative therapeutics to treat rare seizure disorders. Ganaxolone is a positive allosteric modulator of
GABAA receptors that acts on a well-characterized target in the brain known to have anti-seizure, anti-depressant,
and anti-anxiety effects. Ganaxolone is being developed in IV and oral dose forms intended to maximize therapeutic reach to adult
and pediatric patient populations in both acute and chronic care settings. Marinus is conducting the first ever Phase 3 pivotal
trial in children with CDKL5 deficiency disorder, along with a Phase 2 trial in Tuberous Sclerosis Complex, and a Phase 2 biomarker
driven proof of concept trial in PCDH19-related epilepsy. The Company intends to initiate a Phase 3 trial in status epilepticus.
For more information visit 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”, “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 clinical development plans for ganaxolone,
expected dosing in our clinical trials, the clinical development schedule and milestones, our expected timing to begin and complete
enrollment in our clinical trials, the expected protocols for our clinical trials, interpretation of scientific basis for ganaxolone
use, timing for availability and release of data, the potential safety and efficacy of ganaxolone, the therapeutic potential of
ganaxolone, our expectations regarding the effect of the COVID-19 pandemic on our business and clinical development plans, and
our expectations 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,
uncertainties and delays relating to the design, enrollment, completion, and results of clinical trials; unanticipated costs and
expenses; clinical trial results may not support further development in a specified indication or at all; actions or advice of
the U.S. Food and Drug Administration may affect the design, initiation, timing, continuation and/or progress of clinical trials
or result in the need for additional clinical trials; our ability to obtain and maintain regulatory approval for our product candidate;
delays, interruptions or failures in the manufacture and supply of our product candidate; our ability to raise additional capital;
the effect of the COVID-19 pandemic on our business, the medical community and the global economy; and the availability or potential
availability of alternative products or treatments for conditions targeted by us that could affect the availability or commercial
potential of our product candidate. 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:
Sasha Damouni Ellis
Vice President, Investor Relations & Corporate Communications
Marinus Pharmaceuticals, Inc.
484-253-6792
sdamouni@marinuspharma.com
Exhibit 99.2
NASDAQ: MRNS @ MarinusPharma Corporate Overview 2020
©2020 Marinus Pharmaceuticals. All Rights Reserved I Safe Harbor Statement To the extent that statements contained in this presentation are not descriptions of historical facts regarding Marinus, they ar e forward - looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Secu rit ies 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 forwar d - looking statements contained in this presentation include, among others, statements regarding our clinical development plans for ganaxolone; exp ect ed dosing in our clinical trials; the clinical development schedule and milestones; our expected timing to begin and complete enrollment in our clinica l t rials, including our expectation to dose the first patient in our Phase 3 clinical trial for SE in September 2020; the expected trial design, targ et patient population and endpoints for our clinical trials; interpretation of scientific basis for ganaxolone use; timing for availability and release of data, inc luding the expected release of data from the Marigold Study in the third quarter of 2020 and from the proof of concept study in PCDH19 in the first half of 2021; th e potential