Marinus Pharmaceuticals, Inc.

Greetings and welcome to the Marinus Pharmaceuticals approval for quarter and full year 2021 financial results and business update call. At this time, all participants are in a lesson-only mode. After the speaker's presentation, there will be a question and answer session. If you'd like to ask a question during this time, press star followed by the number one on your telephone keypad. If you'd like to withdraw your question, press the palm key. And now it is my pleasure to introduce your host, Sasha Damouni, Vice President of Corporate Affairs and Investor Relations. You may begin.

Thank you, and good morning, everyone. With me from Marinus are Dr. Scott Bronstein, Chief Executive Officer, Dr. Joe Houlihan, Chief Medical Officer, Kimberly McCormick, Senior Vice President of Regulatory Affairs, Christy Schaefer, Chief Commercial Officer, and Steve Fancil, Chief Financial Officer. Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under the securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development program's future results, performance, or achievements to differ significantly from those expressed or implied by such forward-looking statements. These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including Form 10-K, 10-Q, and 8-K. I will now turn the call over to our CEO, Scott Braunstein.

Thank you, Sasha, and welcome to our call. Today marks a historic milestone for Meredith's CDD patients, their families, and caregivers. following the FDA's approval of oral Ganaxalone, which will be commercially known as Zetalme. Zetalme is the first and only approved treatment for seizures associated with CDKL5 deficiency disorder, or CDD, a rare form of genetic epilepsy in patients two years and older. Zetalme is expected to be available in July following scheduling as a controlled substance by the U.S. Drug Enforcement Administration. We believe this approval further validates our clinical development plans for Ganaxalone across a range of seizure disorders and positions us well in our evolution to a commercial stage company. The approval of Zetami would not have been possible without the support of patients, families, caregivers, and investigators who participated in the clinical studies to develop this new treatment option, as well as an unwavering commitment of our Marinus employees. We are humbled by the opportunity to make a difference in the lives of patients suffering with CDD. Shortly, our Chief Commercial Officer, Christy Schaefer, will detail how we plan to support access for patients who are prescribed Zetalmy through our patient assistance efforts, including the Zetalmy One program. She will also discuss our commercial strategy, launch preparedness, and pricing. The approval also enables the potential for significant non-diluted funding in the near term to execute on our business strategy and invest in our future. We have been awarded a rare pediatric disease priority review voucher by the FDA, which we plan to monetize to bolster our financial position. The approval also enables us to draw an additional $30 million in funding under the existing Oak Tree Credit Agreement. Steve will discuss both of these in greater detail during his prepared remarks. As a reminder, in the European Union, the marketing authorization application for Ganaxalone is being evaluated for the treatment of seizures associated with CDD with a CHMP opinion expected by year-end 2022. We have been collaborating extensively with Orion, our European strategic partner, as they prepare Ganaxalone's commercial readiness. we remain committed to identifying opportunities throughout the world to improve the lives of patients suffering with CDD, including our ongoing commitment to the European Expanded Access Program. In addition, we believe that there is a broader global opportunity for the Ganaxalone franchise, and we are exploring the potential for additional ex-U.S. strategic partnerships to expand Ganaxalone's global footprint. Regarding our late-stage oral program, let me discuss our commitment to the tuberous sclerosis complex community. We are actively screening patients in the U.S. for the Phase III TRUST TSC trial and expect to have the majority of U.S. sites initiated and actively enrolling in the second quarter. We have added several critical new elements to the Phase III design that provide us with high confidence in the trial's success and particularly the role of Anaxalone in significantly reducing seizures, most commonly seen in the refractory TSC population. We gained a tremendous amount of insight from our Phase II trial and used that to inform the Phase III protocol. We expect top-line data in the trial during the first half of 2024, and we continue to work with our sites to improve these timelines. Dr. Ian Miller, a highly regarded pediatric epileptologist who joined the organization last year, is playing an important leadership role in this trial. I will leave further comments to Joe Houlihan, our chief medical officer, in his prepared remarks. Turning to the IV development program, we believe that Ganaxalone can dramatically improve outcomes for patients suffering from status epilepticus and prevent the escalation of treatment to IV anesthetics in a significant number of patients. The company continues to press ahead with our IV clinical trials despite setbacks as a result of the impacts from COVID-19 and an unexpected interruption in clinical supply material experienced in the first quarter of this year. We are adding new trial sites and are moving closer to the resupply of our clinical trial materials. As a result of several coordinated internal efforts within Marinus and our contract manufacturing organizations, We are now expecting to resupply our clinical trial sites and resume recruitment for the phase three RAISE trial in refractory status epilepticus in May of this year, a month earlier than previously announced. At the same time, the manufacturing team is making significant efforts to improve the shelf life of IV Ginex Loan to 24 months or greater. As of today, 52 centers are activated and ready to enroll when supply is made available in May. We are confident in our ability to proceed with this trial, given that current hospital resources are less strained by COVID-19, our key US sites are activated, and we have recently seen growing interest from several new sites that previously declined participating in the trial. Additionally, we have received encouraging feedback via our scientific advisory board and have recently implemented a minor protocol amendment that will broaden the entry criteria. We currently expect top-line results in the second half of 2023 and will continue to do all we can to improve these timelines. I am proud that our team has shown the ability to adapt to the challenges raised by the pandemic with a diligent focus on advancing this critically important program. Now turning to what we believe will be the future of the Ganaxalone franchise, our second-generation oral formulation. The goal of this initiative is to deliver an improved pharmacokinetic profile, including better bioavailability, lower variability, and more predictable drug exposure. We expect that our phase one new formulation work will be completed by mid-2022. We are simultaneously focusing research efforts on developing a modified release version of this new formulation. We currently believe that we have a second formulation candidate ready for clinical evaluation in the second half of this year, and this candidate may not require any additional modified release technology to offer twice daily dosing options. Finally, both formulation programs have novel intellectual property. As a reminder, if studies of the new oral formulation demonstrate the expected PK profile, which would be very consistent with historical animal models, We plan to move quickly to a trial in Lennox-Gastaut syndrome and would expect to begin that study in the second half of 2022. Predictable PK of the new formulation would allow us to perform dose-ranging studies to assess both efficacy and tolerability. This is something that has never been thoroughly assessed with oral Ganaxalone, and we hope that such evaluations can add to its clinical utility in future indications. Additionally, we've made some exciting progress in our pro-drug program, which Joe will discuss in detail shortly. Beyond our preclinical work and our ongoing clinical studies, we are making great strides strengthening our intellectual property and bolstering our advocacy efforts. This month, Marinus entered an exclusive license agreement with Abbott Therapeutics to license patents and patent applications in the U.S. and E.U., related to the use of Ganax Loan for the treatment of CDKL5 deficiency disorder. The OVID patents originated from a provisional patent application that was filed on August 11, 2016. With regard to our advocacy efforts, our view is that every patient matters, particularly in the rare and orphan disease area. Our goal is to help educate, engage, and empower patients, their families, and caregivers and to maintain strong and transparent relationships with the advocacy community. Now, I would like to turn the call over to Joe for additional updates on our clinical programs.