PTC Therapeutics MP, Inc.

– Strong revenue performance, supporting increase in full-year revenue guidance to $750-800 million – – Regulatory filings for sepiapterin, Translarna™ and AADC gene therapy under review by FDA – – On track to achieve remaining 2024 clinical and regulatory milestones, including NDA submission for vatiquinone – WARREN, N.J., Nov. 7, 2024 /PRNewswire/ -- PTC Therapeutics, Inc., (NASDAQ: PTCT) today announced a corporate update and financial results for the third quarter ending September 30, 2024. "I am proud of our team's strong execution," said Matthew Klein, M.D., Chief Executive Officer. "We continue to achieve excellent revenue performance allowing us to raise full-year revenue guidance. In addition, we have submitted three approval applications to FDA so far this year, all of which have been accepted for review, and plan a fourth submission for vatiquinone for Friedreich ataxia in December. We are on our way to accomplishing all of our 2024 objectives and are in a strong financial position to execute on our long-term strategic plans." Key Corporate Updates: Third quarter 2024 total revenue of $197 million Third quarter 2024 revenue for the DMD franchise was $124 million Translarna™ (ataluren) net product revenue was $72 million, driven by continued access for patients in existing geographies, continued geographic expansion, high compliance and adherence, and dose adjustments. Emflaza® (deflazacort) net product revenue was $52 million, driven by new patient starts, continued brand loyalty, high compliance and adherence, and dose adjustments. Key Clinical and Regulatory Milestones: PTC submitted an NDA to the FDA for sepiapterin for the treatment of PKU. The file was accepted for review, and the regulatory action date is set for July 29, 2025. PTC resubmitted the NDA for Translarna for the treatment of nmDMD; the file was accepted, and a regulatory action date was not provided. The BLA for PTC's gene therapy for AADC deficiency remains on schedule for a regulatory action date of November 13, 2024. PTC received Fast Track Designation for the PTC518 Huntington's disease program. PTC plans to submit an NDA for vatiquinone for the treatment of Friedreich ataxia in December 2024. PTC expects to share topline data for the CardinALS trial of utreloxastat for the treatment of ALS in the fourth quarter of 2024. Third Quarter 2024 Financial Highlights: Total revenues were $196.8 million for the third quarter of 2024, compared to $196.6 million for the third quarter of 2023. Total revenue includes net product revenue across the commercial portfolio of $135.4 million for the third quarter of 2024, compared to $144.0 million for the third quarter of 2023. Total revenue also includes royalty and manufacturing revenue of $61.4 million in the third quarter of 2024, compared to $52.5 million for the third quarter of 2023. Translarna net product revenues were $72.3 million for the third quarter of 2024, compared to $69.0 million for the third quarter of 2023. Emflaza net product revenues were $51.9 million for the third quarter of 2024, compared to $67.4 million for the third quarter of 2023. Roche reported Evrysdi® 2024 year-to-date sales of approximately CHF 1.2 billion, resulting in royalty revenue of $61.4 million to PTC for the third quarter of 2024, compared to $50.2 million for the third quarter of 2023. Based on U.S. GAAP (Generally Accepted Accounting Principles), GAAP R&D expenses were $161.4 million for the third quarter of 2024, compared to $164.2 million for the third quarter of 2023. The decrease in research and development expenses reflects strategic portfolio prioritization, as PTC continues to focus its resources on its differentiated, high-potential R&D programs. Included in third quarter 2024 R&D expense is $50.0 million in regulatory success-based milestones related to the Censa acquisition. Non-GAAP R&D expenses were $152.0 million for the third quarter of 2024, excluding $9.4 million in non-cash, stock-based compensation expense, compared to $150.2 million for the third quarter of 2023, excluding $14.0 million in non-cash, stock-based compensation expense. GAAP SG&A expenses were $73.5 million for the third quarter of 2024, compared to $80.9 million for the third 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 $63.1 million for the third quarter of 2024, excluding $10.3 million in non-cash, stock-based compensation expense, compared to $67.9 million for the third quarter of 2023, excluding $13.0 million in non-cash, stock-based compensation expense. Change in the fair value of deferred and contingent consideration was a loss of $0.7 million for the third quarter of 2024, compared to a loss of $1.5 million for the third quarter of 2023. Tangible asset impairment and losses (gains) on transactions, net, was a loss of $1.8 million for the third quarter of 2024, compared to $0.0 million for the third quarter of 2023. These results were primarily related to fixed asset impairments. Net loss was $106.7 million for the third quarter