Core Insights - Zevra Therapeutics, Inc. has successfully closed the sale of its Rare Pediatric Disease Priority Review Voucher (PRV) for gross proceeds of $150 million, enhancing its financial flexibility for strategic priorities [1][2] Financial Performance - As of March 31, 2025, Zevra reported available unaudited cash, cash equivalents, and investments totaling $68.7 million. After the sale of the PRV, net cash proceeds of $148.3 million will increase total cash, cash equivalents, and investments to $217.0 million [3] Company Overview - Zevra Therapeutics is a commercial-stage company focused on developing therapies for rare diseases with limited or no treatment options, aiming to bring life-changing therapeutics to patients [4]

Core Viewpoint - Zevra Therapeutics is preparing for its 2025 Annual Meeting of Stockholders, where it has nominated two incumbent directors for re-election while facing a proxy contest initiated by a stockholder proposing alternative candidates. The company emphasizes its progress and strategic focus, urging stockholders to support its current board. Group 1: Company Developments - Zevra Therapeutics filed its preliminary proxy statement with the SEC for the 2025 Annual Meeting, indicating that stockholders do not need to take action at this time [2] - The Board has nominated Wendy L. Dixon, Ph.D., and Tamara A. Favorito for re-election, both of whom bring over 70 years of combined life sciences experience [3][4] - The company has launched its first two products since the last annual meeting and has a cash runway extending into 2029, bolstered by a $150 million sale of a Priority Review Voucher [7] Group 2: Proxy Contest and Board Dynamics - Stockholder Daniel J. Mangless is proposing the election of two candidates, which the Zevra Board believes could disrupt its strategic plan and recommends stockholders reject these efforts [5][8] - The Board asserts that it has made significant progress in transforming the company into a more efficient organization focused on creating value for patients and stockholders [6][9] - Zevra's management has engaged with Mr. Mangless to avoid a costly proxy contest, emphasizing the importance of maintaining board stability for continued execution of its strategic plan [8][9]

Acquisition and Strategic Development - Zevra completed the acquisition of Acer Therapeutics on November 17, 2023, with Acer continuing as a wholly-owned subsidiary[24]. - The acquisition included OLPRUVA, approved by the FDA for certain urea cycle disorders, and investigational candidates like celiprolol for Vascular Ehlers-Danlos syndrome[32]. - The company incurred a cash payment of $12.8 million to acquire Orphazyme's assets and operations, along with assuming a reserve clawback liability of $5.2 million[31]. - Zevra's five-year strategic plan focuses on transforming into a leading rare-disease company, prioritizing late-stage clinical development and commercial opportunities[34]. - The company plans to outsource discovery and early development activities while seeking to expand its pipeline through collaborations and acquisitions[34]. Product Development and Approvals - MIPLYFFA, an orally-delivered treatment for Niemann-Pick disease type C, received FDA approval on September 20, 2024, and became commercially available in November 2024[33]. - Current commercial products include AZSTARYS, OLPRUVA, and MIPLYFFA, with ongoing clinical candidates like celiprolol and KP1077IH[36]. - AZSTARYS is FDA approved and partnered, generating royalties and milestones for the company[36]. - The company aims to submit a Marketing Authorization Application (MAA) for MIPLYFFA in H2 2025[36]. - MIPLYFFA received FDA approval on September 20, 2024, as the first treatment for NPC, with a total of 109 enrollments by December 31, 2025[38]. - The commercial launch of MIPLYFFA in the U.S. began immediately after FDA approval, with availability at specialty pharmacies starting November 21, 2024[40]. - Celiprolol is being advanced as an investigational product for VEDS, with a Phase 3 trial (DiSCOVER) enrolling 150 patients, aiming to demonstrate a reduction in clinical events[56][57]. - Celiprolol has shown a 76% reduction in the risk of arterial events in a COL3A1+ subpopulation based on BBEST trial data[57]. - The company plans to submit a Marketing Authorisation Application for MIPLYFFA in Europe in the second half of 2025[42]. - KP1077 is being developed for IH and narcolepsy, with an orphan drug designation granted for IH treatment[62]. Clinical Trials and Efficacy - KP1077 was well tolerated at all dose levels evaluated in the Phase 