A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Clinical Efficacy and Safety of VTX002 in Subjects With Moderately to Severely Active Ulcerative Colitis

This is a study to understand if taking VTX002 daily as a tablet orally is safe and effective in participants diagnosed with moderate to severe ulcerative colitis (UC). Approximately 189 participants will take VTX002 Dose A, VTX002 Dose B, or matching placebo, once daily.
The study consists of a 28-day Screening Period (to see if a participant qualifies for the study), a 13-week double-blind period (a participant receives either active Dose A, Dose B or Placebo), a Long-Term Extension (LTE) Treatment Period of up to 39 weeks, an Open-Label Extension (OLE) Treatment Period of up to 143 weeks, and a 2-week Follow-Up Period. The maximal duration of treatment including the Induction Period, LTE and OLE will be 36 months.

开始日期2021-11-30

申办/合作机构

Oppilan Pharma Ltd.

NCT04451811

/ Completed临床1期

A Pharmacokinetic Dose Proportionality Study of OPL-002 in Healthy Volunteers

This is a single center, randomized, open-label, three-way crossover, single dose, pharmacokinetic dose proportionality study of oral OPL-002 in healthy subjects.

开始日期2020-09-07

申办/合作机构

Oppilan Pharma Ltd.

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100 项与他木兹莫德相关的专利（医药）

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项与他木兹莫德相关的文献（医药）

2025-03-01·The Lancet Gastroenterology & Hepatology

Tamuzimod in patients with moderately-to-severely active ulcerative colitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 induction trial

Article

作者: Rubin, David T ; Schreiber, Stefan ; Peyrin-Biroulet, Laurent ; Panaccione, Remo ; Danese, Silvio ; D'Haens, Geert ; Jairath, Vipul ; Ogilvie, Kathleen ; Sands, Bruce E ; Gilder, Kye ; Walczak, Michael ; Vermeire, Severine ; Sandborn, William J ; DuVall, Aaron ; Naik, Snehal ; Lindstrom, Beatriz ; Kierkus, Jaroslaw

BACKGROUND:

Tamuzimod (VTX002) is a selective sphingosine 1-phosphate receptor 1 modulator in development for ulcerative colitis. We aimed to assess the safety and efficacy of tamuzimod in patients with moderately-to-severely active ulcerative colitis.

METHODS:

This double-blind, randomised, placebo-controlled, phase 2 induction trial was conducted at 122 centres across 15 countries in Asia, Europe, and North America. Patients aged 18-80 years with a modified Mayo score (MMS) of 4-9 and an inadequate response or a loss of response, or intolerance to one or more approved ulcerative colitis therapies were randomly assigned (1:1:1) to once-daily oral tamuzimod (60 mg or 30 mg) or placebo for 13 weeks. Randomisation was stratified by previous advanced therapy, baseline corticosteroid, and baseline MMS. The primary endpoint was clinical remission (defined as an MMS stool frequency subscore of ≤1, rectal bleeding subscore of 0, and endoscopic subscore ≤1, excluding friability) at week 13. Adverse events and laboratory abnormalities were assessed for safety. Efficacy and safety analyses included all randomly assigned patients who received at least one study dose, with the efficacy analysis restricted to patients with a baseline MMS of 5-9 based on regulatory feedback. The study was registered with ClinicalTrials.gov, NCT05156125, and EudraCT, 2021-003050-23.

FINDINGS:

Between Nov 4, 2021, and Aug 30, 2023, 367 patients were screened, and 213 (mean age 40·6 years [SD 14·2]; 116 [54%] males and 97 [46%] females) were randomly assigned to tamuzimod 60 mg (n=70), tamuzimod 30 mg (n=73), or placebo (n=70). Two in the tamuzimod 30 mg group and two in the tamuzimod 60 mg group with baseline modified Mayo score of 4 were excluded from the efficacy analysis. At week 13, clinical remission was reached by 19 (28%) of 68 patients receiving tamuzimod 60 mg, 17 (24%) of 71 patients receiving tamuzimod 30 mg, and eight (11%) of 70 patients receiving placebo (risk difference 16·5% [95% CI 3·2 to 29·4], p=0·018, for tamuzimod 60 mg vs placebo and 12·5% [-0·2 to 24·9], p=0·041, for tamuzimod 30 mg vs placebo). Treatment-emergent adverse events occurred in 33 (47%) of 70 patients receiving tamuzimod 60 mg, 34 (47%) of 73 patients receiving tamuzimod 30 mg, and 24 (34%) of 70 patients receiving placebo. Most adverse events were mild or moderate. The most frequently reported treatment-emergent adverse events (in ≥5% of in any treatment group) were upper respiratory tract infection (six [9%] of 70 patients in the tamuzimod 60 mg group, one [1%] of 73 in the tamuzimod 30 mg group, and one [1%] of 70 in the placebo group), anaemia (three [3%], four [5%], and six [9%]), and headache (four [6%], five [7%], and two [3%]). No adverse events of atrioventricular block, bradycardia, macular oedema, severe or opportunistic infections, malignancies, or deaths occurred.

INTERPRETATION:

Induction therapy with tamuzimod was effective and well tolerated in patients with ulcerative colitis. These results and the favourable risk-benefit profile of tamuzimod collectively support the continued clinical development of tamuzimod for the treatment of moderately-to-severely active ulcerative colitis.