of 2024, compared to net loss of $133.0 million for the third quarter of 2023. Cash, cash equivalents, and marketable securities was $1,013.4 million on September 30, 2024, compared to $876.7 million on December 31, 2023. Shares issued and outstanding as of September 30, 2024, were 76,952,124. PTC Updates Full Year 2024 Financial Guidance: PTC anticipates total revenues for full year 2024 to be between $750 million and $800 million. PTC anticipates GAAP R&D and SG&A expenses for full year 2024 to be between $740 million and $835 million, including expected R&D expense milestone payments of up to $65 million. PTC anticipates non-GAAP R&D and SG&A expenses for full year 2024 to be between $660 million 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 expenses. As of September 30, 2024, $85 million in milestones have been achieved, of which $65 million has been recorded as R&D operating expenses and $20 million as contingent consideration payable. 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 FA: Friedreich Ataxia FDA: U.S. Food and Drug Administration GAAP: Generally Accepted Accounting Principles HD: Huntington's Disease 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 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 Updates Full Year 2024 Financial 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, 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 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 sepiapterin, including any regulatory submissions and potential approvals, commercialization, 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 PTC's 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; 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, Evrysdi, Tegsedi, Waylivra or sepiapterin. 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

[26-October-2023] – Third quarter 2023 total revenues of $197 million and remain on target for 2023 revenue guidance – – PTC strengthened its financial position following recent restructuring initiatives and Royalty Pharma transaction – – PTC provides regulatory updates for pipeline programs – SOUTH PLAINFIELD, N.J., Oct. 26, 2023 /PRNewswire/ -- PTC Therapeutics, Inc., (NASDAQ: PTCT) today announced a corporate update and financial results for the third quarter ending September 30, 2023. "I am very proud of the progress all of our teams made this quarter," said Matthew Klein, M.D., Chief Executive Officer, PTC Therapeutics, Inc. "The recent Royalty Pharma transaction and restructuring initiatives that we implemented have put the company on a strong financial footing. We believe we are well positioned to deliver on our most promising opportunities for growth, including the potential sepiapterin revenue opportunity of more than $1 billion and the PTC518 HD program." Key Corporate Updates: Finalized strategic partnership transaction with Royalty Pharma, in which Royalty Pharma acquired additional royalties of Evrysdi for $1.0 billion upfront. The agreement included options for PTC to sell the remainder of its royalties of Evrysdi for up to $500 million or for Royalty Pharma to acquire half of such retained royalties for up to $250 million at a later date, less royalties received by PTC. PTC maintains all economics associated with up to $250 million in the remaining commercial sales milestones associated with Evrysdi global net sales. Third quarter 2023 revenue for the DMD franchise was $136 million, supporting increasing 2023 DMD franchise revenue guidance to between $565 million and $595 million. Translarna™ (ataluren) quarterly net product revenue was $69 million, with new patients in existing geographies and continued geographic expansion. Emflaza® (deflazacort) quarterly net product revenue was $67 million, with new patient starts and high compliance. Key Clinical and Regulatory Updates: For Translarna, following the negative opinion from the CHMP, the CHMP gave PTC the option to request re-examination of both opinions or only one opinion. PTC decided to pursue re-examination of the negative opinion on renewal of the conditional authorization only. In accordance with EMA guidelines, PTC expects the opinion from the re-examination procedure in late January 2024, with ratification of that opinion by the European Commission 67 days later. For the United States, a type C meeting with the FDA for Translarna is scheduled for the fourth quarter of 2023. PTC held a pre-NDA meeting in the third quarter with the FDA for sepiapterin in PKU to discuss the NDA submission. At the meeting, the FDA stated that the sepiapterin clinical safety and efficacy data supported NDA submission for the treatment of pediatric and adult PKU patients. It was requested that PTC complete an additional 26-week nonclinical mouse study to assess sepiapterin carcinogenicity potential prior to NDA submission. This nonclinical study was not initially required when sepiapterin was acquired from Censa, as the NDA submission was planned under the Section 505(b)(2) pathway. With PTC's decision to the Section 