safety and efficacy of ganaxolone; the therapeutic potential of ganaxolone; and our expectations regarding the effect of the COVID - 19 pandemic on ou r business and clinical development plans. Forward - looking statements in this presentation 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 - loo king statements. Such risks and uncertainties include, among others, uncertainties and delays relating to the design, enrollment, completion, and r esu lts of clinical trials; unanticipated costs and expenses; clinical trial results may not support further development in a specified indication or at all ; actions or advice of the U.S. Food and Drug Administration may affect the design, initiation, timing, continuation and/or progress of clinical trials or re sul t in the need for additional clinical trials; our ability to obtain and maintain regulatory approval for our product candidate; delays, interruptions or f ail ures in the manufacture and supply of our product candidate; our ability to raise additional capital; the effect of the COVID - 19 pandemic on our business, the medi cal community and the global economy; and the availability or potential availability of alternative products or treatments for conditions targeted by us t hat could affect the availability or commercial potential of our product candidate. Marinus undertakes no obligation to update or revise any forward - looking statemen ts. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward - looki ng 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. Y ou may access these documents for free by visiting EDGAR on the SEC web site at www.sec.gov . 2
©2020 Marinus Pharmaceuticals. All Rights Reserved I Ganaxolone (GNX) Targets Synaptic & Extrasynaptic GABA A Receptors 3 Ganaxolone a positive allosteric GABA A modulator with a well - defined MOA designed to treat patients suffering from epilepsy and neuropsychiatric disorders. GNX is designed to modulate both synaptic and extrasynaptic GABA A receptors to calm over - excited neurons Clinical development focused on status epilepticus and rare genetic epilepsies that have few or no treatment options Multiple dose formulations IV and oral – to meet the needs of adult and pediatric patients in acute and chronic care settings Extensive safety record in more than 1,600 patients both pediatric and adult, at therapeutically relevant dose levels for up to two years GNX is a synthetic analog of allopregnanolone
©2020 Marinus Pharmaceuticals. All Rights Reserved I GANAXOLONE PHASE 1 PHASE 2 PHASE 3 ANTICIPATED MILESTONES Seizure Disorders Initiate mid - 2020 Data Q3 2020 Initiate 1H 2020 Data 2021 Depressive Disorders* Ganaxolone Development Pipeline Treatment Resistant Depression (TRD) Status Epilepticus (SE) 4 * Program on hold pending decision to conduct additional trials PCDH19 - Related Epilepsy (PCDH19) CDKL5 Deficiency Disorder (CDD) Tuberous Sclerosis Complex (TSC)
Status Epilepticus Indication
©2020 Marinus Pharmaceuticals. All Rights Reserved I Status Epilepticus (SE): Definition and Epidemiology Background • Continuous seizures lasting >5 min • Heterogenous patient population with various etiologies, including glioblastoma, vascular disease, encephalitis, drug or alcohol withdrawal or overdose • Pre - existing epilepsy in less than half of SE cases • Prolonged seizure activity can result in permanent neuronal damage and contribute to the high morbidity and mortality rates • SE becomes more difficult to control as its duration increases and is associated with increased mortality 6 SE is the second most common neurologic emergency in the U.S.
