Exhibit 99.1
Marinus Pharmaceuticals Provides Business Update
and Reports First Quarter 2021 Financial Results
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Strategic credit financing agreement with funds managed by Oaktree Capital Management, L.P. (“Oaktree”) will provide up
to $125 million to support continued development and commercial readiness of both the oral and IV ganaxolone programs
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On track to submit NDA for use of ganaxolone in CDKL5 deficiency disorder (CDD) in mid-2021; recent NDA preparation and review resulted
in a final p-value of p=0.0036, not affecting statistical conclusions of the Phase 3 Marigold Study
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Patients in the Marigold open label extension treated with ganaxolone for at least 12 months experienced a median 49.6% reduction
in major motor seizure frequency (n=48)
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CDD EU submission on track for end of Q3 2021
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Plan to initiate Phase 3 trial of ganaxolone in tuberous sclerosis complex (TSC) in Q3 2021 following FDA interactions; continue to
target first patient enrolled during Q4 2021
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Enrollment in Phase 3 clinical trial, the RAISE study, evaluating IV ganaxolone in the treatment of refractory status epilepticus
(RSE) remains on track with top-line data expected in 1H 2022
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Continued progress to expand the ganaxolone opportunity globally as company aligns with the European Medicines Agency (EMA) on Phase
3 design for IV RSE program and progresses constructive dialogue with potential EU commercialization partners
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RADNOR, Pa. – May 17, 2021 -- Marinus Pharmaceuticals,
Inc. (Nasdaq: MRNS), a pharmaceutical company dedicated to the development of innovative therapeutics to treat seizure disorders,
today provided an update on its clinical and regulatory development activities and reported its financial results for the first quarter
ended March 31, 2021.
“I am pleased to announce that we have reached agreement with
Oaktree to secure up to $125 million in credit financing,” said Scott Braunstein, M.D., Chief Executive Officer of Marinus Pharmaceuticals.
“This new credit facility provides a potentially meaningful extension of our cash runway, allowing for continued support of our
commercial, clinical, and next-generation formulations, and reflects Oaktree’s confidence in our anticipated NDA submission, strategy,
and science. We believe this credit agreement will be a valuable financial enabler of our roadmap to further unlock ganaxolone’s
potential.”
Aman Kumar, Co-Portfolio Manager of Life Sciences Lending at Oaktree,
commented, “Oaktree is pleased to partner with Marinus and provide financial support for its upcoming clinical and commercialization
activities at this inflection point in its evolution as a company. With a strong management team in place, compelling clinical data and
a well-defined long-term strategic growth plan, we believe Marinus is well-positioned to capture significant value in treating seizures
and epilepsy.”
Credit Financing:
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Completed a credit financing agreement for up to $125 million with Oaktree, a leader among global investment managers specializing
in alternative investments
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A total of up to $75 million has the potential to be drawn as early as 1H 2022, with $15 million drawn at signing of the credit financing
arrangement, $30 million on FDA acceptance of the CDD NDA filing and $30 million on FDA approval
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An additional $50 million can be drawn at the company’s discretion based on designated milestones associated with the results
of the Phase 3 trials for RSE or TSC, and financial and commercialization targets
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The loan will mature in May 2026 and includes an interest-only period for the initial three years of the agreement
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Morgan Stanley & Co. LLC acted as lead placement agent and H.C. Wainwright & Co. acted as co-placement agent on the financing
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Pipeline Update:
“Building on the momentum we have established
in early 2021, we are making progress in our clinical programs, business operations, and in growing and diversifying our talent pool.
We continue to target the submission of a new drug application to the FDA for the use of ganaxolone in CDKL5 deficiency disorder by mid-2021,
completion of our Phase 2 clinical trial in tuberous sclerosis complex this summer, and expect top-line data for the ongoing Phase 3
RAISE trial in refractory status epilepticus in the first half of 2022,” Dr. Braunstein said. “We are equally focused on
providing access to ganaxolone globally as evidenced by our recent successful regulatory meetings with the EMA discussing the IV and
oral programs. Looking toward the second half of 2021, we are focused on commercial preparedness for our first potential product launch
in the U.S., continued enrollment of our Phase 3 trial in RSE, and the planned initiation of a Phase 3 trial in TSC.”
“We are also pleased to have recently appointed three leading
experts in clinical neurology and pediatric epilepsy to the Marinus Scientific Advisory Board,” continued Dr. Braunstein. “Dr.
Elizabeth Thiele, Dr. Elia Pestana Knight and Dr. Nicola Specchio join us at an exciting and pivotal time as we prepare for our next phase
of investment. They will serve as invaluable resources for our oral pipeline as we work to realize the full potential of ganaxolone as
a treatment for epilepsy.”
CDKL5 Deficiency Disorder (CDD)
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Marinus remains on track to submit an NDA mid-year and EMA marketing authorization application (MAA) in late Q3 2021 for use of ganaxolone
in CDD
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In preparation of the U.S. NDA submission, a final analysis of the Marigold Study data was completed, which includes changes to the
previously reported top-line data. These changes do not affect the statistical or clinical conclusions of the study
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The final data analysis shows that the median percent reduction in major motor seizures was 30.7 percent for ganaxolone and 6.9 percent
for placebo (p=0.0036) compared to 32.2 percent for ganaxolone and 4.0 percent for placebo (p=0.002) in the top-line data analysis previously
reported
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Additionally, results on key secondary endpoints and safety data have not changed
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The previously reported top-line data set included seizure diary entries that were determined to be duplicates of seizures that parents
or caregivers had already entered; this programming and data transfer error affected only 1.7 percent of total seizure entries
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Patients in the Marigold open label extension study treated with ganaxolone for at least 12 months experienced a median 49.6% reduction
in major motor seizure frequency (n=48)
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Long term open-label follow-up data will be submitted for presentation at the American Epilepsy Society 2021 Annual Meeting, December
3-7
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Tuberous Sclerosis Complex (TSC)
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Top-line, open label, Phase 2 trial data from 23 patients are expected in Q3 2021
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An End of Phase 2 meeting with the FDA, based on an interim data analysis, is targeted for early Q3 2021
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Planned protocol assistance meeting with the EMA is targeted for Q4 2021
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A double- blind, placebo-controlled global Phase 3 trial (n=160) is anticipated to begin enrollment during Q4 2021; the primary endpoint
will be percent change in 28-day seizure frequency
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Request for FDA and EMA orphan drug designation targeted for 2H 2021
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Status Epilepticus
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RAISE, the Phase 3, double-blind, placebo-controlled trial of IV ganaxolone for the treatment of refractory status epilepticus (RSE),
remains on track to report top-line data in 1H 2022
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More than half the sites for the Phase 3 RAISE trial are expected to be open by the end of Q2 2021 as COVID-19 delays at hospital
ICUs gradually resolve, with the vast majority of sites open by Q3 2021
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Enrollment at the initiated sites in the RAISE trial is tracking as anticipated, bolstered by strong site engagement
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After alignment with EMA, the company plans to initiate RAISE II, a pivotal registration trial for RSE in Europe:
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RAISE II will be a double- blind, placebo-controlled trial with an expected 70 patients enrolled who have failed first-line benzodiazepine
treatment and at least one prior second-line AED
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Patients will receive either ganaxolone or placebo, administered in combination with a standard-of-care second-line AED
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The RAISE II trial in Europe differs from the RAISE trial in the U.S., with RAISE II using ganaxolone that can be initiated earlier
in the course of RSE. If successful, this trial will provide complementary data to the Phase 3 U.S. RAISE trial
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In established status epilepticus (ESE), the company plans to conduct a Phase 2 trial of ganaxolone as an adjuvant to standard of
care AEDs, with U.S. enrollment targeted for 1H 2022
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Lennox-Gastaut Syndrome (LGS)
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Marinus has decided to pursue ganaxolone development for LGS, given the overlap in seizure types and etiologies with other disorders
where ganaxolone has shown potential, such as CDD and TSC
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The company will present additional details on clinical development plans this fall, targeting initiation of a Phase 2 clinical trial
in mid-2022
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Corporate Update
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Europe-focused commercial partnership discussions for oral and IV franchise continue to be active and on track
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Marinus is growing its commercial team commensurate with planning for a mid-2021 CDD NDA submission of ganaxolone and a mid-year 2022
launch, if approved
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The company continued to strengthen its commercialization preparedness by hiring experienced heads of market access, sales & marketing,
operations, and commercial supply chain
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Marinus Scientific Advisory Board further strengthened with appointment of three leading experts in clinical neurology and pediatric
