Ponesimod

Fanapt® net product sales rose 26% to $29.6 million; total prescriptions increased 32% and new-to-brand prescriptions surged 76% NEREUS™ (tradipitant) launched via nereus.us, an innovative direct-to-consumer platform – the first new prescription medicine in more than 40 years for the prevention of vomiting induced by motion, with convenient online ordering and rapid direct home delivery Full-year 2026 revenue guidance raised to $240-$290 million, including $10-30 million from newly launched NEREUS™ BYSANTI™ (milsaperidone) received FDA approval for bipolar I disorder and schizophrenia on February 20, 2026 Imsidolimab BLA for Generalized Pustular Psoriasis accepted for FDA review; PDUFA target action date of December 12, 2026 WASHINGTON, May 6, 2026 /PRNewswire/ -- Vanda Pharmaceuticals Inc. (Vanda) (Nasdaq: VNDA) today announced financial and operational results for the first quarter ended March 31, 2026. "Vanda delivered strong commercial execution in the first quarter, highlighted by 26% growth in Fanapt sales, the groundbreaking U.S. launch of NEREUS with its pioneering direct-to-consumer platform at nereus.us, and the FDA approval of BYSANTI," said Mihael H. Polymeropoulos, M.D., Vanda's President, CEO and Chairman of the Board. "We believe that these achievements, combined with meaningful pipeline progress and our raised 2026 revenue guidance, position the company for continued growth and value creation." Financial Highlights Total net product sales reached $51.7 million in Q1 2026, a 3% increase compared to $50.0 million in Q1 2025. Fanapt® net product sales were $29.6 million, up 26% year-over-year. HETLIOZ® net product sales were $15.9 million, down 24% year-over-year. PONVORY® net product sales were $6.2 million, up 10% year-over-year. Loss before income taxes was $48.4 million compared with $37.4 million in Q1 2025, reflecting continued investment in new product launches and pipeline advancement. Cash, cash equivalents and marketable securities (Cash) totaled $202.3 million as of March 31, 2026, representing a decrease to Cash of $61.5 million in Q1 2026, which included a one-time payment of a $10.0 million milestone to Eli Lilly due upon approval of NEREUS™ (tradipitant). Key Commercial Highlights Fanapt® saw continued strong momentum with total prescriptions (TRx)1 up 32% and new-to-brand prescriptions (NBRx)1 up 76% versus Q1 2025. In April 2026, weekly TRx for Fanapt® reached an 11-year high of over 2,600 prescriptions for the week ending April 24, 2026. NEREUS™ is now commercially available nationwide through nereus.us, Vanda's innovative direct-to-consumer platform. This pioneering patient-centric model enables convenient ordering online with rapid direct delivery, eliminating traditional pharmacy barriers and providing a seamless, modern access experience. As the first new prescription therapy approved for the prevention of vomiting induced by motion in adults in more than 40 years, NEREUS™ represents a breakthrough in both science and patient access. Key Regulatory & Clinical Development Highlights BYSANTI™ (milsaperidone) received U.S. Food and Drug Administration (FDA) approval for the treatment of bipolar I disorder and schizophrenia. BYSANTI™ is protected by data exclusivity through February 20, 2031 and multiple patents, the latest of which expires on May 31, 2044. Vanda's ongoing late-stage clinical studies are progressing rapidly and are expected to generate topline results in 2026 or early 