2 trial, including the highest dose of 320 mg daily, with most adverse events being mild and similar to other methylphenidate products[68]. - Mean total Epworth Sleepiness Scale (ESS) scores decreased by approximately 9 points after 5 weeks of open-label treatment, indicating clinically meaningful improvements in excessive daytime sleepiness[68]. - At the end of 7 weeks of treatment, mean total ESS scores decreased by 9.4 (once daily) and 8.8 (twice daily), while the mean total IHSS score decreased by 16.1 (once daily) and 12.3 (twice daily)[68]. - The Phase 2 trial of KP1077 provided key information for the design of a potentially pivotal efficacy trial, supporting the initiation of a Phase 3 trial[68]. - No drug-to-drug interactions have been observed to date in clinical studies involving KP1077[68]. Financial Performance and Milestones - Annual net sales of AZSTARYS surpassed $25 million in the first half of 2023, triggering a milestone payment of $5.0 million, and surpassed $50 million in the second half of 2023, triggering a second milestone payment of $10.0 million[74]. - The AZSTARYS License Agreement includes milestone payments of up to $63.0 million upon specified regulatory milestones and additional payments of up to $420 million based on U.S. sales milestones[71]. Regulatory and Compliance - The FDA indicated that a single pivotal study with appropriate confirmatory evidence will be sufficient for submitting a new NDA for KP1077[66]. - The company must submit an NDA to the FDA, which includes data from clinical studies and requires payment of a substantial application user fee[128]. - The FDA imposes substantial requirements on the clinical development, manufacture, and marketing of pharmaceutical products, necessitating significant time and financial resources[116]. - The NDA submission process requires successful completion of clinical trials, which are typically conducted in three phases to establish safety and efficacy[122]. - Pediatric data requirements under the Pediatric Research Equity Act must be met for new active ingredients, with possible deferrals or waivers available[129]. - The FDA has set a review goal of ten months for standard NDAs and six months for priority review applications from the 60-day filing date[1]. - Orphan drug designation must be requested before submitting an NDA, and if granted, it provides exclusivity for seven years for the same indication[147]. - The FDA may require post-marketing studies to monitor the safety and efficacy of approved products[136]. - A CRL indicates that the application cannot be approved in its current form, detailing deficiencies identified by the FDA[133]. - The FDA may impose additional testing or information requirements before approving an NDA, which can delay the approval process[135]. - The FDA closely regulates the marketing and promotion of drugs, allowing only claims consistent with approved labeling[137]. - Changes to the manufacturing process require prior FDA approval or notification, ensuring compliance with cGMP regulations[140]. - The FDA may withdraw product approval if compliance with regulatory standards is not maintained post-marketing[136]. Market and Competitive Landscape - The company faces competition from established pharmaceutical companies and potential generics, particularly for OLPRUVA and MIPLYFFA[100]. - The company is responsible for negotiating coverage, reimbursement, and placement decisions for its product candidates if approved, influenced by factors such as safety, efficacy, and cost-effectiveness[111]. - Third-party payers, including the U.S. government, are applying downward pressure on pharmaceutical product reimbursements, a trend expected to continue[114]. - International reimbursement systems vary significantly, with many countries instituting price ceilings and requiring additional studies for cost-effectiveness assessments[115]. Healthcare Regulations and Legislation - Drug manufacturers are required to provide quarterly discounts of 70% to help reduce the patient coverage gap, which will transition to new requirements starting January 1, 2025[112]. - Medicare Part D provides reimbursement for self-administered drugs, with recent legislation reducing patient responsibility in the coverage gap from 100% in 2010 to 25% currently[112]. - The company must comply with various health regulatory requirements and price reporting metrics if its drug products are available for reimbursement by Medicare or Medicaid[113]. - Compliance with healthcare regulations requires substantial time and financial resources, with potential penalties for non-compliance