epilepsy to support oral ganaxolone development
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Elizabeth A. Thiele, M.D., Ph.D., neurologist and epileptologist at Massachusetts General Hospital. She is the Director of the Pediatric
Epilepsy Service at Mass General and a Professor of Neurology at Harvard Medical School
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Elia M. Pestana Knight, M.D., pediatric epileptologist in the Pediatric Epilepsy Section, Epilepsy Center, Cleveland Clinic Neurological
Institute, Cleveland, Ohio. She is an Associate Professor of Medicine at the Cleveland Clinic Lerner College of Medicine
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Nicola Specchio, M.D., Ph.D., Head of the Epilepsy Unit in the Department of Neuroscience at Bambino Gesù Children's Hospital,
Rome, Italy. Dr. Specchio is a representative of the International League Against Epilepsy (ILAE) Europe and of the Italian Chapter of
the ILAE
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Financial Update
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At March 31, 2021, the company had cash, cash equivalents, and investments of $123.5 million, compared to $140 million at December
31, 2020
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The company believes its cash and cash equivalents as of March 31, 2021 combined with the net upfront proceeds of the Oaktree credit
facility will enable it to fund its current scale of operating expenses and capital expenditures through the second quarter of 2022
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Marinus recognized $1.8 million in federal contract revenue in the three months ended March 31, 2021 as a result of the BARDA contract
the company entered into in September 2020; no federal contract revenue was recognized in the three months ended March 31, 2020
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Research and development expenses were $18.6 million and $15 million for the three months ended March 31, 2021 and 2020, respectively;
the change was due primarily to increased clinical activity including start-up of the RSE Phase 3 trial and increased clinical and CMC
headcount
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General and administrative expenses increased to $10.4 million for the three months ended March 31, 2021, compared to $3.9 million
for the three months ended March 31, 2020; the primary drivers of the increase were increased support for scale up of the company’s
operations as well as preparation for commercialization
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The company reported net losses of $27.1 million and $18.7 million for the three months ended March 31, 2021 and 2020, respectively;
cash used in operating activities increased to $16.2 million for the three months ended March 31, 2021, compared to $14 million for the
same period a year ago
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Readers are referred to, and encouraged to read in its entirety, the company’s Quarterly Report on Form 10-Q for the three months
ended March 31, 2021, to be filed with the Securities and Exchange Commission, which includes further detail on the Oaktree Capital credit
facility and the company’s business plans, operations, financial condition and results of operations
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Corporate Guidance
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For the fiscal year 2021, the company expects total GAAP operating expenses (selling, general & administrative expenses and research
& development expenses) to be in the range of $113 to $118 million, of which the company expects stock-based compensation to be approximately
$16 million. 2021 BARDA contract revenues are projected to be in the range of $9 to $12 million for the full year
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Marinus Pharmaceuticals, Inc.
Selected Financial Data (in thousands, except
share and per share amounts)
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March 31,
2021
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December 31,
2020
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ASSETS
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Cash and cash equivalents
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$
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123,472
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$
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138,509
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Investments
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—
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1,474
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Other assets
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10,387
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10,479
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Total assets
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$
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133,859
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$
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150,462
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LIABILITIES AND STOCKHOLDERS’ EQUITY
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Current liabilities
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$
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16,121
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$
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10,729
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Other long term liabilities
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2,404
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2,534
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Total liabilities
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18,525
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13,263
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Total stockholders’ equity
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115,334
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137,199
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Total liabilities and stockholders’ equity
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$
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133,859
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$
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150,462
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Three Months Ended
March 31,
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2021
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2020
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Federal contract revenue
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$
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1,806
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$
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—
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Expenses:
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Research and development
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$
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18,591
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$
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15,004
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General and administrative
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10,376
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|
|
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3,850
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Loss from operations
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(27,161
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)
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|
|
(18,854
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)
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Interest income
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24
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|
|
|
222
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Other expense, net
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|
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(4
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)
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|
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(40
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)
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Net loss
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$
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(27,141
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)
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$
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(18,672
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)
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|
Deemed dividends on convertible preferred stock
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|
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—
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|
|
|
(8,880
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)
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Net loss applicable to common shareholders
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$
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(27,141
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)
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$
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(27,552
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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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(0.74
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)
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$
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(1.27
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)
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Basic and diluted weighted average shares outstanding
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36,592,394
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|
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21,665,461
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About Marinus Pharmaceuticals
Marinus Pharmaceuticals, Inc. is a pharmaceutical
company dedicated to the development of innovative therapeutics to treat 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, antidepressant and
anti-anxiety effects. Ganaxolone is being developed in IV and oral dose formulations intended to maximize therapeutic reach to adult
and pediatric patient populations in both acute and chronic care settings. Marinus recently completed the first ever Phase 3 pivotal
trial in children with CDKL5 deficiency disorder, is conducting a Phase 2 trial in tuberous sclerosis complex and has recently disclosed
top-line results from its Phase 2 proof-of-concept trial in PCDH19-related epilepsy. The company has initiated a Phase 3 trial in
refractory status epilepticus. For more information visit www.marinuspharma.com.
Ganaxolone development for RSE is being funded, in part, by the Biomedical
Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the
U.S. Department of Health and Human Services, under contract number 75A50120C00159
About Oaktree
Oaktree is a leader among global investment
managers specializing in alternative investments, with $153 billion in assets under management as of March 31, 2021. The firm emphasizes
an opportunistic, value-oriented and risk-controlled approach to investments in credit, private equity, real assets and listed equities.