©2020 Marinus Pharmaceuticals. All Rights Reserved I Goals of a new treatment Rapid cessation Maintenance of seizure control Prevent progression to IV anesthetics Goals of a New Therapy for the Treatment of SE 7 Benzodiazepine Administered Medically induced Coma Established Status Epilepticus (ESE) 1 st line 2 nd line IV AED’s (antiepileptic drugs) 3 rd line IV Anesthetics Super Refractory Status Epilepticus (SRSE) Refractory Status Epilepticus (RSE) IV GNX Limitations of current treatments 1st line Benzodiazepines ineffective in 45% - 50%; limited by cardiovascular and respiratory side effects 2nd line Ineffective in over 50% of established SE 3rd line IV Anesthetics: high morbidity, mortality ~35%; increased duration of hospitalization and costs of care
©2020 Marinus Pharmaceuticals. All Rights Reserved I Treatment Period Loading Dose Maintenance Taper Phase 2 SE Trial Design 8 Diagnosis of convulsive or non - convulsive SE Failed at least one 2 nd line IV AED but had not progressed to 3 rd line IV anesthetics Bolus plus continuous infusion 2 - 4 day infusion 18 hour taper Screening Post - treatment Follow - up 24 hour Weeks 2, 3, 4 SE Patients Cohort Dose of GNX/day N Low 500mg/day 5 Medium 650mg/day 4 High 713mg/day 8 Evaluate safety, tolerability, efficacy, and pharmacokinetics of IV ganaxolone in refractory SE patients Endpoints Primary: number of patients who did not require escalation of treatment with IV anesthetic within the first 24 hours after ganaxolone ini tiation Secondary: additional efficacy, safety and tolerability
©2020 Marinus Pharmaceuticals. All Rights Reserved I Baseline Characteristics 9 Data presented at AES 2019 NCSE: Non - convulsive status epilepticus; CSE: Convulsive status epilepticus; LAC: Lacosamide ; LEV: Levetiracetam • 8 males, 9 females • Mean age: 57 years old (range: 23 - 88) • 5 (29%) CSE, 11 (65%) NCSE, 1 (6%) CSE→NCSE • 7 (41%) yes, 10 (59%) no 17 patients enrolled Types of SE History of Epilepsy Mean # of failed first - and - second line IV AEDs (including benzodiazepines) Mean # of failed 2nd - line IV AEDs • 2.9 (range: 2 - 5) • 2.1 (range: 1 - 4), all failed LEV or LAC • 14/17 patients failed two or more 2nd - line anti - seizure drugs (ASD) • All prior AED’s were administered within recommended dosing guidelines
©2020 Marinus Pharmaceuticals. All Rights Reserved I Phase 2 Trial Results Showed Rapid Onset, Durability of Efficacy at High Dose Cohort No escalation to IV anesthetics within 24 hrs from infusion initiation (Primary Endpoint) Status - free through 24 hrs from infusion initiation No escalation to additional IV AEDs or IV anesthetics for status relapse at any time through 24 hrs after GNX discontinuation No SE Relapse at anytime during the 4 - wk follow up period High (713 mg/day) (n=8) 100% (8 of 8) 88% (7 of 8) 100% (8 of 8) 100% (6 of 6) (1ET, 1 died) Medium (650 mg/day) (n=4) 100% (4 of 4) 100% (4 of 4) 75% (3 of 4) 67% (2 of 3) (1 ET) Low (500 mg/day) (n=5) 100% (5 of 5) 100% (5 of 5) 60% (3 of 5) 50% (1 of 2) (1 died) Immediate Prior AED Administered 4 Hours (mean) to GNX treatment SE Cessation Occurred Rapidly in All Dose Groups (median = 5 minutes) Data presented at AES 2019 10
©2020 Marinus Pharmaceuticals. All Rights Reserved I PK/PD Relationship and Rationale for Target Dose 11 Seizure Burden Reduction Occurred Rapidly in All Dose Groups Modeled PK Curves for All Dose Groups High Dose Achieves Target Range ≥ 500 ng/mL for ~8 hours Only High Dose Provided Sustained Reduction (>80%) Throughout Entire Analysis Window Data presented at AES 2019 PK: Pharmacokinetics / PD: Pharmadynamic 0 6 12 18 24 0 200 400 600 800 1,000 Time (hrs) G N X P l a s m a C o n c e n t r a t i o n ( n g / m L ) Low 500mg/day Medium 650mg/day High 713mg/day -1 -100 -80 -60 -40 -20 0 0 1 2 4 6 8 10 12 14 Time (hrs) % C h a n g e i n E E G S e i z u r e B u r d e n ( s e i z u r e t i m e / t o t a l t i m e p e r i o d ) GNX initiation High 713mg/day Medium 650mg/day Low 500mg/day "High" dose < 500 ng/mL = Time point of seizure recurrence when GNX dosing targets were < 500 ng/mL "Low" dose < 500 ng/mL "Medium" dose < 500 ng/mL