505(b)(1) pathway, the 26-week study is considered a required NDA component needed to inform labeling and is typically completed prior to submission. PTC will continue to discuss with the FDA the potential to submit the mouse study results during the NDA review process. PTC now expects the NDA submission to occur no later than the third quarter of 2024; the submission could be submitted during the second quarter of 2024 if the nonclinical study report can be submitted during the review process. PTC expects to submit an MAA to the EMA for sepiapterin for the treatment of PKU in the first half of 2024. Enrollment in the PIVOT-HD study for PTC518 for Huntington's disease continues outside of the US for both the stage 2 and early stage 3 cohorts. PTC expects the next data update to occur in the first half of 2024. This update will include 12-month data on the initial group of subjects for which data was reported in June of this year. PTC had a type A meeting with the FDA to discuss the clinical safety data needed to enable enrollment of the PIVOT-HD trial at US study sites. At the meeting, the FDA stated that the existing three months of safety data could support 12-week dosing at 5mg and 10mg dose levels and that six months of clinical safety data demonstrating a similar favorable safety pro support 12-month dosing in PIVOT-HD. PTC had a type C written-response-only meeting with FDA for vatiquinone for Friedreich ataxia to determine whether the data from the MOVE-FA study would be sufficient to support an NDA for accelerated approval. In their written response, the FDA stated that while they see the value of upright stability as a clinically meaningful endpoint, they believed a confirmatory study would likely be needed to support NDA submission. PTC has requested a follow-up live meeting to address the issues raised by the FDA. PTC is participating in a scientific advice procedure with the EMA to determine if the MOVE-FA data could support a conditional marketing authorization application in the EEA. PTC expects to have the outcome of this procedure in the first quarter of 2024. PTC had an informal meeting with the FDA for Upstaza for AADC deficiency. The FDA stated that the data PTC has provided to support comparability between the clinical drug product and the intended commercial drug product were still not sufficient. The FDA did say that the available data from the ongoing clinical study in the US assessing the safety of the drug delivery cannula could be used to support a BLA for accelerated approval based on biomarker data demonstrating a treatment-related increase in de novo dopamine production. The FDA suggested that PTC conduct a pre-BLA meeting prior to BLA submission to review BLA contents. This meeting has been scheduled for December 2023, and pending the outcome, PTC expects to submit the BLA shortly thereafter. Third Quarter 2023 Financial Highlights: Total revenues were $196.6 million for the third quarter of 2023, compared to $217.1 million for the third quarter of 2022. Total revenues include net product revenue across the commercial portfolio of $144.0 million for the third quarter of 2023, compared to $134.2 million for the third quarter of 2022. Total revenues also include collaboration, royalty and manufacturing revenue of $52.5 million in the third quarter of 2023, compared to $82.9 million for the third quarter of 2022. Translarna net product revenue was $69.0 million for the third quarter of 2023, compared to $76.6 million for the third quarter of 2022. These results were due to new patients in existing geographies and continued geographic expansion, while the quarter over quarter decrease was due to the timing of bulk government orders. Emflaza net product revenue was $67.4 million for the third quarter of 2023, compared to $54.8 million for the third quarter of 2022. These results reflect new patient starts and high compliance. Roche reported Evrysdi 2023 year-to-date sales of approximately CHF 1,065 million, resulting in royalty revenue of $50.2 million to PTC for the third quarter of 2023, as compared to $32.9 million for the third quarter of 2022. Based on U.S. GAAP (Generally Accepted Accounting Principles), GAAP R&D expenses were $164.2 million for the third quarter of 2023, compared to $165.5 million for the third quarter of 2022. Non-GAAP R&D expenses were $150.2 million for the third quarter of 2023, excluding $14.0 million in non-cash, stock-based compensation expense, compared to $150.4 million for the third quarter of 2022, excluding $15.1 million in non-cash, stock-based compensation expense. GAAP SG&A expenses were $80.9 million for the third quarter of 2023, compared to $80.1 million for the third quarter of 2022. Non-GAAP SG&A expenses were $67.9 million for the third quarter of 2023, excluding $13.0 million in non-cash, stock-based compensation expense, compared to $66.5 million for the third quarter of 2022, excluding $13.6 million in non-cash, stock-based compensation expense. During the third quarter of 2023, PTC incurred