2027, including: The Phase III study of BYSANTI™ as a once-daily adjunctive treatment for major depressive disorder (MDD), with results expected in Q1 2027. The Thetis Phase III study of NEREUS™ for the prevention of vomiting in patients receiving GLP-1 receptor agonist therapies, with results expected in 2026. The Phase III study of VQW-765 in the treatment of adults with social anxiety disorder, with results expected by the end of 2026. The FDA accepted the Biologics License Application (BLA) for imsidolimab in Generalized Pustular Psoriasis (GPP) with a Prescription Drug User Fee Act (PDUFA) target action date of December 12, 2026. The results of the pivotal clinical study were published in the April 28, 2026 issue of the New England Journal of Medicine (NEJM) Evidence2. Corporate Highlight On April 22, 2026, Vanda appointed Charles Duncan, Ph.D. to its Board of Directors. The Board now consists of seven directors, six of whom are independent. GAAP Financial Results Net loss was $48.6 million (diluted loss per share of $0.82) in Q1 2026 compared with a net loss of $29.5 million (diluted loss per share of $0.50) in Q1 2025. 2026 Financial Guidance Vanda is raising its full-year 2026 total revenue guidance to reflect the contribution of the newly launched NEREUS™ while maintaining prior ranges for Fanapt® and other products: Conference Call Vanda has scheduled a conference call for today, Wednesday, May 6, 2026, at 4:30 PM ET. During the call, Vanda's management will discuss the first quarter 2026 financial results and other corporate activities. Investors can call 1-888-596-4144 (domestic) or 1-646-968-2525 (international) and use passcode number 8051722. A replay of the call will be available on Wednesday, May 6, 2026, beginning at 8:30 PM ET and will be accessible until Wednesday, May 13, 2026 at 11:59 PM ET. The replay call-in number is 1-800-770-2030 for domestic callers and 1-609-800-9909 for international callers. The passcode number is 8051722. The conference call will be broadcast simultaneously on Vanda's website, . Investors should click on the Investors tab and are advised to go to the website at least 15 minutes early to register, download, and install any necessary software or presentations. The call will also be archived on Vanda's website for a period of 30 days. References IQVIA Prescription Data Smieszek, S. et al. Efficacy and Safety of Imsidolimab for Generalized Pustular Psoriasis. NEJM Evidence 5, (2026). About Vanda Pharmaceuticals Inc. Vanda is a leading global biopharmaceutical company focused on the development and commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients. For more on Vanda Pharmaceuticals Inc., please visit and follow us on X @vandapharma. CAUTIONARY NOTE REGARDING FORWARD LOOKING STATEMENTS Various statements in this press release, including, but not limited to, the guidance provided under "2026 Financial Guidance" above and statements regarding Vanda's plans for pursuit of FDA approval of imsidolimab for the treatment of GPP, and the related timeline for approval; Vanda's expectations with respect to its continued growth and ability to create value; Vanda's clinical development plans and expected timelines for BYSANTITM for the treatment of MDD, NEREUSTM in the prevention of vomiting induced by GLP-1 therapies, and VQW-765 in the treatment of adults with social anxiety disorder; and Vanda's expectations with respect to the strength of its business are "forward-looking statements" under the securities laws. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Forward-looking statements are based upon current expectations and assumptions that involve risks, changes in circumstances and uncertainties. Important factors that could cause actual results to differ materially from those reflected in Vanda's forward-looking statements include, among others, Vanda's ability to continue to grow its business; the FDA's ability to complete its review of, and reach a decision with respect to, the BLA for imsidolimab by December 12, 2026; Vanda's ability to successfully execute the commercial launches of NEREUSTM for the prevention of vomiting induced by motion and BYSANTI™ for the treatments of bipolar I disorder and schizophrenia; Vanda's ability to continue to advance its late-stage clinical development programs and to obtain regulatory approval for, and successfully commercialize, the late-stage products in development; Vanda's ability to complete the clinical study for BYSANTITM for the treatment of MDD and receive results in in the first quarter of 2027; Vanda's ability to complete the Thetis study and receive results in 2026; and Vanda's ability to complete the clinical study for VQW-765 in the treatment of adults with social anxiety disorder and receive results by the end of 2026. Therefore, no assurance can be given that the results or developments anticipated by Vanda will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Vanda. Forward-looking statements in this press release should be evaluated together with the various risks and uncertainties that affect Vanda's business and market, particularly those identified in the "Cautionary Note Regarding Forward-Looking Statements", "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of Vanda's most recent Annual Report on Form 10-K, as updated by Vanda's subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the U.S. Securities and Exchange Commission, which are available at . All written and verbal forward-looking statements attributable to Vanda or any person acting on its behalf are expressly qualified in their entirety by the cautionary statements contained or referred to herein. Vanda cautions investors not to rely too heavily on the forward-looking statements Vanda makes or that are made on its behalf. The information in this press release is provided only as of the date of this press release, and Vanda undertakes no obligation, and specifically declines any obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Corporate Contact: Kevin Moran Senior Vice President, Chief Financial Officer and Treasurer Vanda Pharmaceuticals Inc. 202-734-3400 [email protected] Jim Golden / Jack Kelleher / Dan Moore Collected Strategies [email protected] Follow us on X @vandapharma SOURCE Vanda Pharmaceuticals Inc. 21% more press release views with Request a Demo

Gao lab 文献分享 发表期刊 Nature Chemistry 发表年份 2025 文章题目 Activity of GPCR-targeted drugs influenced by human gut microbiota metabolism 通讯作者 Andrew L. Goodman 教授（耶鲁大学） Noah W. Palm   教授（耶鲁大学） Jason M. Crawford 教授（耶鲁大学） 原文链接 DOI:10.1038/s41557-025-01789-w G蛋白偶联受体（G protein-coupled receptors, GPCRs）作为维持机体稳态和信号转导的核心蛋白，广泛分布于中枢神经系统、免疫系统及代谢组织中，参与调控炎症反应、激素调节等关键生理过程。由于其药理可塑性高且具有显著的受体亚型特异性，GPCR已成为现代药物研发中最重要的靶点之一。目前，约三分之一临床药物都以GPCRs为作用靶点，涵盖抗抑郁、抗高血压及代谢类疾病治疗药物等多个品类。尽管GPCR药物已广泛应用于临床，其疗效常表现出显著的个体间差异。传统认为，这种差异主要归因于宿主遗传背景及肝脏代谢酶活性的不同；然而，近年来越来越多的研究提示，这背后可能还存在其他潜在的影响因素。 肠道微生物群作为人体内规模最大、代谢最活跃的微生物生态系统，携带有数量庞大、功能多样的代谢酶，可执行多种类型的化学反应，被认为是影响药物反应的重要变量。