EX-99.2 3 tm2037816d1_ex99-2.htm EXHIBIT 99.2

Exhibit 99.2

20-37816-1_pdf final marinus corporate deck_page001.jpg  NASDAQ: MRNS@MarinusPharma Corporate Overview 2020

 

20-37816-1_pdf final marinus corporate deck_page002.jpg Safe Harbor Statement To the extent that statements contained in this presentation 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 presentation 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 trial design, target patient population and endpoints for our clinical trials; interpretation of scientific basis for ganaxolone use; timing for availability and release of data, including the expected release of topline data from our Phase 3 trial in status epilepticus (SE) in 1H 2022; from our proof of concept study in PCDH19 in the first half of 2021, and from our Phase 2 tuberous sclerosis complex (TSC) trial in mid 2021; the potential safety and efficacy and therapeutical potential of ganaxolone; timing and expectation regarding submissions of regulatory applications, including our expectation to submit an NDA for ganaxolone in CDD in mid-2021 and an MAA by the end of Q3 2021; expectations regarding commercial launch of ganaxolone in CDD in 1H 2022; expectations regarding our agreement with BARDA; expectations regarding the potential market opportunities for our product candidates, including oral ganaxolone; potential commercial alliances; and our expectations regarding the effect of the COVID-19 pandemic on our 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-looking 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 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 other regulatory agencies 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 and maintain patent protection for our product candidates; 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. You may access these documents for free by visiting EDGAR on the SEC web site at www.sec.gov.

 

20-37816-1_pdf final marinus corporate deck_page003.jpg Ganaxolone (GNX) Targets Synaptic & Extrasynaptic GABAA Receptors Ganaxolone a positive allosteric GABAA 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 GABAA receptors to calm over-excited neurons GNX is a synthetic analog of allopregnanolone 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

 

20-37816-1_pdf final marinus corporate deck_page004.jpg Corporate Strategy Evaluation of IV and Oral Opportunities Building Upon Status Epilepticus (SE) Maximizing Value for Orphan Epilepsies Leveraging GNX Molecule Expand clinical opportunities from refractory status epilepticus (RSE) to broader SE market Initiate commercial plan Create a global development strategy Develop pharmacoeconomic value proposition Complete BARDA activities Continue CDKL5 deficiency disorder (CDD) and tuberous sclerosis complex (TSC) clinical development Consider expansion opportunities based on scientific rationale Further develop commercial roadmap, including scientific and clinical differentiation Explore opportunities to improve bioavailability and PK Prioritize clinical trials based on unmet need, improved product profile New therapeutic indications driven by scientific rationale

 

20-37816-1_pdf final marinus corporate deck_page005.jpg Ganaxolone Development Pipeline

 

20-37816-1_pdf final marinus corporate deck_page006.jpg  Status Epilepticus Indication

 

20-37816-1_pdf final marinus corporate deck_page007.jpg Status Epilepticus (SE): Definition and Epidemiology Background Continuous seizures lasting >5 min SE is the second most common neurologic emergency in the U.S. 1 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 high morbidity and mortality SE becomes more treatment refractory as it progresses 1. Anaethesia and Intensive Care Medicine, February 02, 2018 , Update on the management of status epilepticus ©2020 Marinus Pharmaceuticals. All Rights ReservedI7

 

20-37816-1_pdf final marinus corporate deck_page008.jpg Goals of a New Therapy for the Treatment of SE Established Status Epilepticus (ESE) Refractory Status Epilepticus (RSE) Medically induced Coma Super Refractory Status Epilepticus (SRSE) 1st line2nd line 3rd line Benzodiazepine Administered IV AED’s (antiepileptic drugs) IV GNX IV Anesthetics ©2020 Marinus Pharmaceuticals. All Rights ReservedI8

 

Pharmacokinetics/Pharmacodynamics Well Suited for Acute SE Treatment Experimental PK – plasma and brain1 Human PD – EEG changes2 Ganaxolone targets the extrasynaptic receptor, is associated with high brain concentrations, and delivers a rapid onset of action Brain and plasma concentration after ganaxolone 3 mg/kg IM in mice Human PK2 Following 20 mg ganaxolone bolus (over 2 minutes): Cmax 1,240 ng/mL Tmax 0.08 hrs EEG bispectral index in healthy volunteers following IV ganaxolone 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. Data on file, Marinus Pharmaceuticals, inc. ©2020 Marinus Pharmaceuticals. All Rights ReservedI9

 

