CDKL5 program (Amicus Therapeutics)

ZTALMY® (ganaxolone) Q3 net product revenue of $5.4 million; 2023 net product revenue guidance increased to between $18.5 and $19 million Over 75% of patients required for the interim analysis are now enrolled in the Phase 3 RAISE trial in refractory status epilepticus; if the trial meets pre-defined stopping criteria at the interim analysis, topline data now anticipated Q2 2024 Initiated the Marinus Access Program to expand global availability of ZTALMY Cash runway projected into Q4 2024 with cash, cash equivalents and short-term investments of $176.4 million as of September 30, 2023 Marinus to host conference call on November 7, 2023, at 8:30 a.m. ET RADNOR, Pa.--(BUSINESS WIRE)-- Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS), a pharmaceutical company dedicated to the development of innovative therapeutics to treat seizure disorders, today reported business highlights and financial results for the third quarter ended September 30, 2023. “With strong quarter over quarter growth and robust payer coverage one year into the launch of ZTALMY, we continue to demonstrate our unique commercial capabilities in the orphan epilepsy space and are enthused by the opportunity ZTALMY and the ganaxolone franchise represent as an important long-term value driver for Marinus,” said Scott Braunstein, M.D., Chairman and Chief Executive Officer of Marinus. Dr. Braunstein continued, “We remain acutely focused on advancing our Phase 3 clinical trials in refractory status epilepticus and tuberous sclerosis complex. While we’re disappointed that we now project RAISE enrollment to conclude by the end of the first quarter, we remain confident in the benefit that IV ganaxolone could bring to critically ill RSE patients and the significant commercial opportunity. We are committed to successfully completing both the RAISE and TrustTSC trials in 2024 and continue to make the investments to prepare for these commercial launches.” ZTALMY® ZTALMY® (ganaxolone) oral suspension CV net product revenue of $5.4 million for the third quarter of 2023 Continued growth in commercial patients with approximately 140 patients active on therapy at the end of the third quarter Increased full year 2023 expected ZTALMY net product revenues to between $18.5 and $19 million from a range of $17 to $18.5 million CDKL5 Deficiency Disorder Initiated the Marinus Access Program expanding global availability of ZTALMY for eligible patients with seizures associated with CDKL5 deficiency disorder (CDD) in geographies where the product is not commercially available and as supported by local regulatory requirements The Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted and granted priority review of a New Drug Application (NDA) for ZTALMY in CDD; the NDA was submitted in China by Tenacia Biotechnology under the terms of a collaboration agreement with Marinus Orion Corporation continues to prepare for commercial launches of ZTALMY in select European countries in 2024 Clinical Pipeline Status Epilepticus Over 75% of patients required for an interim analysis are now enrolled in the Phase 3 RAISE trial of intravenous (IV) ganaxolone in refractory status epilepticus (RSE) Enrollment for the interim analysis expected to conclude in the first quarter of 2024 with topline data now anticipated in the second quarter of 2024, assuming pre-defined stopping criteria for an interim analysis are met 21 patients have now been treated for super refractory status epilepticus (SRSE) under emergency investigational new drug (EIND) applications Phase 3 RAISE II trial in RSE (for European registration) enrollment anticipated to begin before year end 2023 To focus additional resources on the expansion of RSE clinical programs, including further investigation of potential development opportunities in SRSE, Marinus voluntarily discontinued the Phase 2 RESET trial in established status epilepticus Ganaxolone development in the RAISE trial is being funded in part by the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response at the U.S. Department of Health and Human Services, under contract number 75A50120C00159. Tuberous Sclerosis Complex Continue to enroll patients in the global Phase 3 TrustTSC trial of oral ganaxolone in tuberous sclerosis complex with topline data anticipated mid-2024 Second Generation Product Development Enrollment in the multiple ascending dose (MAD) trial is well underway with preliminary data expected by year end 2023 Planning to finalize clinical program design for Lennox-Gastaut syndrome in the first half of 2024, pending results of the MAD trial General Business and Financial Update For the fiscal year 2023, the Company is updating its revenue and operating expense guidance: The Company now expects ZTALMY net product revenues of between $18.5 and $19 million; this represents an increase from the previous guidance of between $17 and $18.5 million The Company now expects GAAP operating expenses, inclusive of G&A and R&D, to be in the range of $158 to $162 million, of which the Company expects stock-based compensation to be approximately $16 million; this represents a decrease from the prior guidance range of $160 to $165 million Expect that cash, cash equivalents, and short-term investments of $176.4 million as of September 