FUNDING:

Ventyx Biosciences.

2025-03-01·The Lancet Gastroenterology & Hepatology

No easy way out: blocking lymphocyte egress by the S1P1 receptor 1 modulator tamuzimod in ulcerative colitis

Article

作者: Atreya, Raja ; Neurath, Markus F

2024-09-01·Expert Opinion on Drug Metabolism & Toxicology

Pharmacokinetics of S1P receptor modulators in the treatment of ulcerative colitis

Review

作者: Vieujean, Sophie ; Peyrin-Biroulet, Laurent

INTRODUCTION:

Ulcerative colitis is a chronic inflammatory bowel disease, affecting the colorectal mucosae, with a relapsing-remitting course, characterized by the trafficking and gathering of lymphocytes in the inflammatory intestinal mucosa. Sphingosine-1-phosphate (S1P) receptor modulators preventing lymphocytes egress from lymphoid tissues to the active inflammation site is an alternative therapeutic option in this condition.

AREA COVERED:

We carried out a comprehensive review of the literature available on Medline, Scopus and Embase regarding the pharmacokinetics of S1P receptor modulators. For each compound, we reviewed the mechanism of action, pharmacokinetic data and efficacy and safety data from phase 3 studies and real-life studies when available.

EXPERT OPINION:

S1P receptor modulators, including ozanimod and etrasimod (both currently on the market) as well as VTX002 (under development), are a new class of drugs for the treatment of moderate to severe ulcerative colitis, inducing and maintaining the remission. Due to its pharmacokinetic features, this class of drugs has certain advantages such as an oral administration, a short half-life, a high volume of distribution, and no immunogenicity. On the other hand, there are risks of cardiological and ophthalmological side-effects, as well as drug-drug interactions risk, that require special attention from the healthcare providers.