The firm has over 1,000 employees and offices in 19 cities worldwide. For additional information, please visit Oaktree’s website
at http://www.oaktreecapital.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 expected clinical development plans, enrollment in our clinical trials, regulatory communications and
submissions and product launches for ganaxolone, and the timing thereof; our expectations regarding the Oaktree credit facility and its
effects on our cash runway and business plans; our expectations that our cash and cash equivalents combined with the net upfront proceeds
of the Oaktree credit facility will be sufficient to fund our operating expenses and capital expenditures through the second quarter of
2022; and the potential safety and efficacy of ganaxolone, as well as its therapeutic potential in a number of indications.
Forward-looking statements in this press 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; early clinical trials may not be indicative of the results in later clinical trials;
clinical trial results may not support regulatory approval or further development in a specified indication or at all; actions or advice
of the FDA or EMA 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; our ability to obtain, maintain,
protect and defend intellectual property for our product candidates; the potential negative impact of third party patents on our ability
to commercialize ganaxolone; delays, interruptions or failures in the manufacture and supply of our product candidate; the size and growth
potential of the markets for the company’s product candidates, and the company’s ability to service those markets; the company’s
cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the company’s expectations,
projections and estimates regarding expenses, future revenue, capital requirements, and the availability of and the need for additional
financing; the company’s ability to obtain additional funding to support its clinical development programs; the company’s
ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market
acceptance of the company’s product candidates; 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. This list is not exhaustive and these and other risks
are described in the company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current
reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission. and available at www.sec.gov. Any forward-looking
statements that the company makes in this press release speak only as of the date of this press release. The company assumes no obligation
to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press
release.
Company Contact
Sasha Damouni Ellis
Vice President, Investor Relations & Corporate Communications
Marinus Pharmaceuticals, Inc.
484-253-6792
sdamouni@marinuspharma.com
Exhibit 99.2
©2021 Marinus Pharmaceuticals. All Rights Reserved I Corporate Presentation May 2021
©2021 Marinus Pharmaceuticals. All Rights Reserved I 2 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 w ell 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 expected revenue and operating expenses for 20 21; 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 trial design, target patient population and endpoints for our cl ini cal trials; interpretation of scientific basis for ganaxolone use; timing for availability and release of data; the potential safety and efficacy and therapeutic potential of ganaxolone ; timing and expectations regarding regulatory communications and submissions; our commercialization plans and the expected tim ing thereof; expectations regarding our agreement with BARDA; expectations regarding the potential market opportunities for our product ca ndi dates, including oral ganaxolone ; potential commercial alliances; and our expectations regarding the effect of the COVID - 19 pandemic on our business and clinica l 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 results of clinical trials; interpretation of results of clinical trials; unanticipated costs and expenses; early clinical trials may not be indicative of the results i n l ater clinical trials; clinical trial results may not support regulatory approval or further development in a specified indication or at all; actions or advice of the FDA or other regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for addition al clinical trials; our ability to obtain and maintain regulatory approval for our product candidate; our ability to obtain and maintain patent protection for our prod uct candidates; the potential negative impact of third party patents on our ability to commercialize ganaxolone ; 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, t he medical community and the global economy; and the availability or potential availability of alternative products or treatments for conditions targe ted by us that could affect the availability or commercial potential of our product candidate. Marinus undertakes no obligation to update or revise any forwa rd - looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these fo rwa rd - 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 Co mmi ssion. You may access these documents for free by visiting EDGAR on the SEC web site at www.sec.gov.
©2021 Marinus Pharmaceuticals. All Rights Reserved I 3 Ganaxolone (GNX) Targets Synaptic & Extrasynaptic GABA A Receptors Ganaxolone a positive allosteric GABA A receptor 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 The main inhibitory neurotransmitter in the brain is “GABA”. By binding to specific receptors, GABA can bring about decreased seizure activity. GNX
©2021 Marinus Pharmaceuticals. All Rights Reserved I Evaluation of IV and Oral Opportunities Building Upon Status Epilepticus (SE) Maximizing Value for Orphan Epilepsies • Expand clinical opportunities to broader status epilepticus indications • Build U.S. commercial strategy • Execute global development plan • Develop pharmacoeconomic, value proposition and outcomes assessment • CDKL5 deficiency disorder (CDD) commercialization strategy • Advance tuberous sclerosis complex (TSC) clinical development • Research scientifically based expansion opportunities • Global integrated commercialization strategy Leveraging GNX Molecule • Explore opportunities to improve bioavailability, PK profile & clinical outcomes • Engage in strategic collaborations on novel technologies & formulations • Evaluate new indications based on unmet need, and scientific rationale • Establish strategic commercial collaborations to expand geographic footprint 4 Corporate Strategy
©2021 Marinus Pharmaceuticals. All Rights Reserved I 5 Ganaxolone Development Pipeline
Orphan Epilepsy Franchise
CDKL5 Deficiency Disorder “CDKL5 is painful. It’s a hard, sad at times, thing that we face. When you have a relationship with people like Marinus and their researchers, you are able to help be a driving force behind that work. - Karen Utley, Mother to Samantha, President of International Foundation for CDKL5 Research
©2021 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 Incidence • 1:40,000 live births 1 ; approx. 75 - 100 newborn in US and EU5 • Predominantly affects females • Genetic testing available • Orphan Disease Treatments • No disease - specific treatments are approved Rationale • Potential GABAergic dysfunction, achieved Primary endpoint in Marigold Phase 3 study 8 CDKL5 Deficiency Disorder (CDD) 1 Symonds JD 2019 Brain