20-37816-1_pdf final marinus corporate deck_page010.jpg Phase 2 SE Trial Design Evaluate IV ganaxolone in refractory SE patients SE Patients Diagnosis of convulsive or non-convulsive SE Failed at least one 2nd line IV AED but had not progressed to 3rd line IV anesthetics Screening Treatment Period Loading DoseMaintenanceTaper Post-treatment Follow-up 24 hourWeeks 2, 3, 4 Bolus plus continuous infusion 2-4 day infusion18-hour taper CohortDose of GNX/dayN Low500mg/day5 Medium650mg/day4 High713mg/day8 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

 

20-37816-1_pdf final marinus corporate deck_page011.jpg Patient Demographics of Phase 2 Trial 17 patients enrolled 8 males, 9 females Mean age: 57 years old (range: 23-88) History of Epilepsy 7 (41%) yes, 10 (59%) no Types of SE 5 (29%) CSE, 11 (65%) NCSE, 1 (6%) CSE→NCSE Mean # of failed first-and-second line IV AEDs (including benzodiazepines) 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 7 vascular 4 tumor Etiologies 2.9 (range: 2-5) AEDs All prior AEDs were administered within recommended dosing guidelines 2 autoimmune 2 drug overdose 2 unknown

 

20-37816-1_pdf final marinus corporate deck_page012.jpg 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 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) SE Cessation Occurred Rapidly in All Dose Groups (median = 5 minutes) Data presented at AES 2019 AEDs – antiepileptic drugs ©2020 Marinus Pharmaceuticals. All Rights ReservedI12

 

20-37816-1_pdf final marinus corporate deck_page013.jpg PK/PD Relationship and Rationale for Target Dose Modeled PK Curves for All Dose Groups Seizure Burden Reduction Occurred Rapidly in All Dose Groups High Dose Achieves Target Range ≥ 500 ng/mL for ~8 hoursOnly High Dose Provided Sustained Reduction (>80%) Throughout Entire Analysis Window Data presented at AES 2019 PK: Pharmacokinetics / PD: Pharmadynamic ©2020 Marinus Pharmaceuticals. All Rights ReservedI13

 

20-37816-1_pdf final marinus corporate deck_page014.jpg IV Ganaxolone Safety Summary 10 SAEs in 6 patients (also included in AEs) 50 AEs in 16 patients 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 Intubation: 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) 9 patients were not intubated upon enrollment. Of these, 6 remained intubation-free during the entire ganaxolone treatment period Data presented at AES 2019 AE: adverse event / SAE: serious adverse event ©2020 Marinus Pharmaceuticals. All Rights ReservedI14

 

20-37816-1_pdf final marinus corporate deck_page015.jpg 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 ©2020 Marinus Pharmaceuticals. All Rights ReservedI15

 

20-37816-1_pdf final marinus corporate deck_page016.jpg RSE Phase 3 RAISE Clinical Planning Treatment PeriodFollow-up Period Initiation Status Site identification through initiation underway Drug and placebo supply ready for shipment to sites Daily S CHours 0 -24 Day 2 Hours 24-36 Hours 36-48 Daily hours Weeks 1,2,3 & 4 Currently recruiting patients R EBolus Edose N Continuous Infusion Infusion Taper Phase 3 Target Plasma Concentration IContinuous Infusion N G Taper Treatment is planned to be 2 days (including a 12-hour taper). Dose Initiation (Time 0) Trial Overview 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 ©2020 Marinus Pharmaceuticals. All Rights ReservedI16

 

20-37816-1_pdf final marinus corporate deck_page017.jpg 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 100 %of Patients Progressing to 3rd-line IV anesthetics 60 40 20 Patients with non-convulsive status epilepticus (NCSE) 0 1 2 nd median + 95% CI Of those that escalate to 3rd-line IV anesthesia, they do so in ~2.5 hours median following failure of the second 2nd-line IV AED Clear unmet medical need in patients that fail two or more 2nd line IV AEDs Guides site selection and approximates placebo response for escalation to IV anesthesia co-primary # of failed 2 -line IV AEDs ©2020 Marinus Pharmaceuticals. All Rights ReservedI17

 

20-37816-1_pdf final marinus corporate deck_page018.jpg 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. ©2020 Marinus Pharmaceuticals. All Rights ReservedI18

 

20-37816-1_pdf final marinus corporate deck_page019.jpg  Commercial Opportunity

 