additional reductions in workforce as part of the continued strategic portfolio prioritization, which resulted in a one-time charge of approximately $22.6 million recorded to R&D and SG&A expense. The change in the fair value of deferred and contingent consideration was a loss of $1.5 million for the third quarter of 2023, compared to a gain of $5.3 million for the third quarter of 2022. The net loss was $133.0 million for the third quarter of 2023, compared to a net loss of $109.3 million for the third quarter of 2022. Cash, cash equivalents, and marketable securities was $294.8 million on September 30, 2023, compared to $410.7 million at December 31, 2022. Shares issued and outstanding as of September 30, 2023, were 75,459,022. PTC Updates Full Year 2023 Financial Guidance as Follows: PTC anticipates total revenues for full-year 2023 to be between $940 million and $1.0 billion. PTC anticipates net product revenue for the DMD franchise for full-year 2023 to be between $565 million and $595 million. PTC anticipates GAAP R&D and SG&A expenses for full-year 2023 to be between $915 million and $965 million. PTC anticipates Non-GAAP R&D and SG&A expenses for full year 2023 to be between $810 million and $860 million, excluding estimated non-cash stock-based compensation expense of $105 million. PTC expects to incur $37 million of one-time expenses related to the achievement of clinical success-based milestones from previous acquisitions and expenses associated with a rights exchange agreement, which have already been paid in equity and cash. 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: BLA: Biologics License Application CHF: Confoederatio Helvetica Francs (Swiss francs) CHMP: Committee for Medicinal Products for Human Use 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 NDA: New Drug Application PKU: Phenylketonuria R&D: Research and Development SG&A: Selling, General and Administrative SMA: Spinal Muscular Atrophy STRIDE: Strategic Targeting of Registries and International Database of Excellence 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 kokeefe@ptcbio.com Media: Jeanine Clemente +1 (908) 912-9406 jclemente@ptcbio.com 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 Updates Full Year 2023 Revenue Guidance as Follows", including with respect to (i) 2023 total revenue guidance, (ii) 2023 net product revenue guidance for the DMD franchise, (iii) 2023 GAAP and non-GAAP R&D and SG&A expense guidance and (iv) 2023 acquisition related one-time 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; 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 Medicines Agency (EMA) determines in the re-examination process of the Committee for Medicinal Products for Human Use's negative opinion that the benefit-risk balance of Translarna authorization supports renewal of such authorization; PTC's ability to complete Study 041, which is a specific obligation to continued marketing authorization in the EEA; PTC's ability to utilize results from 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, to support a renewal of the conditional marketing authorization for Translarna for the treatment of nmDMD in the EEA and 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. Company Codes: NASDAQ-NMS:PTCT

“全球药物研发进展一周速递”精选本周新药研发领域最新动态，新药研发进展、竞争格局、前沿技术等信息一文速览。药物研发进展1.君圣泰HTD1801治疗2型糖尿病II期研究成功5月15日，君圣泰医药（HighTide Therapeutics, Inc.）宣布其核心产品HTD1801在针对2型糖尿病（T2DM）患者的2期临床试验中达到主要终点以及多个重要次要终点。数据显示，与安慰剂组相比，HTD1801治疗组达到优效且有临床意义的糖化血红蛋白（HbA1c）改善，且安全性和耐受性与安慰剂组相似。公开资料显示，HTD1801是君圣泰的核心产品。在分子机理上，HTD1801具有标本兼治的特点，可以改善多条代谢通路、减少炎症、优化肠道菌群等，其设计理念与现有药物不同，深具创新性。本次公布的是一项随机、双盲、安慰剂对照的2期临床，旨在评估HTD1801针对2型糖尿病患者的疗效和安全性。该研究共招募了113名饮食和运动控制不佳的型糖尿病患者，其中约半数的受试者基线时显示可能患有脂肪肝，与既往流行病学报道数据相当。入组的所有受试者被随机分配至HTD1801低剂量组、HTD1801高剂量组和安慰剂组，并接受12周的治疗。试验数据显示，治疗期结束后，相较安慰剂组，HTD1801组可有效改善受试者的糖代谢，显著降低HbA1c水平和血糖水平。同时，HTD1801治疗可显著改善受试者肝功能相关的生物标记物，且对于肝功能异常受试者，改善作用更加明显。此外，HTD1801对血脂亦有改善效果，并在本试验中显示出良好的安全性和耐受性。2.华东医药小分子GLP-1R激动剂获批临床5月15日，中国国家药监局药品审评中心（CDE）官网公示，华东医药子公司中美华东申报的1类新药HDM1002片获批临床，拟开发治疗成人2型糖尿病。根据华东医药公开资料，HDM1002为该公司研发的小分子GLP-1R激动剂。胰高血糖素样肽-1（GLP-1）是肠道细胞分泌的一种多肽类激素，它通过与GLP-1受体相结合，刺激胰岛素的分泌，并且抑制胰高血糖素的分泌，从而促进葡萄糖的新陈代谢。同时它还能够能延缓胃排空和抑制食欲。因此，GLP-1被认为是治疗肥胖症和2型糖尿病的有力靶点。公开资料显示，目前中国已上市的GLP-1R激动剂均为肽类注射剂，存在长期频繁注射或患者依从性较差等问题。HDM1002是华东医药自主研发的小分子GLP-1R激动剂，本次在中国获批临床的适应症为成人2型糖尿病。根据华东医药官网资料，该产品也已经于2023年4月完成美国IND申请递交。3.阿斯利康三款1类新药在中国获批临床5月15日，中国国家药监局药品审评中心（CDE）官网公示，阿斯利康（AstraZeneca）三款1类新药获得临床试验默示许可，分别是：1）抗体偶联药物（ADC）AZD9592，拟用于单药和与抗癌药物联合用药治疗晚期实体瘤；2）松弛素模拟物AZD3427注射用浓溶液，拟用于治疗心力衰竭合并左心疾病所致肺高血压；3）口服雌激素受体降解剂（SERD）AZD9833片，拟用于中或高复发风险的雌激素受体阳性/人表皮生长因子受体2阴性（ER+/HER2-）早期乳腺癌患者的延长治疗。AZD9592是一款以EGFR-cMET为靶点的创新产品，利用阿斯利康内部专有的ADC技术研发，以拓扑异构酶-1为载药。它可通过靶向癌细胞表面的EGFR和cMET蛋白，并将细胞毒性药物直接递送至癌细胞。这种有针对性的方法旨在最大限度地减少对健康细胞的损害并减少副作用。AZD3427是阿斯利康心血管疾病领域在研管线中的一款松弛素模拟物。松弛素（Relaxin）是一种内源性异二聚胰岛素样肽，在心血管系统中具有有益的生理作用，并且具有较好的安全性。许多临床前和临床研究表明，松弛素可能通过增强内皮介导的血管舒张机制、促进心血管系统中的心脏保护和抗纤维化作用，对心脏和血管产生有益作用。AZD9833（camizestrant）是一款下一代口服雌激素受体降解剂（SERD）。SERD可通过与癌细胞表面的雌激素受体（ER）相结合降低雌激素受体的稳定性，诱导它们被细胞正常的蛋白降解机制降解，降低雌激素受体水平，从而抑制癌细胞的生长。4.FDA拒绝批准新型HER2 ADC SYD985上市5月15日，Byondis宣布收到FDA就SYD985用于治疗HER2阳性乳腺癌的生物制品许可申请（BLA）发出的完整回复函（CRL）。