©2021 Marinus Pharmaceuticals. All Rights Reserved I 9 Completed Global Phase 3 Trial Design Baseline 6 weeks Historical Control 8 weeks Double - Blind Phase Open - Label Phase Maintenance 13 weeks Titration 4 weeks Open - Label Phase ► Trial Details • Evaluated the use of oral ganaxolone in children and young adults • Global, double - blind, placebo - controlled, clinical trial enrolled 101 patients between the ages of 2 and 19 with a confirmed disease - related CDKL5 gene variant • Ages 2 - 19, ≥16 major motor seizures/month; up to 4 concomitant AEDs ► Endpoints • Primary endpoint of the trial was percent change in 28 - day major motor seizure frequency * • Non - seizure secondary outcome measures: Behavioral/neuropsychiatric changes correlated with domains of attention & sleep * Major motor seizures were defined as bilateral tonic, generalized tonic - clonic, atonic/drop, bilateral clonic, or focal to bil ateral tonic - clonic Titration 4 weeks
©2021 Marinus Pharmaceuticals. All Rights Reserved I 10 Marigold Baseline Clinical Characteristics Characteristic Placebo (n=51) Ganaxolone (n=50) Total (n=101) Baseline Primary Seizure Frequency, per 28 days (median, IQR) 49.2 ( 18.7 – 120.0) 54.0 (31.3 – 147.3) - Number of AED Medications Taken Prior (median) 7 7 7 Concomitant AED Medications, n (%) Valproate 16 (31.4) 18 (36.0) 34 (33.7) Levetiracetam 13 (25.5) 13 (26.0) 26 (25.7) Clobazam 13 (25.5) 12 (24.0) 25 (24.8) Vigabatrin 12 (23.5) 10 (20.0) 22 (21.8) Baseline seizure burden and AED history highlights unmet need
©2021 Marinus Pharmaceuticals. All Rights Reserved I 11 Ganaxolone Achieved Primary Efficacy Endpoint in Seizure Reduction and Secondary Endpoint for Seizure Severity Caregiver Global Impression of Change in Seizure Intensity / Duration (CGI - CSID) Ganaxolone Placebo 0 10 20 30 40 M e d i a n P e r c e n t R e d u c t i o n 2 8 - d a y F r e q u e n c y o f M a j o r M o t o r S e i z u r e s 30.7% 6.9% = 27.1% (47.9 - 9.6)* p = 0.0036** *Hodges-Lehman Estimate of Median Difference **Wilcoxon Rank-Sum Test
©2021 Marinus Pharmaceuticals. All Rights Reserved I 12 Marigold Cumulative Response Curve 0% 5 10 15 20 25 30 35 40 45 50 0 10 20 30 40 50 60 70 80 90 100 Percent Reduction 28-day Frequency of Major Motor Seizures % o f P a t i e n t s Ganaxolone Placebo 24.5% 9.8% p = 0.064 a = 14.7 (-4.7, 33.8) b * * * * * * * *p<0.05 a a Fisher's Exact b Difference (95% CI)
©2021 Marinus Pharmaceuticals. All Rights Reserved I Consistent Efficacy Signal Across the Broader CDD Population ► Ganaxolone demonstrated a similar efficacy signal across multiple subgroups related to baseline demographics and seizure frequency • Supports beneficial effect in the U.S. patient population 13 U.S. AU/FR/IL/IT/UK RU/PL 0 10 20 30 40 P e r c e n t R e d u c t i o n i n M e d i a n M a j o r M o t o r S e i z u r e F r e q u e n c y ( p e r 2 8 d a y s ) Ganaxolone Placebo 32.0% -2.2% 29.4% 9.5% (n=41) (n=35) (n=24) 21.5% 25.1% Δ a =34.2% Δ a =25.2% Δ a =12.5% a Hodges-Lehman Estimate of Median Difference Female Male -10 0 10 20 30 40 50 Gender P e r c e n t R e d u c t i o n i n M e d i a n M a j o r M o t o r S e i z u r e F r e q u e n c y ( p e r 2 8 d a y s ) Ganaxolone Placebo 27.5% 10.2% 32.0% -7.5% (n=79) (n=21)
©2021 Marinus Pharmaceuticals. All Rights Reserved I 14 Phase 3 Safety Summary Treatment Emergent Adverse Events (TEAE) Preferred Term Placebo (n=51) Ganaxolone (n=50) Any TEAE, n (%) 45 (88.2) 43 (86.0) Somnolence 8 (15.7) 18 (36.0) Pyrexia 4 (7.8) 9 (18.0) Upper Respiratory Tract Infection 3 (5.9) 5 (10.0) Constipation 3 (5.9) 3 (6.0) Salivary Hypersecretion 1 (2.0) 3 (6.0) Sedation 2 (3.9) 3 (6.0) Includes AEs that occurred >5% of subjects in ganaxolone arm and ganaxolone > placebo Preferred Term Placebo (n=51) Ganaxolone (n=50) Any Serious TEAE, n (%) 5 (9.8) 6 (12.0) Bronchitis 0 (0.0) 1 (2.0) Rhinovirus Infection 0 (0.0) 1 (2.0) Urinary Tract Infection 0 (0.0) 1 (2.0) Pneumonia Mycoplasmal 1 (2.0) 0 (0.0) Pneumonia Viral 1 (2.0) 0 (0.0) Respiratory Syncytial Virus Bronchiolitis 1 (2.0) 0 (0.0) Oxygen Saturation Decreased 0 (0.0) 1 (2.0) Food Refusal 0 (0.0) 1 (2.0) Pneumonia Aspiration 0 (0.0) 1 (2.0) Hypoxia 1 (2.0) 0 (0.0) Faecaloma 1 (2.0) 0 (0.0) Hypotonia 1 (2.0) 0 (0.0) Seizure 1 (2.0) 0 (0.0) Unresponsive to Stimuli 1 (2.0) 0 (0.0) Serious Treatment Emergent Adverse Events
©2021 Marinus Pharmaceuticals. All Rights Reserved I 15 Ganaxolone’s Potential to Provide Durable Seizure Improvements in the Open Label Extension • Seizures associated with CDD are often refractory to treatment with existing AEDs and improvements may be short - lived (<3 months) 1 • Preliminary analysis* of the open - label extension (OLE) provides insights into the extended duration effects of ganaxolone (GNX) in CDD 1. M üller A, et al. Eur. J. Paediatr. Neurol. 2016 *Data as of February 24, 2021 Patients treated with ganaxolone for at least 12 months experienced a median 49.6% reduction in major motor seizure frequency Patients transitioning from placebo to ganaxolone demonstrated seizure frequency improvements No new safety findings emerged in the OLE to date Primary Endpoint (17 wks) 1-2 3-4 5-6 7-8 9-10 11-12 0 10 20 30 40 50 60 70 Time in OLE (Months) P e r c e n t R e d u c t i o n i n M e d i a n M a j o r M o t o r S e i z u r e F r e q u e n c y ( p e r 2 8 d a y s ) Ganaxolone Placebo (DB) Ganaxolone (OLE) Open-Label Ganaxolone 33.5% n=43 7.7% n=45 36.3% n=43 40.4% n=39 30.1% n=38 24.0% n=39 33.3% n=34 30.4% n=38 Placebo (DB) 30.7% n=49 6.9% n=51 38.8% n=34 32.8% n=34 46.5% n=22 53.8% n=26
©2021 Marinus Pharmaceuticals. All Rights Reserved I 16 Average Ganaxolone Levels Correlate with Seizure Reduction • Logarithms of plasma GNX level and percentage change in major motor seizure frequency were negatively correlated • Patients in the Medium and High GNX level groups had an average GNX concentration of 120 ng/mL and a median 38.5% reduction in seizure frequency – Incidence of CNS - related adverse events was similar across GNX dose level groups Log e percentage change in major motor seizure frequency was calculated as log e (percentage change + 100) 3.0 3.5 4.0 4.5 5.0 5.5 6.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 Loge GNX Level (ng/mL) L o g e P e r c e n t C h a n g e M a j o r M o t o r S e i z u r e F r e q u e n c y E q u i v a l e n t % C h a n g e i n M a j o r M o t o r S e i z u r e F r e q u e n c y r = -0.512 p = 0.001 *Pearson correlation * 145 48.4 -10.0 -45.4 -66.9 -79.9 -87.8 Equivalent GNX Level (ng/mL) 20.1 33.1 54.6 90.0 148 245 403 Low (40 ng/mL*) Medium (70 ng/mL*) High (170 ng/mL*) -100 -75 -50 -25 0 25 50 75 100 P e r c e n t C h a n g e i n M a j o r M o t o r S e i z u r e F r e q u e n c y **p = 0.01 *mean GNX level within Group **Kruskal-Wallis Test n=13 n=13 n=12
©2021 Marinus Pharmaceuticals. All Rights Reserved I 17 PK Analysis: Adult Focal Onset Seizure Trial vs. Marigold Age Group AUC 24 (ng* hr /mL) C min (ng/mL) C max (ng/mL) 2 to <6 years 3903 85 247 6 to <12 years 3998 84 269 12 to <18 yrs 4106 84 293 ≥18 years 4100 84 292 Abbreviations: AUC 24 =24 - hour area under the ganaxolone plasma concentration time curve; C max =maximum ganaxolone plasma concentration; C min =minimum ganaxolone plasma concentration. Marigold Trial PK Adults Focal Onset Phase 3 Trial vs. Phase 1 PK Lower levels than predicted from Ph1 C min ~ 40 - 45 ng/mL C min ~ 85 ng/mL Adult focal onset program was discontinued as noted in the 10 - Q
Tuberous Sclerosis Complex “Many individuals with TSC continue to experience uncontrolled seizures despite a cocktail of multiple antiepileptic drugs. Because new options are always needed, the TSC community welcomes clinical evaluation of new epilepsy treatments” - Kari Luther Rosbeck, President & CEO of the Tuberous Sclerosis Alliance
©2021 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 Incidence Prevalence • 1:6,000 live births • ~25K - 40K refractory TSC patients in the U.S.* Treatments • Despite available treatments, continued unmet medical need Mechanistic Rationale • Potential neurosteroid deficiency 1 • Pathophysiology may involve GABAergic dysfunction 19 Tuberous Sclerosis Complex (TSC) 1 diMichele, et al, J. Neuro Neurosurg Psychiatry , 2003 *Failure of two prior antiseizure medications with ongoing, frequent seizures.