©2020 Marinus Pharmaceuticals. All Rights Reserved I IV Ganaxolone Safety Summary 12 Intubation: 9 patients were not intubated upon enrollment. Of these, 6 remained intubation - free during the entire ganaxolone treatment perio d Data presented at AES 2019 AE: adverse event / SAE: serious adverse event 10 SAEs in 6 patients (also included in AEs) 2 related in 2 patients • 2 severe sedation 8 non - related in 4 patients • 1 Death due to withdrawal of life support - 1 Respiratory depression • 1 Bowel perforation (fatal) • 1 Sepsis (fatal) • 1 Fall - 1 Loss of consciousness - 1 Pneumothorax - 1 Multiple fracture 13 related in 7 patients • 6 mild (2 hypotension, 2 somnolence, 1 urinary retention, 1 hypercarbia) • 5 moderate (4 somnolence; 1 hypercarbia) • 2 severe (2 sedation) 37 not - related in 12 patients • 20 mild • 8 moderate (2 pain; 2 pneumonia, 2 dysphagia, • 1 delirium, 1 hypertension) • 9 severe (respiratory depression, death due to withdrawal of support, sepsis, embolic stoke, perforated bowel, fall, loss of consciousness, multiple fractures, pneumothorax) 50 AEs in 16 patients
©2020 Marinus Pharmaceuticals. All Rights Reserved I Phase 3 SE Plan 13 • Target dose range extends GNX exposure ≥ 500 ng/mL to 12 hours; IV bolus followed by 36 - hour infusion followed by a 12 - hour taper (48 hours in total) • SE cessation within 30 minutes, No progression to IV anesthesia for at least 24 hours • Focus on clinically meaningful effects: rapid onset of action, durability of effect, and prevention of treatment escalation • Randomized, double blind, placebo - controlled trial (added to standard - of - care) • Convulsive or nonconvulsive SE • Failure of benzodiazepine therapy and two additional antiseizure medications • Healthcare utilization metrics, e.g., hospital/ICU length of stay • Additional clinical outcomes Trial Design Target Patient Population Dosing Co - Primary Endpoints Secondary Endpoints
©2020 Marinus Pharmaceuticals. All Rights Reserved I SE Phase 3 Clinical Planning: On Track for First Patient In September 14 • 1:1 randomized, double - blind, placebo - controlled trial • Failure of a benzodiazepine and 2 second - line IV AEDs • 3 - minute bolus, 36 - hr infusion, 12 - hr taper • Approx. 125 randomized patients • 80 - 100 sites Trial Overview S C R E E N I N G Dose Initiation (Time 0) Treatment Period Follow - up Period Weeks 1,2,3,& 4 Daily 24 - 120 hours Day 2 Hours 24 - 36 Hours 36 - 48 Daily Hours 0 - 24 Bolus dose Continuous Infusion Taper Treatment is planned t be 2 days (including a 12 - hour taper). 0 6 12 18 24 30 36 42 48 0 200 400 600 800 1,000 Time (hrs) M o d e l e d G N X P l a s m a C o n c e n t r a t i o n ( n g / m L ) Target dose range Day 1 Day 2 Continuous Infusion Infusion Taper
CDKL5 Deficiency Disorder
©2020 Marinus Pharmaceuticals. All Rights Reserved I Cause Mutation of the cyclin - dependent kinase - like 5 (CDKL5) gene, located on the X chromosome Symptoms Early - onset, treatment refractory seizures, & severe neuro - developmental delay Most can’t walk, talk or care for themselves Suffer from scoliosis, visual impairment, gastrointestinal difficulties & sleeping disorders Prevalence ~12,500 children US and EU5, predominantly affects females Genetic testing available Orphan Drug designation Treatments No disease - specific treatments are approved Mechanistic Rationale Potential GABA A dysfunction CDKL5 Deficiency Disorder (CDD) – Rare, Serious Epileptic Condition 16 Cause
©2020 Marinus Pharmaceuticals. All Rights Reserved I 26 weeks ganaxolone 600 mg 3x/day maximum 12 weeks Trial Details 2 sites in US; 1 site in Italy 6 females, 1 male – ages 2 - 16 Confirmed CDKL5 mutation, stable background treatment, >4 seizures per 28 - day period in baseline Baseline Characteristics Mean number seizures – 206 (range 34 to 669) Median number seizure - free days - 4 (range 0 to 9) Endpoints Primary: % change in seizure frequency per 28 days relative to baseline Secondary: % increase in seizure free days from baseline, safety and tolerability, CGI CDD - Phase 2 Trial Design 17 Open - Label Phase 52 weeks 600 mg 3x/day maximum Treatment Baseline