FDA在CRL中表示，需要更多的信息来支持审批决定，这些信息也需要额外的时间来审查。Byondis方对FDA的决定感到遗憾，但是也表示将继续推进SYD985在欧盟和英国的上市。SYD985的上市申请已于2022年7月获欧洲药品管理局（EMA）受理，目前该机构尚未作出审批决定。SYD985的BLA主要是基于关键III期TULIP研究的数据。该试验是一项随机、多中心、开放标签的临床试验（n=436），比较了SYD985与医生选择的方案（physician’s choice, PC）治疗不可切除的HER2+局部晚期或转移性乳腺癌患者的疗效。研究的主要终点为无进展生存期（PFS）。Byondis在ESMO 2021大会上公布了TULIP3研究的初步结果。结果显示，相比于PC组，SYD985组患者的PFS显著延长（7.0 vs 4.9个月；HR=0.64；P=0.002）。此外，SYD985组患者的总生存期（OS）呈改善趋势，HR为0.83（P=0.153）。SYD985（trastuzumab duocarmazine）是Byondis利用其专有的基于duocarmazine的linker-drug技术平台ByonZine®开发的新一代HER2 ADC，由曲妥珠单抗和可切割的linker-drug缬氨酸-瓜氨酸-seco-DUocarmycin-hydroxyBenzamide-Azaindole（vc-seco-DUBA）组成。SYD985与癌细胞表面的HER2结合后被细胞内化，随后linker在蛋白酶的作用下断裂，释放出细胞毒素药物seco-DUBA，诱导DNA损伤，最终导致肿瘤细胞死亡。5.中生康元个性化肿瘤DC疫苗IND获批5月15日，据CDE官网公示，中生康元生物科技（北京）有限公司的个性化树突状细胞注射液获得临床试验默示许可，拟用于治疗恶性实体肿瘤。个性化树突状细胞注射液（ZSNeo-DC1.1注射液）是一款负载多个肿瘤新生抗原多肽的治疗性肿瘤DC疫苗产品，通过体外诱导分化培养的患者自体树突状细胞（DC细胞），自然吞噬和递呈由体外化学合成得到肿瘤新生抗原多肽，制备成高纯度活DC细胞制剂，经局部皮下注射到肿瘤患者体内，活化和扩增肿瘤抗原特异性T淋巴细胞，激活全身抗肿瘤免疫反应。DC细胞是抗肿瘤免疫应答的核心和基础，也是理想的治疗性肿瘤疫苗的抗原递送载体。DC疫苗制备简单，功能强大，和其他治疗性肿瘤疫苗相比，DC疫苗具有以下几方面的优势：第一，对肿瘤细胞的清除精准高效，能够有效修复、恢复和增强患者自身细胞免疫功能，打破肿瘤患者体内免疫耐受状态，实现免疫重建；第二，能持续动员体内各种细胞因子参与清除肿瘤细胞，在清除肿瘤细胞的同时极大降低对正常细胞的损伤，具有极高安全性；第三，回输的DC细胞可以激活静息T细胞产生初次免疫应答细胞（一个DC细胞能激活100～3000个T细胞），少部分成为能长期存活的记忆性T细胞，下一次接触到同类型肿瘤细胞后可以立刻启动高强度免疫应答。因此肿瘤新抗原DC疫苗重建的免疫防护系统可以持续发挥作用数十年，实现治疗和预防的有机结合。6.西安新通乙肝新药甲磺酸帕拉德福韦片申报上市5月16日，CDE官网显示，西安葛蓝新通制药的甲磺酸帕拉德福韦片上市申请已被药监局受理。甲磺酸帕拉德福韦片是一款采用HepDirectTM前药技术开发的阿德福韦（PMEA）的前药。该药提高了抗病毒效率，抗耐药性也更强，同时还解决了阿德福韦酯肾毒性大的问题。新通药物的甲磺酸帕拉德福韦片是新通药物子公司凯华公司于2011年1月从LGND授权引进而来。随后该公司完成了甲磺酸帕拉德福韦片临床前研究，发现了最佳给药剂量并选择一线对照药物开展了I/II/III期临床试验。此前II期临床研究显示，接受帕拉德福韦组患者的HBV DNA下降量、HBeAg血清水平等指标非劣效于替诺福韦。2020年9月，西安新通在国内启动了一项甲磺酸帕拉德福韦片治疗慢性乙型肝炎的随机、双盲、阳性药平行对照、多中心的III期临床试验。该研究主要疗效指标：与富马酸替诺福韦二吡呋酯片相比，接受甲磺酸帕拉德福韦片治疗48周后血清HBV DNA(PCR法)＜29IU/ml的受试者百分比；安全性指标：48周后，甲磺酸帕拉德福韦组较富马酸替诺福韦二吡呋酯组的安全性数据。7.阿斯利康RSV单抗Nirsevimab拟纳入优先审评5月16日，CDE官网显示，阿斯利康的Nirsevimab注射液拟纳入优先审评，适用于预防以下婴幼儿呼吸道合胞病毒（RSV）引起的下呼吸道感染：即将进入或在第一个RSV感染季期间出生的新生儿和婴儿。5月12日，该产品上市申请已获药监局受理。2022年11月4日，nirsevimab在欧盟迎来全球首批，商品名为Beyfortus，用于新生儿和婴儿，帮助他们在首个呼吸道合胞病毒（RSV）流行季到来时预防RSV下呼吸道感染疾病。这是首个且唯一、可广泛应用于婴儿人群的单剂次被动免疫制剂，包括足月或早产的健康婴儿，或健康状况特殊的婴儿。多项研究证明了Beyfortus的疗效和安全性，包括III期MELODY、II/III期MEDLEY和一项IIb期临床研究。RSV是引起婴儿下呼吸道感染最常见的病原，包括毛细支气管炎和肺炎。RSV也是导致全球婴儿住院的首要致病因素，且大多数住院发生在健康足月婴儿中。目前国内尚无治疗或预防RSV的药物，艾棣维欣的RSV疫苗ADV110已进展至II期临床，优锐医药从Bavarian Nordic引进的MVA-BN RSV疫苗已在国内获批临床，而爱科百发、歌礼制药、联拓生物等公司则专注于开发RSV治疗性药物。今年3月，GSK已在中国递交RSV疫苗GSK3844766A的临床试验申请，该款疫苗已于5月3日获FDA批准上市。5月8日，苏州旺山旺水生物医药口服核苷类抗病毒药物氢溴酸氘瑞米德韦干混悬剂（VV116）获CDE批准临床，拟用于治疗呼吸道合胞病毒（RSV）感染。8.恒瑞旗下两款1类新药在国内获批临床5月16日，恒瑞医药发布公告，旗下两款新药SHR0302口服溶液以及SHR-2017注射液已获批临床。SHR0302是一种高选择性的JAK1抑制剂，可通过抑制JAK1信号传导发挥抗炎和抑制免疫的生物学效应，拟用于移植物抗宿主病的治疗。本品作为口服溶液剂，具有分散度大、吸收快，且有很好的患者顺应性。目前，针对该适应症的JAK抑制剂，国内仅有芦可替尼片于2023年3月获国家药监局批准上市，用于对糖皮质激素或其他系统治疗应答不充分的12岁及以上急性移植物抗宿主病患者的治疗。2022年芦可替尼片全球销售额约为39.7亿美元。截至目前，SHR0302相关研发项目累计已投入研发费用约为72933万元。SHR-2017注射液是由恒瑞自主研发的双特异性抗体产品，拟用于治疗实体肿瘤骨转移患者和多发性骨髓瘤患者中骨相关事件的预防。目前，暂无同靶点双抗产品获批上市。截至目前，SHR-2017注射液相关项目累计已投入研发费用约为1592万元。9.阿斯利康CD3/CLDN 18.2双抗AZD5863申报临床5月16日，CDE网站显示，阿斯利康的CD3/CLDN 18.2双抗AZD5863在国内申报临床。该产品为第5款在中国申报临床的CD3/CLDN 18.2双抗。AZD5863（原研发代号：HBM7022）是和铂医药利用其专有的HBICE（基于HCAb的免疫细胞衔接器）技术平台开发的一款全人源双特异性抗体，其采用了二价高亲和力抗CLDN 18.2和单价低亲和力抗CD3的结构，在保证高杀伤活性的同时，降低了产生细胞因子风暴的风险。2022年4月，阿斯利康与和铂医药达成协议，以3.5亿美元的总交易额获得AZD5863的全球独家权益。临床前研究显示，AZD5863不但对CLDN 18.2阳性的胃癌有显著效用，还对胰腺癌和CLDN 18.2突变的胃癌有很好的效用。目前，全球共11款在研CD3/CLDN 18.2双抗，其中4款已进入临床阶段，分别为AMG 910（安进/百济神州）、ASP2138（安斯泰来/Xencor）、IBI389（信达生物）和QLS31905（齐鲁制药）。10.先声药业/凌科药业JAK1抑制剂II期研究结果积极5月16日，先声药业与凌科药业共同宣布，JAK1抑制剂LNK01001治疗类风湿关节炎的II期临床试验取得了积极结果。本次获得突破性进展的临床试验是一项随机、双盲、安慰剂对照、多中心的II期临床研究，由曾小峰教授领衔完成。研究结果显示，治疗12周后，LNK01001高低两个剂量组的患者病情显著改善，疗效皆超过所有预定的主要终点及关键次要终点，相对安慰剂都显示了有统计学意义的疗效差异。治疗24周后，高低剂量组的ACR20达标比例均超过90%。此外，研究药物整体安全性和耐受性良好，绝大部分治疗期出现的不良事件严重程度较轻，试验药物组均未发生严重不良事件。类风湿关节炎是一种常见的慢性、高致残性自身免疫疾病，病情多反复且逐渐加重，其发病机制目前尚不明确，基本病理表现为滑膜炎、血管翳形成，并逐渐出现关节软骨和骨破坏，最终造成关节畸形和功能丧失，导致患者残疾、丧失劳动力，且可并发肺部疾病、心血管疾病、恶性肿瘤及抑郁症等，给患者、家庭及社会带来沉重负担。目前类风湿关节炎仍无法根治，临床治疗目标主要为控制疾病症状、减缓疾病进展、降低病残率、改善预后、提高患者生活质量。JAK1是胞内非受体酪氨酸激酶家族JAKs中一种重要亚型，与多种自身免疫疾病发病密切相关。LNK01001是一款高选择性JAK1抑制剂，对其它的JAK亚型，特别是JAK2的抑制性较弱，临床前数据结果显示，与已上市JAK抑制剂相比，LNK01001具有更高选择性和潜在更佳安全性，有望为患者提供更安全有效的新型治疗方案。11. Viking NASH新药VK2809 IIb期研究成功5月16日，Viking宣布肝靶向性甲状腺激素受体β（THR-β）激动剂VK2809治疗非酒精性脂肪肝炎（NASH）的IIb期Voyage研究达到主要终点。Voyage是一项全球性、多中心、随机、双盲、安慰剂对照的临床试验，旨在评估VK2809在经活检确认的伴肝纤维化NASH患者中的有效性、安全性和耐受性。入组患者必须满足通过磁共振成像-质子密度脂肪分数（MRI-PDFF）测量的肝脏脂肪含量≥8%、NASH活动度评分（NAS）≥4且肝纤维化1-3级（F1~F3）的条件。最多25%的入组患者伴有1级肝纤维化，并且这些患者至少有患糖尿病、肥胖或高血压等疾病之一的风险。研究的主要终点为第12周患者肝脏脂肪含量的变化，次要终点为第52周肝活检的组织学情况和肝纤维化无恶化的患者比例。结果显示，与安慰剂组相比，VK2809（1~10mg）组患者的中位肝脏脂肪含量具有统计学意义的降低（-37.5%~-55.1% vs -5.4%），2.5~10mg组平均肝脏脂肪含量也具有统计学意义的降低（-36.8%~-51.7% vs -3.7%）。重要的是，VK2809组肝脏脂肪含量至少降低30%的患者比例最高达84.9%。此外，与安慰剂组相比，VK2809组患者的低密度脂蛋白胆固醇（LDL-C）、甘油三酯和致动脉粥样硬化的脂蛋白水平亦显著降低。安全性方面，VK2809组报告的治疗相关不良事件（TRAE）的严重程度大多（94%）为轻度或中度。12.博锐生物泽贝妥单抗注射液在国内获批上市5 月 17 日，NMPA 发布公告批准浙江博锐生物制药有限公司申报的泽贝妥单抗注射液（商品名：安瑞昔）上市。该药品适用于CD20 阳性弥漫大 B 细胞淋巴瘤，非特指性（DLBCL，NOS）成人患者，应与标准 CHOP 化疗（环磷酰胺、阿霉素、长春新碱、泼尼松）联合治疗。泽贝妥单抗注射液为针对 B 细胞表面 CD20 抗原的人-鼠嵌合型单克隆抗体，可特异性结合 B 细胞表面的 CD20 抗原，从而启动 B 细胞溶解的免疫反应，发挥抗肿瘤作用。DLBCL 是起源于 B 淋巴细胞的一类存在较大异质性的恶性肿瘤，呈弥漫性生长，肿瘤细胞的核与正常组织细胞的核大小相近或大于组织细胞的核，通常大于正常淋巴细胞的 2 倍。