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– Strong revenue performance across product portfolio – – Submitted MAA for sepiapterin and BLA for Upstaza – – On target to achieve remaining 2024 clinical and regulatory milestones, including global submissions for sepiapterin – WARREN, N.J., April 25, 2024 /PRNewswire/ -- PTC Therapeutics, Inc., (NASDAQ: PTCT) today announced a corporate update and financial results for the first quarter ending March 31, 2024. "We are off to a strong start in 2024, with outstanding commercial performance and achievement of all planned clinical and regulatory milestones for the first quarter," said Matthew Klein, M.D., Chief Executive Officer, PTC Therapeutics, Inc. "We remain on track to achieve the many planned 2024 clinical and regulatory milestones, including global regulatory submissions for sepiapterin." Key Corporate Updates: First quarter 2024 total revenue of $210 million First quarter 2024 revenue for the DMD franchise was $161 million Translarna™ (ataluren) net product revenue was $104 million, driven by new patients in existing geographies and continued geographic expansion. Emflaza® (deflazacort) net product revenue was $57 million, resulting from new patient starts and high compliance. Key Clinical and Regulatory Milestones: PTC submitted an MAA to the EMA for sepiapterin for the treatment of PKU in March 2024. The company expects to submit an NDA to the FDA for sepiapterin no later than the third quarter of 2024 and to complete regulatory submissions in Japan and Brazil in 2024. PTC submitted a BLA to the FDA for Upstaza™ for the treatment of AADC deficiency in March 2024. Based on FDA feedback, PTC plans to resubmit the NDA for Translarna for the treatment of nmDMD in mid-2024. Based on FDA feedback, PTC plans to submit an NDA for vatiquinone for the treatment of FA in late 2024. The interim data update for the PIVOT-HD trial of PTC518 for HD patients remains on schedule for the second quarter of 2024. This update will include 12-month data on the initial group of subjects for whom data were reported in June 2023, as well as 12-week data on a larger number of stage 2 and stage 3 HD patients. PTC expects to report topline data for the CardinALS trial of utreloxastat for ALS in the fourth quarter of 2024. First Quarter 2024 Financial Highlights: Total revenues were $210.1 million for the first quarter of 2024, compared to $220.4 million for the first quarter of 2023. Total revenue includes net product revenue across the commercial portfolio of $177.6 million for the first quarter of 2024, compared to $187.6 million for the first quarter of 2023. Total revenue also includes collaboration, royalty, and manufacturing revenue of $32.5 million in the first quarter of 2024, compared to $32.8 million for the first quarter of 2023. Translarna net product revenues were $103.6 million for the first quarter of 2024, compared to $115.1 million for the first quarter of 2023, driven by new patients in existing geographies and continued geographic expansion. The decrease was due to the timing of bulk patient orders. Emflaza net product revenues were $57.5 million for the first quarter of 2024, compared to $54.6 million for the first quarter of 2023. These results were driven by new patient starts and high compliance. Roche reported Evrysdi® 2024 year-to-date sales of approximately $400 million, resulting in royalty revenue of $31.2 million to PTC for the first quarter of 2024, as compared to $30.8 million for the first quarter of 2023. Based on U.S. GAAP (Generally Accepted Accounting Principles), GAAP R&D