20-37816-1_pdf final marinus corporate deck_page020.jpg 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. 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 $$There’s a potential pharmacoeconomic opportunity to quantify cost of care and characterize clinical outcomes based on treatment progression to IV anesthetics. Understanding the spectrum of clinical and economic burden based on disease severity will help support treatment value Sutter R et al. 2014 Neurology Hawkes MA et al. 2019 Crit. Care Med. 3Marchi NA et al. 2015 Crit. Care Med. ©2020 Marinus Pharmaceuticals. All Rights ReservedI20

 

20-37816-1_pdf final marinus corporate deck_page021.jpg RSE is a Neurological Emergency With Significant Unmet Need in a Severely Impaired and Costly Patient Population 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 Marinus estimates that effective therapeutics that prevent progression to SRSE (i.e., treatment with IV anesthetics) may reduce mortality rates by ~70% and $30,000 in hospital cost *Indicates p<0.05 across all pairwise comparisons Ŧindicates p<0.05 C1 or C2 vs. C3 Manuscript in preparation ©2020 Marinus Pharmaceuticals. All Rights ReservedI21

 

20-37816-1_pdf final marinus corporate deck_page022.jpg Potential Launch Into the Hospital Setting Designed to be Driven by Data, Customer Collaboration & Protocolization of Ganaxolone in RSE Critical Success Factors for RSE Launch Clinical and Economic Evidence Society Guideline & Account Access Experienced Hospital Sales • Ph3 data to support clinical adoption and Protocol Inclusion• Early engagement with Pharmacy to best frame Force budget model • Clear clinical benefit eg, SE cessation, IV escalation • Economic advantage – LOS, ICU duration 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 Clinical Adoption value proposition • Determine formulary process and requirements • Reimbursement, logistics and operational processes ite, Pharmacy, & Admin Engagement • Navigate and influence hospital decision makers • Educate and generate customer usage data • Collaborate with physicians to protocolize usage Pull-Through LOS – Longer length of stay HEOR – Health economics and outcomes research ©2020 Marinus Pharmaceuticals. All Rights ReservedI22

 

20-37816-1_pdf final marinus corporate deck_page023.jpg Additional Commercial Opportunities Along SE Continuum Potential to leverage existing hospital sales force to address > 3x patient population in ESE & SRSE ESETT DeLorenzo RJ Pellock JM Towne AR Boggs JG. Epidemiology of status epilepticus. J Clin Neurophysiol. 1995; 12: 316-325 ©2020 Marinus Pharmaceuticals. All Rights ReservedI23 Rossetti and Lowenstein. Management of refractory status epilepticus in adults Lancet Neurol. 2011 Oct; 10(10): 922–930

 

20-37816-1_pdf final marinus corporate deck_page024.jpg Potential Expansion of Ganaxolone into Established Status Epilepticus (ESE) Emergency RoomICU Tertiary Center ICU Unique Environment: -No EEG -Risk of rapid escalation of care -Convulsive patients: new dosing paradigm – bolus and short infusion time (2-24 hours)

 

 Established Status Epilepticus – Use of Ganaxolone in Emergency Room Pilot: N = 4-5 per cohort Failed benzodiazepine Open bolusIV ganaxolone infusion Standard of care IV AED Blinded: N = 40 per arm Failed benzodiazepine 1:1 bolus Placebo bolus IV ganaxolone: Placebo Standard of care IV AED Screening Randomization Double-blind treatment (2-24h) <30 min 2-24h • Not enough time for consent -Exception from Informed Consent (EFIC) -Community consent activities • First patient expected to be enrolled in 1H of 2022 ©2020 Marinus Pharmaceuticals. All Rights Reserved I25

 

20-37816-1_pdf final marinus corporate deck_page026.jpg  Genetic Epilepsy Franchise

 

20-37816-1_pdf final marinus corporate deck_page027.jpg  CDKL5 Deficiency Disorder

 

20-37816-1_pdf final marinus corporate deck_page028.jpg CDKL5 Deficiency Disorder (CDD) 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 TreatmentsNo disease-specific treatments are approved Rationale Potential GABAA dysfunction, promising data in Phase 2 led to double-blind placebo-controlled trial

 

20-37816-1_pdf final marinus corporate deck_page029.jpg Global Phase 3 Pivotal Trial Design Historical Control 8 weeks Baseline 6 weeks Titration 4 weeks Maintenance 13 weeks Titration 4 weeks Open-Label Phase Double-Blind PhaseOpen-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 bilateral tonic-clonic

 

20-37816-1_pdf final marinus corporate deck_page030.jpg Subject Baseline Clinical Characteristics & Prior/Concomitant Medications Baseline seizure burden and AED history highlights unmet need