©2020 Marinus Pharmaceuticals. All Rights Reserved I Efficacy & Safety Data in Phase 2 Trial in CDD Data presented at AES 2018 18 • Patients experienced a median ‘minimally improved’ rating on CGI - I scale (Clinician rated) correlated with % change in seizure frequency • GNX was generally safe and well - tolerated (no SAEs). No reports of somnolence or dizziness. − 2 of the 7 patients discontinued prior to completing treatment due to lack of efficacy 44.4% Reduction in seizure frequency *excludes 6 days of data from one patient deemed unreliable by the PI and caregiver Very much improved Very much worse 1: very much improved 2: much improved 3: minimally improved 4: no change 5: minimally worse 6: much worse 7: very much worse Correlation between change in seizure frequency and CGI - I scale CGI - I scale: Clinical Global Impression – Improvement scale Very much improved no change Very much worse
©2020 Marinus Pharmaceuticals. All Rights Reserved I Durable Responses Seen out to 18 Months in CDD Phase 2 Extension • 4 of 7 patients entered the extension period • Ganaxolone demonstrated preliminary evidence of sustained, long - term (out to 18 months) efficacy in a small cohort of CDD patients • Efficacy of existing AEDs and the ketogenic diet in patients with the CDKL5 mutation is low and the durability of effect is s hor t 1 19 Clinical data presented at AES 2018 1 Müller, A. et al., European Journal of Paediatric Neurology, Volume 20 (2016), 147 - 151. OLE: open - label extension 54% Median change in seizure frequency at 6 months 66% Median change frequency improved to 66% in extension period (as of 12/31) Patients Entering OLE Patient 1 Patient 2 Patient 3 Patient 4 %
©2020 Marinus Pharmaceuticals. All Rights Reserved I Global Phase 3 Pivotal Trial Design 20 Baseline 6 weeks Historical Control 8 weeks Double - Blind Phase Open - Label Phase Maintenance 13 weeks Titration 4 weeks Titration 4 weeks Open - Label Phase Trial Details • Evaluate the use of oral ganaxolone in children and young adults • Global, double - blind, placebo - controlled, clinical trial has enrolled 101 patients between the ages of 2 and 21 with a confirmed disease - related CDKL5 gene variant • Ages 2 - 21, 16 major motor drop seizures/month; up to 4 concomitant AEDs Endpoints • Primary endpoint of the trial is percent change in 28 - day seizure frequency • Non - seizure secondary outcome measures: Behavioral/neuropsychiatric changes correlated with domains of attention & sleep • Data expected in Q3 2020
Tuberous Sclerosis Complex
©2020 Marinus Pharmaceuticals. All Rights Reserved I Allo - S as Potential Biomarker Across Various Genetic Epilepsies 22 Scientific literature associates genetic orphan epilepsies with neurosteroid imbalances Marinus has identified abnormal neurosteroid levels in several patient subtypes These findings lead to stratification by Allo - S biomarker in clinical trials Control PCDH19 CDD TSC 0 1 2 3 4 5 20 A l l o p r e g n a n o l o n e - s u l f a t e ( n g m L - 1 ) Patients/subjects aged 1-14
©2020 Marinus Pharmaceuticals. All Rights Reserved I Cause Defect or mutation of TSC1 and/or TSC2 genes Symptoms Benign tumors, seizures, cognitive impairment, behavioral problems, skin abnormalities Prevalence ~25K-40K refractory TSC patients in the U.S.* Treatments Limited approved treatments Mechanistic Rationale Potential neurosteroid deficiency 1 Tuberous Sclerosis Complex – Rare, Serious Genetic Disorder 23 1 diMichele , et al, J. Neuro Neurosurg Psychiatry , 2003 *Failure of two prior antiseizure medications with ongoing, frequent seizures.
