L-Sepiapterin

- Label includes full spectrum of PKU patients - - European launch preparations underway - WARREN, N.J., April 25, 2025 /PRNewswire/ -- PTC Therapeutics, Inc. (NASDAQ: PTCT) announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion on the marketing authorization application for Sephience™ (sepiapterin) for the treatment of children and adults living with phenylketonuria (PKU). The opinion includes a broad label inclusive of all ages and disease severities. "This positive opinion is great news for the PKU patient community in Europe for whom there remains a significant unmet medical need," said Matthew B. Klein, M.D., Chief Executive Officer of PTC Therapeutics. "We look forward to initiating the European launch immediately following the adoption of this positive opinion by the European Commission. The data collected to date continue to support the potential for Sephience to provide a safe and effective treatment that not only lowers phenylalanine levels but also enables diet liberalization even for those with the most severe disease subtypes." Launch planning in Europe is well underway with priorities in Germany and other key European markets where named patient access will be immediately available. PTC expects the European Commission to ratify the marketing authorization for Sephience in approximately two months. The decision will be applicable to all 27 European Union member states, as well as Iceland, Norway and Liechtenstein. The New Drug Application (NDA) for sepiapterin is under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of July 29, 2025. Review of approval applications is ongoing in several other countries including Japan and Brazil. About Sephience™ (sepiapterin) Sephience, an oral formulation of synthetic sepiapterin, has a dual mechanism of action to increase activity of the phenylalanine hydroxylase (PAH) enzyme. First, Sephience is a precursor compound that is rapidly absorbed and converted intracellularly to tetrahydrobiopterin (BH4), a critical cofactor of PAH. Sephience also has an independent pharmacological chaperone effect, correcting PAH misfolding to enhance the enzyme function. Through this dual mechanism of action, Sephience effectively reduces blood phenylalanine (Phe) levels and has the potential to treat a broad range of PKU patients. About Phenylketonuria Phenylketonuria (PKU) is a rare, inherited metabolic disease, which affects the brain. It is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine (Phe). If left untreated or poorly managed, Phe – an essential amino acid found in all proteins and most foods – can build up to harmful levels in the body. This causes severe and irreversible disabilities, such as permanent intellectual disability, seizures, delayed development, memory loss, and behavioral and emotional problems. Newborns with PKU initially don't have any symptoms, but symptoms are usually progressive, and damage caused by toxic levels of Phe in the first few years of life is irreversible. Diagnosis of PKU usually takes place during newborn screening programs. There are an estimated 58,000 people living with PKU globally. About PTC Therapeutics, Inc. PTC is a global biopharmaceutical company that discovers, develops and commercializes clinically differentiated medicines that provide benefits to children and adults living with rare disorders. PTC's ability to innovate new therapies and to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines. To learn more about PTC, please visit us at and follow us on Facebook, X, and LinkedIn. For More Information: Investors: Ellen Cavaleri +1 (615) 618-6228 [email protected] Media: Jeanine Clemente +1 (908) 912-9406 [email protected] Forward-Looking Statement This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including statements regarding: the future expectations, plans and prospects for PTC, including with respect to the expected timing of clinical trials and studies, availability of data, regulatory submissions and responses, commercialization and other matters with respect to its products and product candidates; expectations with respect to Sephience, including any regulatory decision made by the European Commission; PTC's strategy, future operations, future financial position, future revenues, projected costs; and the objectives of management. Other forward-looking statements may be identified by the words, "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with third party payors for PTC's products or product candidates that PTC commercializes or may commercialize in the future; expectations with respect to Sephience, including any regulatory submissions and potential approvals, commercialization and the potential achievement of regulatory and sales milestones and contingent payments that PTC may be obligated to make; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of PTC's products and product candidates; PTC's scientific approach and general development progress; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including Sephience. The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law. SOURCE PTC Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