30, 2023, will be sufficient to fund the Company’s operating expenses, capital expenditure requirements, and maintain the minimum cash balance of $15 million required under the Company’s debt facility into the fourth quarter of 2024 During the quarter, a total of 3.7 million shares were sold through the Company’s at-the-market (ATM) facility contributing net proceeds of $25.9 million Financial Results Recognized $5.4 million and $13.0 million in net product revenues for the three and nine months ended September 30, 2023, respectively, as compared to $0.6 million in each of the same periods in the prior year. Net product revenue consists of ZTALMY product sales, which was launched in the U.S. in the third quarter of 2022. Recognized $1.9 million and $10.8 million in Biomedical Advanced Research and Development Authority (BARDA) federal contract revenue for the three and nine months ended September 30, 2023, respectively, as compared to $1.8 million and $5.1 million for the same periods in the prior year, respectively. The increase on a year-to-date basis was primarily driven by activities associated with the startup of the API onshoring initiative. Research and development (R&D) expenses were $23.7 million and $73.0 million for the three and nine months ended September 30, 2023, respectively, as compared to $19.0 million and $58.5 million, respectively, for the same periods in the prior year; the increase on a year-to-date basis was due primarily to increased investment associated with our API onshoring effort, increased TSC and RSE clinical trial activity, and increased headcount. Selling, general and administrative (SG&A) expenses were $14.9 million and $45.8 million for the three and nine months ended September 30, 2023, respectively, as compared to $13.4 million and $42.2 million, respectively, for the same periods in the prior year; the increase on a year-to-date basis was due primarily to increased headcount associated with the U.S. launch of ZTALMY. The Company had net losses of $33.0 million and $99.6 million for the three and nine months ended September 30, 2023, respectively; cash used in operating activities was $91.0 million for each of the nine months ended September 30, 2023 and 2022 At September 30, 2023, the Company had cash, cash equivalents, and short-term investments of $176.4 million, compared to $240.6 million at December 31, 2022. Readers are referred to, and encouraged to read in its entirety, the Company’s Quarterly Report on Form 10-Q for the nine months ended September 30, 2023, to be filed with the Securities and Exchange Commission, which includes further detail on the company’s business plans, operations, financial condition, and results of operations. Financial Results Selected Financial Data (in thousands, except share and per share amounts) September 30, 2023 (unaudited) December 31, 2022 ASSETS Cash and cash equivalents $ 140,437 $ 240,551 Short-term investments 35,919 - Other assets 24,450 18,967 Total assets $ 200,806 $ 259,518 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities $ 30,555 $ 25,017 Long term debt, net 64,783 71,018 Revenue interest financing payable, net 32,855 29,857 Other long-term liabilities 18,076 17,626 Total liabilities 146,269 143,518 Total stockholders’ equity 54,537 116,000 Total liabilities and stockholders’ equity $ 200,806 $ 259,518 Three Months Ended September 30, (unaudited) Nine Months Ended September 30, (unaudited) 2023 2022 2023 2022 Revenue: Product revenue, net $ 5,429 $ 555 $ 13,010 $ 555 Federal contract revenue 1,891 1,785 10,753 5,088 Collaboration revenue 18 — 36 12,673 Total revenue 7,338 2,340 23,799 18,316 Expenses: Research and development 23,661 19,002 73,006 58,488 Selling, general and administrative 14,868 13,389 45,794 42,187 Cost of product revenue 455 48 1,047 48 Cost of IP license fee — — — 1,169 Total expenses: 38,984 32,439 119,847 101,892 Loss from operations (31,646) (30,099 ) (96,048) (83,576 ) Interest income 1,895 514 6,366 610 Interest expense (4,242) (2,634 ) (12,597) (6,982 ) Gain from sale of priority review voucher, net — 107,375 — 107,375 Other income (expense), net 1,021 (114 ) 1,105 (1,179 ) (Loss) income before income taxes (32,972) 75,042 (101,174) 16,248 (Provision) benefit for income taxes — (1,752 ) 1,538 (1,752 ) Net (loss) income $ (32,972) $ 73,290 $ (99,636) $ 14,496 Net income allocated to preferred shareholders — 1,656 — 336 Net (loss) income applicable to common shareholders (32,972) 71,634 (99,636) 14,160 Per share information: Net (loss) income per share of common stock—basic $ (0.61) $ 1.93 $ (1.89) $ 0.38 Net (loss) income per share of common stock—diluted $ (0.61) $ 1.89 $ (1.89) $ 0.37 Basic weighted average shares outstanding 53,920,109 37,202,269 52,755,114 37,084,060 Diluted weighted average shares outstanding 53,920,109 37,910,511 52,755,114 38,393,754 Other comprehensive income (loss) Unrealized gain (loss) on available-for-sale securities 43 — (71) — Total comprehensive (loss) income $ (32,929) 73,290 (99,707) 14,496 Conference Call Information Participants may access the conference call via webcast on the Investor page of Marinus’ website at ir.marinuspharma.com/events-and-presentations. An archived version of the call will be available approximately two hours after the completion of the event on the website. About Marinus Pharmaceuticals Marinus is a commercial-stage pharmaceutical company dedicated to the development of innovative therapeutics for seizure disorders. The Company first introduced FDA-approved prescription medication ZTALMY® (ganaxolone) oral suspension CV in the U.S. in 2022 and continues to invest in the potential of ganaxolone in IV and oral formulations to maximize therapeutic reach for adult and pediatric patients in acute and chronic care settings. For more information visit . 