©2021 Marinus Pharmaceuticals. All Rights Reserved I PART A PART B Baseline (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 20 TSC - Phase 2 Open - Label Clinical Trial Design ► n = Approx. 25 ► 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 ► Patient enrollment to be completed March 2021 ► Top - line data expected Q3 2021 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 with a motor component that are coun tab le Baseline Period Treatment Period OLE Period Screening Visit Baseline Treatment Visit 2 - week taper upon GNX discontinuation (if not continuing to Part B)
©2021 Marinus Pharmaceuticals. All Rights Reserved I ► Trial Details • Evaluates the use of oral ganaxolone in children and adults with seizures associated with TSC • Global, double - blind, placebo - controlled clinical trial • Aims to enroll ~160 total patients between the ages of 1 and 65 (1:1 randomization) • Up to 60 sites, including ex - US (e.g., EU, Canada, Australia, Russia). • Projected first patient enrolled in Q4 ► Primary Efficacy Endpoint • Percent change in 28 - day primary endpoint seizure frequency* 21 Proposed Phase 3 TSC Trial Design Baseline 4 weeks Historical Data (if available) 8 weeks Double - Blind Phase Open - Label Phase Maintenance 12 weeks Titration 4 weeks Open - Label Phase * Primary endpoint seizure types: focal motor seizures without impairment of consciousness or awareness, focal seizures with imp airment of consciousness or awareness, focal seizures evolving to bilateral generalized convulsive seizures, and generalized seizures with a motor com pon ent that are countable Titration 4 weeks
Formulation Development
©2021 Marinus Pharmaceuticals. All Rights Reserved I 23 Efforts to Improve Ganaxolone Exposure in Chronic Epilepsies ► Dosing regimen: Marigold Study was the first Phase 3 trial of ganaxolone to evaluate three times a day (TID) dosing • Predicted pharmacokinetic (PK) curves for TID and two times a day (BID) dosing demonstrate increase trough GNX levels which may provide improved seizure control ► Support the continued study of ganaxolone TID dosing in other epilepsies ► Formulation development: new oral ganaxolone formulations in development that aim to improve PK properties to better achieve target ganaxolone levels Dose regimen C max (ng/mL) AUC 0 - 24 (ng ∙ h/mL) % time (>100 ng/mL GNX) TID 281 3763 78 BID 286 3135 53
©2021 Marinus Pharmaceuticals. All Rights Reserved I 24 Ganaxolone Formulation Work in Progress for Second Generation Candidate Step down IV to oral Pediatric Dosing IV Dosing Oral Dosing • Exploring opportunities to improve bioavailability and PK profile • Potential expansion into new indications and into new therapeutic areas • Targeting IV - to - oral step down for patients that may benefit from continued therapy
©2021 Marinus Pharmaceuticals. All Rights Reserved I Commercial Opportunity
©2021 Marinus Pharmaceuticals. All Rights Reserved I 26 Commercialization Preparedness Refining and Optimizing Value Proposition for Market Testing with key stakeholders – Providers, Payers Developing organizational and infrastructure needs – home office, field, systems and processes Readying supply chain to support patient services, channel strategy and scale up needs Key Objectives is to create operational leverage across indications Evaluating Life Cycle plans to scale up Access, Scientific Affairs and Commercial teams *TPP – Target Product Profile
©2021 Marinus Pharmaceuticals. All Rights Reserved I 27 Key Findings from Recently Conducted Market Research Show that Ganaxolone is Well Suited for Broad Clinical Adoption Across Indications Awareness Mechanism of Action TPP Reactions Primary Usage Drivers Source: ZS Associates Primary Research and Analysis (N=35 HCP Interviews), (TPP – May 2020; o ther market research – June 2020) Neurologists who treat both CDD and TSC patients had high awareness of ganaxolone Ganaxolone’s extrasynaptic mechanism of action well understood and viewed as differentiable Many HCPs are excited about the opportunity to use ganaxolone, especially for CDD, given favorable reactions to its efficacy and durability data, and safety profile • Disease - specific indication, response rate, and durability of response in a highly refractory patient population • Ability to be used with antiseizure medications across mechanisms (i.e., sodium channel blockers, GABA transmission inhibitors, cannabidiol) in refractory patients
©2021 Marinus Pharmaceuticals. All Rights Reserved I Status Epilepticus
©2021 Marinus Pharmaceuticals. All Rights Reserved I 29 Status Epilepticus (SE): Definition and Epidemiology Background ► Prolonged continuous seizures ► 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 ► Status epilepticus can result in permanent neuronal damage and contribute to high morbidity and mortality ► Becomes more treatment refractory with progression SE is the second most common neurologic emergency in the U.S. 1 150,000 SE patients 2 1. Anaethesia and Intensive Care Medicine, February 02, 2018 , Update on the management of status epilepticus 2. DeLorenzo RJ Pellock JM Towne AR Boggs JG. Epidemiology of status epilepticus. J Clin Neurophysiol. 1995; 12: 316 - 325
©2021 Marinus Pharmaceuticals. All Rights Reserved I 30 Goals of a New Therapy for the Treatment of SE 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
©2021 Marinus Pharmaceuticals. All Rights Reserved I 31 Pharmacokinetics/Pharmacodynamics Well Suited for Acute SE Treatment Experimental PK – plasma and brain 1 Brain and plasma concentration after ganaxolone 3 mg/kg IM in mice Human PD – EEG changes 2 EEG bispectral index in healthy volunteers following IV ganaxolone 1. Zolkowska D, Wu CY, Rogawski MA. Intramuscular allopregnanolone and ganaxolone in a mouse model of treatment - resistant status epilepticus. Epilepsia. 2018 Oct;59:220 - 7. 2. Data on file, Marinus Pharmaceuticals, inc . Human PK 2 Following 20 mg ganaxolone bolus (over 2 minutes): C max 1,240 ng/mL T max 0.08 hrs Ganaxolone activates the extrasynaptic GABA A receptor, is associated with high brain concentrations, and delivers a rapid onset of action
©2021 Marinus Pharmaceuticals. All Rights Reserved I Treatment Period Loading Dose Maintenance Taper 32 Phase 2 RSE Trial Design 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 IV ganaxolone in refractory SE patients Goals of a new treatment Rapid cessation Maintenance of seizure control Prevent progression to IV anesthetics 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; further decreased response in refractory SE 3rd line IV Anesthetics: high morbidity, mortality ~35%; increased duration of hospitalization and costs of care Endpoints Primary: Percent of patients who did not require escalation of treatment with IV anesthetic within the first 24 hours after ganaxolone initiation Secondary: Additional efficacy, safety and tolerability
