Obicetrapib

-- Approval decisions from EMA, UK and Switzerland regulators for obicetrapib and obicetrapib/ezetimibe fixed dose combination expected in 2H26 -- -- Phase 3 PREVAIL CVOT blinded event rate tracking in line with observed event rate in BROADWAY-- -- Topline data from RUBENS Phase 3 trial in patients with type 2 diabetes and metabolic syndrome expected by year-end 2026 -- -- $728.9 million in cash, cash equivalents and marketable securities at December 31, 2025 -- NAARDEN, the Netherlands and MIAMI, Feb. 18, 2026 (GLOBE NEWSWIRE) -- NewAmsterdam Pharma Company N.V. (Nasdaq: NAMS or “NewAmsterdam” or the “Company”), a late-stage, clinical biopharmaceutical company developing oral, non-statin medicines for patients at risk of cardiovascular disease (“CVD”) with elevated low-density lipoprotein cholesterol (“LDL-C”), for whom existing therapies are not sufficiently effective or well-tolerated, today announced financial results for the full year ended December 31, 2025 and provided a corporate update. “2025 marked a year of meaningful clinical and regulatory progress for NewAmsterdam, as we advanced our mission to bring a potentially transformative therapy with obicetrapib to cardiometabolic disease patients who continue to struggle to reach their LDL-C goals,” said Michael Davidson, M.D., Chief Executive Officer of NewAmsterdam. “Marketing Authorization Applications for obicetrapib and the fixed dose combination were accepted for review by the European Medicines Agency (“EMA”), Switzerland, and United Kingdom regulators, and we anticipate a decision from each in the second half of 2026. In parallel, together with our partner Menarini, we are actively preparing for a potential commercial launch in Europe. In the United States, we continue to expand our commercial capabilities with the notable hiring of Steve Albers, former senior vice president of market access and public affairs at Novo Nordisk, who will now lead our market access and public affairs efforts, further strengthening our established team.” “At the same time, we remain focused and well positioned to execute our clinical development strategy, including the advancement of obicetrapib in our three ongoing Phase 3 trials: PREVAIL, REMBRANT and RUBENS. In December 2025, we initiated the RUBENS trial, which will evaluate obicetrapib alone and in combination with ezetimibe in patients with type 2 diabetes or metabolic syndrome that require additional lowering of LDL-C despite treatment with available therapy, with topline data expected by year-end 2026. Our PREVAIL cardiovascular outcomes trial continues to progress well, where the overall blinded MACE event rate in PREVAIL through the initial 12-months was in line with what we observed in BROADWAY. NewAmsterdam continues to operate from a position of financial strength, with cash runway expected to be sufficient to fund operations through the PREVAIL readout and, if approved, support the subsequent U.S. commercial launch. Additionally, following positive biomarker results from the Alzheimer’s disease analysis in the BROADWAY trial, we plan to initiate a new clinical trial evaluating obicetrapib in early Alzheimer’s disease patients this year.” Clinical Development and Regulatory Updates NewAmsterdam is developing obicetrapib, an oral, low-dose and once-daily, highly-selective cholesteryl ester transfer protein (“CETP”) inhibitor, as a monotherapy and in fixed-dose combination with ezetimibe, as the preferred LDL-C lowering therapy to be used in patients at risk of CVD for whom existing therapies are not sufficiently effective or well-tolerated. In