including fines and exclusion from government programs[176]. - The federal Anti-Kickback Statute prohibits remuneration to induce referrals for services reimbursable under federal healthcare programs, with broad interpretations of "remuneration"[171]. - The federal False Claims Act prohibits presenting false claims for payment to the federal government, with violations potentially leading to civil whistleblower actions[172]. - The federal Physician Payments Sunshine Act requires manufacturers to report specified payments to healthcare providers and teaching hospitals annually[175]. - Failure to comply with healthcare laws can result in significant penalties, including criminal, civil, and administrative actions, which could adversely affect the company's business[176]. - The Affordable Care Act (ACA) has significantly impacted the U.S. pharmaceutical industry, imposing new fees and increasing Medicaid rebates[180]. - The Inflation Reduction Act (IRA) requires drug manufacturers to negotiate prices with Medicare starting in 2026 and imposes rebates for price increases exceeding inflation[183]. European Union Regulations - The EU's new Clinical Trials Regulation (CTR) harmonizes clinical trial assessments across member states, allowing a single application for multi-center trials[195]. - In the EU, new products receive eight years of data exclusivity and an additional two years of market exclusivity upon marketing authorization[203]. - The EU orphan designation provides ten years of market exclusivity for approved indications, extendable by two years for compliance with a pediatric investigation plan[205]. - The orphan exclusivity period may be reduced to six years if the product no longer meets the orphan criteria or if it is shown to be sufficiently profitable[206]. - The company must comply with EU and member state laws regarding clinical trials and marketing authorization, with penalties for non-compliance including product withdrawals and fines[211]. - The EU legislation does not classify narcotic or psychotropic substances differently, but follows UN conventions for control measures[208]. - All signatories of the UN Conventions must ensure controlled substances are available for medical purposes while preventing abuse[209]. - The obligations under the UN Conventions are implemented at the national level, with variations among EU member states[209]. Company Information - As of December 31, 2024, the company employed 59 full-time employees[213]. - The company was incorporated in Iowa in October 2006 and reincorporated in Delaware in May 2014, changing its name to Zevra Therapeutics, Inc. on February 21, 2023[214]. - The company’s website is www.zevra.com[214].

Financial Data and Key Metrics Changes - In Q4 2024, the company reported net revenue of $12 million, including $10.1 million from MIPLYFFA, marking a record level of quarterly product revenue [41][42] - The net loss for Q4 2024 was $35.7 million, compared to a net loss of $19.6 million in the same quarter a year ago [44] - For the full year 2024, net revenue was $23.6 million, with a net loss of $105.5 million, compared to a net loss of $46 million in 2023 [46][48] Business Line Data and Key Metrics Changes - MIPLYFFA's early launch exceeded expectations, with 109 patient enrollment forms received in Q4, reflecting strong demand in the NPC community [10][23] - OLPRUVA saw an increase in enrollments to four in Q4, compared to three in Q3, with market access remaining consistent at 76% of covered lives [35][36] Market Data and Key Metrics Changes - The company estimates approximately 900 people with NPC in the U.S., with 300 to 350 diagnosed, indicating a significant market opportunity [24][102] - The European market is expected to have about 1,100 patients living with NPC, with plans to submit a marketing authorization application in the second half of 2025 [11][53] Company Strategy and Development Direction - The company is focused on expanding MIPLYFFA's availability outside the U.S. and enhancing commercial capabilities for both MIPLYFFA and OLPRUVA [11][12] - A strategic review led to the decision to outsource in-house discovery efforts, allowing the company to focus investments where there is the greatest potential for impact [17] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the momentum from 2024 and the strength of the company's position to execute on strategic priorities in 2025 [20][48] - The management team emphasized the importance of building financial strength and disciplined capital allocation to support long-term transformation [19][47] Other Important Information - The company entered into an agreement to monetize its priority review voucher for $150 million, which will provide non-dilutive capital for future growth [20][46] - The company has a cash runway extending into 2029, excluding potential proceeds from the sale of the PRV [48] Q&A Session Summary Question: Can you provide guidance on the European filing timeline? - Management indicated plans to file for MIPLYFFA in Europe in the second half of 2025, with confidence in the acceptance of the filing [53][56] Question: How do you expect the European market dynamics to affect patient identification? - The management noted that the European market is more mature due to the long-standing presence of miglustat, which could facilitate patient identification and treatment [53][54] Question: Can you provide more details on MIPLYFFA sales and patient enrollment? - The company reported $10.1 million in MIPLYFFA revenue for Q4, with 109 total prescription enrollment forms received [41][23] Question: What is the average time from enrollment to reimbursement? - Management stated it is too early to provide specifics on the average time from enrollment to reimbursement but noted that many patients received their first fill and refill quickly [104] Question: How are reimbursement conversations progressing? - The management reported that most patients are getting covered through direct formulary or medical exceptions, with ongoing discussions with payers about the clinical benefits of MIPLYFFA [91][93] Question: What are the expected discontinuation rates for MIPLYFFA? - Management indicated it is too early to assess discontinuation rates but noted high continuity of care observed in previous programs [113][115]

Financial Data and Key Metrics Changes - In Q4 2024, the company reported net revenue of $12 million, which included $10.1 million from MIPLYFFA, $0.1 million from OLPRUVA, and $1.1 million from net reimbursements from the French EAP for arimoclomol [41][44] - The full year 2024 net revenue was $23.6 million, with a net loss of $105.5 million or $2.28 per share, compared to a net loss of $46 million or $1.30 per share in 2023 [44][46] - Operating expenses for Q4 were $24.5 million, with R&D expenses decreasing to $8.4 million, while SG&A expenses increased to $16.1 million [43][45] Business Line Data and Key Metrics Changes - MIPLYFFA's launch exceeded expectations, with 109 patient enrollment forms received in Q4, reflecting strong demand in the NPC community [10][23] - OLPRUVA saw four new enrollments in Q4, an increase from three in Q3, with market access remaining consistent at 76% of covered lives [12][35] Market Data and Key Metrics Changes - The company estimates approximately 900 people with NPC in the U.S., with 300 to 350 diagnosed, indicating a significant market opportunity for MIPLYFFA [24][28] - The European market is expected to have around 1,100 patients living with NPC, with plans to submit a marketing authorization application in the second half of 2025 [11][53] Company Strategy and Development Direction - The company aims to expand MIPLYFFA's availability outside the U.S. and is focused on regulatory submissions in Europe [11][20] - The strategic plan includes four pillars: commercial excellence, pipeline and innovation, talent and culture, and corporate foundation [7][19] - The company is rationalizing its in-house discovery efforts and outsourcing activities to focus investments where there is the greatest potential for impact [17] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the early success of MIPLYFFA and the potential for significant market penetration in both the U.S. and Europe [20][28] - The company is focused on building financial strength and disciplined capital allocation to support long-term transformation [19][47] Other Important Information - The company refinanced existing debt and completed a secondary offering, providing financial stability [19] - A priority review voucher was monetized for $150 million, expected to provide non-dilutive capital for future growth [20][46] Q&A Session Summary Question: Can you provide guidance on the European filing timeline? - Management indicated plans to file in the second half of 2025 and is confident in the acceptance of the filing based on improved long-term data [53][56] Question: How do you expect the European market dynamics to affect patient identification? - The European market is more mature, with more patients diagnosed and treated due to the long-standing presence of miglustat [53] Question: Can you provide more quantitative details on MIPLYFFA sales during the