About Marinus Pharmaceuticals

Marinus Pharmaceuticals, Inc. operates as a commercial-stage pharmaceutical company dedicated to the development of innovative therapeutics for the treatment of seizure disorders, including rare genetic epilepsies and status epilepticus. On March 18, 2022, the U.S. Food and Drug Administration (FDA) approved the company’s new drug application (NDA) for the use of ZTALMY (ganaxolone) oral suspension for the treatment of seizures associated with Cyclin-dependent Kinase-like 5 Deficiency Disorder (CDD) in patients 2 years of age and older. In June 2022, the U.S. Drug Enforcement Administration (DEA) published an interim final rule in the Federal Register placing ganaxolone and its salts in schedule V (CV) of the Controlled Substances Act (CSA), which rule became final on December 9, 2022. ZTALMY, the company’s first FDA approved product, became available for commercial sale and shipment to patients with a prescription in the U.S. in the third quarter of 2022. The company plans to develop ganaxolone for the treatment of other rare genetic epilepsies, including Tuberous Sclerosis Complex (TSC), and for the treatment of status epilepticus (SE). The company is developing ganaxolone in formulations for two different routes of administration: intravenous (IV) and oral. The different formulations are intended to maximize potential therapeutic applications of ganaxolone for adult and pediatric patient populations, in both acute and chronic care, and for both in-patient and self-administered settings. While the precise mechanism by which ganaxolone exerts its therapeutic effects in the treatment of seizures associated with CDD is unknown, its anticonvulsant effects are thought to result from positive allosteric modulation of the gamma-aminobutyric acid type A (GABAA) receptor in the central nervous system (CNS). Ganaxolone is a synthetic analog of allopregnanolone, an endogenous neurosteroid. Ganaxolone acts at both synaptic and extrasynaptic GABAA receptors, a target known for its anti-seizure, antidepressant and anxiolytic potential. Strategy The key elements of the company’s strategy include pursuing orphan, genetic epilepsy indications for ganaxolone; pursuing hospital-based orphan indications for ganaxolone; reformulation and prodrug compounds; and building on its product pipeline. Products and Product Candidates ZTALMY (ganaxolone) oral suspension CV ZTALMY is an oral suspension given three times per day that the comopany has developed for the treatment of CDD. ZTALMY was approved by the FDA in March 2022 for the treatment of seizures associated with CDD in patients 2 years of age and older. In June 2022, the DEA published an interim final rule in the Federal Register placing ganaxolone and its salts in schedule V of the CSA, which rule became final on December 9, 2022. ZTALMY, the company’s first FDA approved product, became available for commercial sale and shipment to patients with a prescription in the U.S. in the third quarter of 2022. CDD is a serious and rare genetic disorder that is caused by a mutation of the CDKL5 gene, located on the X chromosome. CDD is a severely debilitating and potentially fatal genetic condition, which occurs with an estimated frequency of 1:40,000 live births in the U.S. It predominantly affects females and is characterized by early onset, difficult to control seizures and severe neurodevelopmental impairment. The CDKL5 gene encodes proteins essential for normal brain function. Most children affected by CDD have neurodevelopmental deficits, such as difficulty walking, talking and taking care of itself. Many also suffer from scoliosis, gastrointestinal dysfunction or sleep disorders. In June 2017, the company was granted FDA orphan drug designation for ganaxolone for the treatment of CDD. The company owns families of patents and pending patent applications that claim certain formulations of ganaxolone and cover certain therapeutic uses of ganaxolone, including for treating CDD. The 20-year terms for patents, and applications that issue as patents, in these families run from 2026 through 2042, absent any available patent term adjustments or extensions. The company has also licensed from Ovid certain patents that claim certain therapeutic uses of ganaxolone for the treatment of CDD. The licensed patents include a granted U.S. patent, and pending applications in the U.S. and Europe. The 20-year term for these licensed patents and applications that issue as patents will run through 2037, absent any available patent term adjustments. Commercial Strategy: Key launch strategies have included and continue to include establishing the company’s supply chain network and quality management system to assure product is available to patients; driving clinical awareness of ZTALMY as the first and only FDA approved product indicated specifically for seizures associated with CDD; deploying its field sales force to target physicians who treat this rare pediatric patient population; engaging commercial and government payers with the objective of obtaining insurance coverage; and developing its internal capabilities (such as Finance, Human Resources, Information Technology, Data Analytics and Compliance) to support its first launch as a commercial company. Marketing Strategy: The company’s marketing strategy is to reinforce that seizures are central to the constellation of CDD symptoms, establish ZTALMY as central to the comprehensive management of seizures associated with CDD, and ensure that patients have seamless access to ZTALMY from prescription through fulfillment. The company’s marketing campaign for ZTALMY is active, and its integrated commercial launch activities initiated in