August 2025, NewAmsterdam announced acceptance of MAAs for review by the EMA for obicetrapib 10 mg monotherapy and 10 mg obicetrapib plus 10 mg ezetimibe FDC for patients with primary hypercholesterolemia, both heterozygous familial (“HeFH”) and non-familial or mixed dyslipidemia. Subsequently, MAAs were also submitted to regulators in UK and Switzerland and accepted for review. The MAAs were submitted by NewAmsterdam’s partner, A. Menarini International Licensing S.A. (“Menarini”), who is responsible for communications with regulatory authorities in Europe and for the commercialization and local development of obicetrapib in Europe and other collaborative activities pursuant to an exclusive License Agreement (the “Menarini License”). NewAmsterdam is entitled to tiered double-digit percentage royalties ranging from the low double-digits to mid-twenties on net sales in the European countries covered by the Menarini License and up to an additional €833 million upon the achievement of various clinical, regulatory and commercial milestones. In August 2025, NewAmsterdam presented pooled data from its pivotal Phase 3 BROADWAY and BROOKLYN trials on the impact of obicetrapib on major adverse cardiovascular events at the European Society of Cardiology Congress (“ESC”) 2025, along with the simultaneous publication in the Journal of the American College of Cardiology, highlighting obicetrapib’s performance across diverse lipid-lowering backgrounds observed in these trials. The presentation and publication underscore the Company’s continued momentum in advancing obicetrapib as a differentiated oral therapy for patients with elevated LDL-C. In June and July 2025, NewAmsterdam announced positive data from the prespecified AD biomarker analysis in the BROADWAY clinical trial and presented at the 2025 Alzheimer’s Association International Conference (“AAIC”). The pre-specified analysis was conducted to assess the effect of obicetrapib on plasma biomarkers of AD in both the full analysis set and in patients carrying the apolipoprotein E4 (“ApoE4”) gene, based on phenotypic analysis. NewAmsterdam observed statistically significant reductions in p-tau217, a key biomarker of AD pathology, in both the full analysis set (p<0.002, n=1,515) and in ApoE4 carriers (p=0.0215, n=367), which NewAmsterdam believes support an emerging link between CETP-inhibition and neurodegeneration. In ApoE4/E4 carriers, the highest risk category for Alzheimer’s disease, obicetrapib was observed to reduce p-tau217 levels by 20.5%, over 12 months, compared to placebo (p=0.010, n=29). In October 2025, the data was published in the Journal of Prevention of Alzheimer's Disease. Upcoming Milestones and Ongoing Trials: Following the successful completion and positive topline results of the Phase 3 BROADWAY, TANDEM, and BROOKLYN trials, NewAmsterdam plans to announce additional data from these trials relating to obicetrapib and the FDC of obicetrapib plus ezetimibe during 2026. The following Phase 3 trials are currently ongoing: PREVAIL Phase 3 trial: PREVAIL is a CVOT evaluating obicetrapib in patients with a history of ASCVD, whose LDL-C is not adequately controlled despite being on maximally tolerated lipid-lowering therapy. NewAmsterdam completed enrollment of over 9,500 patients in April 2024. REMBRANDT Phase 3 trial: The REMBRANDT trial utilizes coronary computed tomography angiography imaging to evaluate the effect of obicetrapib plus ezetimibe FDC on coronary plaque burden. The placebo-controlled, double-blind, randomized, Phase 3 trial is being conducted in adult participants with