©2021 Marinus Pharmaceuticals. All Rights Reserved I 33 Patient Demographics of Phase 2 Trial 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 2nd - line IV AEDs • 2.1 (range: 1 - 4), all failed LEV or LAC • 14/17 patients failed two or more 2nd - line AEDs • All prior AEDs were administered within recommended dosing guidelines Mean # of failed first - and - second line IV AEDs (including benzodiazepines) 2.9 (range: 2 - 5) 7 Vascular 4 Tumor 2 Autoimmune 2 Drug overdose 2 Unknown Etiologies
©2021 Marinus Pharmaceuticals. All Rights Reserved I 34 Phase 2 Trial Results Demonstrated Rapid Onset And Durability of Effect Cohort No escalation to IV anesthetics within 24 hours from infusion initiation (Primary Endpoint) Status - free through 24 hours from infusion initiation (investigator determination) No escalation to additional IV AEDs or IV anesthetics for status relapse at any time through 24 hours after ganaxolone 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 ganaxolone treatment SE Cessation Occurred Rapidly in All Dose Groups (median = 5 minutes) Data presented at AES 2019 AEDs – antiepileptic drugs
©2021 Marinus Pharmaceuticals. All Rights Reserved I 35 PK/PD Relationship and Rationale for Target Dose 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
©2021 Marinus Pharmaceuticals. All Rights Reserved I 36 IV Ganaxolone Safety Summary 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 stroke, perforated bowel, fall, loss of consciousness, multiple fractures, pneumothorax) 50 AEs in 16 patients
©2021 Marinus Pharmaceuticals. All Rights Reserved I 37 Overview of U.S. Phase 3 RSE RAISE Trial Design Trial design • Randomized, placebo - controlled (adjunctive to standard - of - care) clinical trial Target patient population • Status epilepticus patients (n=124) who have failed benzodiazepines and ≥ 2 IV AEDs Dosing • 36 - hour infusion followed by a 12 - hour taper (48 - hour treatment) • Phase 2 dose paradigm and extends ganaxolone plasma exposure ≥ 500 ng/mL for 12 hours Co - primary endpoints • Proportion of participants with SE cessation within 30 minutes of study drug initiation without medications for the acute treatment of SE • Proportion of participants with no progression to IV anesthesia for 36 hours following study drug initiation Secondary endpoints • No progression to IV anesthesia for 24 hours off study drug (i.e., 72 hours) • Time to SE cessation • Healthcare utilization metrics (eg, length of stay, # of days in the ICU) • Functional outcomes • Safety measures
©2021 Marinus Pharmaceuticals. All Rights Reserved I 38 RSE Phase 3 RAISE Clinical Planning • 1:1 randomized, double - blind, placebo - controlled trial • Failure of a benzodiazepine and 2 second - line IV AEDs • 3 - minute bolus, 36 - hour infusion, 12 - hour 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 to be 2 days (including a 12 - hour taper). Phase 3 Target Plasma Concentration Continuous Infusion Infusion Taper Currently recruiting patients Topline data expected 1H 2022 38
©2021 Marinus Pharmaceuticals. All Rights Reserved I 39 RAISE Trial Sites Standard of Care Progression to IV Anesthesia ► Surveyed PI’s at selected RAISE Trial sites to learn more about their standard of care natural history progression to IV anesthesia following the failure of one versus more than one 2nd - line IV AEDs Trial population Of those that escalate to 3 rd - line IV anesthesia, they do so in ~2.5 hours following failure of the second 2 nd - line IV AED Clear unmet medical need in patients that fail two or more 2 nd line IV AEDs Guides site selection and approximates placebo response for escalation to IV anesthesia co - primary Patients with non - convulsive status epilepticus (NCSE) median 1 2 0 20 40 60 80 100 # of failed 2 nd -line IV AEDs % o f P a t i e n t s P r o g r e s s i n g t o 3 r d - l i n e I V a n e s t h e t i c s median + 95% CI
Commercial Opportunity
©2021 Marinus Pharmaceuticals. All Rights Reserved I 41 Quantifying the Significant Clinical and Economic Burden of RSE The Phase 3 trial of ganaxolone in refractory SE aims to demonstrate rapid onset of action capable of preventing escalation to IV anesthetics, and downstream associated clinical outcomes Treatment with IV anesthetics has been reported to lead to increased length of hospital admission and risk of infections, new disability, and death 1 - 3 Pharmacoeconomic opportunity to quantify cost of care and characterize clinical outcomes based on treatment progression to IV anesthetics 1 Sutter R et al. 2014 Neurology 2 Hawkes MA et al. 2019 Crit. Care Med. 3 Marchi NA et al. 2015 Crit. Care Med. $ $ To support value - based economics / approach will be a key tool with reimbursement experts
©2021 Marinus Pharmaceuticals. All Rights Reserved I 42 High Cost of Care Currently Associated with RSE Population Ganaxolone may provide an opportunity to reduce hospital costs and save lives by altering how medicine is practiced Utilization and Cost Outcomes Metric Cohort 1 (≤ 1 IV AED) Cohort 2 (> 1 IV AED) Cohort 3 ( ≥ 1 IV anesthetic) All Unique RSE patient encounter, N (%) 14,694 (33.4) 10,140 (23.1) 19,154 (43.5) 43,988 (100) Hospital length of stay (LOS) (days) Mean* 4.7 7.2 12.0 8.4 Median* 3 4 8 5 ICU LOS (for ICU patients only) Mean* 2.7 3.1 6.6 5.4 Median* 2 2 4 3 Total hospital cost* ($USD) Mean* $11,532 $18,328 $41,858 $26,304 Median* $6,812 $10,592 $24,105 $13,201 Clinical Outcomes Metric Cohort 1 (≤ 1 IV AED) Cohort 2 (> 1 IV AED) Cohort 3 ( ≥ 1 IV anesthetic) All Unique RSE patient encounter, N (%) 14,694 (33.4) 10,140 (23.1) 19,154 (43.5) 43,988 (100) Discharge disposition (%) Expired * 4.6 6.3 18.9 11.2 Hospital - acquired condition (%Y) 14.0 19.4 23.1 19.2 Catheter - associated UTI (%) 12.0 17.4 18.3 16.0 Miscellaneous infection Ŧ (%) 1.6 1.7 4.3 2.8 Vascular catheter - associated infection Ŧ (%) 0.2 0.2 0.4 0.3 Mechanical ventilator - associated complication (%) 0.2 0.2 1.6 0.8 * Indicates p<0.05 across all pairwise comparisons Ŧ I ndicates p<0.05 C1 or C2 vs. C3 Marinus estimates that safe and effective therapeutics that prevent progression to SRSE (i.e., treatment with IV anesthetics) may reduce mortality rates and hospital costs Source: Guteran EL 2021 JAMA Neurol.