the third quarter of 2022. Sales Strategy: The company’s commercial sales force includes 16 regional account managers experienced in rare disease. The company’s field force is targeting identified key accounts and centers of excellence for CDD. Marketing Authorization Application In August 2021, the Committee for Medicinal Products for Human Use (CHMP) of the EMA granted the company’s request for accelerated assessment of ganaxolone for the treatment of seizures associated with CDD. The marketing authorization application (MAA) for ganaxolone was submitted to the EMA on October 11, 2021 and on October 28, 2021 the company received formal notification from the EMA that the CDD MAA was validated. With this validation, the EMA began its formal review of the MAA under the centralized procedure. In February 2022, the MAA was converted to a standard review timeline. Further, the CHMP granted an extension to its Day 120 clock stop, and as a result, the company submitted its Day 120 responses to the EMA on November 22, 2022. The company received the Day 180 report, including a List of Outstanding Issues (LoOI) from the EMA on January 26, 2023. Pipeline The company is developing ganaxolone in indications where there is a mechanistic rationale for ganaxolone to provide a benefit. In January 2021, the company enrolled the first patient in the Phase 3 pivotal RAISE trial. The RAISE trial is a randomized, double-blind, placebo-controlled clinical trial in patients with RSE. The company expects approximately 80 trial sites in hospitals, primarily across the U.S. and Canada, to participate. The RAISE trial is designed to enroll approximately 124 patients, who will be randomized to receive ganaxolone or placebo added to standard of care. With this number of patients, the trial is designed to provide over 90% power to detect a 30% efficacy difference between ganaxolone and placebo. The company is working closely with key investigators and site coordinators to support enrollment efficiencies at existing RAISE trial sites and are also increasing the number of U.S. centers participating in the trial. Additionally, the company plans to expand the trial to sites in Canada and Australia. Consistent with the prior announcement, the company expects its top-line data readout for the RAISE trial to be available in the second half of 2023. In September 2021, the U.S. Patent and Trademark Office (USPTO) granted the company a patent on a method of treating SE, including dosing regimens. This issued patent expires in 2040. That patent is a member of a patent family it owns that includes pending patent applications that claim certain therapeutic regimens for the treatment of SE, including RSE, using intravenous ganaxolone. On July 26, 2022, the U.S. Patent and Trademark Office (USPTO) issued a patent to Ovid with claims that encompass the company’s product candidate for the treatment of SE. In August 2021, the company announced top-line data from its open-label Phase 2 trial (CALM trial) evaluating the safety and efficacy of adjunctive oral ganaxolone in 23 patients with seizures associated with TSC. The CALM trial enrolled 23 patients ages 2 to 32 who entered a four-week baseline period followed by a 12-week treatment period, during which they received up to 600 mg of ganaxolone (oral liquid suspension) three times a day. In response to its request for an End of Phase 2 meeting with the FDA regarding a proposed Phase 3 TSC trial, the FDA provided written responses to the company’s questions in lieu of a meeting. In response to its request for Protocol Assistance, which is a special form of scientific advice available for developers of designated orphan medicines for rare diseases, the EMA provided written feedback in December 2021 in lieu of a meeting. The company plans to announce top-line data from the TrustTSC trial in the first quarter of 2024. The company plans to pursue the development of ganaxolone for LGS, a severe form of epilepsy that typically begins between one and eight years of age. The company is planning to utilize a second-generation formulation of ganaxolone for the LGS development program, with a Phase 2 trial targeted to begin in the fourth quarter of 2023. Preclinical Pharmacology and Toxicology The company has completed preclinical safety pharmacology and toxicology testing, including reproductive toxicology. Animal pharmacokinetic and in vitro studies show that ganaxolone is metabolized primarily by the Cytochrome P450, family 3, subfamily A (CYP3A) family of liver enzymes, a common route of drug metabolism. All in vitro studies have shown that ganaxolone has low potential for interaction with other drugs at several multiples of observed human ganaxolone levels. Intellectual Property The patents and patent applications owned by the company comprise approximately 17 different patent families, filed in various jurisdictions around the world. Nanoparticle Ganaxolone Formulations: The company owns approximately four patent families directed to nanoparticle formulations of ganaxolone and complexing agents that deliver consistent exposure and improved stability of ganaxolone, and certain uses of the formulations. One of the patent families includes eight issued U.S. patents with claims directed to certain solid and liquid ganaxolone formulations and certain methods for the making and use thereof. Corresponding foreign patents have been granted in Australia, Canada, China, Europe, Hong Kong, India, Israel, Japan, Mexico, South Africa, New Zealand, Singapore and South Korea. The 20-year term for patents in this family runs through 2026, absent any available patent term adjustments or extensions. The company has filed for a patent term