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 commercialization and marketing plans for ZTALMY; our net product revenue guidance; the potential benefits ZTALMY will provide for physicians and patients; the potential benefits from the U.S. onshoring of the manufacturing capabilities for ganaxolone API; statements regarding our expected clinical development plans, enrollment in our clinical trials, regulatory communications and submissions for ganaxolone, and the timing thereof; our expected data readouts; our expected cash runway; our expectations and beliefs regarding the FDA and EMA with respect to our product candidates; our expectations regarding the development of new formulations and prodrug candidates; our expectations regarding our strategic partners; our financial projections; the potential safety and efficacy of ganaxolone, as well as its therapeutic potential in a number of indications; and other statements regarding the company's future operations, financial performance, financial position, prospects, objectives and other future event. 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, unexpected results or delays in the commercialization of ZTALMY; unexpected market acceptance, payor coverage or future prescriptions and revenue generated by ZTALMY; unexpected actions by the FDA or other regulatory agencies with respect to our products; competitive conditions and unexpected adverse events or patient outcomes from being treated with ZTALMY, uncertainties and delays relating to the design, enrollment, completion, and results of clinical trials; unanticipated costs and expenses; the varying interpretation of clinical data; our ability to comply with the FDA’s requirement for additional post-marketing studies in the required time frames; the timing of regulatory filings for our other product candidates; the potential that regulatory authorities, including the FDA and EMA, may not grant or may delay approval for our product candidates; 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 develop new formulations of ganaxolone or prodrugs; our ability to obtain, maintain, protect and defend intellectual property for our product candidates; the potential negative impact of third party patents on our or our collaborators’ 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 and commercial programs; the potential for our ex-US partners to breach their obligations under their respective agreements with us or terminate such agreements in accordance with their respective terms; the risk that drug product quality requirements may not support continued clinical investigation of our product candidates and result in delays or termination of such clinical studies and product approvals; the effect of the COVID-19 pandemic on our business, the medical community, regulators 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 our 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 . Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume 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. View source version on businesswire.com: Contacts Investors Jim DeNike Senior Director, Investor Relations Marinus Pharmaceuticals, Inc. jdenike@marinuspharma.com Media Molly Cameron Director, Corporate Communications & Investor Relations Marinus Pharmaceuticals, Inc. mcameron@marinuspharma.com Source: Marinus Pharmaceuticals View this news release online at:

ZTALMY is the first treatment approved by the European Commission for seizures associated with CDKL5 deficiency disorder in children and adolescents RADNOR, Pa.--(BUSINESS WIRE)-- Marinus Pharmaceuticals, Inc. (Nasdaq: MRNS), a pharmaceutical company dedicated to the development of innovative therapeutics to treat seizure disorders, today announced that the European Commission (EC) has granted approval of ZTALMY® (ganaxolone) oral suspension for the adjunctive treatment of epileptic seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients two to 17 years of age. ZTALMY may be continued in patients 18 years of age and older. “The approval by the European Commission represents a significant milestone for children, families and physicians who, until now, have long been challenged by the impact of seizures and lack of treatments available for CDD,” said Scott Braunstein, M.D., Chairman and Chief Executive Officer of Marinus. “This achievement reflects our organization’s unwavering commitment to bring an effective treatment option to individuals living with CDD and we are grateful to all the stakeholders who made the approval possible.” The EC approval of ZTALMY in CDD is supported by data from the Phase 3 Marigold double-blind placebo-controlled trial, in which 101 patients were randomized and individuals treated with ZTALMY showed a median 30.7% reduction in 