high-risk ASCVD with evidence of coronary plaque who are not adequately controlled by their maximally tolerated lipid-modifying therapy, to assess the impact of the obicetrapib 10 mg plus ezetimibe 10 mg FDC daily on coronary plaque and inflammation characteristics. The trial is expected to complete enrollment of approximately 300 patients in 2026. RUBENS Phase 3 trial: Initiated in December 2025, the RUBENS trial will evaluate obicetrapib alone or in combination with ezetimibe in patients with type 2 diabetes or metabolic syndrome that require additional lowering of LDL-C despite treatment with available therapy. The trial is expected to enroll approximately 300 patients, with topline data expected by year end 2026. Additionally, NewAmsterdam expects to initiate a new clinical trial evaluating obicetrapib in early Alzheimer’s disease patients in 2026. Full Year 2025 Financial Results Cash Position: As of December 31, 2025, NewAmsterdam reported cash, cash equivalents and marketable securities of $728.9 million, compared to $834.2 million as of December 31, 2024. The decrease was primarily driven by cash outflows related to research and development costs as the Company continues development of obicetrapib and spending on selling, general and administrative expenses to support the Company’s ongoing operations, partially offset by cash inflows from the exercise of options and warrants. Revenue: NewAmsterdam recognized $22.5 million in revenue for the year ended December 31, 2025, compared to $45.6 million in the year ended December 31, 2024. The decrease in revenue related to clinical development milestones pursuant to the Menarini License was partially offset by an increase in the amount of revenue recognized in the current period related to the development cost contributions under the Menarini License. Research and Development (“R&D”) Expenses : R&D expenses were $141.8 million for the year ended December 31, 2025, compared to $151.4 million in the year ended December 31, 2024. The decrease was primarily driven by a decrease in clinical expenses mainly due to the completion of several Phase 3 clinical trials in the second half of 2024 and cost phasing in ongoing clinical trials, partially offset by increases in non-clinical expenses, manufacturing expenses, personnel expenses and regulatory expenses. Share-based payment expenses included within R&D expenses totaled $19.6 million in the year ended December 31, 2025, compared to $13.3 million in the year ended December 31, 2024. Selling, General and Administrative (“SG&A”) Expenses : SG&A expenses were $106.4 million for the year ended December 31, 2025, compared to $70.4 million in the year ended December 31, 2024. This increase was primarily due to increases in personnel expenses, marketing and communication expenses and costs related to our intellectual property. Share-based payment expenses included within SG&A expenses totaled $39.9 million in the year ended December 31, 2025, compared to $20.3 million in the year ended December 31, 2024. Net loss: Net loss for the year ended December 31, 2025, was $203.8 million, compared to net loss of $241.6 million in the year ended December 31, 2024. The individual components of the change are described above in addition to non-cash losses related to changes in the fair value of our derivative liabilities and foreign exchange gains/(losses). About Obicetrapib Obicetrapib is a novel, oral, low-dose CETP inhibitor that NewAmsterdam is developing to overcome the limitations of current LDL-lowering treatments. In each of the Company’s Phase 2 trials, ROSE2, TULIP, ROSE, and