extension of a granted U.S. patent in this patent family that covers ZTALMY. The company’s patent term extension application requests an extension of five (5) years, which is the maximum extension available under the Hatch-Waxman Act. If the full extension is granted, this U.S. patent would be extended to November 28, 2031. The application for patent term extension is pending at the USPTO. Pursuant to the company’s agreement with Domain Russia Investments Limited (DRI), it assigned to DRI patent rights, which rights were subsequently assigned to NovaMedica LLC (NovaMedica), along with the right to develop and commercialize ganaxolone in Russia and certain other member countries of the Eurasian Patent Organization. The company has approximately four patent families consisting of three pending U.S. provisional applications directed to ganaxolone analogs and/or additional formulations of ganaxolone, and an international application filed under the Patent Cooperation Treaty (PCT) that is directed to additional formulations of ganaxolone. The 20-year term for patents based on this international application will run through 2042, absent any available patent term adjustments. Process for Manufacturing Ganaxolone: The company’s patent portfolio contains patents issued in Australia, Brazil, Canada, China, Europe, Hong Kong, India, Israel Japan, Mexico, New Zealand, South Korea, and the U.S. covering its synthetic process for manufacturing ganaxolone. The 20-year term for patents in this family runs through 2030, absent any available patent term adjustments or extensions. The European patent has been validated in France, Germany, Ireland, Italy, Spain, and Switzerland. Intravenous Ganaxolone FormulationsL The company owns approximately four patent families directed to its IV ganaxolone formulations that it is developing for the treatment of SE and certain other disorders. One of the patent families includes pending applications in Australia, Canada, China, Europe, Israel, India, Japan, South Africa, and the U.S. that claim certain injectable ganaxolone formulations containing sulfobutyl ether-beta-cyclodextrin and certain methods of use of the formulations, including for the treatment of SE. The 20-year term for this patent family runs through to 2036, absent any available patent term adjustments or extensions. A second patent family includes one issued U.S. patent with claims directed to certain therapeutic regimens for the treatment of SE using IV ganaxolone, and an international application filed under the PCT that is directed to certain therapeutic regimens for the treatment of SE using IV ganaxolone. The company intends to file national phase applications in various foreign jurisdictions based on this PCT application before applicable deadlines. A third patent family consists of a pending international application filed under the PCT that is directed to certain therapeutic uses of IV ganaxolone. The company intends to file national phase applications in various foreign jurisdictions based on the PCT application before applicable deadlines. The 20-year term for patents based on this international application will run through 2041, absent any applicable available patent term adjustments. A fourth patent family consists of a pending international application filed under the PCT directed to certain therapeutic uses for SE. The company intends to file national phase applications in various foreign jurisdictions based on this PCT application before applicable deadlines. The 20-year term for patents based on this international application will run through 2042, absent any available patent term adjustments. Additional Therapeutic Uses: The company owns approximately four patent families directed to certain therapeutic uses of ganaxolone, including for treating genetic epilepsy disorders, such as CDD and PCDH19-Related Epilepsy (PCDH19-RE), and TSC. One of the patent families includes pending applications filed in Australia, Canada, China, Eurasia, Europe, Japan, Korea, Malaysia, New Zealand, Singapore, and the U.S. that claim certain methods of treating epileptic disorders. The 20-year term for patents in this family runs through 2038, absent any available patent term adjustments or extensions. A second patent family includes one pending international patent application filed under the PCT that claims certain methods of treating TSC. The company intends to file national phase applications in various foreign jurisdictions based on this PCT application before applicable deadlines. The 20-year term for patents based on this family run through 2040, absent any available patent term adjustments or extensions. A third family comprises one pending international patent application filed under this PCT directed to certain therapeutic regimens for certain disorders using ganaxolone. The company intends to file national phase applications in various foreign jurisdictions based on this PCT application before applicable deadlines. The 20-year term for patents based on this family run through 2041, absent any available patent term adjustments or extensions. A fourth patent family consists of a pending international patent application filed under this PCT directed to certain therapeutic regimens for certain disorders using ganaxolone. The company intends to file national phase applications in various foreign jurisdictions based on this PCT application before applicable deadlines. The 20-year term for patents based on this family run through 2042, absent any available patent term adjustments or extensions. The company has also licensed from Ovid certain patents that are directed to certain therapeutic uses of ganaxolone for the treatment of CDD. The