 

20-37816-1_pdf final marinus corporate deck_page031.jpg Ganaxolone Achieved Primary Efficacy Endpoint in Seizure Reduction and Secondary Endpoint in Caregiver Impression of Change Median Percent Reduction 28-day Frequency of Major Motor Seizures = 29.7%* p = 0.002** Caregiver Global Impression of Change in Seizure Intensity / Duration (CGI-CSID) 3032.2% 20 10 4.0% 0 GanaxolonePlacebo *Hodges-Lehman Estimate of Median Difference **Wilcoxon Rank-Sum Test

 

20-37816-1_pdf final marinus corporate deck_page032.jpg Marigold Cumulative Response Curve ** ** *p < 0.05 * * * * * Ganaxolone Placebo % of Patients 40 20 0 50 *Fisher's Exact Test % Reduction in Major Motor Seizure Frequency

 

20-37816-1_pdf final marinus corporate deck_page033.jpg 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 Percent Reduct ion in M edian M ajor M ot or Seizure Frequency (per 28 days) 35.9% 30 20 10 31.4 % 7.0 % Gan axolon e Placeb o 27.3% 17.5% Percent Reduct ion in M edian M ajor M ot or Seizure Frequency (per 28 days) 4 0 31.8% 30 20 10 0 10 .2% 33.3% Gan axolon e Placeb o Percent Reduct ion in M edian M ajor M ot or Seizure Frequency (per 28 days) 4 0 32.2% 30 20 .9% 20 11.1% 10 35.9% 16.5% 0 -1.4 % U.S.AU/ FR/ IL/ IT/ UKRU/ PL (n =4 1)(n =35)(n =24 ) -10 Fem aleM ale (n =79)(n =21) Gender -7.8 % 0 -10 -4 .1% <3535 - 93>93 (n =32)(n =34 )(n =34 ) Baseline M ajor M ot or Seizure Frequency (p er 28 d ays)

 

20-37816-1_pdf final marinus corporate deck_page034.jpg Phase 3 Safety Summary Treatment Emergent Adverse Events (TEAE) Serious Treatment Emergent Adverse Events 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)

 

20-37816-1_pdf final marinus corporate deck_page035.jpg 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 Percent Reduct ion in M edian M ajor M ot or Seizure Frequency (per 28 days) Gan axolon e 60Placeb o (D B) Gan axolon e (OLE) 52.7% n =17 Patients treated with ganaxolone for approximately 12 months experienced a 50 4 0 32.2% 30 20 10 0 Placeb o (D B) 33.3% n =39 4 .0 % 12.7% n =38 37.2% n =36 22.6% n =34 4 4 .5% n =26 35.0 % n =24 29.6% n =20 median 52.7% 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 Prim ary Endpoint (17 w k s) 1-23-45-67-8 O p e n -La b e l Ga n a xolon e Tim e in OLE (M ont hs) Müller A, et al. Eur. J. Paediatr. Neurol. 2016 ©2020 Marinus Pharmaceuticals. All Rights ReservedI35 *Data as of September 1, 2020

 

20-37816-1_pdf final marinus corporate deck_page036.jpg 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 43% reduction in seizure frequency –Incidence of CNS-related adverse events was similar across GNX dose level groups Equivalent GNX Level (ng/ m L) Log e Percent Chang e M ajor M ot or Seizure Frequency Equivalent % Chang e in M ajor M ot or Seizure Frequency 5.5 5.0 4 .5 4 .0 3.5 3.0 2.5 * r = -0 .4 99 p = 0 .0 0 1 14 5 4 8 .4 -10 .0 -4 5.4 -66 .9 -79 .9 -8 7.8 Percent Change in M ajor M ot or Seizure Frequency 50 25 0 -25 -50 -75 -10 0 **p = 0 .0 1 3.03.54 .04 .55.05.56 .0 Log e GN X Level (ng / m L) Low (4 0 n g/ m L*) M edium (70 ng/ m L*) H igh (170 ng/ m L*) *Pearson correlat ion Loge percentage change in major motor seizure frequency was calculated as loge(percentage change + 100) n =13n =13n =12 *m ean GNX level w it h in Grou p **Kru sk al-W allis Test ©2020 Marinus Pharmaceuticals. All Rights ReservedI36

 

20-37816-1_pdf final marinus corporate deck_page037.jpg Efforts to Improve Ganaxolone Exposure in Chronic Epilepsies Dosing regimen: Marigold Study was the first Phase 3 study 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 Dose regimen Cmax (ng/mL) AUC0-24 (ng ∙ h/mL) % time (>100 ng/mL GNX) TID 281 3763 78 BID 286 3135 53 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.