OCEAN, as well as the Company’s Phase 3 BROOKLYN, BROADWAY and TANDEM trials, evaluating obicetrapib as monotherapy or combination therapy, the Company observed statistically significant LDL-lowering combined with a side effect pro to that of placebo. The Company commenced the Phase 3 PREVAIL cardiovascular outcomes trial in March 2022, which is designed to assess the potential of obicetrapib to reduce occurrences of MACE. The Company completed enrollment of PREVAIL in April 2024 and randomized over 9,500 patients. Commercialization rights of obicetrapib in Europe, either as a monotherapy or as part of a fixed-dose combination with ezetimibe, have been exclusively granted to the Menarini Group, an Italy-based, leading international pharmaceutical and diagnostics company. About Cardiovascular Disease Cardiovascular disease remains the leading cause of death globally, despite the availability of lipid-lowering therapies (“LLTs”). By 2050 more than 184 million U.S. adults are expected to be affected by CVD and hypertension, including 27 million with coronary heart disease and 19 million with stroke. In the United States from 2019 through 2022, CVD age-adjusted mortality rates increased by 9%, reversing the trend observed since 2010 and undoing nearly a decade of progress. Despite the availability of high-intensity statins and non-statin LLTs, LDL-C target level attainment remains low, contributing to residual cardiovascular risk, and underscoring a significant clinical need for improved therapeutic regimens. Even with 269 million LLT prescriptions written over the last 12 months, 30 million under-treated US adults are not at their risk-based LDL-C goal, of which 13 million have ASCVD. Less than 1 in 4 patients with ASCVD achieve an LDL-C goal of less than 70 mg/dL and only 10% of very high risk ASCVD patients achieve the goal below 55 mg/dL. In addition to the 30 million under-treated U.S. adults, there are 10 million patients diagnosed with elevated LDL-C who are not taking any LLTs including statins. Beyond LDL-C, additional factors are at play, such as lifestyle choices, tobacco use, and obesity, as well as inflammation, thrombosis, triglyceride levels, elevated Lp(a) levels, and type 2 diabetes. Alzheimer’s Analysis In BROADWAY, a pre-specified analysis was designed to assess plasma biomarkers of Alzheimer’s disease (“AD”) in patients enrolled in the BROADWAY trial and evaluated the effects of longer duration of therapy (12 months) with a prespecified ApoE population, based on phenotypic analysis. The analysis included 1,535 patients, including 367 ApoE4 carriers (ApoE3/E4 or ApoE4/E4), whose ApoE status was able to be determined. Because this analysis was based on a subset of patients from BROADWAY (which was designed to evaluate LDL-C reductions in an ASCVD and/or HeFH population), the AD analysis was not controlled for baseline differences between the treatment and placebo populations, but statistical analyses were adjusted for baseline biomarker values and age. The absolute and percent change over 12 months in p-tau217, a key biomarker of AD pathology, was measured among patients with baseline and end of study datapoints above the lower limit of quantitation. Additional outcome measures included NFL, GFAP, p-tau181, and Aβ42/40 ratio absolute and percent change over 12 months. NewAmsterdam observed statistically significant lower absolute changes in p-tau217 compared to placebo over 12 months in both the full analysis set (p=0.002; n= 1,535) and in ApoE4 carriers (p=0.02; n=367) as well as favorable trends in the other AD biomarkers. Although