licensed patent family includes a granted U.S. patent and a pending application in Europe. The 20-year term for patents based on this international application will run through 2037, absent any available patent term adjustments. In addition to patents, the company relies upon unpatented trade secrets, know-how and continuing technological innovation to develop and maintain a competitive position. Licenses and Collaborations Orion On July 30, 2021, the company entered into a collaboration agreement (Orion Collaboration Agreement) with Orion Corporation (Orion), whereby Orion received exclusive rights to commercialize the oral and IV dose formulations of ganaxolone in the European Economic Area, United Kingdom and Switzerland in multiple seizure disorders, including CDD, TSC and RSE. Tenacia On November 16, 2022, the comopany entered into a collaboration and supply agreement with Tenacia Biotechnology (Shanghai) Co., Ltd. (Tenacia), whereby Tenacia received exclusive rights to develop and commercialize certain oral and IV formulations of ganaxolone in Mainland China, Hong Kong, Macau and Taiwan for the diagnosis, prevention and treatment of certain human diseases, disorders or conditions, initially for the treatment of CDD, TSC and SE. Other Distribution Agreements The company has entered into an agreement for commercialization of ganaxolone in other territories with NovaMedica whereby NovaMedica has the right to market and sell ganaxolone in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Turkmenistan, Ukraine and Uzbekistan. The company continues to assess opportunities in other markets to further expand the distribution and commercialization of ganaxolone globally. CyDex In March 2017, the comopany entered into a License Agreement and a Supply Agreement with CyDex Pharmaceuticals, Inc. (CyDex). Under the terms of the License Agreement, CyDex granted it an exclusive license to use CyDex’s sulfobutylether beta-cyclodextrin, or Captisol, drug formulation system and related intellectual property in connection with the development and commercialization of ganaxolone in any and all therapeutic uses in humans, with some exceptions. As of March 24, 2022, the comopany has achieved one milestone under the License Agreement, which occurred and was paid in the first quarter of 2021. Certain patents relating to Captisol, including some that were licensed to the company by CyDex, have expired, while other patents that are licensed to it remain in force. Under the terms of the Supply Agreement, the company is required to purchase all of its requirements for Captisol with respect to ganaxolone from CyDex, and CyDex is required to supply it with Captisol for such purposes, subject to certain limitations. Purdue Neuroscience Company (Purdue) In September 2004, the company entered into a license agreement with Purdue, which was amended and restated in May 2008 (Purdue License Agreement), that granted it exclusive rights to certain know-how and technology relating to ganaxolone, excluding the field of treatment of unpleasant sensory or emotional experience associated with actual or potential tissue damage or described in terms of such damage. The company is obligated to pay royalties as a percentage in the range of high single digits up to 10% of net product sales for direct licensed products, such as ganaxolone. Ovid License In March 2022, the company entered into an exclusive patent license agreement (License Agreement) with Ovid Therapeutics Inc. (Ovid). Under the License Agreement, the company has an exclusive, non-transferable (except as provided in the License Agreement), royalty-bearing, sublicensable license under certain of Ovid’s patent(s) and patent applications to develop, make, have made, commercialize, promote, distribute, sell, offer for sale and import, ganaxolone, including any analogues or derivatives, including its salts, and pharmaceutical formulations of the foregoing (Licensed Products), in the U.S., the member states of the EU, Iceland, Lichtenstein, Norway, the United Kingdom, and Switzerland (Territory) for the treatment of CDD in humans (Field). Under the License Agreement, the company has the sole right and responsibility for, and control over, all development, manufacturing, and commercialization activities, including all regulatory activities, with respect to the Licensed Products in the Field in the Territory. Commercial Operations In connection with the commercialization of ZTAMLY, its first FDA approved product, the company has built a commercial operations infrastructure, including, marketing infrastructure, market access capabilities, and sales field force to reach high prescribing neurologists, critical care, epilepsy specialists and other target physician populations in the U.S. ZTALMY is regulated by the DEA as a controlled substance under the CSA as a schedule V drug. ZTALMY became available for commercial sale and shipment to patients with a prescription in the U.S. in the third quarter of 2022. Government Regulation As a clinical stage pharmaceutical company that operates in the United States, the company is subject to regulation by the U.S. Food and Drug Administration, and other federal, state, and local regulatory agencies. The Federal Food, Drug, and Cosmetic Act (FDC Act) and its implementing regulations set forth, among other things, requirements for the research, testing, development, manufacture, quality control, safety, effectiveness, approval, packaging, labeling, storage, record keeping, reporting, distribution, import, export, advertising and promotion of the company’s products. History Marinus Pharmaceuticals, Inc. was founded in 2003. The company was incorporated in Delaware in 2003.