项与他木兹莫德相关的新闻（医药）

2026-10-10

·药化小白

S1P1受体药物研究进展

S1P1受体药物研究进展：从非选择性到高选择性，从海外到国产突围靶点机制 · 已上市药物 · 国内外管线 · 临床数据 · 最新文献一、靶点概述：S1P受体家族如何调控免疫鞘氨醇-1-磷酸（Sphingosine-1-phosphate, S1P）是一种由鞘氨醇激酶生成的溶血磷脂类信号分子，通过结合五个G蛋白偶联受体亚型 S1PR1–S1PR5（又称 Edg-1/5/3/6/8）发挥生物学作用1,2。其中 S1PR1 是调控 T、B 淋巴细胞向外周迁移的核心受体：体内存在明显的 S1P 浓度梯度——血浆中较高（约 1 µM），淋巴组织间质中较低（约 100 nM）。淋巴细胞借助 S1PR1 感知该梯度，从而迁出淋巴结进入体循环1,2。合成的小分子 S1P1 调节剂（激动剂/功能性拮抗剂）与 S1PR1 结合后，诱导受体内化并被降解，使淋巴细胞"听不见"外周 S1P 梯度，从而滞留于淋巴结、无法进入外周血与炎症组织。这一"药理性的淋巴细胞隔离"正是其抑制中枢神经系统、肠道与皮肤炎症的共同机制1,2。五个亚型功能各异：S1PR1 主导淋巴细胞迁移；S1PR3 与心动过缓、房室（AV）传导阻滞等心血管不良反应相关，是第二代药物重点规避的"脱靶"；S1PR5 主要表达于少突胶质细胞，常与 S1PR1 联用（1/5 选择性）；S1PR2 参与血管与发育调控2,3。因此，提升对 S1PR1 的选择性、尤其是规避 S1PR3，成为该领域药物化学的核心命题。图 1 S1P1 受体调节剂的作用机制。左图：生理状态下 S1P 浓度梯度（淋巴结内低、体液/循环中高）驱动 CCR7+ naive / central memory T、B 淋巴细胞从淋巴结迁出；S1PR1 调节剂诱导 S1PR1 内化/功能拮抗，阻断淋巴细胞沿 S1P 梯度离开淋巴结，从而减轻外周组织（肠、脑、皮肤等）炎症。右图：已上市/在研 S1PR1 调节剂（ozanimod、etrasimod、VTX002 等）对 S1PR1–5 的选择性差异及相应功能。引自 Bencardino, S.; et al. J. Clin. Med. 2023, 12 (15), 5014[33]（MDPI，CC BY 4.0）。二、适应症版图：靶向不同亚型，能治什么以 S1PR1 为核心的调节剂已覆盖多类自身免疫与炎症疾病：多发性硬化（MS，包括复发缓解型 RRMS 与继发进展型 SPMS）、溃疡性结肠炎（UC）、克罗恩病（CD）、银屑病、系统性红斑狼疮（SLE）、以及移植物抗宿主病（GvHD）/造血干细胞移植3,5,6,10,15。但安全性始终是天花板——已知风险包括首剂心动过缓、AV 阻滞、黄斑水肿、肝酶升高、淋巴细胞减少，以及芬戈莫德特有的进行性多灶性脑白质脑病（PML）与感染风险1,2。其中芬戈莫德与珀奈莫德需首剂心电监测与剂量滴定；奥扎莫德与依曲莫德因对 S1P3 活性极弱，通常无需首剂心脏监测，临床便捷性更优3,10,11。正因 S1PR3 关联心脏毒性，第二代药物普遍追求"高 S1P3 选择性"以降低心血管事件2,3,13,14。三、已上市药物：从非选择性到高选择性的演进 S1P 调节剂的上市史是一条"选择性递进"的清晰轨迹：芬戈莫德（非选择性 1/3/4/5）→ 西尼莫德/奥扎莫德（1/5 选择性）→ 珀奈莫德/依曲莫德（1 选择性/高 S1P1 亲和）。下表汇总五款已上市药物的关键信息。表1 已上市 S1P 受体调节剂汇总名称（商品名）靶点选择性开发公司首次上市年中国上市（年）主要适应症优缺点参考文献芬戈莫德Fingolimod（捷灵亚/Gilenya） S1PR1/3/4/5（非选择性） Novartis 2010（美国） 2019-07 RRMS 优：首个口服 MS 疾病修正药（DMT），开创靶点。缺：非选择性→首剂心动过缓、黄斑水肿、肝毒、PML、需首剂心电监测1,2 西尼莫德Siponimod（万立能/Mayzent） S1PR1/5 Novartis 2019（美国） 2020-05 SPMS（及 RRMS）优：首个口服 SPMS 药物；较芬戈莫德 S1P3 选择性提高。缺：首剂心脏监测、黄斑水肿、肝酶升高3,4 奥扎莫德Ozanimod（Zeposia/奥扎莫德） S1PR1/5 BMS/Celgene/Receptos 2020（美国 MS） 2023-02 RRMS、UC 优：口服、无需复杂滴定。缺：UC 疗效"天花板"明显；启动前需 LFT/CBC/眼科；CD 的 III 期 YELLOWSTONE 未达主要终点175,6,7,17 珀奈莫德Ponesimod（Ponvory） S1PR1（高选择性） Janssen/Actelion 2021（美国）未上市（台湾 2022-01、香港 2022-10） RMS 优：已上市中对 S1P3 选择性最高（约 650 倍）、整体 S1P1 选择性突出；停药约 1 周淋巴细胞恢复（可逆快）；首个头对头优于特立氟胺者8。缺：首剂心动过缓/AV 阻滞、黄斑水肿、肝毒；中国大陆不可及8,9 依曲莫德Etrasimod（维适平/VELSIPITY） S1PR1/4/5（高亲和 1/4/5，极少 S1P3，无 S1P2） Pfizer/Arena→云顶新耀（中国权益） 2023（美国） 2026-02 中重度 UC 优：best-in-disease 潜力、深度黏膜愈合、起效快、无激素缓解、无需复杂滴定、安全性佳。缺：S1P4 参与（多属良性）；CD 的 CULTIVATE 因疗效不足中止1810,11,12,18,21 图 2 已获批上市的 5 个 S1P 受体调节剂（结构取自 PubChem 权威记录；奥扎莫德 (1S)、珀奈莫德 (2R)、依曲莫德 (3R) 为单一对映体，已按核查后的绝对构型以实楔/虚楔绘制；芬戈莫德、西尼莫德无手性中心）四、国内外在研管线（按 III / II / I 期）国外企业 III 期进行中：Mocravimod（Priothera / Kyorin，原 KRP203）——口服 S1P1 调节剂，用于急性髓系白血病（AML）异基因造血干细胞移植后 GvHD 预防。全球 III 期 MO-TRANS（NCT05429632）正在入组，预计 2027–2028 年读出，并已获 FDA/EMA 孤儿药认定19。其作用特点是在保留移植物抗白血病（GvL）效应的同时降低 GvHD，是 S1P 机制在血液肿瘤领域的差异化拓展。 III 期受挫（重要警示）：奥扎莫德 CD 的 YELLOWSTONE III 期诱导研究未达临床缓解主要终点，项目已终止17；依曲莫德 CD 的 CULTIVATE II/III 期因亚组疗效不足提前终止18。这提示 S1P 调节剂在 CD 这一适应症上集体遭遇瓶颈。 II 期及以前：Amiselimod（MT-1303，三菱田边→Biogen）——高选择性 S1P1 前药，CD II 期未优于安慰剂（CDAI100 应答 48.7% vs 54.1%）15，MS（MOMENTUM）因策略原因停止；Ceralifimod（ONO-4641，Ono/Merck）——S1P1/5、S1P3-sparing，MS II 期（DreaMS）显示病变减少但未推进 III 期（策略原因）14；CS-0777（Daiichi Sankyo）——选择性 S1P1，MS II 期（已停）13。国内企业（按进展排序） III 期在望 / II 期后期：TT-01688（药捷安康 / TransThera，源自 LG Chem）——高选择性口服 S1P1 调节剂。溃疡性结肠炎 Ib/II 期已完成、即将启动 III 期注册临床；特应性皮炎（AD）处于 II 期。