这些代谢酶不仅可以参与调控宿主的生理过程，还可显著改变外源化合物的结构与活性。当前已有少量研究报道肠道微生物能够代谢心血管药物、抗癌药物及免疫抑制剂等，并影响其在宿主体内的利用效率或毒性。但目前尚不清楚这种作用是否也对GPCR药物起作用。于是，作者提出了本文的核心问题——肠道微生物能否通过代谢改造GPCR的靶向药物，进而影响其与受体的相互作用与生物活性？ 为解答这一问题，作者从化学和生物功能两个层面进行综合考量，系统地勾勒出微生物对药物的代谢图谱，并验证了这些代谢产物是否会对药物与受体之间的相互作用产生影响。该研究采用了代谢组学、功能筛查、动物实验等多项技术手段，为理解药物反应提供了全新的见解，也为未来基于微生物组的精准用药策略奠定了坚实的基础。 首先，作者介绍了本项研究整体的实验流程（图 1）。为系统评估人体肠道微生物对GPCR靶向药物的代谢影响，作者构建了一个包含30种常见肠道菌株的合成菌群模型（Bac-Mix），涵盖Firmicutes、Bacteroidetes、Actinobacteria和Proteobacteria四大门类，以再现人体肠道的代谢多样性。随后，作者选取了127种具有代表性的口服GPCR靶向药物，分别在含活菌（Bac+）与无菌的对照体系（Bac-，经3 kDa过滤除酶和细胞）中孵育。培养24小时后进行LC-MS/MS代谢组分析，并利用PRESTO-Tango体系检测药物代谢前后的GPCR活性变化。通过对代谢谱与药理功能的系统比较，研究团队筛选出被显著代谢且功能改变的药物，并进一步利用结构鉴定、单菌验证与动物实验阐明了代谢途径及药理学后果。 图1 探究肠道菌群和GPCR药物之间相互作用的实验流程。 首先，作者展示了127种GPCR药物的筛查结果及其化学空间分布（图 2）。通过主成分分析与化学指纹聚类，作者确认所选药物覆盖了GPCR靶向药物的主要结构类型，包括酯类、小分子芳香化合物、含杂环结构药物及多种免疫调节剂。这表明药物库具有较高的结构多样性，足以考察不同化学骨架对微生物代谢的敏感程度。同时，作者展示了所构建Bac-Mix的菌种组成，其涵盖了主要的菌群门类，具备执行多类型代谢反应的潜力。通过对药物孵育结果的LC-MS定量分析，约三分之一的药物在Bac+体系中出现明显消耗，其中12种药物的降解率超过80%，表明微生物对部分药物具有很强的代谢能力。随后，作者对代谢前后的药物功能进行了PRESTO-Tango检测，包括iloperidone，ponesimod，ozanimod，azilsartan medoxomil，GSK1292263等多个常用临床药物在代谢后活性显著降低，而selexipag，trimethobenzamide，SB756050等药物反而活性增强。由此可见，肠道微生物代谢可双向调节药物功能。进一步的化学聚类分析表明，代谢敏感药物通常具有酯键、芳香甲氧基及异恶唑环等易被酶识别的结构单元。 图2 细菌药物代谢筛查显示，与特定结构相关的受体活性变化呈现高度保守的特征。 在识别出潜在的受微生物代谢影响的候选药物后，作者进一步利用代谢组学分析深入解析这些变化背后的化学本质（图 3）。通过计算质量差、解析MS/MS数据并结合SIRIUS等工具注释代谢物结构等手段，研究团队进一步明确了药物活性变化所对应的具体微生物代谢反应，其中包括 O-去甲基化、酯键水解、芳环还原以及杂环的开环与重排等多种反应类型。这些代谢反应形成了一个丰富的化学反应图谱，表明微生物代谢能够对药物结构进行深层次的修饰。更重要的是，作者将这些反应类型与药物原有结构特征进行比较时，发现易被代谢的药物通常含有较为活泼的官能团，如酯键、芳香甲氧基等杂环结构，而相对稳定的芳香结构则不易被微生物代谢。 图3 代谢物的结构测定揭示了六种药物通过非常规途径改变药物活性。 基于上述筛查结果，作者选取了精神类药物iloperidone进行深入分析。该药物在Bac+条件下显著减少，同时生成多个较为独特的代谢产物，分子离子峰分别为m/z 430、432和444。通过MS/MS解析、分离纯化以及1D/2D NMR结构解析，作者确定其中m/z 430的产物为异恶唑环开裂后的水解产物，m/z 432则是在此基础上的进一步的还原产物。m/z 444中含有硫元素，是一种极为少见的噻吩骨架重排产物。研究推测该反应可能是经历了异恶唑环开裂、硫源亲核加成及脱水环化等步骤后的产物。这一反应在已知生物体系中极其少见，显示出肠道微生物具备无法通过传统代谢途径预测的化学重构能力。更加关键的是，PRESTO-Tango检测显示，该含硫产物完全丧失了原药物对多巴胺D₂受体的拮抗活性。该发现首次揭示了肠道微生物能够执行生物体中罕见的C-S键形成反应，显著拓展了已知的生物化学反应类型。 图4 比较代谢组学的分析揭示了iloperidone的非常规药物代谢途径。 为进一步追溯不同代谢反应的来源，作者随后针对多种菌株进行了靶向代谢验证（图 5）。作者选取了12种具有代表性的肠道菌，研究结果表明代谢呈现出显著的菌种特异性：Clostridium sporogenes与Eggerthella lenta在多种药物的O-去甲基化与酯水解反应中起关键作用，而Bacteroides thetaiotaomicron则主要催化selexipag的酯键断裂。此外，一些涉及复杂结构重组的反应（如ponesimod的去氯和还原）则需要多个菌株协同完成。这表明群体代谢具有互补性和协同性，单一菌株无法完全实现群体代谢的功能。 图5 多种细菌的药物代谢图。 在解析了 iloperidone 的主要代谢产物来源之后，作者注意到某些代谢特征仍无法得到很好的解释，因此将目光集中在代谢指纹较为独特的Morganella morganii 上，这一菌株在初筛中能够生成其他菌株完全无法产生的加成型衍生物。LC-MS 分析显示，M. morganii 能够生成多种比原药分子量更大的代谢物，例如 m/z 491、493 与 477 等，这些高分子量产物均保留了 iloperidone 的核心结构，却在外围基团上出现了显著扩增。为了追踪这些额外结构的来源，作者利用稳定同位素标记了部分氨基酸（如¹³C₅-赖氨酸和D₄-鸟氨酸），结果显示这些氨基酸确实被整合进药物骨架中，提示 M. morganii 可利用环境中的小分子氨基酸对药物进行共价加成，形成此前未被报道过的三环杂环结构。这一过程属于高度复杂的化学生物合成重构，彻底改变了药物骨架的电子结构与空间构型，使得其对GPCR的结合能力完全丧失。该发现揭示了肠道微生物对药物的影响并不局限于破坏性代谢，还可通过构建新化学键、整合外源小分子等机制，使药物发生深度的骨架重排，进而彻底改变其药理性质。 图6 M. morganii D82通过氨基酸利用使iloperidone失活。 最终，为了确认这些代谢反应在生理环境中是否真实发生，作者进行了体内验证实验。在定殖了Bac-Mix的小鼠和无菌小鼠口服iloperidone后，作者对其盲肠和结肠内容物进行了LC-MS分析。结果显示，在含菌小鼠中可检测到iloperidone的主要代谢产物ilo-430与ilo-432，而在无菌对照组中未检测到，说明这些代谢反应在体内同样发生。尽管ilo-444等含硫重排产物未被检测到，但整体结果仍证明了体外观察到的代谢现象具有生理相关性，作者解释出现这一现象的原因可能与其生成速率低或代谢速率快有关。这一体内验证使研究结论从化学层面延伸至生理层面，进一步强调了肠道微生物在药物代谢与调控中的重要作用。 图7 生理环境下iloperidone的细菌代谢。 本研究系统揭示了人体肠道微生物能够通过多样的化学反应调控GPCR靶向药物的生物活性，建立了“微生物代谢-药物结构-受体功能”的因果联系。研究发现，微生物通过水解、去甲基化、还原及杂环重排等反应可改变药物骨架，导致药物活性改变。以iloperidone为例，微生物代谢可引发前所未有的硫代重排与氨基酸偶联反应，从根本上改变了药物与受体的结合方式。该研究不仅拓宽了药物代谢学的研究边界，也为精准用药提供了新的理论依据。未来，考虑肠道菌群的代谢潜能将成为药物研发与个体化治疗不可或缺的环节。 END 供稿：尚成彬 编辑：王玉杰 审核：高翔、焦绪瑶、吕惠惠 责编：焦绪瑶 ←扫码了解Gaolab 扫码关注公众号 →