Status Epilepticus Development Plan
©2021 Marinus Pharmaceuticals. All Rights Reserved I 44 Status Epilepticus Patient Populations & Development Plan Convulsive SE Non - Convulsive SE/ Focal SE (55% of total SE population) 1 Benzodiazepines IV AED’s IV Anesthetics IV AED’s IV Anesthetics ESE Phase 2 Trial ICU / Neuro ICU time Established SE Refractory SE Super - Refractory SE Benzodiazepines Emergency Dept. / ICU ~15% transition to NCSE/Focal SE Drugs Administered IV Ganaxolone’s clinical development programs address patient populations in different treatment settings across the SE continuum ICU Emergency Dept . 1 Leitinger M 2019 Epilepsia (45% of total SE population) 1
©2021 Marinus Pharmaceuticals. All Rights Reserved I 45 Additional Commercial Opportunities Along SE Continuum Potential to leverage future hospital sales force to address > 3x patient population in ESE & SRSE 1. DeLorenzo RJ Pellock JM Towne AR Boggs JG. Epidemiology of status epilepticus. J Clin Neurophysiol. 1995; 12: 316 - 325 2. Kapur et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus N Engl J Med 2019;381:2103 - 13. 3. Rossetti and Lowenstein. Management of refractory status epilepticus in adults Lancet Neurol. 2011 Oct; 10(10): 922 – 930 ESE Treatment Trial
©2021 Marinus Pharmaceuticals. All Rights Reserved I 46 Emergency Room ICU Tertiary Center ICU Treatment of Refractory Status Epilepticus Failure of Benzodiazepines and Initial Second Line AEDs Failure of Benzodiazepines and Two or More Second Line AEDs • Ganaxolone can be initiated earlier in the course of RSE • Patient population failing benzodiazepine and initial second line AED
©2021 Marinus Pharmaceuticals. All Rights Reserved I ► Trial Goals: • Support potential European approval in RSE • Potential indication expansion opportunity (relative to the RAISE study population) 47 Proposed Phase 3 Trial in Refractory SE (RAISE II) Trial Attributes Trial Population Failure of benzodiazepines and at least one IV AED’s (RSE) (n=70) Failure of benzodiazepines and at least two IV AED’s (RSE) (n=124) Comparator Ganaxolone vs. Placebo with concurrent IV AED initiation Ganaxolone vs. Placebo in patients receiving background standard of care Primary Endpoint Responder analysis: SE cessation within 30 min and no escalation of care within 36 hrs Co - primary: (1)SE cessation within 30 min (2) no escalation to IV anesthesia within 36 hrs Geographic Location EU/UK/US US only
©2021 Marinus Pharmaceuticals. All Rights Reserved I 48 Emergency Room ICU Tertiary Center ICU Established Status Epilepticus – Potential Use of Ganaxolone in Emergency Room • Unique Environment: - No EEG - Risk of rapid escalation of care - Convulsive patients: new dosing paradigm – bolus and short infusion time (2 - 24 hours)
©2021 Marinus Pharmaceuticals. All Rights Reserved I 49 Established Status Epilepticus – Potential Use of Ganaxolone in Emergency Room • Not enough time for consent - Exception from Informed Consent (EFIC) / Community consent activities • First patient expected to be enrolled in 1H of 2022 Failed benzodiazepine Open B olus IV ganaxolone infusion Screening Double - blind treatment (2 - 24h) Failed benzodiazepine Randomization 1:1 Standard of care IV AED Placebo bolus B olus Placebo IV ganaxolone: <30 min Pilot: N = 4 - 5 per cohort Blinded: N = 40 per arm Standard of care IV AED 2 - 24h P roposed ESE Clinical T rial D esign
Financial Update
©2021 Marinus Pharmaceuticals. All Rights Reserved I Credit Financing Overview Credit financing agreement with Oaktree Capital Management , a leader among investment managers specializing in alternative investments Financing has potential to provide incremental cash of up to $125 million total through 2023* ( gross proceeds before fees) $75 million ** available to be drawn through 2H 2022 based on anticipated regulatory milestones associated with the CDKL5 Deficiency Disorder indication Marinus has option to draw the final $50 million based on additional ganaxolone milestones* Transaction proceeds enable continued investment in commercialization, R&D, and manufacturing scale up Monetization of the anticipated Priority Review Voucher is permitted and Marinus maintains ability to execute a U.S. synthetic royalty monetization deal *Availability subject to meeting of certain regulatory, clinical, financing, and revenue thresholds **15 million drawn at closing in May 2021 Morgan Stanley & Co. LLC acted as lead placement agent and H. C. Wainwright & Co. acted as co - placement agent on the transaction The loan will mature in May 2026 and includes an interest only period for the initial three years of the agreement 51
©2021 Marinus Pharmaceuticals. All Rights Reserved I Financial Overview: Q1 2021 Analyst Coverage * : • Cantor Fitzgerald: Alethia Young • Cowen: Joseph Thome, Ph.D. • H.C. Wainwright & Co: Douglas Tsao • Jefferies: Andrew Tsai • JMP Securities: Jason N. Butler, Ph.D. • Ladenburg Thalman : Michael Higgens • Leerink : Marc Goodman • Oppenheimer: Jay Olson • Truist : Joon Lee, M.D., Ph.D. • RW Baird: Brian Skorney * Note: Opinions, estimates, and forecasts of the individual analysts regarding Marinus do not represent opinions, estimates, and forecasts of Marinus. The listing above does not imply endorsement or concurrent with their information, conclusions, or recommendations. Investor Relations – Nasdaq: MRNS Updated 2021 Guidance • Revenue • FY 2021 projected to be between $9 - $12 million • Operating Expenses • FY 2021 loss from operations of between $113 - $118 million • Total includes approximately $16 million of non - cash stock - based compensation Financial Summary (at March 31, 2021): • $123.5 million in cash and cash equivalents • $0 in debt • 36.6 million shares outstanding • 5.4 million options, RSUs & convertible preferred stock outstanding 52
©2021 Marinus Pharmaceuticals. All Rights Reserved I 53 BARDA Contract – Refractory Status Epilepticus Key Contract Parameters ► BARDA to contribute $21 million in base contract to support the Phase 3 RAISE clinical trial in RSE and preclinical studies of ganaxolone in nerve agent exposure animal models. ► BARDA may contribute up to an additional $30 million in support of manufacturing, supply chain, clinical, regulatory and toxicology activities based on favorable clinical and pre - clinical outcomes. ► Total contract value = $84 million; $51 million BARDA / $33 million Marinus - if all options are undertaken. ► On successful development, BARDA and Marinus may negotiate for a supply of ganaxolone for a potential response to nerve gas exposure threats.