a safety analysis was not performed in the AD analysis population, in BROADWAY obicetrapib was observed to be well-tolerated, with safety results comparable to placebo. About NewAmsterdam NewAmsterdam (Nasdaq: NAMS) is a late-stage biopharmaceutical company whose mission is to improve patient care in populations with metabolic diseases where currently approved therapies have not been adequate or well tolerated. We seek to fill a significant unmet need for a safe, well-tolerated and convenient LDL-lowering therapy. In multiple phase 3 trials, NewAmsterdam is investigating obicetrapib, an oral, low-dose and once-daily CETP inhibitor, alone or as a fixed-dose combination with ezetimibe, as LDL-C lowering therapies to be used as an adjunct to statin therapy for patients at risk of CVD with elevated LDL-C, for whom existing therapies are not sufficiently effective or well tolerated. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995 and are subject to the “safe harbor” provisions created thereunder. All statements that are not historical facts are hereby identified as forwarding-looking statements for this purposes and include, among others, statements relating to: expectations regarding the timing of potential approval decisions from the EMA, UK and Switzerland regulators with respect to MAAs for obicetrapib and the FDC of obicetrapib plus ezetimibe, and preparations for commercial launch, if approved; the initiation of a new clinical trial evaluating obicetrapib in early Alzheimer disease in 2026; the therapeutic potential of the Company’s product candidates; the timing for commencing trials, enrolling patients and completing trials, and the timing and forums for announcing data; expected milestones and business objectives for 2026 and beyond; the Company’s expectation that its cash runway will be sufficient to fund operations through the PREVAIL readout and, if approved, support the subsequent U.S. commercial launch; and other statements regarding the Company's future operations, financial performance, financial position, prospects, objectives, strategies and other future events. These forward-looking statements are based upon management’s current expectations and assumptions, and are subject to a number of risks, uncertainties and other factors that could cause actual results and events to differ materially and adversely from those indicated by such forward-looking statements including, among others: uncertainties and delays regarding the initiation, enrollment and completion of the Company’s clinical trials; uncertainties regarding the outcome of the Company’s clinical trials, and whether such outcomes will be adequate to support regulatory review and approval of its product candidates; whether topline, initial or preliminary results or analyses from a particular clinical trial will be predictive of the final results of that trial and whether results of early clinical trials and analyses will be indicative of the results of later clinical trials and analyses, or whether projections regarding clinical outcomes will reflect actual results in future clinical trials or clinical use of the Company’s product candidates; the potential for varying interpretation of the results of clinical trials and analyses; risks related to the Company’s ability to achieve its business plans, objectives and milestones, including approval of the Company’s product candidates and potential commercialization; unanticipated costs and expenses impacting the Company’s cash runway; the Company’s ability to continue to source the raw materials for its product candidates and ensure