– Full year 2024 revenue of $807 million, exceeding guidance – – All 2024 clinical and regulatory milestones were achieved on schedule, including four NDA submissions, all of which were accepted for filing – – License and collaboration agreement with Novartis for PTC518 Huntington's disease program closed in January 2025 – – Cash of over $2.0 billion as of January 2025 – WARREN, N.J., Feb. 27, 2025 /PRNewswire/ -- PTC Therapeutics, Inc., (NASDAQ: PTCT) today announced a corporate update and financial results for the fourth quarter ending December 31, 2024. "Our strong fourth quarter rounds out a year of significant accomplishment across every part of our company," said Matthew B. Klein, M.D., Chief Executive Officer. "In 2024, our commercial team delivered another outstanding performance, we achieved all clinical and regulatory milestones on schedule and we solidified our balance sheet. We now have over $2 billion in cash to support our planned commercial and R&D activities in 2025 and beyond. With the many accomplishments of 2024 and our team's demonstrated ability to execute across every part of the business, we have built a strong foundation for continued success." Key Corporate Updates: Fourth quarter 2024 total revenue of $213 million Fourth quarter 2024 revenue for the DMD franchise of $144 million, including net product revenue for Translarna™ of $94 million and for Emflaza® of $50 million Sold Rare Disease PRV received with FDA approval of Kebilidi™ for $150 million License and collaboration agreement signed with Novartis for PTC518 Huntington's disease program, closed in January 2025 Key Clinical and Regulatory Milestones: PTC submitted four regulatory approval applications to FDA in 2024, all of which have been accepted for review: Kebilidi (eladocagene exuparvovec-tneq) gene therapy for the treatment of AADC deficiency in the U.S., approved in November 2024 Sepiapterin for children and adults with PKU, with a target regulatory action date of July 29, 2025 Vatiquinone for children and adults with Friedreich's ataxia, granted priority review with a target regulatory action date of August 19, 2025 Translarna for nmDMD PTC submitted several additional marketing authorization applications outside the U.S. for sepiapterin in 2024, with CHMP opinion on sepiapterin MAA expected in Q2 2025 and a regulatory decision in Japan expected in Q4 2025. Type C meeting with FDA held in December 2024 to discuss HTT lowering as potential surrogate endpoint to support accelerated approval for PTC518 for HD. The Agency was aligned with the scientific rationale for HTT lowering as a potential surrogate endpoint and asked that PTC provide additional clinical data, such as those being collected in PIVOT-HD, to show associations between HTT lowering and changes in clinical outcome measures. 12-month results from the PIVOT-HD Phase 2 study of PTC518 expected in Q2 2025. Fourth Quarter and Full Year 2024 Financial Highlights: Total revenues were $213.2 million for the fourth quarter of 2024, compared to $307.1 million for the fourth quarter of 2023. Total revenue was $806.8 million for full year 2024, compared to $937.8 million for full year 2023. Total revenue includes net product revenue across the commercial portfolio of $154.7 million for the fourth quarter of 2024 and $601.0 million for full year 2024, compared to $155.1 million for the fourth quarter of 2023 and $661.2 million for full year 2023. Total revenue also includes royalty, collaboration, and manufacturing revenue of $58.5 million in the fourth quarter of 2024 and $205.8 million for full year 2024, compared to $152.0 million for the fourth quarter of 2023 and $276.6 million for full year 2023. Translarna net product revenues were $93.7 million for the fourth quarter of 2024, compared to $75.2 million for the fourth quarter of 2023. Translarna net product revenues were $339.9 million for full year 2024, compared to $355.8 million for full year 2023. Emflaza net product revenues were $50.5 million for the fourth quarter of 2024, compared to $67.4 million for the fourth quarter of 2023. Emflaza net product revenues were $207.2 million for full year 2024, compared to $255.1 million for full year 2023. These results were driven by the expiration of Emflaza's orphan drug exclusivity in February 2024. Roche reported Evrysdi® full year 2024 sales of approximately 1,631 CHF million, resulting in royalty revenue of $203.9 million to PTC for full year 2024, as compared to $168.9 million for full year 2023. Also in the fourth quarter of 2023, PTC recorded a sales milestone of $100.0 million for the achievement of $1.5 billion in worldwide annual net sales from Evrysdi. This sales milestone was recorded as collaboration revenue. Based on U.S. GAAP (Generally Accepted Accounting Principles), GAAP R&D expenses were $124.8 million for the fourth quarter of 2024, compared to $121.4 million for the fourth quarter of 2023. GAAP R&D expenses were $534.5 million for full year 2024, compared to $666.6 million for full year 2023. The slight increase in R&D expense for the fourth quarter of 2024 reflects additional costs due to manufacturing, regulatory filings, and inspections primarily related to Kebilidi and sepiapterin. The decrease in R&D expense for full year 2024 relates to decreases in program spend related to our strategic portfolio prioritization as we continue to focus our resources on our differentiated, high potential research and development programs. R&D expense also included a total of $65.0 million regulatory success-based milestones paid to the former Censa securityholders for the year