expenses were $116.1 million for the first quarter of 2024, compared to $195.1 million for the first quarter of 2023. The decrease in research and development expenses reflects strategic portfolio prioritization as the Company continues to focus its resources on its differentiated, high-potential R&D programs. Non-GAAP R&D expenses were $107.2 million for the first quarter of 2024, excluding $9.0 million in non-cash, stock-based compensation expense, compared to $179.8 million for the first quarter of 2023, excluding $15.3 million in non-cash, stock-based compensation expense. GAAP SG&A expenses were $73.3 million for the first quarter of 2024, compared to $86.9 million for the first quarter of 2023. The decrease in selling, general and administrative expenses reflects lower employee costs as a result of the reduction in workforce in 2023. Non-GAAP SG&A expenses were $63.9 million for the first quarter of 2024, excluding $9.4 million in non-cash, stock-based compensation expense, compared to $73.4 million for the first quarter of 2023, excluding $13.5 million in non-cash, stock-based compensation expense. Change in the fair value of deferred and contingent consideration was a gain of $0.1 million for the first quarter of 2024, compared to a loss of $2.4 million for the first quarter of 2023. The net loss was $91.6 million for the first quarter of 2024, compared to a net loss of $139.0 million for the first quarter of 2023. Cash, cash equivalents, and marketable securities was $884.8 million on March 31, 2024, compared to $876.7 million on December 31, 2023. Shares issued and outstanding as of March 31, 2024, were 76,653,960. PTC Reaffirms Full Year 2024 Financial Guidance: PTC anticipates total revenues for full year 2024 to be between $600 million and $680 million. PTC anticipates GAAP R&D and SG&A expense for full year 2024 to be between $740 and $835 million. PTC anticipates Non-GAAP R&D and SG&A expense for full year 2024 to be between $660 and $755 million, including expected R&D expense milestone payments of up to $65 million and excluding estimated non-cash, stock-based compensation expense of $80 million. PTC anticipates up to $90 million of payments for full year 2024 upon achievement of potential regulatory success-based milestones from previous acquisitions, of which up to $65 million will be recorded as R&D operating expense. 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 ALS: Amyotrophic Lateral Sclerosis BLA: Biologics License Application CHF: Confoederatio Helvetica Francs (Swiss francs) DMD: Duchenne Muscular Dystrophy EMA: European Medicines Agency FA: Friedreich Ataxia FDA: U.S. Food and Drug Administration GAAP: Generally Accepted Accounting Principles HD: Huntington's Disease MAA: Marketing Authorization Application NDA: New Drug Application nmDMD: Nonsense Mutation Duchenne Muscular Dystrophy PKU: Phenylketonuria 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 patients 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, on Twitter at @PTCBio, and on LinkedIn. For More Information: Investors: Kylie O'Keefe +1 (908) 300-0691 [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 Reaffirms Full Year 2024 Revenue Guidance", including with respect to (i) 2024 total revenue guidance, (ii) 2024 GAAP and non-GAAP R&D and SG&A expense guidance and (iii) 2024 acquisition related milestone payment 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; the extent, timing and financial aspects of our strategic pipeline prioritization and reductions in workforce; 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; 