DLBCL 是全球最常见的成人非霍奇金淋巴瘤（NHL），占所有地域 NHL 的 30％~40％。在中国，DLBCL 占所有 NHL 的40.8％。与美罗华相比，泽贝妥单抗具有不同的氨基酸序列和不同的结合表位。在体外生物学活性研究中表现出更强的 ADCC 活性；在人体药代动力学研究中表现出更大的稳态分布容积和较低的血清药物暴露水平；在人体药效动力学研究中具有对 B 细胞更持久的清除作用和对 CD3+/CD8+T 细胞更持久的激活作用。在 III 期确证性临床研究中，泽贝妥单抗注射液联合 CHOP 治疗弥漫大 B 细胞淋巴瘤初治患者在 ORR 上非劣于 R-CHOP，且在治疗结束时 CR 率显著更高；在长期生存获益上，泽贝妥单抗注射液组的 1 年 PFS 和 OS 呈现出显著优于美罗华组的趋势；治疗生发中心 B 细胞样和骨髓未受累两个亚型人群中，泽贝妥单抗注射液组的 CR 率均显著更高，1 年 PFS 和 OS 同样有显著优于美罗华组的趋势。13.南京圣和药业创新药奥磷布韦获批上市，用于治疗丙肝5月17日，药监局官网显示，南京圣和药业申报的1类创新药奥磷布韦片（商品名：圣诺迪）已通过优先审评审批程序获批上市。这是首个上市的国产的丙肝全基因口服治愈的药物。该药为我国自主研发并拥有自主知识产权的创新药，适用于与盐酸达拉他韦联用，治疗初治或干扰素经治的基因1、2、3、6型成人慢性丙型肝炎病毒（HCV）感染，可合并或不合并代偿性肝硬化。奥磷布韦是HCV NS5B RNA依赖性RNA聚合酶（为病毒复制所必需）抑制剂，是一种核苷酸前体药物，在细胞内代谢为具有药理活性的代谢产物（SH229M3），可被NS5B聚合酶嵌入HCV RNA中而终止复制。该药品的上市为成人慢性丙型肝炎病毒患者提供了新的治疗选择。作为一款核苷类前体药物，奥磷布韦可通过肝脏代谢，转化为具有抗病毒活性的非天然核苷三磷酸。该非天然核苷三磷酸可以与丙肝病毒复制所需的NS5B聚合酶发生竞争性结合，“假扮”成病毒复制时需要的天然核苷三磷酸掺入到HCV RNA链中，形成错误的病毒RNA模板，导致病毒RNA链的延长提前终止，丙肝病毒的复制也因此被终止。一项多中心III期临床研究，旨在确证奥磷布韦片联合盐酸达拉他韦片的疗效和安全性，研究期间未发生受试者死亡事件，仅发生1例导致受试者提前退出的不良事件。在治疗后出现的不良事件（TEAE）中，绝大多数为轻度或中度，仅有14例（4.3%）受试者发生了3级及以上的实验室检查异常，包括甘油三酯升高、血肌酸磷酸激酶升高、血钙降低、血钾降低、血小板计数降低。试验中未出现任何3级及以上的肝功能（ALT、AST、胆红素）异常情况。该研究结果表明，奥磷布韦联合盐酸达拉他韦的治疗方案具有较好的安全性。14.兴齐眼药硫酸阿托品滴眼液拟纳入优先审评5月17日，CDE官网显示，兴齐眼药硫酸阿托品滴眼液（SQ-729）的上市申请被拟纳入优先审评，适应症为用于延缓儿童近视进展。硫酸阿托品滴眼液是以硫酸阿托品为活性成分的眼用制剂，本品为改良型新药，属于化学药品2.4 类含有已知活性成份的新适应症的药品。此前，2016年6月，兴齐眼药与新加坡国立眼科中心（SNEC）签署合作协议，在SNEC国内独家授权的硫酸阿托品滴眼液处方及5年临床试验数据的基础上，开展了硫酸阿托品滴眼液III期临床试验。该研究是一项多中心、随机、双盲、安慰剂对照的III期临床试验，共纳入406例6-12岁儿童受试者，经过了为期1年的用药观察，停药后0.5年的随访观察，评估硫酸阿托品滴眼液延缓儿童近视进展的有效性和安全性。研究结果显示，相比安慰剂组，硫酸阿托品滴眼液组在主要疗效指标上有统计学意义的显著性差异。此外，硫酸阿托品滴眼液安全性良好，患者使用依从性好。近视是儿童最常见的眼病。2021年7月，国家卫生健康委发布，2020年我国儿童青少年总体近视率为52.7%。其中6岁儿童为14.3%，小学生为35.6%，初中生为71.1%，高中生为80.5%。截至目前，国内尚无延缓儿童近视进展的低浓度硫酸阿托品滴眼液获批上市。15.罗氏BTK抑制剂II期研究成功，治疗多发性硬化症5月17日，罗氏宣布其三代BTK抑制剂fenebrutinib治疗复发性多发性硬化症（RMS）的II期FENopta研究取得了积极结果。FENopta研究是一项全球性、随机、双盲、安慰剂对照的临床试验，共纳入109例18-55岁RMS患者，旨在评估fenebrutinib的有效性、安全性和药代动力学。研究的主要终点为第12周通过脑部磁共振（MRI）扫描发现的钆造影剂增强的新发T1病灶数量，次要终点包括第4/8/12周通过脑部磁共振（MRI）扫描发现的新发或扩大T2病灶数量、第4/8/12周有新发T1病灶或新发或扩大T2病灶的患者比例等。T1病灶是活动性炎症的标志物，T2病灶代表疾病负担或病变负荷量。结果显示，与安慰剂组相比，fenebrutinib组患者的新发T1病灶数量显著减少（P=0.0022），新发或扩大T2病灶数量亦显著减少。此外，与安慰剂组相比，fenebrutinib组有新发T1病灶或新发或扩大T2病灶的患者比例更低。多发性硬化症（MS）是一种慢性疾病，影响全球超过2万人。当免疫系统异常攻击中枢神经系统（脑、脊髓和视神经）中的神经细胞（髓鞘）周围的绝缘层和支撑时，就会导致MS，从而导致炎症和随之而来的损伤。这种损伤会导致一系列症状，包括肌肉无力、疲劳和视力困难，并最终可能导致残疾。BTK是一种调节B细胞发育和活化的酶，也参与先天免疫系统髓系细胞（如巨噬细胞和小胶质细胞）的激活。fenebrutinib是一种口服、可逆、非共价BTK抑制剂，可阻断BTK的功能。临床前数据显示，fenebrutinib具有强活性和高度选择性，其对BTK的选择性是其他激酶的130倍。16. 阿斯利康宣布三代EGFR抑制剂奥希替尼联合化疗III期研究成功5月17日，阿斯利康宣布三代EGFR抑制剂奥希替尼联合化疗治疗携带EGFR突变的非小细胞肺癌（NSCLC）的III期Flaura2研究取得了积极结果。Flaura2研究是一项全球性、多中心、随机、开放标签的临床试验，共纳入586例患者，旨在评估奥希替尼联合或不联合化疗（培美曲塞+顺铂/卡铂）一线治疗携带EGFR突变的局部晚期（IIIB-III期）或转移性（IV期）NSCLC患者的有效性和安全性。研究的主要终点为无进展生存期（PFS）。高水平积极结果显示，与奥希替尼单药组相比，奥希替尼联合化疗组患者的PFS具有统计学意义和临床意义的延长。在进行此次分析时，总生存期（OS）数据尚不成熟，将在随后的分析中正式评估。安全性数据和不良事件导致的停药率与每种药物的既往研究数据一致。阿斯利康肿瘤学研发执行副总裁Susan Galbraith表示：“这些重要的FLAURA2结果表明，奥希替尼有可能为患者提供一种新的一线治疗选择，以帮助延长他们的生存时间且疾病无进展。这次有意义的结果是建立在一系列临床试验的基础上的，既往多项研究已经证明奥希替尼可以改善EGFR突变肺癌患者的临床获益。”17.强生眼科基因疗法国内申报临床5月17日，强生用于治疗眼科疾病基因疗法JNJ-81201887在国内的临床申请获国家药监局受理。年龄相关性黄斑变性（AMD）患者通常CD59水平较低，CD59是一种保护视网膜免受人体自然免疫反应“补体”系统造成损伤的蛋白质。地图样萎缩是AMD的一种晚期进行性病变形式，在地图样萎缩症中，补体的过度活跃破坏了视网膜的中心区域黄斑（负责中央视觉和看到细节）细胞，并导致失明的持续发展。JNJ-81201887（AAVCAGsCD59） 是杨森从Hemera Biosciences引进的一款AAV基因治疗管线，主要被开发用于治疗继发于干性年龄相关性黄斑变性 （AMD） 的地理萎缩 （GA）。JNJ-1887旨在增加可溶性CD59（sCD59）的表达，保护视网膜细胞，从而减缓和预防疾病进展。JNJ-81201887使用AAV作为载体，携带可溶性CD59基因（sCD59），通过玻璃体腔注射的给药形式，将其递送至视网膜细胞，使得视网膜细胞能够表达可溶性CD59。在GA，补体的高活性会破坏黄斑处的细胞从而发展为失明，CD59能够保护视网膜免受补体的伤害。JNJ-81201887用于治疗60岁及以上晚期干性AMD地图样萎缩成人的IIb期PARASOL研究正在招募患者。JNJ-1887已获得美国FDA的快速通道指定和欧洲药品管理局（EMA）的先进治疗药物（ATMP）指定。18.恒瑞PD-1组合疗法在美申报上市，一线治疗肝癌5月17日，恒瑞医药合作伙伴Elevar Therapeutics宣布，已向FDA递交卡瑞利珠单抗（PD-1单抗）联合甲磺酸阿帕替尼片（VEGFR2抑制剂）一线治疗不可切除肝细胞癌（uHCC）患者的新药申请（NDA）。此次上市申请主要是基于一项在13个国家/地区的95个研究中心进行的国际多中心III期CARES 310研究（NCT03764293）的积极结果。该研究共纳入543例患者，已于2022年5月达到主要终点：与索拉非尼相比，卡瑞利珠单抗+阿帕替尼治疗后能够显著延长晚期肝细胞癌患者的无进展生存期（PFS）以及总生存期（OS）。具体结果如下：卡瑞利珠单抗+阿帕替尼 vs. 索拉非尼的中位总生存期分别为22.1、15.2个月，HR为0.62[95% CI 0.49-0.80]，单侧p值<0.0001。此外，卡瑞利珠单抗+阿帕替尼 vs. 索拉非尼的中位无进展生存期为5.6个月 vs. 3.7个月，HR为0.52[95% CI 0.41-0.65]，单侧p值<0.0001。卡瑞利珠单抗+阿帕替尼组经确认的客观缓解率（ORR）为25.4%，而索拉非尼为5.9%。今年1月底，该组合疗法已获国家药监局批准一线治疗既往未接受过系统治疗的不可切除或转移性肝细胞癌患者，成为国内首个获批用于治疗晚期肝细胞癌的PD-1抑制剂与小分子抗血管生成药物的组合，为晚期肝癌患者带来了用药新选择。MD安德森癌症中心Ahmed Omar Kaseb教授说：“卡瑞利珠单抗+阿帕替尼联合疗法作为晚期肝细胞癌潜在疗法已展现出确切的前景，我对本次NDA深受鼓舞，期待FDA尽快完成审查。”19.拜耳创新疗法非奈利酮在中国获批拓展适应症5月17日，拜耳（Bayer）宣布，中国国家药品监督管理局（NMPA）批准非奈利酮（finerenone，英文商品名为Kerendia）的拓展适应症，以纳入3期FIGARO-DKD研究的心血管获益结果。该研究表明，非奈利酮降低了1-4期与2型糖尿病（T2D）相关慢性肾病（CKD）患者的心血管事件风险。此次批准也使得非奈利酮在中国的适应症扩展至与2型糖尿病相关的慢性肾脏病的早期阶段。非奈利酮是一种非甾体选择性盐皮质激素受体拮抗剂，在临床前研究中显示可阻断盐皮质激素受体过度激活造成的有害影响。在糖尿病患者中，盐皮质激素受体过度激活被认为会通过靶器官的炎症和纤维化，导致慢性肾病进展和心血管受损。在中国，非奈利酮于2022年6月获得NMPA首次批准，用于与2型糖尿病相关的慢性肾脏病成人患者（肾小球滤过率估计值[eGFR]≥25至<75mL/min/1.73㎡，伴白蛋白尿），可降低eGFR持续下降、终末期肾病的风险。根据拜耳公开资料，非奈利酮用于治疗与2型糖尿病相关的慢性肾脏病患者的3期临床项目纳入了全球13000多名患者，该项目包括两个研究FIDELIO-DKD和FIGARO-DKD，旨在评价在接受标准治疗基础上，非奈利酮与安慰剂相比在肾脏和心血管方面的获益。20.卫材抗癫痫新药吡仑帕奈口服混悬液在中国获批5月17日，中国国家药监局（NMPA）官网公示，卫材（Eisai）抗癫痫新药吡仑帕奈口服混悬液已获得批准。根据中国国家药监局药品审评中心（CDE）优先审评公示，该产品本次获批适应症为：成人和4岁及以上儿童癫痫部分性发作（伴有或不伴有继发全面性发作）的治疗。癫痫是最为常见的神经疾病之一，极度影响了患者正常生活。其中，部分发作性癫痫患者占到了60%。癫痫的发作与大脑有关——大脑中充满了电信号，但当大脑内突然出现强烈的电信号爆发，就会影响大脑正常的功能，诱发癫痫发作。