adequate supply of product for clinical trials and, if approved, commercialization; the impact of competing product candidates on the Company’s business; risks and uncertainties relating to intellectual property and regulatory exclusivities; changes in domestic and foreign business, market, financial, political, and legal conditions; and those risks, uncertainties and other factors discussed under the caption “Item 1A. Risk Factors” and elsewhere in the Company’s most recent Form 10-K, Form 10-Q and other public filings with the Securities and Exchange Commission, which are available at As a result, you should not place undue reliance on any forward-looking statements. The forward-looking statements made in this press release speak only as of the date of this press release, and the Company undertakes no obligation to update such forward-looking statements, whether as a result of new information, future developments or otherwise. Company Contact Matthew Philippe P: 1-917-882-7512 matthew.philippe@newamsterdampharma.com Media Contact Real Chemistry on behalf of NewAmsterdam Christian Edgington P: 1-513-310-6410 cedgington@realchemistry.com Investor Contact Precision AQ on behalf of NewAmsterdam Austin Murtagh P: 1-212-698-8696 austin.murtagh@precisionaq.com NewAmsterdam Pharma Company N.V. Consolidated Balance Sheet As at December 31, 2025 2024 (In thousands of USD) Assets Current assets: Cash and cash equivalents 490,002 771,743 Prepayments and other receivables 38,138 24,272 Employee receivables — 4,951 Marketable securities, current 146,239 62,447 Restricted cash 1,321 — Total current assets 675,700 863,413 Marketable securities, net of current portion 92,609 — Property, plant and equipment, net 383 242 Operating right of use asset 185 431 Intangible assets 407 534 Total assets 769,284 864,620 Liabilities and Shareholders' Equity Current liabilities: Accounts payable 8,970 4,744 Accrued expenses and other current liabilities 15,422 13,608 Deferred revenue, current 3,987 6,008 Lease liability, current 136 246 Derivative earnout liability, current — 44,798 Derivative warrant liabilities 57,272 37,514 Total current liabilities 85,787 106,918 Lease liability, net of current portion 66 202 Total liabilities 85,853 107,120 Commitments and contingencies (Note 13) Shareholders' Equity: Ordinary shares, €0.12 par value; 400,000,000 shares authorized; 114,399,326 and 108,064,340 shares issued and outstanding at December 31, 2025 and 2024, respectively 14,278 13,444 Additional paid-in capital 1,426,750 1,298,160 Accumulated loss (762,390 ) (558,571 ) Accumulated other comprehensive income 4,793 4,467 Total shareholders' equity 683,431 757,500 Total liabilities and shareholders' equity 769,284 864,620 NewAmsterdam Pharma Company N.V. Consolidated Statements of Operations and Comprehensive Loss For the year ended December 31, 2025 2024 2023 (In thousands of USD, except per share amounts) Revenue 22,503 45,563 14,090 Operating expenses: Research and development expenses 141,832 151,406 159,424 Selling, general and administrative expenses 106,354 70,446 37,633 Total operating expenses 248,186 221,852 197,057 Operating loss (225,683 ) (176,289 ) (182,967 ) Other income (expense): Interest income 27,592 16,881 11,283 Fair value change – earnout 3,992 (37,010 ) (266 ) Fair value change – warrants (22,775 ) (38,583 ) (10,018 ) Foreign exchange gains/(losses) 13,055 (6,598 ) 5,058 Loss before tax (203,819 ) (241,599 ) (176,910 ) Income tax expense (benefit) — (1 ) 27 Loss for the year (203,819 ) (241,598 ) (176,937 ) Other comprehensive income/(loss) Unrealized gain on