Intellectual Property
©2021 Marinus Pharmaceuticals. All Rights Reserved I 55 Multiple Layers Of Potential Protection Patent/Patent Applications Expiration Date IV formulations containing exclusively in - licensed proprietary Captisol ® product 2033 SE – patent application pending on IV formulations and methods of use 2036 SE – patent application pending on clinical treatment regimen 2040 Oral Formulations – nanoparticulate formulations (2026 + up to 5 Year PTE) 2031 CDD & PCDH19 – patent application pending on methods of use, patient stratification 2038 TSC – patent application pending on methods of use 2040 Oral Formulations containing cyclodextrin 2042 Orphan drug designations for CDD and PCDH19 provide 7 and 10 years regulatory exclusivity in US and EU, respectively. Orphan drug designation for SE provides 7 years regulatory exclusivity in US.
Thank You
Appendix
CDKL5 Deficiency Disorder
©2021 Marinus Pharmaceuticals. All Rights Reserved I 59 Subject Baseline Demographics & Country Enrollment in Marigold Study (CDD) Demographic Placebo (n=51) Ganaxolone (n=50) Total (n=101) Age, median 7.0 5.0 6.0 Gender, n (%) Male 10 (19.6) 11 (22.0) 21 (20.8) Female 41 (80.4) 39 (78.0) 80 (79.2) Ethnicity, n (%) Hispanic or Latino 6 (11.8) 4 (8.0) 10 (9.9) Not - Hispanic or Latino 43 (84.3) 44 (88.0) 87 (86.1) Unknown 1 (2.0) 1 (2.0) 2 (2.0) Not reported 1 (2.0) 1 (2.0) 2 (2.0) Race, n (%) White 47 (92.2) 46 (92.0) 93 (92.1) Asian 3 (5.9) 2 (4.0) 5 (5.0) Other 1 (2.0) 2 (4.0) 3 (3.0) US IT RU UK PL FR AU IL 42 15 14 10 7 6 6 1
©2021 Marinus Pharmaceuticals. All Rights Reserved I 60 Responder Analysis – Marigold Study Percent Reductions in Major Motor Seizure Frequency 25% 50% 75% 0 20 40 60 80 100 Percent Reduction 28-day Frequency of Major Motor Seizures % o f P a t i e n t s Ganaxolone Placebo 57.1% 23.5% 24.5% 9.8% 10.2% 3.9% p=0.064 a a Fisher's Exact Test p=0.001 a
Tuberous Sclerosis Complex
©2021 Marinus Pharmaceuticals. All Rights Reserved I 62 Unmet Need in TSC Epilepsy and Scientific Rationale for Ganaxolone ► Epilepsy present in ~90% of individuals affected with TSC 1 ► Existing treatments fail to control seizures in ~60% of individuals with TSC - associated epilepsy 2 ► Uncontrolled seizures, especially early in life, may lead to developmental delays and cognitive dysfunction Clear need to evaluate treatments with a differentiated mechanism of action Data generated in collaboration with the TS Alliance and utilization of their biosample repository Patients aged 1 - 14 1. Canevini MP et al 2018 Am J of Med Genetics_ Current concepts on epilepsy management in TSC. 2. ChuShore CJ et al Epilepsia_The natural history of epilepsy in TSC.
Status Epilepticus
©2021 Marinus Pharmaceuticals. All Rights Reserved I 64 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 Patient Characteristics for Phase 2 SE Trial *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)
©2021 Marinus Pharmaceuticals. All Rights Reserved I 65 Potential Launch Into the Hospital Setting Designed to be Driven by Data, Customer Collaboration & Protocolization of Ganaxolone in RSE • Phase 3 data to support clinical adoption and budget model • Clear clinical benefit eg, SE cessation, IV escalation • Economic advantage – LOS*, ICU duration, clinical outcomes Compelling Clinical and HEOR* Data • Partner with KOLs and societies to update RSE treatment guidelines • Collaborative approach to protocol augmentation with health systems and local hospitals Society Guideline & Account Protocol Inclusion • Early engagement with hospital stakeholders to best understand and frame value proposition • Determine formulary process and requirements • Reimbursement, logistics and operational processes C - Suite, Pharmacy, & Admin Engagement • Identify, navigate and influence unique hospital decision makers • Educate and generate customer usage data • Collaborate internally to protocolize usage and translate success Experienced Hospital Sales Force Clinical and Economic Evidence Access Pull - Through Clinical Adoption Critical Success Factors for RSE Launch *LOS – Longer length of stay *HEOR – Health economics and outcomes research
PCDH19 Related Epilepsy
©2021 Marinus Pharmaceuticals. All Rights Reserved I 67 Biomarker Stratified Proof of Concept (POC) Study in PCDH19 Trial Details ► Ages 1 - 17 with 8 or more seizures in 8 weeks, failed 2 or more AEDs ► Completed double - blind portion of the trial with 21 patients ► Primary efficacy analysis based on change in seizure frequency in all patients ► Stratify patients into one of two biomarker groups based on baseline allopregnanolone sulfate levels and randomized (ganaxolone or placebo) within each stratum R 1:1 PCDH19 (all - patients) n =21 Biomarker + Low Allo - S Primary efficacy analyses conducted using all patients 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 Open - Label Phase (52 weeks) * not drawn to scale Titration 4 weeks Screening Visit Titration 4 weeks
©2021 Marinus Pharmaceuticals. All Rights Reserved I 68 Ganaxolone Demonstrates Directional Improvement in Change in Seizure Frequency Primary endpoint seizure types are defined as countable focal seizures with impaired awareness or generalized seizure with a cle ar motor component. Ganaxolone (n=10) Placebo (n=11) 0 10 20 30 40 50 60 70 80 90 P e r c e n t R e d u c t i o n i n P r i m a r y E n d p o i n t S e i z u r e F r e q u e n c y ( p e r 2 8 d a y s ) 61.5% 24.0% p=0.17 25% 50% 75% 0 10 20 30 40 50 60 70 80 90 100 Percent Reduction in Primary Endpoint Seizure Frequency P r o p o r t i o n o f P a t i e n t s ( % ) Ganaxolone Placebo 80.0% 45.5% 36.4% 36.4% 50.0% 50.0% Baseline Primary Endpoint 28 - day Seizure Frequency (median) 14.5 17.7 Ganaxolone Placebo