quarter? - MIPLYFFA revenue of $10.1 million included initial patient dispenses and refills, with inventory levels maintained at target levels [65] Question: What is the expected long-term net patient addition rate? - The focus will be on finding diagnosed but untreated patients, with expectations for steady growth in patient enrollments [67] Question: How many patients are currently treated at centers of excellence? - Most diagnosed patients have connections to centers of excellence, with ongoing efforts to expand treatment access [78] Question: What is the average time from enrollment to reimbursement? - It is too early to provide specifics, but initial experiences indicate a quick turnaround for some patients [104] Question: Have there been any patient denials for enrollment? - A few patients have faced initial denials, but the company has robust support systems in place to assist them [108]

Financial Performance - FY 2024 net revenue was $23.6 million, with Q4 2024 product net revenue reaching a record $10.2 million[1] - Net revenue for the year ended December 31, 2024, was $23,612,000, a decrease of 14% from $27,461,000 in 2023[39] - The net loss for FY 2024 was ($105.5) million, or ($2.28) per share, compared to a net loss of ($46.0) million, or ($1.30) per share in FY 2023[9] - Net loss for 2024 was $105,511,000, compared to a net loss of $46,049,000 in 2023, representing a 129% increase in losses[39] Revenue Sources - MIPLYFFA generated $10.1 million in net revenue for Q4 2024, while OLPRUVA contributed $0.1 million[12] Operating Expenses - Operating expenses for FY 2024 totaled $97.0 million, with R&D expenses at $42.1 million, reflecting a $2.3 million increase from FY 2023[9] - Total operating expenses increased to $96,963,000 in 2024, up 31% from $74,120,000 in 2023[39] - Research and development expenses rose to $42,095,000 in 2024, an increase of 5% from $39,806,000 in 2023[39] - Selling, general and administrative expenses surged to $54,868,000 in 2024, up 60% from $34,314,000 in 2023[39] - SG&A expenses for Q4 2024 were $16.1 million, an increase of $1.4 million compared to Q4 2023[12] Cash and Investments - As of Dec. 31, 2024, cash, cash equivalents, and investments were $75.5 million, with a cash runway forecast extending into 2029[9] - Cash and cash equivalents decreased to $33,785,000 as of December 31, 2024, down from $43,049,000 in 2023[41] Assets and Liabilities - Total assets increased to $178,127,000 in 2024, compared to $172,327,000 in 2023[42] - Total liabilities rose to $138,461,000 in 2024, up from $110,463,000 in 2023, indicating a 25% increase[41] Share Information - The weighted average number of shares outstanding increased to 46,251,239 in 2024 from 35,452,460 in 2023[39] Regulatory and Market Activities - Zevra initiated the commercial launch of MIPLYFFA on Nov. 21, 2024, following FDA approval on Sep. 20, 2024[5] - The company plans to file for regulatory approval of MIPLYFFA in the EU in the second half of 2025[5] - The company received 109 total prescription enrollment forms for MIPLYFFA as of Dec. 31, 2024[5] - Zevra entered into an asset purchase agreement for the sale of a Rare Pediatric Disease Priority Review Voucher (PRV) for $150 million[8] Focus on Rare Diseases - The company has received Orphan Drug designation for both Celiprolol and KP1077, indicating a focus on rare disease treatments[31][32]

Core Insights - Zevra Therapeutics reported FY 2024 net revenue of $23.6 million, with Q4 2024 net revenue of $12.0 million, driven by the commercial launch of MIPLYFFA [1][11] - The company entered into an asset purchase agreement for the sale of a Rare Pediatric Disease Priority Review Voucher (PRV) for $150 million [6] - Zevra's strategic plan focuses on four pillars: commercial excellence, pipeline and innovation, talent and culture, and corporate foundation [2] Financial Highlights - Q4 2024 net revenue breakdown: $10.1 million from MIPLYFFA, $0.1 million from OLPRUVA, $1.1 million in net reimbursements from the French EAP for arimoclomol, and $0.7 million in royalties under the AZSTARYS license agreement [11] - Operating expenses for Q4 2024 were $24.5 million, including $4.0 million in non-cash stock compensation [10] - FY 2024 net loss was $105.5 million, or $2.28 per share, compared to a net loss of $46.0 million, or $1.30 per share in FY 2023 [12][37] Commercial Launch and Pipeline - MIPLYFFA was launched immediately after FDA approval on September 20, 2024, with U.S. commercial availability starting on November 21, 2024 [8] - As of December 31, 2024, Zevra received 109 total prescription enrollment forms for MIPLYFFA [8] - The company is targeting regulatory approval in the EU for MIPLYFFA, with a Marketing Authorisation Application filing planned for the second half of 2025 [8] Talent and Culture - In Q4 2024, Zevra consolidated its development and scientific functions under the leadership of its Chief Medical Officer, Adrian Quartel, M.D. [5] Corporate Foundation - The sale of the PRV is expected to provide net proceeds of $148.3 million after fees, enhancing the company's cash position [10][11] - As of December 31, 2024, Zevra had cash, cash equivalents, and investments totaling $75.5 million, extending its cash runway into 2029 [11]