available-for-sale securities, net of tax 326 45 — Total comprehensive loss for the year, net of tax (203,493 ) (241,553 ) (176,937 ) NewAmsterdam Pharma Company N.V. Consolidated Statements of Shareholders' Equity (In thousands of USD, except share amounts) Shares Amount Additional Paid-In Capital Accumulated Loss Accumulated other comprehensive income (loss) Total Shareholders' Equity Opening balance at January 1, 2023 81,559,780 10,055 555,625 (140,036 ) 4,422 430,066 Exercise of warrants 749,741 97 10,116 — — 10,213 Exercise of stock options 160,247 21 269 — — 290 Share-based compensation - - 24,761 — — 24,761 Total loss and comprehensive loss for the year - — — (176,937 ) — (176,937 ) As at December 31, 2023 82,469,768 10,173 590,771 (316,973 ) 4,422 288,393 February 2024 Issuance of Ordinary Shares and Pre-Funded Warrants, net of issuance costs 5,871,909 759 189,206 — — 189,965 December 2024 Issuance of Ordinary Shares and Pre-Funded Warrants, net of issuance costs 14,667,347 1,851 451,564 — — 453,415 Exercise of Pre-Funded Warrants 2,105,248 279 (279 ) — — — Exercise of warrants 1,288,790 168 27,673 — — 27,841 Exercise of stock options 1,661,278 214 5,496 — — 5,710 Share-based compensation — — 33,729 — — 33,729 Total loss and comprehensive loss for the year — — — (241,598 ) 45 (241,553 ) As at December 31, 2024 108,064,340 13,444 1,298,160 (558,571 ) 4,467 757,500 Issuance of Earnout Shares 1,743,136 226 40,581 — — 40,807 Exercise of Pre-Funded Warrants 1,293,938 162 (162 ) — — - Exercise of warrants 142,477 19 4,636 — — 4,655 Exercise of stock options 3,012,434 408 24,129 — — 24,537 Vesting of RSUs 143,001 19 (19 ) — — - Share-based compensation — — 59,425 — — 59,425 Total loss and comprehensive loss for the year — — — (203,819 ) 326 (203,493 ) As at December 31, 2025 114,399,326 14,278 1,426,750 (762,390 ) 4,793 683,431 NewAmsterdam Pharma Company N.V. Consolidated Statements of Cash Flows For the year ended December 31, 2025 2024 2023 (In thousands of USD) Operating activities: Loss for the year (203,819 ) (241,598 ) (176,937 ) Non-cash adjustments to reconcile loss for the year to net cash flows: Depreciation and amortization 220 113 49 Non-cash rent expense — 12 6 Fair value change - derivative earnout and warrants 18,783 75,593 10,284 Loss on disposal of property, plant and equipment 12 — — Foreign exchange (gains)/losses (13,055 ) 6,598 (5,058 ) Amortization of premium/discount on available-for-sale debt securities (1,405 ) (227 ) — Share-based compensation 59,425 33,619 24,572 Changes in working capital: Changes in prepayments (current and non-current) and other receivables (13,280 ) (17,459 ) 4,031 Changes in accounts payable 4,909 (12,948 ) 5,070 Changes in accrued expenses and other current liabilities 2,448 1,686 5,470 Changes in deferred revenue (2,021 ) (3,953 ) (8,705 ) Net cash used in operating activities (147,783 ) (158,564 ) (141,218 ) Investing activities: Purchase of property, plant and equipment, including internal use software (246 ) (672 ) (24 ) Maturities of marketable securities 122,063 — — Purchases of marketable securities (296,733 ) (62,176 ) — Net cash used in investing activities (174,916 ) (62,848 ) (24 ) Financing activities: Proceeds from February 2024 offering of Ordinary Shares and Pre-Funded Warrants — 190,481 — Transaction costs on February 2024 issue of Ordinary Shares and Pre-Funded Warrants — (515 ) — Proceeds from December 2024 offering of Ordinary Shares and Pre-Funded Warrants — 455,026 — Transaction costs on December 2024 issue of Ordinary Shares and Pre-Funded Warrants (1,586 ) (25 ) — Proceeds from