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 our trials in Translarna; expectations with respect to Upstaza, including any regulatory submissions and potential approvals, commercialization, manufacturing capabilities, the potential achievement of development, regulatory and sales milestones and contingent payments that PTC may be obligated to make; expectations with respect to the commercialization of Evrysdi under our SMA collaboration; expectations with respect to the commercialization of Tegsedi and Waylivra; the timing of and actual expenses incurred in connection with the discontinuation of PTC's preclinical and early research programs in gene therapy and reductions in workforce, which may be in different periods and may be materially higher than estimated; the savings that may result from the discontinuation of PTC's strategic pipeline prioritization and reductions in workforce, which may be materially less than expected; 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; the potential financial impact and benefits of PTC's leased biologics manufacturing facility; PTC's ability to satisfy its obligations under the terms of its lease agreements, including for its leased biologics manufacturing facility; 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 Quarterly Report on Form 10-Q and 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, Evrysdi, Tegsedi or Waylivra. 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.

点击上方的 行舟Drug ▲ 添加关注核酸药物是人工合成的具有疾病治疗功能的 DNA 或 RNA 片段，通过靶向 mRNA，作用于蛋白质合成上游。核酸是 DNA 和 RNA 的总称。主要包括：小核酸药物、小分子核苷类药物 和 mRNA 疫苗。小核酸药物的分类及作用机制小核酸药物，又称寡核苷酸药物，由序列经过特定设计的核苷酸构成，主要作用于细胞质的 mRNA，通过碱基互补配对的方式，识别和调控靶 mRNA。长度小于 30nt 的寡核苷酸序列，可通过与靶分子的 RNA 结合，通过调控翻译，从而达到治疗疾病的目的。广义的小核酸包括小干扰 RNA （ siRNA ） 、 反义寡核苷酸 （ ASO ）、微小 RNA （miRNA）、核酸适配体（Aptamer）及其它。药物具有治疗效率高、特异性强、药物毒性小和应用领域广等优点。小核酸药物作用机制，是与靶分子的RNA结合，抑制其翻译或调控。主要应用于基因治疗和基因编辑领域。小核酸药物的研发流程包括：适应症选择、靶点筛选、序列设计、 化学修饰、药物递送、工艺放大等。其适应症包括：肿瘤、遗传罕见病、 代谢疾病、自免疫疾病以及感染等。通过多种下游生物学功能实验，对候选的系列靶点进行验证，从而确认靶点是否产生对应的调节作用，以及生物活性，最终确定最佳结合位点。通过序列的化学修饰，可以提高小核酸药物的亲和力、稳定性、代谢性质等。小核酸药物，在人体内通过核酸酶降解、 血液循环中的免疫识别、靶组织中的积累、跨膜转运以及从内涵体 和溶酶体逃逸等发挥药效。其合成反应完成后，需要对产品进行分离纯化，以去除副产物和杂质。小核酸药物技术难点包括：靶点的序列设计优化、化学修饰、小核酸药物的合成（原 料和设备）、递送载体等。 靶点筛选与序列设计小核酸药物基于致病基因，设计并筛选出相对应RNA 序列。小核酸合成小核酸药物研发上游的重要原材料小核酸单体，尚处于市场早期。其存在多种挑战，合成技术环节多，工艺复杂、投入成本高，运输标准要求高等。小核酸药物合成反应完成后，需通过反相 HPLC 液相色谱系统，进行分离纯化。化学修饰通过对核酸药物进行化学修饰，提高药物稳定性，增强其抵抗内源性内切酶和外切酶降解能力，以及提高在体内递送效率。产业链递送系统小核酸药物需借助递送系统的帮助，以提升药物治疗的有效性和安全性。小核酸药物递送系统包括：脂质纳米颗粒（Lipid Nanoparticle， LNP）递送系统和 N-乙酰化的半乳糖胺(GalNac)递送系统。GalNac：GalNAc 能以三价态的方式共价偶联至核酸 3’末端，能以高亲和力与 肝脏细胞表面的唾液酸糖蛋白受体（ASGPR）结合，随后受体在网 格蛋白介导的内吞作用下将 GalNAc 及核酸摄取进入细胞。LNP ：一种带正电的纳米脂质体，能与带负电的 RNA 结合，将 RNA 包裹在脂质囊泡内。据有关数据，预估全球小核酸药物销售额，在2025年将突破 100 亿美元；我国小核酸药物市场，将在2030年达到 100 亿元。全球获批的小核酸药物截至2023 年下半年，全球 15 款小核酸药物获批上市ASO：Vitravene（撤市）、Kynamro（撤市）、Exondys、Spinraze、Tegsedi、Waylivra、Vyondys 53、Viltepso、Amondys 45；siRNA：Onpattro、Givlaari、Oxlumo、Leqvio、AMVUT TRA；aptamer：Macugen（撤市）小核酸抗体偶联药物AOC是一类抗体与寡核苷酸偶联合成的新型药物。通过将单抗和寡核苷酸偶联，达到有效的靶向治疗能力，具有精准靶向和更好的药代动力学特性。AOC已成为靶向寡核苷酸药物递送的潜在载体。优势具有靶向性，增加生物利用度，减少毒作用；提高稳定性，增加半衰期，提高有效性。偶联方式现主流的偶联方式包括基于电荷亲和，链霉亲和素/生物素的结合，直接偶联以及碱基互补配对偶联等，AOC药物有多种寡核苷酸和抗体的偶联方式。直接偶联离子相互作用亲和性连接生物分析AOC药物生物分析相对复杂，需要结合LBA分析平台，LC-MS分析平台，以及qPCR分析平台等，共同完成对偶联药物的生物分析。其中包括：总抗体、偶联抗体、偶联/游离寡核苷酸、免疫原性和生物标志物等。全球在研AOC企业包括：Avidity Biosciences、Dyne Therapeutics、Tallac Therapeutics、Denali Therapeutics等。AOC作为一种新型偶联药物，利用抗体将小核酸药物，递送至特定细胞或组织，可一定程度上用于解决目前小核酸药物递送难题。AOC因其特异性高､简便､副作用更小的组合式创新递送手段等优势，或将在多种疾病的治疗领域取得突破性进展。文章信息源于公众号小白学药，登载该文章目的为更广泛的传递行业信息，不代表赞同其观点或对其真实性负责。文章版权归原作者及原出处所有，文章内容仅供参考。本网拥有对此声明的最终解释权，若无意侵犯版权，请联系小编删除。学如逆水行舟，不进则退；心似平原走马，易放难收。行舟Drug每日更新 欢迎订阅+医药大数据|行业动态|政策解读