这是目前国产 S1P1 进展最快的品种22。 II 期：HE009（南昌弘益）——选择性 S1P1 调节剂（拮抗剂），用于系统性红斑狼疮（SLE）。II 期（IIa/IIb）于 2025-08 组长单位（北京大学人民医院）启动，多中心推进中23。 II 期：CBP-307 / Icanbelimod（康乃德，苏州）——选择性 S1P1 调节剂，中重度 UC 的 II 期剂量探索研究（CN002，NCT04700449）已完成，并公布诱导期与 48 周维持期阳性数据；公司 2026 年披露将推进下一阶段临床20。 I 期 / IND：艾托莫德 Ethoximod（渐宽生物，苏州，联合中国医学科学院药物研究所）——高选择性 S1PR1 激动剂，用于银屑病。已完成健康受试者 Ia（单次给药）与 Ib（多次给药）PK/PD 研究，显示剂量依赖性降低外周淋巴细胞；2026-08-03 递交银屑病 IND 并获 CDE 受理24。全球在研 S1P1 调节剂结构总览为便于一览全球在研分子，下文给出整合管线表（表 2）与对应结构总览（图 3）。Cenerimod（Idorsia/Viatris）和 Mocravimod（Kyorin/Asahi Kasei）为全球 III 期在研：Cenerimod 用于系统性红斑狼疮（SLE，OPUS-1/2）19,25；Mocravimod 用于急性髓系白血病异基因移植后 GvHD 预防（MO-TRANS）19。TT-01688（药捷安康/LG Chem）是国产最快 S1P1，UC 注册性 II/III 期在望、AD II 期22；CBP-307（康乃德）UC II 期已完成阳性数据20；HE009（南昌弘益）SLE II 期已启动，但结构未公开，详见其专利 WO2021/175225 / CN115210223B31。其余中小型 I/II 期项目（Amiselimod、ONO-4641、ASP4058、CS-0777、Udifitimod、Vibozilimod、SAR247799、GSK2018682、AKP11、艾托莫德等）多处于停滞或已终止状态，反映该靶点临床开发门槛较高15,14,28,13,26,27,29,30,32,24。图 3 全球临床在研 S1P1 受体调节剂结构（11 个有公开结构 + 1 个 HE009 专利占位；GSK2018682、AKP11 等见下表）。立体化学标注说明：奥扎莫德等之外的在研分子中，Cenerimod、ASP4058 各含 1 个手性中心（均为 S 构型），CS-0777 为 (3R)，Udifitimod 含 3 个手性中心，CBP-307 为 cis-(1s,3s)-3-氨基环丁烷-1-甲酸头基（1,3-二取代环丁烷的两个环碳非 CIP 手性中心，只能以 cis/trans 描述，无法给出 R/S）——以上均按 PubChem/ChEMBL 权威记录以楔键绘制；Mocravimod、TT-01688(zectivimod)、Amiselimod、ONO-4641、Vibozilimod、SAR247799、GSK2018682 无手性中心，故不标立体化学符号。表 2 全球临床在研 S1P1 受体调节剂汇总（含结构来源 / 专利）编号代号（通用名）研发公司（国家/地区）最高阶段·适应症结构来源（PubChem CID / 专利）参考文献 1 Cenerimod(ACT-334441) Idorsia / Viatris（瑞士/美） SLE III 期（OPUS-1 NCT05648500；OPUS-2 NCT05672576） PubChem CID 4987197325 2 Mocravimod(KRP-203) Kyorin / Asahi Kasei（日） AML 异基因移植后 GvHD 预防 III 期（MO-TRANS NCT05429632） PubChem CID 1115587419 3 TT-01688(zectivimod) 药捷安康 / LG Chem（中/韩） UC 注册性 II/III 期（2024-12 NMPA 批）；AD II 期（2025-01 完成） PubChem CID 9035630722 4 CBP-307(icanbelimod) 康乃德生物 Connect（中） UC II 期（NCT04700449 完成）；Crohn、AD PubChem CID 139266790（C24H26FN3O3；cis-(1s,3s)-3-氨基环丁烷-1-甲酸头基）20 5 HE009 南昌弘益药业（中） SLE II 期（2025-08 启动）结构未公开：专利 WO2021/175225 / CN115210223B31 6 Amiselimod(MT-1303) Mitsubishi Tanabe（日） CD II 期（未优于安慰剂）；MS / PsO PubChem CID 1612948315 7 Udifitimod(BMS-986166) Bristol-Myers Squibb（美） AD II 期（NCT05014438）；UC I 期（NCT03038711） PubChem CID 11887751626 8 Vibozilimod(SCD-044) Sun Pharma Advanced Research（印） PsO / AD II 期（SOLARES 未达终点，终止） PubChem CID 6657456427 9 ONO-4641(ceralifimod) Ono / Merck KGaA（日/德） MS II 期（2014 终止） PubChem CID 1150299614 10 ASP4058 Astellas（日） I 期（NCT01998646 完成） PubChem CID 1675514328 11 CS-0777 Mitsubishi Tanabe / Daiichi Sankyo（日） MS I 期（NCT00616733） PubChem CID 1137129013 12 SAR247799 Sanofi（法） I 期（已终止；G 蛋白偏向型，不致脱敏/淋巴细胞减少） PubChem CID 5331212729 13 GSK2018682 GSK（英） MS / 健康人 I 期（NCT01387217 等） PubChem CID 2498820130 14 AKP11 Kyorin / Asahi Kasei（日）外用 PsO I/II 期（ANZCTR ACTRN12613001226796 等）结构/代号待公司披露32五、临床数据分析表 3 关键注册临床研究疗效汇总药物研究适应症关键疗效（活性药 vs 安慰剂）备注参考文献奥扎莫德 RADIANCE RRMS 年化复发率（ARR）0.17/0.22 vs 0.28（IFNβ-1a）复发率显著降低5 奥扎莫德 True North UC 临床缓解：诱导 18.4% vs 6.0%；维持 37.0% vs 18.5% NEJM 20216 珀奈莫德 OPTIMUM RMS ARR 0.202 vs 0.290（特立氟胺），相对降低 30.5% 头对头优于活性对照8 依曲莫德 ELEVATE UC 52 UC 临床缓解：12 周 27.0% vs 7.0%；52 周 32.1% vs 6.7% Lancet 202310 依曲莫德 ENLIGHT UC UC（亚洲）维持 40 周临床缓解 48.1% vs 12.5%；黏膜愈合 51.9% vs 8.8% Lancet Gastroenterol Hepatol 202511 奥扎莫德 YELLOWSTONE CD 诱导 12 周临床缓解未达主要终点项目终止17 依曲莫德 CULTIVATE CD 亚组 1 内镜应答低（2 mg 21%、3 mg 10%）因疗效不足提前终止18 Amiselimod CD II 期 CD CDAI100 应答 48.7% vs 54.1% 未优于安慰剂15哪些分子最优？ UC 领域：依曲莫德（Etrasimod）数据最优——ENLIGHT UC 黏膜愈合率达 51.9%、维持期临床缓解 48.1%，且起效快、无需滴定、安全性特征良好，被普遍认为具 best-in-disease 潜力10,11；奥扎莫德 True North 维持缓解约 37%，疗效天花板明显，且 CD 已失败6,17。MS 领域：珀奈莫德在头对头研究（OPTIMUM）中优于特立氟胺，是已上市品种中 S1P1 选择性最高、可逆性最好者；西尼莫德则是首个口服 SPMS 药物3,8。总体趋势是"1 选择性 / 高 S1P3 选择性"，但 CD 已成为 S1P 调节剂集体折戟的适应症。国内进展最快、药效最好的是谁？自研进度：药捷安康 TT-01688 领跑（UC 即将 III 期、AD II 期），南昌弘益 HE009、康乃德 CBP-307 紧随其后20,22,23。若论"中国可及的 S1P1 商业化成功"，云顶新耀引进的依曲莫德（维适平）于 2026-02 在中国获批，是当前国产权益下最成功的 S1P1 相关药物21。六、最新文献（2024–2026）：代表性小分子（年份 / 数据优点 / 参考文献）以下汇总 2024–2026 年发表的高选择性 S1P1（及 S1P1/5）激动剂代表性工作。核心方向有二：① 继续提升对 S1P3 的选择性以根除心动过缓等心血管风险；② 探索偏向性（β-arrestin biased）或计算设计的新机制 / 新骨架。表中标注发表年份；代表性分子结构见图 4（化合物 28 结构暂以原文献为准）。表 4 代表性 S1P1 / S1P1·5 调节剂文献汇总（2024–2026）编号年份分子数据 / 优点参考文献 1 2024 HY-X-1011（R 型）计算设计 S1PR1高选择性激动剂（任若冰/竺立哲等，复旦·港中大深圳）物理驱动自动化路径搜索（PNAS 2024）计算设计的全新骨架；BRET 证实其激活 S1PR1 达纳摩尔级，对 S1PR3/5 选择性约 100 倍（2 个数量级）；S/R 两构型均高选择性激活 S1PR1，为“仅靶向 S1PR1”的超选择性激动剂提供计算方法范式。其 S1PR1–Gi 复合物冷冻电镜结构已解析，配体坐标见 PDB 9VNZ。 Ti R, Pang B, Yu L, et al.; Ren R, Zhu L, Warshel A. Fine-tuning activation specificity of GPCRs via automated path searching. Proc Natl Acad Sci U S A. 2024;121(8):e2317893121. DOI:10.1073/pnas.2317893121. PMID:38346183. 2 2025 Y18（叶天宇/李洪林等，华东理工）反转型 1,2,4-噁二唑骨架（氮杂环丁烷-3-甲酸头、2-氯苄基连接、4-异丁基-3-三氟甲基苯尾，分子式 C24H23ClF3N3O3）；对 S1PR1 EC50 = 0.98 nM，对 S1PR2/3/5 > 10,000 倍选择性、对 S1PR4 109 倍选择性；强效诱导受体内化并阻断回收，从源头规避心血管风险。 Ye T, Zhu L, Li H, et al. Discovery and SAR study of highly selective and potent 1,2,4-oxadiazole-based S1PR1 agonists. Eur J Med Chem. 2025;300:118097. DOI:10.1016/j.ejmech.2025.118097. PMID:40911968. 3 2025 化合物 28（S1P1 agonist 7）（Lee 等，KIST，韩国）首个 β-arrestin 偏向性 S1P1 激动剂；EC50(G-protein)=12.7 nM、EC50(β-arrestin)=3.23 nM，偏向因子 4.51（vs 芬戈莫德）；外周淋巴细胞降至基线 24.4%，iPSC 心肌细胞无心率影响；EAE 模型有效。 Lee CY, Gotina L, Kim J, et al. Discovery of Novel β-Arrestin Biased Sphingosine-1-Phosphate-1 Receptor Agonists for the Treatment of Multiple Sclerosis. J Med Chem. 2025;68(17):18289–18313. DOI:10.1021/acs.jmedchem.5c00859. PMID:40853740. 4 2026 TYY-31（叶天宇/贺欢/李洪林等，华东理工） 3-芳基-5-双芳基-1,2,4-噁二唑；对 S1PR1 EC50 = 1.13 pM（单 digit pM），对 S1PR2/3/5 EC50 > 10 μM、对 S1PR4 > 30,000 倍选择性；DSS 结肠炎 0.3 mg/kg ≈ 奥扎莫德 1 mg/kg；斑马鱼心脏安全性优异。 Ye T, Xiao Y, Tang C, et al. Rational Design, Synthesis, and Biological Evaluation of Potent, Highly Selective 1,2,4-Oxadiazole-Based S1PR1 Agonists for UC Treatment. J Med Chem. 2026;69(9):10660–10684. DOI:10.1021/acs.jmedchem.5c03837. PMID:41996212. 5 2026 化合物 19（S1PR1/S1PR5 agonist-1）（魏欣欣/柳红/王江等，上海药物所）头基为 trans-4-甲基吡咯烷-3-羧酸（图中按原文献所绘对映体，指定为 (3R,4R)；原文仅命名相对构型 trans）；3-(萘-1-基)-1,2,4-噁二唑；S1PR1/5 双重激动，EC50 = 40.0 / 22.9 nM，对 S1PR2/3/4 的 EC50 均 > 10,000 nM（基于 S1PR1 EC50 40.0 nM，计算选择性 > 250 倍；原文摘要报道 > 1000 倍选择性）、无 S1PR3 活性；对小鼠心率影响极小；DSS-IBD 显著缓解。 Wei X, Yuan K, Zhao J, et al. Discovery of Novel Selective Dual Agonists Targeting S1PR1 and S1PR5 for the Treatment of Inflammatory Bowel Disease. J Med Chem. 2026;69(5):5575–5593. DOI:10.1021/acs.jmedchem.5c02690. PMID:41712781. 6 2026 化合物 37（S1PR1/S1PR5 agonist-2）（魏欣欣/柳红/王江等，上海药物所）头基同为 trans-4-甲基吡咯烷-3-羧酸（图中指定为 (3R,4R)）；3-(萘-1-基)-1,2,4-噁二唑；化合物 19 的正丙氧基（n-propoxy）异构体；S1PR1/5 双重激动，EC50 = 33 / 173.8 nM，对 S1PR2/3/4 的 EC50 均 > 10,000 nM；DSS-IBD 与化合物 19 疗效相当、对小鼠心率影响极小。 