exercise of warrants 1,638 13,761 8,622 Proceeds from exercise of options 29,468 1,768 290 Payment of withholding taxes related to net share settlement of exercised options — (989 ) — Net cash provided by financing activities 29,520 659,507 8,912 Net change in cash, cash equivalents and restricted cash (293,179 ) 438,095 (132,330 ) Foreign exchange differences 12,759 (6,802 ) 5,052 Cash, cash equivalents and restricted cash at the beginning of the year 771,743 340,450 467,728 Cash, cash equivalents and restricted cash at the end of the year 491,323 771,743 340,450 Noncash financing and investing activities Recognition of ROU asset — 562 — Issuance of earnout shares 40,807 — — Supplemental cash flow disclosures Cash paid for income taxes — 1 27 Reconciliation of cash, cash equivalents and restricted cash to the Consolidated Balance Sheets Cash and cash equivalents 490,002 771,743 340,450 Restricted cash 1,321 — — 491,323 771,743 340,450

每年体检季，无数人对着化验单上“↑”的血脂指标发愁。他汀类药物作为基石治疗已应用数十年，但临床中仍存在两类困境：一是部分患者LDL-C（低密度脂蛋白胆固醇）不达标，二是脂蛋白(a)等“坏脂蛋白”缺乏针对性干预手段。2026年伊始，高血脂治疗领域迎来多个重量级临床试验进展。不同于以往的药物迭代，本轮新药研发呈现出三个鲜明特征：口服制剂挑战注射剂便利性、小核酸药物从罕见病走向普通人群、双靶点技术尝试“一箭双雕”。本文梳理当前处于临床试验阶段的多类新型降脂药物，不涉及具体疗效数据，仅呈现技术路径与研究状态，帮助读者理解血脂管理的未来图景。---一、口服PCSK9抑制剂：打破“注射”垄断前蛋白转化酶枯草溶菌素9（PCSK9）是近年来最成功的降脂靶点。既往PCSK9抑制剂均为单抗注射液，需每2周或每月皮下注射。2026年，口服小分子PCSK9抑制剂进入公众视野。代表性药物：Enlicitide decanoate这款药物属于口服小分子PCSK9抑制剂，目前已完成52周安慰剂对照临床试验。研究入选对象包括已发生动脉粥样硬化性心血管疾病事件、LDL-C水平未达标者，以及具有高危因素的一级预防人群。该药物的临床意义在于：将PCSK9抑制机制从“注射蛋白”转化为“口服化学药”。若后续进展顺利，可为惧怕针剂的患者提供新的用药选择。研究状态：52周核心研究已完成，处于临床数据分析阶段。---二、小核酸药物：从单靶点到双靶点跃迁小核酸药物（包括siRNA和反义寡核苷酸）是本次新药浪潮的技术核心。其优势在于长效：皮下注射后疗效可维持数月。1. ANGPTL3靶向siRNA：针对难治性家族高胆固醇血症代表性药物：Zodasiran该药靶向血管生成素样蛋白3（ANGPTL3），通过RNA干扰机制抑制其表达。ANGPTL3是独立于LDL受体的脂代谢调节靶点，对纯合子家族性高胆固醇血症（HoFH）患者具有独特价值——这类患者LDL受体功能严重受损，常规他汀疗效有限。研究状态：GATEWAY研究是一项开放标签、随机化II期试验，患者接受皮下注射给药。目前研究已结束招募，进入长期开放标签扩展阶段。2. 脂蛋白(a)靶向siRNA：瞄准“沉默的风险因子”脂蛋白(a)是遗传决定的独立心血管风险因素，目前全球尚无专门针对Lp(a)升高获批的药物。代表性药物：SRSD216该siRNA药物设计用于调控LPA基因，抑制肝脏载脂蛋白(a)生成。2025年12月，该药在中国和美国同步完成II期临床试验首例患者给药。研究设计：随机、双盲、安慰剂对照，设三个剂量组，主要终点为安全性评估。代表性药物：Pelacarsen这是一款反义寡核苷酸药物，目前正处于III期临床阶段。一项新启动的研究正在探索Pelacarsen联合Inclisiran（已上市的PCSK9 siRNA） 的方案，针对Lp(a)与LDL-C双重升高的ASCVD患者。研究状态：临床试验处于招募中，计划入组340例患者。3. 全球首款双靶向siRNA：同一分子抑制两个基因2026年初，RNAi治疗领域迎来里程碑事件——全球首个进入临床的双靶点siRNA完成首例受试者给药。代表性药物：ARO-DIMER-PA该分子设计独特：单个siRNA分子可同时沉默PCSK9和APOC3两个基因。APOC3是富含甘油三酯脂蛋白代谢的关键调节因子，双靶点策略旨在同时降低LDL-C和甘油三酯，覆盖混合型高脂血症。研究状态：I/IIa期剂量递增研究正在进行，针对混合型高脂血症成人受试者。代表性药物：RN5681另一款双靶向siRNA，同时靶向PCSK9和LPA。该药已于2025年底递交澳大利亚临床试验申请，I期试验预计2026年第一季度启动。技术看点：双靶点策略并非两种药物的简单联合，而是通过化学修饰使单一寡核苷酸链同时识别两个基因序列，对药物设计能力要求极高。---三、单克隆抗体：新靶点延续经典路径虽然小分子与核酸药物势头强劲，抗体类药物仍在新靶点拓展中发挥作用。代表性药物：SHR-1918靶向ANGPTL3的全人源单克隆抗体，近期公布了针对纯合子家族性高胆固醇血症的非随机临床试验结果。研究状态：已完成初步临床探索。---四、CETP抑制剂：老靶点的新应用场景胆固醇酯转移蛋白（CETP）抑制剂是降脂领域的“老兵”，早年间多个候选药物因安全性或疗效问题折戟。代表性药物：Obicetrapib该药在降低LDL-C的同时，可显著升高HDL-C。值得关注的是，近期研究将其应用场景延伸至神经退行性疾病领域——一项涉及1727例心血管病患者的III期研究采集了阿尔茨海默病血浆生物标志物数据。研究状态：III期BROADWAY研究已完成12个月随访，同时采集了多种AD生物标志物。提示：该适应症尚处早期探索阶段，不代表CETP抑制剂可干预认知障碍，仅为生物标志物探索性分析。---五、技术趋势解读：2026高血脂临床研究的三个关键词1. 从“单次”到“长效”小核酸药物的给药间隔已达每3个月、每6个月，甚至探索每年1次。这不仅是便利性问题，更是治疗哲学的转变：将慢性病用药从“每日服药”模式中部分解放。2. 从“单靶”到“双靶”混合型高脂血症、LDL-C与Lp(a)双高、难治性家族高胆固醇血症……单一机制难以解决的临床问题催生了双靶点技术。2026年或将成为“双靶向siRNA临床元年”。3. 从“罕见病”到“常见病”值得注意的历史轨迹：PCSK9抑制剂先获批家族性高胆固醇血症，后拓展至普通动脉粥样硬化患者；siRNA药物同样遵循这一路径——先在罕见遗传性血脂异常中验证安全性，再向数百万计的普通高脂血症人群延伸。---写给患者的结语对于正在服用降脂药的朋友，这些新药大多与你当下的治疗无关，也无需等待。现有他汀、依折麦布、PCSK9抑制剂等方案已能有效管理绝大多数血脂异常。新药研发的意义在于：填补未被满足的需求——· 对于LDL-C顽固不达标者，未来可能有更强效、更长效的注射方案；· 对于Lp(a)天生升高者，首次出现针对性干预手段；· 对于混合型高脂血症，或许某天只需一针便可同时管理胆固醇与甘油三酯。但这些都还在路上。临床试验阶段意味着安全性与有效性仍在接受科学检验，距离获批上市、进入医保尚有流程。血脂管理的基本盘从未改变：低盐低脂饮食、规律运动、遵嘱服药。新药拓展的是“武器库”的上限，而非日常防线的底线。---本文科普内容，不构成医疗建议，疾病诊断、治疗请遵线下医生医嘱