 

20-37816-1_pdf final marinus corporate deck_page038.jpg Ganaxolone Formulation Work in Progress for Second Generation Candidate 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 IV Dosing Oral Dosing Step down IV to oral Pediatric Dosing

 

20-37816-1_pdf final marinus corporate deck_page039.jpg  Tuberous Sclerosis Complex

 

20-37816-1_pdf final marinus corporate deck_page040.jpg Allo-S as Potential Biomarker Across Various Genetic Epilepsies 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

 

20-37816-1_pdf final marinus corporate deck_page041.jpg Tuberous Sclerosis Complex CauseDefect or mutation of TSC1 and/or TSC2 genes Symptoms abnormalities Prevalence~25K-40K refractory TSC patients in the U.S.* TreatmentsLimited approved treatments Mechanistic RationalePotential neurosteroid deficiency1 1 diMichele, et al, J. Neuro Neurosurg Psychiatry, 2003 *Failure of two prior antiseizure medications with ongoing, frequent seizures. ©2020 Marinus Pharmaceuticals. All Rights ReservedI41

 

20-37816-1_pdf final marinus corporate deck_page042.jpg 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 Clear need to evaluate treatments with a differentiated mechanism of action Patients aged 1-14 In collaboration with the TS Alliance and utilization of their Biosample Repository “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

 

20-37816-1_pdf final marinus corporate deck_page043.jpg  PART A Base (4 Weeks) GNX Titration (4 Weeks) GNX Maintenance (8 Weeks) Baseline Period PART B Open-Label Extension (OLE) (24 Weeks) * Available to patients that respond to GNX as defined per protocol OLE Period 2-week taper upon GNX discontinuation Screening Visit Baseline Treatment Visit (if not continuing to Part B) •n = 30 8 - 15 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 Top-line data expected mid 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 countable

 

20-37816-1_pdf final marinus corporate deck_page044.jpg  PCDH19 Related Epilepsy

 

20-37816-1_pdf final marinus corporate deck_page045.jpg PCDH19-Related Epilepsy CauseInherited mutation of protocadherin 19 (PCDH19) gene. Located on X chromosome Symptoms Early-onset seizures, cognitive and sensory impairment, and 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 TreatmentsNo disease-specific treatments are approved Mechanistic RationaleAssociated with low levels of allopregnanolone1 and potential GABAergic dysfunction 1Gecz, et.al, Human Molecular Genetics, 2015 ©2020 Marinus Pharmaceuticals. All Rights ReservedI45

 

20-37816-1_pdf final marinus corporate deck_page046.jpg Seizure Reduction Observed 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 Clinical data presented at AES 2018 ©2020 Marinus Pharmaceuticals. All Rights ReservedI46

 

20-37816-1_pdf final marinus corporate deck_page047.jpg Biomarker Stratified Proof of Concept (POC) Study in PCDH19 Primary efficacy analyses will be conducted using this cohort PCDH19 (all-patients) n~20-22 Low Allo-S Biomarker + High Allo-S Biomarker - R 1:1 R 1:1 Placebo Ganaxolone Up to 600 mg 3x/day Placebo Ganaxolone Up to 600 mg 3x/day Ganaxolone Up to 600 mg 3x/day Pre-baseline Screening Baseline 12 weeksTitration 4 weeks Maintenance 13 weeks Titration 4 weeks Open-Label Phase (52 weeks) * not drawn to scale Trial Details Screening Visit 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 ~20-22 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 in 1H 2021 ©2020 Marinus Pharmaceuticals. All Rights ReservedI47

 

20-37816-1_pdf final marinus corporate deck_page048.jpg  Commercial Opportunity

 

20-37816-1_pdf final marinus corporate deck_page049.jpg Commercialization Preparedness Executing research with Payers and Physicians around TPP / Value Proposition Identifying organizational needs for field resources, systems and processes Developing plans to scale up Advocacy, Scientific Affairs and Commercial teams Readying supply chain to support packaging and scale up needs to commercialize Potential for operational leverage across indications within concentrated rare epilepsy care model TPP – Target Product Profile ©2020 Marinus Pharmaceuticals. All Rights ReservedI49

 