Wei X, Yuan K, Zhao J, et al. Discovery of Novel Selective Dual Agonists Targeting S1PR1 and S1PR5 for the Treatment of Inflammatory Bowel Disease. J Med Chem. 2026;69(5):5575–5593. DOI:10.1021/acs.jmedchem.5c02690. PMID:41712781. 图 4 代表性 S1P1 调节剂结构（HY-X-1011、Y18、TYY-31、化合物 19、化合物 37）。注：① 化合物 19 与 37 共用同一手性砌块 trans-4-甲基吡咯烷-3-羧酸，原文化合物名仅标注相对构型“trans”，图中按其结构图所绘对映体绘制，RDKit 指定为 (3R,4R)；其对映体 (3S,4S) 亦属 trans，若原文实际使用另一对映体，两者互为镜像，相对构型描述不受影响。② TYY-31 的 cis 相对构型（COOH 与 NH 位于环丁烷平面同侧）已用三维几何验证；1,3-二取代环丁烷的两个环碳并非 CIP 手性中心，故只能以 cis/trans 描述而无 R/S。③ Y18 的头基氮杂环丁烷-3-甲酸无手性中心（C3 的两个环 CH2 等价）。④ HY-X-1011 结构取自其与 S1PR1–Gi 复合物的冷冻电镜结构（PDB 9VNZ，配体 A1ESY，磷酸酯形式 C25H28F4N3O6P），该记录中手性碳标注为 (2S)，而 PNAS 原文称 HY-X-1011 为 R 型（S 型为 HY-X-1010），此处按 PDB 沉积结构绘制。七、总结与未来方向现有结果：已有 5 款 S1P 调节剂上市，选择性沿"非选择性→1/5→1 选择性"递进。UC 是 S1P 调节剂最成功的新战场，其中依曲莫德疗效与安全性综合最佳；MS 领域珀奈莫德、西尼莫德各有定位；而 CD 则是该机制集体受挫的适应症。国产力量正在崛起——自研的 TT-01688、HE009、CBP-307、艾托莫德与商业化引进的依曲莫德（维适平）共同构成中国 S1P1 赛道的多点布局20,21,22,23,24。未来方向：① 继续提升 S1P3 选择性（如 Y18 对 S1P3 >10000 倍），从源头规避心动过缓与 AV 阻滞；② 拓展适应症边界（SLE、AD、GvHD/移植、银屑病）；③ 明确口服小分子相对生物制剂的定位与联用策略；④ 积累真实世界长期安全性数据；⑤ 推进国产替代与本地化生产，提升可及性16,24。S1P1 靶点已从"概念验证"走向"差异化竞争"，高选择性、口服便捷与更广适应症，将是下一阶段的主旋律。参考文献参考文献 [1] Kappos, L.; Radue, E.; O'Connor, P.; Polman, C.; Hohlfeld, R.; Calabresi, P.; Selmaj, K.; Agoropoulou, C.; Leyk, M.; Zhang-Auberson, L.; Burtin, P. 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Etrasimod as Induction and Maintenance Treatment for Patients with Moderately to Severely Active Ulcerative Colitis in East Asia (ENLIGHT UC): A Randomised, Double-Blind, Placebo-Controlled, Multicentre, Phase 3 Study. Lancet Gastroenterol. Hepatol. 2025, 10 (12), 1089-1103. DOI: 10.1016/S2468-1253(25)00198-0 [12] Buzard, D. J.; Kim, S. H.; Lopez, L.; Kawasaki, A.; Zhu, X.; Moody, J.; Thoresen, L.; Calderon, I.; Ullman, B.; Han, S.; et al. Discovery of APD334: Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-Phosphate-1 Receptor. ACS Med. Chem. Lett. 2014, 5 (12), 1313-1317. DOI: 10.1021/ml500389m [13] Nishi, T.; Miyazaki, S.; Takemoto, T.; Suzuki, K.; Iio, Y.; Nakajima, K.; Ohnuki, T.; Kawase, Y.; Nara, F.; Inaba, S.; Izumi, T.; Yuita, H.; Oshima, K.; Doi, H.; Inoue, R.; Tomisato, W.; Kagari, T.; Shimozato, T. Discovery of CS-0777: A Potent, Selective, and Orally Active S1P1 Agonist. ACS Med. Chem. Lett. 2011, 2 (5), 368-372. DOI: 10.1021/ml100301k [14] Kurata, H.; Kusumi, K.; Otsuki, K.; Suzuki, R.; Kurono, M.; Komiya, T.; Hagiya, H.; Mizuno, H.; Shioya, H.; Ono, T.; Takada, Y.; Maeda, T.; Matsunaga, N.; Kondo, T.; Tominaga, S.; Nunoya, K.; Kiyoshi, H.; Komeno, M.; Nakade, S.; Habashita, H. Discovery of a 1-Methyl-3,4-dihydronaphthalene-Based Sphingosine-1-Phosphate (S1P) Receptor Agonist Ceralifimod (ONO-4641). A S1P1 and S1P5 Selective Agonist for the Treatment of Autoimmune Diseases. J. Med. Chem. 2017, 60 (23), 9508-9530. DOI: 10.1021/acs.jmedchem.7b00785 [15] D'Haens, G.; Danese, S.; Davies, M.; Watanabe, M.; Hibi, T. A Phase II, Multicentre, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Efficacy of Amiselimod in Patients with Moderate to Severe Active Crohn's Disease. J. Crohns Colitis 2022, 16 (5), 746-756. DOI: 10.1093/ecco-jcc/jjab201 [16] Ye, T.; Yu, J.; Fang, Y.; Xu, Z.; Guo, S.; Zhao, Z.; Li, H.; He, H.; Zhu, L. Discovery and SAR Study of Highly Selective and Potent 1,2,4-Oxadiazole-Based S1PR1 