Core Points - Zevra Therapeutics launched a new awareness campaign titled 'Learn NPC, Read Between the Signs' on Rare Disease Day to promote early recognition and diagnosis of Niemann-Pick disease type C (NPC) [1][2][3] - The campaign aims to provide educational resources and testing information to healthcare professionals and treatment teams in the U.S. [2][3] - MIPLYFFA (arimoclomol), Zevra's approved therapy for NPC, was highlighted, which received FDA approval on September 20, 2024, and has shown to halt disease progression in clinical trials [4][5] Company Overview - Zevra Therapeutics is a commercial-stage company focused on developing therapies for rare diseases with significant unmet needs [15] - The company emphasizes a data-driven approach to drug development and commercialization to address challenges in bringing new therapies to the market [15] Disease Information - Niemann-Pick disease type C (NPC) is characterized as an ultra-rare, progressive, and neurodegenerative lysosomal storage disorder, leading to cholesterol accumulation in cells, particularly neurons [14] - The disease can affect both children and adults, presenting with varying symptoms and often resulting in irreversible disease progression and early mortality [14]

Core Viewpoint - Zevra Therapeutics has launched a new awareness campaign, 'Learn NPC, Read Between the Signs,' on Rare Disease Day to promote early recognition and diagnosis of Niemann-Pick disease type C (NPC), an ultra-rare neurodegenerative disorder [2][3][4] Company Initiatives - The campaign aims to provide educational resources and testing information to healthcare professionals and treatment teams in the U.S. to improve the diagnosis of NPC [3][4] - Zevra's Chief Commercial Officer emphasized the company's commitment to addressing unmet needs in rare diseases and supporting the NPC community [3] Product Information - MIPLYFFA (arimoclomol) is Zevra's approved therapy for NPC, which received FDA approval on September 20, 2024 [5] - The drug works by activating transcription factors that regulate lysosomal expression and has shown to halt disease progression in a pivotal phase 3 trial [5] - MIPLYFFA is indicated for use in combination with miglustat for treating neurological manifestations of NPC in patients aged 2 years and older [6] Disease Overview - Niemann-Pick disease type C is characterized by the body's inability to transport cholesterol and lipids, leading to their accumulation in cells, particularly neurons [15] - The disease presents with varying symptoms and can lead to significant physical and cognitive limitations, often resulting in early mortality [15] Company Background - Zevra Therapeutics focuses on developing therapies for rare diseases with limited treatment options, aiming to create transformational therapies through data-driven strategies [16]

Core Insights - Zevra Therapeutics, Inc. has entered into a definitive asset purchase agreement to sell its Rare Pediatric Disease Priority Review Voucher (PRV) for gross proceeds of $150 million, expected to close within 30 to 45 days, subject to customary closing conditions [1][2] Financial Impact - The sale of the PRV will provide non-dilutive capital, strengthening the company's balance sheet with an addition of $150 million in gross cash proceeds [2] - This capital will support continued investment in strategic priorities, including the commercial launches of MIPLYFFA™ and OLPRUVA®, as well as advancing the pipeline of product candidates for rare diseases [2] Product and Regulatory Context - The PRV was granted to Zevra in September 2024 following the FDA approval of MIPLYFFA (arimoclomol), which is indicated for treating neurological manifestations of Niemann-Pick disease type C (NPC) in patients aged 2 years and older [2] - The transaction is subject to customary closing conditions, including the expiration of the applicable waiting period under the Hart-Scott Rodino Antitrust Improvements Act (HSR) [2]