卫材研发的吡仑帕奈（perampanel，商品名：卫克泰）是一款选择性、非竞争性的AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）受体拮抗剂，它通过靶向抑制突触后膜上AMPA受体的谷氨酸活性，从而降低与癫痫发作相关的神经元的过度兴奋。2020年1月，吡仑帕奈片在中国上市，用于加用治疗12岁及以上癫痫患者的部分性癫痫发作（伴或不伴继发性全面性癫痫发作）。2021年7月，吡仑帕奈片在中国获批新适应症，用于成人和4岁及以上儿童癫痫部分性发作（伴有或不伴有继发全面性发作）的治疗。此次在中国获批上市的为吡仑帕奈的口服混悬液。据卫材早前发布的新闻稿介绍，该产品适合吞咽障碍和儿科患者。此前，在一项全球开放性3期临床研究（研究311）中 ，研究人员已在4~12岁以下部分性癫痫发作或原发性全身强直阵挛性癫痫发作（PGTCS）控制不佳的儿童癫痫患者中，评估了吡仑帕奈口服混悬液作为辅助治疗药物的安全性、耐受性和暴露疗效关系。试验结果显示，该产品的疗效与对12岁及以上患者观察到的相似，研究中观察到的最常见的不良事件与该产品的安全特性一致。21.奥拉帕利国内首仿来了！齐鲁制药拔得头筹5 月 17 日，NMPA 发布批件，齐鲁制药的 4 类仿制药奥拉帕利获批上市，成为国产首仿。奥拉帕利由阿斯利康研发，是全球首款获批上市的 PARP 抑制剂。2014 年，奥拉帕利首次获 FDA 批准上市，用于 BRCA 突变的晚期卵巢癌患者。此后，其适应症不断拓展，在 2017 年获批卵巢癌维持治疗；2018 年进入乳腺癌领域，获批用于 BRCA 突变转移性乳腺癌；2020 年 5 月同月内获批两项适应症，包括一项贝伐珠单抗联合疗法，以及去势抵抗性前列腺癌适应症；22 年 3 月又拓展至乳腺癌辅助治疗。在中国，奥拉帕利最初于 2018 年 8 月获批上市，目前已经获批多个适应症，包括铂敏感的复发性卵巢癌、输卵管癌或原发性腹膜癌的维持治疗、BRCA 突变的晚期卵巢癌、输卵管癌或原发性腹膜癌的一线维持治疗、BRCA 突变且在既往新型激素药物治疗后出现疾病进展的转移性去势抵抗性前列腺癌单药治疗、同源重组修复缺陷（HRD）阳性的晚期上皮性卵巢癌、输卵管癌或原发性腹膜癌维持治疗。奥拉帕利是当之无愧的重磅炸弹药物，获批以来，其销售额持续猛增，同类产品的陆续上市也未能撼动其王者之势。据企业年报显示，其 2022 年全球销售额已达 26.38 亿美元，同比增长 12.35%。22.PTC苯丙酮尿症新药3期研究成功5月17日，PTC Therapeutics宣布，其苯丙酮尿症（PKU）治疗药物sepapterin在成人和儿童患者的3期APHENITY试验中达到了主要终点。PKU是一种可导致苯丙氨酸毒性积聚的罕见疾病，患者因为遗传性代谢问题通常无法自行分解肉和蛋等食物中的苯丙氨酸，随着苯丙氨酸的累积最终导致记忆和神经问题。在美国，大约每2.5万人中就有1人患有这种疾病。2020年，PTC收购了Censa Pharmaceuticals，因此获得后者开发的CNSA-001，也就是现在的sepapterin。sepapterin是四氢生物蝶呤（BH4）天然前体的口服生物可利用形式，与BH4相比，该药在PKU患者中展现出更强的降低苯丙氨酸的能力。APHENITY试验共纳入了156例PKU儿童和成人患者，旨在评估sepapterin对照安慰剂用于降低血液中苯丙氨酸水平的疗效。根据新闻稿，接受sepapterin治疗的患者记录到苯丙氨酸平均减少了63%，相比之下，接受安慰剂治疗的患者减少幅度不明显。此外，该治疗在试验中没有严重的安全问题，最常见的不良事件是头痛和腹泻。PTC的首席执行官Matthew B. Klein在电话会议上表示，这些数据令人鼓舞，公司将尽快与监管机构进行沟通，并在美国和欧洲提交新药上市申请。23.百泰生物尼妥珠单抗新适应症申报上市5月18日，CDE网站显示，百泰生物的EGFR单抗尼妥珠单抗在国内申报新适应症。根据已公开的临床进展，推测此次申报的适应症为联合放化疗治疗不可切除局部晚期头颈癌。尼妥珠单抗是百泰生物开发的一种靶向EGFR的人源化比例达到95%的单克隆体，是我国第一款人源化单克隆抗体药物。2008年1月，尼妥珠单抗在国内获批上市，用于联合放疗治疗EGFR表达阳性的III/IV期鼻咽癌。目前，尼妥珠单抗已在多个国家获批联合放化疗治疗局部晚期食管癌和头颈癌。食管癌III期NEXCELL1311研究的主要终点为总生存（OS），次要终点为无进展生存（PFS）、客观缓解率（ORR）、疾病控制率（DCR）和生活质量（QoL）。中期分析结果显示尼妥珠单抗联合放化疗较单纯放化疗治疗局晚期不可切除食管鳞癌，试验组和对照组完全缓解率（CRR）分别为32.5% vs 12.2%，P=0.002，完全缓解率提高了20.3%；两组的ORR分别为93.8% vs 72%，P＜0.001，提高了21.8%；DCR也有提高趋势，分别为98.8% vs 91.5%，P=0.064。由于PFS、OS事件数不足以进行统计分析，研究者尚未确认ORR、DCR等短期疗效的改善能否转化为长期生存获益，该研究仍在进一步随访观察中，随访将于2025年8月结束。中国食管癌发病数和死亡数在2015-2020年一直呈上升趋势，疾病负担重。与欧美国家不同，中国食管癌约90%为鳞癌，70%患者就诊时已处于中晚期，失去手术机会，在进一步优化疗效的探索中，无论是提高放疗剂量还是放化疗前加入诱导化疗均未显示获益。因此需要寻找新的有效联合治疗策略。24.华东医药申报长效 GLP-1R/GCGR/FGF21R 三靶点降糖药5 月 18 日，CDE 官网显示，华东医药控股子公司道尔生物注射用 DR10624首次在国内申报临床并获得受理。此前在 22 年 4 月其 IND 申请在新西兰获批，并在同年 6 月启动了 I 期临床试验。DR10624 为全球首创（first-in-class）的一种靶向 GLP-1 受体（GLP-1R）、GCG 受体（GCGR）和 FGFR1c/Klothoβ（FGF21R）的长效三靶点激动剂，拟用于治疗 2 型糖尿病、肥胖、代谢综合征等。这是同类药物中全球首款进入临床开发的品种。随着人口老龄化、城市进程的加快，糖尿病患病数的不断上升，糖尿病领域仍存在较大未被满足的临床需求，糖尿病治疗用药长期具备广阔的发展空间。中国的糖尿病患者数位居世界第一，2019 年中国有 1.16 亿成年人糖尿病患者，预计 2030 年将增至 1.40 亿人。因此，DR10624 不仅有望满足临床治疗需求，也存在巨大的潜在市场空间。华东医药深耕糖尿病领域，在内分泌领域以 GLP-1 靶点为核心，打造了领先的肥胖、糖尿病和糖尿病并发症创新药物研发平台，并建立了涵盖口服、注射剂等多种剂型的长效和多靶点全球创新药和生物类似药相结合的 GLP-1 及相关靶点产品管线。25.干眼新药获FDA批准上市，恒瑞医药拥有中国权益5月18日，博士伦（Bausch + Lomb）公司和Novaliq公司宣布，美国FDA已批准全氟己基辛烷滴眼液（此前称NOV03）上市，用于治疗干眼的体征和症状，这是一种直接针对泪液蒸发的干眼创新疗法。公开资料显示，恒瑞医药拥有该药在中国的独家权利，并已经在中国递交该药的上市申请。干眼（DED）是常见的眼表疾病，通常与睑板腺功能障碍（MGD）相关。据估计，86%的干眼患者泪液蒸发过度，其中MGD是主要原因。睑板腺是泪膜脂质层的唯一天然来源，其功能障碍可导致睑脂异常最终出现泪液过度蒸发。目前临床治疗方法如物理疗法和人工泪液等因存在局限性，未能达到满意的治疗效果。公开资料，本次获批的全氟己基辛烷滴眼液（商品名：MIEBO）是一种无色、透明的滴眼液，由100%全氟己基辛烷组成，能迅速扩散至整个眼表，并与泪膜的亲脂部分相互作用，覆盖在泪膜水液层表面，稳定泪膜、防止泪液过度蒸发。此外，该滴眼液可穿透睑板腺，与腺体相互作用并溶解腺体中的粘性分泌物，从而达到治疗睑板腺功能障碍相关蒸发过强型干眼的作用。根据博士伦公司新闻稿介绍，本次FDA批准MIEBO是基于两项为期57天、多中心、随机、双盲、盐水对照的关键3期GOBI和MOJAVE研究的结果，在两项3期关键研究中，MIEBO达到了主要体征和症状疗效终点，即第8周（第57±2天）总角膜荧光素染色（tCFS）和眼干的严重程度评分（VAS）与基线相比的变化。患者早在第15天和第57天出现症状缓解，两项研究中观察到的VAS眼干评分均有统计学显著降低；此外，在第15天和第57天，两项研究均观察到有利于MIEBO的tCFS显著减少。26.艾伯维JAK抑制剂乌帕替尼获FDA批准治疗克罗恩病5月18日，FDA宣布批准Rinvoq（乌帕替尼，45mg[诱导剂量]，15mg和30mg[维持剂量]）用于治疗中度至重度活动性克罗恩病（CD）成人患者，这些患者对一种或多种肿瘤坏死因子阻滞剂反应不足或不耐受。此前，乌帕替尼已于今年4月获欧盟委员会批准该适应症，该药物也是全球首个获批治疗中重度CD的口服产品。克罗恩病是一种慢性全身性疾病，临床表现为胃肠道炎症，发作时会引起持续性腹泻和腹痛。它是一种进行性疾病，会随着时间的推移而恶化，也可能会出现需要紧急医疗护理（包括手术）的并发症。FDA的批准得到了两项诱导治疗研究（U-EXCEED和U-EXCEL）和一项维持治疗研究（U-ENDURE）的数据支持。乌帕替尼在诱导治疗和维持治疗研究中的共同主要终点和关键次要终点相较于安慰剂均具有统计学意义。这3项III期研究是多中心、随机、双盲、安慰剂对照研究，旨在评估乌帕替尼诱导治疗（45mg，每日1次）和维持治疗（15mg/30mg，每日1次）中重度活动性克罗恩病成人患者的疗效和安全性。这3项研究均达到了临床缓解（clinical remission）和内镜应答（endoscopic response)的共同主要终点。其中，临床缓解通过克罗恩病活动指数（CDAI）或患者报告的大便频率/腹痛症状（SF/AP）来衡量。27.Satsuma鼻用偏头痛新药上市申请获FDA受理5月18日，Satsuma Pharmaceuticals宣布，其偏头痛新药STS101的新药上市申请已获FDA受理，预计PDUFA日期为2024年1月。该申请主要基于STS101的I期药代动力学（2021年6月完成）和III期ASCEND试验数据。ASCEND是一项开放标签、多中心的III期长期安全性试验，旨在评估STS101在6个月和12个月内急性治疗偏头痛发作的安全性和耐受性，以及长期治疗的有效性。研究共纳入482名受试者，其中466名受试者接受了至少1剂STS101治疗。结果显示，STS101表现出良好的安全性、耐受性和有效性，未报告治疗相关的严重不良事件。长期以来，抗偏头痛药物甲磺酸二氢麦角胺（DHE）一直是指南推荐急性偏头痛的一线治疗选择。STS101是DHE的一种独特的鼻腔给药粉末配方，通过Satsuma公司专有的鼻腔给药装置给药。与现有的偏头痛急性治疗药物相比，STS101具有明显的优势，包括易于携带、快速、方便的自我给药和其他临床优势。2022年11月，Satsuma公布的SUMMIT试验关键数据显示，STS101在给药后两小时（3、4、6、12、24和48小时）的所有时间点以及多个关键点上显示出相较于安慰剂的次要终点优势差异(p<0.001)，表现出了强大持续的偏头痛治疗作用。28.礼来PD-1激动剂2期临床达主要终点，治疗类风湿关节炎5月18日，《新英格兰医学杂志》（NEJM）发表了礼来（Eli Lilly and Company）在研PD-1激动剂peresolimab治疗难治性类风湿关节炎（RA）的2a期研究的详细结果，试验达到了主要疗效终点，不良事件发生率与安慰剂组相似。礼来在新闻稿中表示，这些数据证明了刺激内源性PD-1抑制通路可能是治疗风湿病的有效方法。程序性细胞死亡蛋白受体1（PD-1）在肿瘤治疗中已经发挥了极其重要的作用，但这一靶点在自身免疫疾病治疗中的潜力还远远未被发掘。