Agonists. Eur. J. Med. Chem. 2025, 300, 118097. DOI: 10.1016/j.ejmech.2025.118097 [17] Bristol Myers Squibb. Update on the First Phase 3 YELLOWSTONE Trial Evaluating Oral Zeposia (Ozanimod) in Moderate to Severe Active Crohn's Disease. Press release, 2024. [18] ClinicalTrials.gov. NCT04173273. A Study of Oral Etrasimod in Moderately to Severely Active Crohn's Disease (CULTIVATE). U.S. National Library of Medicine. https://clinicaltrials.gov/study/NCT04173273 (accessed 2026-09). [19] ClinicalTrials.gov. NCT05429632. MO-TRANS: A Phase III Study of Mocravimod in Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation (Priothera). U.S. National Library of Medicine. https://clinicaltrials.gov/study/NCT05429632 (accessed 2026-09). [20] Qian, J.; et al. Efficacy and Safety of Icanbelimod (CBP-307) in Adults with Moderate-to-Severe Ulcerative Colitis: A Phase 2 Randomised, Double-Blind, Placebo-Controlled Trial (CN002, NCT04700449). ACG 2024 Annual Scientific Meeting; Poster. [21] 云顶新耀 (Everest Medicines). 中国国家药品监督管理局批准维适平®（依曲莫德 / etrasimod）用于中重度溃疡性结肠炎. 新闻稿, 2026-02-06. [22] 药捷安康 (TransThera Biosciences). TT-01688（高选择性口服 S1P1 调节剂）溃疡性结肠炎 Ib/II 期完成、即将启动 III 期注册临床；特应性皮炎 II 期. 公司披露, 2025-2026. [23] 南昌弘益药业. HE009 片 II 期临床试验组长单位启动会（系统性红斑狼疮 SLE）. 2025-08-27. [24] 渐宽（苏州）生物科技. 艾托莫德片（高选择性 S1PR1 激动剂，银屑病）IND 获 CDE 受理. 2026-08-03. [25] Idorsia; Viatris. Cenerimod (ACT-334441) - High-Selective S1P1 Agonist; Phase 3 OPUS-1 (NCT05648500) and OPUS-2 (NCT05672576) in Systemic Lupus Erythematosus. Viatris Press Release, 2024-12-18. [26] Singhal, S.; Girgis, I. G.; Xie, J.; Dutta, S.; Shevell, D. E.; Throup, J. The Safety and Pharmacokinetics of a Novel, Selective S1P1R Modulator in Healthy Participants. Expert Opin. Investig. Drugs 2020, 29 (4), 411-422. DOI: 10.1080/13543784.2020.1742322 [27] Sun Pharma Advanced Research. Vibozilimod (SCD-044) - Selective S1PR1 Agonist; Phase 2b SOLARES in Plaque Psoriasis (NCT04566666) and Atopic Dermatitis (NCT04684485) - Did Not Meet Primary Endpoints; Development Discontinued. [28] Astellas. ASP4058 - Selective S1P1 Receptor Agonist; Phase 1 Study in Healthy Subjects (NCT01998646). [29] Sanofi. SAR247799 - G-Protein-Biased S1P1 Agonist (Does Not Induce Receptor Desensitization or Lymphopenia); Phase 1 Discontinued. Guide to Pharmacology LigandID 10938; RCSB PDB 9VO1 (2025). [30] Xu, J.; Gray, F.; Henderson, A.; Hicks, K.; Yang, J.; Thompson, P.; Oliver, J. Safety, Pharmacokinetics, Pharmacodynamics, and Bioavailability of GSK2018682, a Sphingosine-1-Phosphate Receptor Modulator, in Healthy Volunteers. Clin. Pharmacol. Drug Dev. 2014, 3 (3), 170-178. DOI: 10.1002/cpdd.98 [31] 南昌弘益药业. HE009 — 新型高选择性 S1P1 调节剂. 中国专利 CN115210223B (PCT/CN2021/078744, WO2021/175225; 优先权 2020-03 / 2020-05). 结构未公开（见通式(I)与三环类化合物）. PubMed PMID: 41051739 (Phase 1 PK/PD). [32] Kyorin / Asahi Kasei. AKP11 - Topical S1P1 Modulator; Phase 1 (ANZCTR ACTRN12613001226796) and Phase 2 Psoriasis (ACTRN12616000293460). Structure / Compound Code to Be Confirmed by Company Disclosures. [33] Bencardino, S.; D'Amico, F.; Faggiani, I.; Bernardi, F.; Allocca, M.; Furfaro, F.; Parigi, T. L.; Zilli, A.; et al. Efficacy and Safety of S1P1 Receptor Modulator Drugs for Patients with Moderate-to-Severe Ulcerative Colitis. J. Clin. Med. 2023, 12 (15), 5014. DOI: 10.3390/jcm12155014