20-37816-1_pdf final marinus corporate deck_page050.jpg Our Oral Franchise Model is Driven by Ganaxolone Scientific Rationale and Unmet Need in Debilitating Rare Epilepsy Disorders Given CDKL5 and TSC patient seizure burden, overlap of CDKL5 and TSC prescribers, and common market dynamics, we group both indications under a franchise go to market CDKL5 Deficiency Disorder (CDD) model Tuberous Sclerosis Complex (TSC) 4-5K addressable patients in US and 50-100 newborn cases per year1 20-25K addressable US patient population2 Genetic testing in major global markets driving diagnosis rates Severe, difficult to manage patients with high medication reliance and need for more durable options No indicated treatments available or clinical trials conducted addressable patients Overlapping prescribers and similar behavior across each disease state Physicians seeking safe, effective, and durable treatment options Large refractory population despite available treatment options Severe patients still in need of more efficacious medications Given refractory population, opportunity exists for later stage treatments (eg, 3rd line) Jakimeic et. al 2020 NORD (https://rarediseases.org/rare-diseases/tuberous-sclerosis) ©2020 Marinus Pharmaceuticals. All Rights ReservedI50

 

20-37816-1_pdf final marinus corporate deck_page051.jpg Our Goal: Build a Sustainable Franchise in Rare Epilepsy Opportunity to expand treated population through future clinical development Phase 2 (TSC) 40,000 patients2 Rare Epilepsy ~163,0005 Phase 3 (CDKL 5) ~5,500 patients1 80-90% refractory3 50-60% refractory3 20-40% refractory4 ~ 4,400 CDKL 5 Patients Addressable Patient Population ~ 20,000 TSC patients ~48,900 Rare Epilepsy Identification of Biomarker Sensitive Population (including PCDH19) Jakimeic et. al 2020 NORD (https://rarediseases.org/rare-diseases/tuberous-sclerosis) Marinus market research Ryan et. al 2015 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540245/) Quintana market research

 

20-37816-1_pdf final marinus corporate deck_page052.jpg Key Findings from Recently Conducted Market Research Show that Ganaxolone is Well Suited for Broad Clinical Adoption Across Indications Mechanism of Action Ganaxolone’s extrasynaptic mechanism of action well understood and viewed as differentiable TPP Reactions 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 Primary Usage Drivers Disease-specific indication, response rate, and durability of response Ability to be used with antiseizure medications across mechanisms (i.e., sodium channel blockers, GABA transmission inhibitors, cannabidiol) in refractory patients Awareness More Neuros were aware of ganaxolone than any drug in development for CDD or TSC Source: ZS Associates Primary Research and Analysis (N=35 HCP Interviews)

 

20-37816-1_pdf final marinus corporate deck_page053.jpg  Intellectual Property

 

20-37816-1_pdf final marinus corporate deck_page054.jpg Multiple Layers Of Potential Protection 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.

 

20-37816-1_pdf final marinus corporate deck_page055.jpg  NASDAQ: MRNS@MarinusPharma Thank You

 

20-37816-1_pdf final marinus corporate deck_page056.jpg  Appendix

 

20-37816-1_pdf final marinus corporate deck_page057.jpg Details on Baseline Patient Characteristics for Phase 2 SE Trial 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) Drug Overdose / 7MediumYesCSELOR, LEV1,000mg (1000-3000mg) Withdrawal 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 TumorYesNCSELOR, LEV, VPA700mg (1000-3000mg) AutoimmuneNoNCSELOR, LEV1,000mg (1000-3000mg) VascularNoNCSELOR, LAC, LEV, PHT200mg (200-600mg) VascularYesCSELOR, LEV1,000mg (1000-3000mg) TumorNoNCSELOR, LAC, LEV400mg (200-600mg) AutoimmuneNoNCSELOR, fPHT, LAC, LEV, VPA200mg (200-600mg) 13 Target 14 Target 15 Target 16 Target 17 Target *Bolded, underlined IV AED’s were the last ones administered prior to GNX ©2020 Marinus Pharmaceuticals. All Rights ReservedI57

 

20-37816-1_pdf final marinus corporate deck_page058.jpg 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 IT15 RU14 PL10 UK7 FR 6 AU 6 IL1

 

20-37816-1_pdf final marinus corporate deck_page059.jpg Responder Analysis – Marigold Study 100 % of Patients p=0.001* 6057.1% Ganaxolone Placebo Percent Reductions in Major Motor Seizure Frequency 40p=0.064* 23.5%24.5% 20 9.8%10.2% 0 3.9% 75% *Fisher's Exact Test Reduction in Major Motor Seizure Frequency