动物模型中已有研究显示，PD-1/L1与多种自身免疫性疾病的发生有关，包括系统性红斑狼疮、心肌炎、类风湿关节炎和炎症性肠病等。而PD-1激动剂可以与PD-1结合，并抑制淋巴细胞的激活和扩增，从而减弱T细胞的功能。因此，科学家们正在探索PD-1激动剂在自身免疫性疾病中的应用。由礼来开发的peresolimab注射液（LY3462817）正是一款PD-1激动剂。它属于一种人源化免疫球蛋白（Ig）G1单克隆抗体，可与人类PD-1结合并作为其激动剂，抑制淋巴细胞的激活和扩增。礼来曾在公开资料中表示，PD-1抑制与自身免疫性副作用广泛相关，包括结肠炎、自身免疫性糖尿病和炎症性关节炎等。Peresolimab与PD-1结合有望刺激生理免疫抑制通路，从而恢复免疫调节，这有望成为一种治疗自身免疫性疾病或自身炎症性疾病患者的新方法。该研究第一作者、礼来研发副总裁Jay Tuttle博士表示，研究显示了peresolimab在难治性RA患者中表现出有意义的结果。29.德琪医药ATG-031成为全球首个进入临床的抗CD24单抗5月18日，德琪医药有限公司（简称“德琪医药”，香港交易所股票代码：6996.HK）宣布，全球首创（first-in-class）抗CD24单克隆抗体ATG-031的I期临床试验申请（IND）已获美国食品药品管理局（FDA）批准。PERFORM研究是一项在晚期实体瘤或B-NHL患者中开展的首次人体、多中心、开放性I期剂量探索试验。该研究的主要目的为评估ATG-031单药的安全性和耐受性，并确定II期研究的使用剂量。该研究的次要目的为确定ATG-031的药理特性和免疫原性，评估该药物的初步疗效。ATG-031是全球首创（first-in-class）人源化抗CD24单克隆抗体，它可阻断肿瘤微环境（TME）中的 “别吃我” 信号。经过特别设计的ATG-031可通过与肿瘤细胞表面的CD24高亲和力结合并阻断CD24与在肿瘤相关巨噬细胞（TAM）上表达的Siglec-10受体的相互作用，强化由巨噬细胞介导的肿瘤细胞吞噬并促进肿瘤微环境中杀伤性T细胞的浸润。德琪医药早期药物研发执行总监，ATG-031早期研发负责人侯冰博士表示：“靶向肿瘤‘别吃我’信号是一个非常有潜力的癌症治疗策略。与CD47单抗等现有‘别吃我’抑制剂相比，ATG-031克服了CD47抑制剂存在的在靶脱瘤毒性，从而具有更宽的安全窗。CD24是一个非常小并且高度糖基化的蛋白，这给抗体开发带来了很大挑战。德琪大分子团队通过不断地实验探索和对靶点的深刻理解，采取了独特的抗体发现及筛选策略，成功得到具有优异活性和成药性的ATG-031。在短短3年多时间里，成功将ATG-031推进至临床阶段，对此我们感到非常欣喜。”30.康宁杰瑞PD-L1/CTLA-4双抗一线鳞状NSCLC未能成功揭盲5月19日，康宁杰瑞发布公告，称由于总生存期（OS）暂未达到统计学显著性差异，PD-L1/CTLA-4双抗KN046一线联合治疗鳞状非小细胞肺癌（NSCLC）的ENREACH-LUNG-01研究（KN046-301）近期未能成功完成揭盲。因此，独立数据监察委员会建议研究继续进行并进一步收集后续的OS数据直至最终OS分析。ENREACH-LUNG-01是一项KN046联合含铂化疗在晚期不可切除或转移性鳞状非小细胞肺癌患者中开展的多中心、随机、双盲、安慰剂对照性III期临床研究，用以评估KN046联合化疗的安全性和有效性，主要终点为无进展生存期（PFS）和OS。KN046是康宁杰瑞自主研发的全球性首创PD-L1/CTLA-4双特异性抗体，同时靶向具有明显结构差异的PD-L1及CTLA-4，可改变肿瘤微环境的定位及减少脱靶毒性。2022年3月，该研究完成第一次期中分析，并达到预设PFS终点。康宁杰瑞当时表示：“基于这个结果，将计划递交新药上市申请。此次期中分析，未涉及OS分析。随着研究继续进行，后续将进一步获得OS数据。”合作动态1.吉利德科学达成约10亿美元合作，扩大炎症管线5月15日，吉利德科学（Gilead Sciences）和Arcus Biosciences公司共同宣布，双方已经扩大了之前达成的专注于肿瘤学的新药研发合作，将针对炎症性疾病的创新疗法纳入其中。吉利德科学将获得针对多达四种炎症性疾病靶点候选药物独家许可的早期选择权，并向Arcus公司支付可能高达10亿美元的期权费和里程碑付款。Arcus公司成立于2015年，是一家处于临床阶段的全球生物医药公司，旨在为癌症患者开发针对特征明确的生物靶点的差异化创新药及联合疗法。该公司目前已将多种研究药物推进临床研究阶段，包括针对TIGIT、PD-1、腺苷信号通路（CD73和A2a/A2b受体）和HIF-2α等靶点的创新药及联合疗法。早在2020年，吉利德科学就和Arcus公司达成为期十年的合作伙伴关系，共同开发和商业化新一代癌症免疫疗法。在该协议下，吉利德科学获得Arcus公司针对关键生物学途径的、临床及临床前管线中的多个免疫肿瘤学候选产品，Arcus公司将收到1.75亿美元的前期付款和2亿美元的股权投资，以及高达16亿美元针对现有临床候选产品的潜在研发资金、选择加入及里程碑付款。而在本次扩大合作的条款下， Arcus公司将收到3500万美元的预付款，并将针对双方共同选择的最多四个适用于炎症性疾病的靶标启动研究计划。吉利德科学可以行使选择权，在两个单独的、预先指定的时间点引进每个项目。如果其在前两个目标项目的较早时间点行使其选择权，Arcus公司将有资格获得高达4.2亿美元的选择权和里程碑付款以及每个选择项目的分层特许权使用费。对于吉利德科学为四个目标项目行使的任何其他选择权，双方将有权共同开发和分担全球开发成本，并在美国共同商业化和分享选择项目的利润。2.开发创新siRNA药物！大睿生物与康诺亚达成合作5月16日，大睿生物（RONA Therapeutics）宣布与康诺亚达成合作，共同研发创新siRNA药物以治疗一种严重肾脏疾病——慢性肾炎。此次合作将建立在大睿生物针对肝脏和肝外组织的核酸药物开发平台上，借助双方的科学和技术专长，优势互补，共同探索慢性肾炎领域的更多可能性。慢性肾炎是肾功能损害的主要原因之一，大约占所有终末期肾病的25%~30%。IgA肾病、狼疮性肾炎、膜性肾病等是原发性慢性肾炎的常见形式。目前，慢性肾炎获批的治疗药物较为有限，患者亟需更多创新治疗方案。根据协议，大睿生物将使用其RAZOR平台来发现和寻找针对慢性肾炎相关新靶点的siRNA先导化合物，康诺亚将贡献其临床研究和转化医学专业知识和能力。未来，双方将进一步共同开发和商业化从这些发现工作中产生的候选产品。该项目预计2024年上半年进入临床阶段。康诺亚创始人、董事长兼首席执行官陈博博士表示，很高兴能够与大睿生物达成合作，康诺亚始终专注于亟需且未被满足的临床需求，致力于为患者提供高质量、可负担的创新疗法。期待通过大睿生物开创性的下一代siRNA平台技术的赋能，结合康诺亚的生物学专业知识，共同推动创新药物研发，探索更多潜在靶点。大睿生物创始人兼首席执行官史艺宾女士表示，非常期待携手合作伙伴康诺亚共同为全球患者发现和开发变革性核酸药物疗法，大睿生物下一代siRNA平台技术和康诺亚生物学专业知识相得益彰，双方高度的战略契合将加速推进开发针对慢性肾炎等严重未满足需求疾病的siRNA治疗药物。3.美国联邦贸易委员会反对，安进收购Horizon或遇阻5月16日，美国联邦贸易委员会（FTC）对安进提起诉讼，称该公司收购Horizon的交易存在垄断市场的嫌疑且未来可能会进行捆绑销售（提供多产品折扣）。此外，FTC还对安进在与付款人的药品定价谈判过程中的药品议价能力表示担忧。Horizon的核心产品主要是Tepezza和Krystexxa。Tepezza（teprotumumab）是一款抗IGF-1R单抗，也是目前唯一一款获批上市的IGF-1R单抗，其适应症为甲状腺相关性眼病。巧的是，Tepezza也是目前唯一一款获批用于治疗甲状腺相关性眼病的药物。Krystexxa是一款用于治疗慢性难治性高尿酸血症（痛风）的重组尿酸氧化酶（UO）药物，也是唯一一款获批该适应症的药物。2010年9月，Krystexxa在美国获批上市，其近3年的年销售额分别为4.06亿、5.65亿和7.16亿美元，增长势头大好。FTC竞争管理局局长Holly Vedova说：“制药行业的大规模并购给大公司制造了垄断的机会，这些大公司可以借此过度提高处方药价格，阻止患者获得更实惠的仿制药，并妨碍救命药物市场的创新。”SVB证券分析师认为，可能是这两款药物在市场上缺乏竞争对手，导致安进成功收购Horizon后将拥有垄断甲状腺相关性眼病市场和慢性难治性痛风市场的能力，因而FTC对该交易持反对意见。不过，SVB方也认为FTC没有充分的证据证明这起并购交易违反了反垄断法，毕竟Horizon的产品和安进的产品没有重叠之处。安进方表示：“安进和Horizon提供的药物大体上适用于不同的疾病领域和患者群体，不存在产品重叠的担忧。联邦贸易委员会声称安进可能会在未来某个时候“捆绑”这些药物（提供多产品折扣），这完全是推测性的，并且委员会没有反映罕见病药物市场背后的真实世界竞争动态。我们已经承诺过不会将Horizon和安进的产品捆绑在一起。但是，委员会仍然要反对这起交易。此外，据我们所知，先前没有任何一起并购交易因捆绑理论被阻止。”4.阿斯利康与Revvity达成合作，获得基因编辑技术5月18日，美国马萨诸塞州生物技术公司Revvity宣布，阿斯利康与Revvity公司签署了一项非独家授权协议，将使用该公司专有的基因编辑技术来开发针对癌症和免疫介导疾病的细胞疗法，交易的金额未公开。Revvity的生命科学高级副总裁Alan Fletcher表示，与阿斯利康的合作将帮助Revvity实现其碱基编辑平台从临床前研究转化为临床，并最终造福患者。本次交易的核心在于Revvity的Pin-point碱基编辑平台及其底层技术。该技术使用一种经修饰的Cas酶来对单个或多个基因进行可控、精确和高效的编辑，同时限制脱靶和对细胞活性或其他功能的意外影响。与传统的基于CRISPR的基因编辑技术产生双链断裂不同，Revvity的方法只切割一条DNA链来纠正有缺陷的碱基。该公司表示，Pin-point也是一种完全模块化的技术，可以根据特定的基因靶点，将其各个组件进行不同的组合，以实现最佳的治疗效果。Pin-point已在诱导多能干细胞和T细胞中显示出潜力，表明该平台可应用于多种细胞类型和适应证。除了碱基编辑，Pin-point还可以插入基因以实现基于细胞的药物，如CAR-T疗法。阿斯利康是细胞与基因治疗的坚定支持者，布局了从早期学术到产品转化的整个CGT链条。本次协议将进一步强化阿斯利康不断增长的CGT能力。阿斯利康目前已经集齐“CRISPR工具箱”，其中包括使用短RNA分子保护脱靶位点不受CRISPR切割的CRISPR GUARD工具；以及可以确定CRISPR系统在整个基因组中潜在脱靶效应的CRISPR VIVO工具。阿斯利康正在与世界各地的领先研究机构合作开发这些工具。版权声明本文内容均由智慧芽生物医药小编收集于公开网络平台，版权由智慧芽所有，未经智慧芽授权不得转载。已获授权的应在授权范围内使用，并注明来源，违反上述声明者，智慧芽将追究其相关法律责任。如您发现相关信息有任何版权侵扰或者信息错误，请及时联系我们进行删改处理。授权相关事宜请联系：phs@patsnap.com智慧芽新药情报库，以“聚焦生物医药前沿，洞察研发投资风向，跟踪全球新药进展”为宗旨，致力于打造医药行业一站式大数据服务平台。对全球海量医药相关数据进行实时自动化ETL，结合自然语言处理和机器学习等AI技术搭建从数据监测、数据挖掘到数据应用的大数据体系。我们还有一支强大的药学专家团队提供数据指导和审核，确保数据的准确性。此外，智慧芽新药情报库还将与智慧芽的Bio生物序列库、Chemical化学结构库等形成产品矩阵，为生物医药相关企业提供全面解决方案。