©2020 Marinus Pharmaceuticals. All Rights Reserved I Unmet Need in TSC Epilepsy and Scientific Rationale for Ganaxolone • Epilepsy present in ~90% of individuals affected with TSC • Existing treatments fail to control seizures in ~60% of individuals with TSC - associated epilepsy • Uncontrolled seizures, especially early in life, may lead to developmental delays and cognitive dysfunction 24 Clear need to evaluate treatments with a differentiated mechanism of action In collaboration with the TS Alliance and utilization of their Biosample Repository TSC Control 0 1 2 3 4 5 6 A l l o p r e g n a n o l o n e - S u l f a t e ( n g m L - 1 ) Patients/subjects aged 1-14 mean + SEM Patients aged 1 - 14
©2020 Marinus Pharmaceuticals. All Rights Reserved I PART A PART B Base (4 Weeks) GNX Titration (4 Weeks) GNX Maintenance (8 Weeks) Open - Label Extension (OLE) (24 Weeks) * Available to patients that respond to GNX as defined per protocol TSC - Phase 2 Open - Label Clinical Trial Design • n = 30 • 4 - 8 U.S. sites • Electronic diaries will be used for data capture • At least 8 seizures per month • Primary efficacy endpoint: % change in 28 - day primary seizure frequency through the end of 12 - week treatment period relative to 4 - week baseline period Primary seizure types: focal motor seizures without impairment of consciousness or awareness, focal seizures with impairment of consciousness or awareness, focal seizures evolving to bilateral generalized convulsive seizures, and generalized seizures wi th a motor component that are countable 25 Baseline Period Treatment Period OLE Period Screening Visit Baseline Treatment Visit 2 - week taper upon GNX discontinuation (if not continuing to Part B)
PCDH19 Related Epilepsy
©2020 Marinus Pharmaceuticals. All Rights Reserved I Cause Inherited mutation of protocadherin 19 (PCDH19) gene. Located on X chromosome Symptoms Early - onset seizures, cognitive and sensory impairment, & psychiatric and behavioral disorders. Seizures last from days to weeks; sensitive to fever Prevalence Affects ~10K children US and EU Predominantly females Genetic testing becoming more readily available Orphan Drug designation Treatments No disease - specific treatments are approved Mechanistic Rationale Associated with low levels of allopregnanolone 1 and potential GABA A dysfunction PCDH19 - Related Epilepsy – Rare, Serious Epileptic Condition 27 1 Gecz, et.al , Human Molecular Genetics, 2015 NCSE: Non - convulsive status epilepticus, CSE: Convulsive status epilepticus, LAC: Lacosamide , LEV: Levetiracetam, LOR: Lorazepam, PHT: Phenytoin, fPHT : Fosphenytoin , VPA: Valproic Acid
©2020 Marinus Pharmaceuticals. All Rights Reserved I Seizure Reduction in PCDH19 - RE Phase 2 Trial in Patients with Low Allo Levels • 25% decrease in median seizure frequency reported in Phase 2 (n=11) • Stratification of patients by baseline plasma Allo levels identifies a subpopulation with expected improved efficacy on GNX • When comparing seizure frequency at 6 months to baseline: − The biomarker+ group (low Allo ) significantly improved − The biomarker - group (high Allo ) deterioration was not statistically significant Biomarker N= Median % change in seizure rates P - value (Wilcoxon) Biomarker + ( Allo - S <2,500 pg mL - 1 ) 7 - 50% P=0.02 Biomarker – ( Allo - S >2,500 pg mL - 1 ) 4 84% P=0.63 28 Clinical data presented at AES 2018