ended December 31, 2024, as compared to a $30.0 million success-based development milestone payable to the former Censa securityholders for the year ended December 31, 2023. Non-GAAP R&D expenses were $116.0 million for the fourth quarter of 2024, excluding $8.8 million in non-cash, stock-based compensation expense, compared to $113.2 million for the fourth quarter of 2023, excluding $8.1 million in non-cash, stock-based compensation expense. Non-GAAP R&D expenses were $497.9 million for full year 2024, excluding $36.6 million in non-cash, stock-based compensation expense, compared to $613.6 million for full year 2023, excluding $52.9 million in non- cash, stock-based compensation expense. GAAP SG&A expenses were $84.7 million for the fourth quarter of 2024, compared to $76.3 million for the fourth quarter of 2023. GAAP SG&A expenses were $300.9 million for full year 2024, compared to $332.5 million for full year 2023. The increase in SG&A expense for the fourth quarter of 2024 reflects our continued investment to support commercial activities, including expanding our commercial portfolio. The decrease in SG&A expense for full year 2024 was primarily due to lower employee costs as a result of the reduction in the workforce in 2023. Non-GAAP SG&A expenses were $76.3 million for the fourth quarter of 2024, excluding $8.4 million in non-cash, stock-based compensation expense, compared to $67.9 million for the fourth quarter of 2023, excluding $8.4 million in non-cash, stock-based compensation expense. Non-GAAP SG&A expenses were $262.9 million for full year 2024, excluding $38.0 million in non-cash, stock-based compensation expense, compared to $283.8 million for full year 2023, excluding $48.7 million in non- cash, stock-based compensation expense. The change in the fair value of deferred and contingent consideration was a gain of $10.2 million for the fourth quarter of 2024, compared to a gain of $2.7 million for the fourth quarter of 2023. Change in the fair value of deferred and contingent consideration was a gain of $4.5 million for full year 2024, compared to a gain of $127.7 million for full year 2023. The full year 2024 change is primarily related to the Company's strategic portfolio prioritization and decision to discontinue its preclinical and early research programs in its gene therapy platform in May 2023, which included programs for FA and Angelman syndrome. The intangible asset impairment was $159.5 million for the fourth quarter and full year 2024, compared to $0.0 million for fourth quarter and $217.8 million for the full year 2023, which represented a non-cash charge. For the fourth quarter and full year 2024, we impaired $159.5 million related to a decrease in projected cash flows due to refinements in current market assumptions and the timing of patient treatments for AADC. For the full year 2023, we fully impaired the FA and Angelman syndrome intangible assets and recorded impairment expense of $217.8 million. Net loss was $65.9 million for the fourth quarter of 2024, compared to net loss of $155.8 million for the fourth quarter of 2023. Net loss was $363.3 million for full year 2024, compared to net loss of $626.6 million for full year 2023. Cash, cash equivalents, and marketable securities was $1,139.7 million on December 31, 2024, compared to $876.7 million on December 31, 2023. Shares issued and outstanding as of December 31, 2024, were 77,704,188. PTC Full Year 2025 Financial Guidance: PTC anticipates total revenues for full year 2025 to be between $600 million and $800 million, including in-line products, potential new product launches, and royalty revenue from Evrysdi. PTC anticipates GAAP R&D and SG&A expenses for full year 2025 to be between $805 million and $835 million. PTC anticipates non-GAAP R&D and SG&A expenses for full year 2025 to be between $730 million and $760 million, excluding estimated non-cash, stock-based compensation expense of $75 million. Non-GAAP Financial Measures: In this press release, the financial results of PTC are provided in accordance with GAAP and using certain non-GAAP financial measures. In particular, the non-GAAP R&D and SG&A expense financial measures exclude non-cash, stock-based compensation expense. These non-GAAP financial measures are provided as a complement to financial measures reported in GAAP because management uses these non-GAAP financial measures when assessing and identifying operational trends. In management's opinion, these non-GAAP financial measures are useful to investors and other users of PTC's financial statements by providing greater transparency into the historical and projected operating performance of PTC and the company's future outlook. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. Quantitative reconciliations of the non-GAAP financial measures to their respective closest equivalent GAAP financial measures are included in the table below. Acronyms: AADC: Aromatic L-Amino Acid Decarboxylase CHF: Confoederatio Helvetica Francs (Swiss francs) CHMP: Committee for Medicinal Products for Human Use DMD: Duchenne Muscular Dystrophy FA: Friedreich's Ataxia FDA: U.S. Food and Drug Administration GAAP: Generally Accepted Accounting Principles HD: Huntington's Disease HTT: Huntingtin MAA: Marketing Authorization Application NDA: New Drug Application nmDMD: Nonsense mutation Duchenne muscular dystrophy PKU: Phenylketonuria PRV: Priority Review Voucher R&D: Research and Development SG&A: Selling, General, and Administrative Today's Conference Call and Webcast Reminder: To access the call by phone, please click here to register and you will be provided with dial-in details. To avoid delays, we recommend participants dial in to the conference call 15 minutes prior to the start of the call. The webcast conference call can be accessed on the Investor section of the PTC website at . A replay of the call will be available approximately two hours after completion of the call and will be archived on the company's website for 30 days following the call. About PTC Therapeutics, Inc. PTC is a global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to children and adults living with rare disorders. PTC's ability to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines and our mission to provide access to best-in-class treatments for patients who have an unmet medical need. The company's strategy is to leverage its strong scientific expertise and global commercial infrastructure to maximize value for its patients and other stakeholders. To learn more about PTC, please visit us at and follow us on Facebook, X, and LinkedIn. For More Information: Investors: Ellen Cavaleri +1 (615) 618-6228 [email protected] Media: Jeanine Clemente +1 (908) 912-9406 [email protected] Forward-Looking Statements: This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including the information provided under the heading "PTC Full Year 2025 Financial Guidance", including with respect to (i) 2025 total revenue guidance and (ii) 2025 GAAP and non-GAAP R&D and SG&A expense guidance, and statements regarding: the future expectations, plans and prospects for PTC, including with respect to the expected timing of clinical trials and studies, availability of data, regulatory submissions and responses, commercialization and other matters with respect to its products and product candidates; PTC's strategy, future operations, future financial position, future revenues, projected costs; and the objectives of management. Other forward-looking statements may be identified by the words, "guidance," "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with third party payors for PTC's products or product candidates that PTC commercializes or may commercialize in the future; PTC's ability to maintain its marketing authorization of Translarna for the treatment of nmDMD in Brazil, Russia, the European Economic Area (EEA) and other regions, including whether the European Commission adopts the negative opinion from the Committee for Medicinal Products for Human Use (CHMP) for the conditional marketing authorization for Translarna in the EEA, or PTC's ability to identify other potential mechanisms by which it may provide Translarna to nmDMD patients in the EEA; PTC's ability to use the clinical data from its international drug registry study and real-world evidence concerning Translarna's benefits to support a continued marketing authorization for Translarna for the treatment of nmDMD in the EEA; PTC's ability to use the results of Study 041, a randomized, 18-month, placebo-controlled clinical trial of Translarna for the treatment of nmDMD followed by an 18-month open-label extension, and from its international drug registry study to support a marketing approval for Translarna for the treatment of nmDMD in the United States; whether investigators agree with PTC's interpretation of the results of clinical trials and the totality of clinical data from its trials in Translarna; expectations with respect to PTC's license and collaboration agreement with Novartis Pharmaceuticals Corporation including its right to receive development, regulatory and sales milestones, profit sharing and royalty payments from Novartis; expectations with respect to Upstaza/Kebilidi, including commercialization, manufacturing capabilities, and the potential achievement of sales milestones and contingent payments that PTC may be obligated to make; expectations with respect to sepiapterin, including any regulatory submissions and potential approvals, commercialization, and the potential achievement of regulatory and sales milestones and contingent payments that PTC may be obligated to make; expectations with respect to vatiquinone, including any regulatory submissions and potential approvals, commercialization, and the potential achievement of regulatory and sales milestones and contingent payments that PTC may be obligated to make; expectations with respect to the commercialization of Evrysdi under PTC's SMA collaboration; expectations with respect to the commercialization of Tegsedi and Waylivra; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of PTC's products and product candidates; PTC's scientific approach and general development progress; PTC's ability to satisfy its obligations under the terms of its lease agreements; the sufficiency of PTC's cash resources and its ability to obtain adequate financing in the future for its foreseeable and unforeseeable operating expenses and capital expenditures; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including Translarna, Emflaza, Upstaza, Kebilidi, Evrysdi, Tegsedi, Waylivra, sepiapterin or vatiquinone. The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law. SOURCE PTC Therapeutics, Inc. 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