28-day major motor seizure frequency, compared to a median 6.9% reduction for those receiving placebo, achieving the trial’s primary endpoint (p=0.0036). In the Marigold open label extension study, patients treated with ZTALMY for at least 12 months (n=48) experienced a median 49.6% reduction in major motor seizure frequency. In the clinical development program, ZTALMY demonstrated efficacy, safety and tolerability with the most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) in the ZTALMY group being somnolence, pyrexia, salivary hypersecretion and seasonal allergy. In May 2022, the results from the Marigold study were published in The Lancet Neurology.1 The approval follows a positive opinion issued in May 2023 by the Committee for Medicinal Products for Human Use of the European Medicines Agency and is applicable to all 27 European Union member states plus Iceland, Norway and Liechtenstein. In July 2021, Marinus and Orion Corporation entered into a collaboration agreement which grants Orion the right to commercialize ZTALMY in Europe. About CDKL5 Deficiency Disorder CDKL5 deficiency disorder (CDD) is a serious and rare genetic disorder characterized by early‑onset, difficult‑to‑control seizures and severe neuro‑developmental impairment.2 It is caused by a mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, located on the X chromosome. The CDKL5 gene produces a protein that is important for normal brain development and function.3 About ZTALMY® ZTALMY (ganaxolone) is a neuroactive steroid GABAA receptor modulator that acts on a well-characterized target in the brain known to have anti-seizure effects. ZTALMY is an oral prescription medicine approved by the European Commission for the adjunctive treatment of epileptic seizures associated with CDKL5 deficiency disorder in patients two to 17 years of age. ZTALMY may be continued in patients 18 years of age and older. Full European Summary of Product Characteristics for ZTALMY will be available from the EMA website at . About Marinus Pharmaceuticals Marinus is a commercial-stage pharmaceutical company dedicated to the development of innovative therapeutics for seizure disorders. The Company first introduced FDA-approved prescription medication ZTALMY® (ganaxolone) oral suspension CV in the U.S. in 2022 and continues to invest in the potential of ganaxolone in IV and oral formulations to maximize therapeutic reach for adult and pediatric patients in acute and chronic care settings. For more information about Marinus visit . About Orion Corporation Orion is a globally operating Finnish pharmaceutical company – a builder of well-being. Orion develops, manufactures and markets human and veterinary pharmaceuticals and active pharmaceutical ingredients. The company has an extensive portfolio of proprietary and generic medicines and self-care products. The core therapy areas of its pharmaceutical R&D are oncology and pain. Proprietary products developed by Orion are used to treat cancer, neurological diseases and respiratory diseases, among others. Orion's A and B shares are listed on Nasdaq Helsinki. 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, our commercial and clinical strategy, development plans and timelines and other future events. 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, unexpected market acceptance, payor coverage or future prescriptions and revenue generated by ZTALMY; the pricing and reimbursement process can be time consuming and may delay commercialization of ZTALMY in one or more European countries; our dependence on Orion to commercialize ZTALMY in Europe pursuant to the exclusive collaboration agreement; unexpected actions by the FDA or other regulatory agencies with respect to our products; competitive conditions and unexpected adverse events or patient outcomes from being treated with ZTALMY, uncertainties and delays relating to the design, enrollment, completion, and results of clinical trials; unanticipated costs and expenses; the company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; our ability to comply with the FDA’s requirement for additional post-marketing studies in the required time frames; the timing of regulatory filings for our other product candidates; 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; 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 expectations, projections and estimates regarding expenses, future revenue, capital requirements, and the availability of and the need for additional financing; delays, interruptions or failures in the manufacture and supply of our product candidates; the company’s ability to obtain additional funding to support its clinical development and commercial programs; the company’s ability to protect its intellectual property; and the effect of the COVID-19 pandemic on our business, the medical community, regulators and the global economy. This list is not exhaustive and these and other risks are described in our periodic reports, including our annual reports 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 . Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume 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. 1 The Lancet Neurology, Volume 21, Issue 5, P417-427, May 01, 2022 2 Olson H et al. 2019 Pediatric Neurology 3 Jakimiec M et al. 2020 Brain Sci.