©2020 Marinus Pharmaceuticals. All Rights Reserved I Biomarker Stratified Proof of Concept (POC) Study in PCDH19 29 Trial Details • Ages 1 - 17 with 8 or more seizures in 8 weeks, failed 2 or more AEDs • Expect to complete double - blind portion of the trial with ~15 - 20 patients • Stratify patients into one of two biomarker groups based on baseline allopregnanolone sulfate levels and randomized ( ganaxolone or placebo) within each stratum • Data expected first half 2021 R 1:1 PCDH19 (all - patients) n ~ 15 - 20 Biomarker + Low Allo - S Primary efficacy analyses will be conducted using this cohort Biomarker - High Allo - S R 1:1 Ganaxolone Up to 600 mg 3x/day Placebo Ganaxolone Up to 600 mg 3x/day Placebo Ganaxolone Up to 600 mg 3x/day Pre - baseline Screening Maintenance 13 weeks Baseline 12 weeks Titration 4 wks Open - Label Phase (52 weeks) * not drawn to scale Titration 4 wks Screening Visit
Intellectual Property
©2020 Marinus Pharmaceuticals. All Rights Reserved I Patent Expected Patent Life Synthesis patents issued in US, Australia, China, Europe, Japan, Mexico & New Zealand 2030 IV formulations containing exclusively in - licensed proprietary Captisol ® product 2033 SE – pending patent on IV formulations and methods of use 2036 SE – pending patent on clinical treatment regimen 2040 CDD & PCDH19 – pending patent on methods of use, patient stratification 2038 TSC - pending patent on methods of use 2040 Multiple Layers Of Potential Protection 31 Orphan drug designation for SE, CDD, PCDH19 - RE provides 7 and 10 years exclusivity in US and EU, respectively.
Thank You
©2020 Marinus Pharmaceuticals. All Rights Reserved I Appendix 33 NCSE: Non - convulsive status epilepticus CSE: Convulsive status epilepticus LAC: Lacosamide LEV: Levetiracetam LOR: Lorazepam PHT: Phenytoin fPHT : Fosphenytoin VPA: Valproic Acid Details on Baseline Characteristics for SE Patients *Bolded, underlined IV AED’s were the last ones administered prior to GNX Patient Dosing Cohort Etiology History of Epilepsy Type of SE Failed Antiseizure Medications Prior to GNX* Dose of Last IV AED Administered Prior to GNX (Recommended Dose) 1 Low Vascular No NCSE LAC , LEV 200mg (200 - 600mg) 2 Low Unknown Yes NCSE fPHT , LEV 1,000mg (1000 - 3000mg) 3 Low Vascular No NCSE LOR, LAC , LEV 600mg (200 - 600mg) 4 Low Vascular No NCSE LOR, LAC , LEV 600mg (200 - 600mg) 5 Low Tumor No CSE LOR, LAC, LEV 2,000mg (1000 - 3000mg) 6 Medium Vascular No NCSE LOR, LAC , LEV 600mg (200 - 600mg) 7 Medium Drug Overdose / Withdrawal Yes CSE LOR, LEV 1,000mg (1000 - 3000mg) 8 Medium Unknown Yes CSE → NCSE LOR, LAC, LEV 1,000mg (1000 - 3000mg) 9 Medium Tumor Yes NCSE LAC, LEV, PHT 200mg (100mg) 10 Target Vascular Yes CSE LOR, LAC , VPA 400mg (200 - 600mg) 11 Target Drug Overdose / Withdrawl No CSE LOR, LAC , LEV 400mg (200 - 600mg) 12 Target Tumor Yes NCSE LOR, LEV, VPA 700mg (1000 - 3000mg) 13 Target Autoimmune No NCSE LOR, LEV 1,000mg (1000 - 3000mg) 14 Target Vascular No NCSE LOR, LAC , LEV, PHT 200mg (200 - 600mg) 15 Target Vascular Yes CSE LOR, LEV 1,000mg (1000 - 3000mg) 16 Target Tumor No NCSE LOR, LAC , LEV 400mg (200 - 600mg) 17 Target Autoimmune No NCSE LOR, fPHT , LAC , LEV, VPA 200mg (200 - 600mg)