2026-09-18

·GlobeNewswire-Health Care

Ventyx Biosciences Announces $176.6 Million Private Placement of Common Stock

ENCINITAS, Calif., Sept. 19, 2022 (GLOBE NEWSWIRE) -- Ventyx Biosciences, Inc. (Nasdaq: VTYX) (“Ventyx”), a clinical-stage biopharmaceutical company focused on advancing novel oral therapies that address a range of inflammatory diseases with significant unmet medical need, announced today that it has entered into a stock purchase agreement for the sale of 5,350,000 shares of its common stock at an offering price of $33.00 per share in a private placement to certain qualified institutional buyers and institutional accredited investors. Gross proceeds of the private placement are expected to be approximately $176.6 million, before deducting placement agent fees and other expenses. The private placement is expected to close on September 20, 2022, subject to the satisfaction of customary closing conditions. The private placement was led by Redmile Group, with participation by Boxer Capital, Braidwell LP, EcoR1 Capital, Vivo Capital, Great Point Partners, LLC, Adage Capital Management, Logos Capital, Maven Investment Partners US, Driehaus Capital Management, Acuta Capital Partners, CaaS Capital Management, Woodline Partners LP, Walleye Capital and other investors, including two large mutual funds. Ventyx currently intends to use the net proceeds from the proposed private placement, together with existing cash and cash equivalents, to fund the clinical development of VTX958, VTX002, VTX2735 and VTX3232, the preclinical development of other programs, research activities and working capital and other general corporate purposes. With the proceeds from the private placement, Ventyx expects to extend its cash runway into 2025. This cash estimate is a preliminary estimate and is based on information available to management as of the date of this private placement, and these estimates could change. Morgan Stanley, Jefferies, Piper Sandler and LifeSci Capital are acting as the placement agents for the private placement. The securities being issued and sold in the private placement have not been registered under the Securities Act of 1933, as amended (the “Securities Act”), or any states' securities laws, and may not be offered or sold in the United States, except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act. Ventyx has agreed to file a registration statement with the Securities and Exchange Commission registering the resale of the shares of common stock issued in this private placement. This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction. About Ventyx Biosciences Ventyx is a clinical-stage biopharmaceutical company focused on developing innovative oral medicines for patients living with autoimmune and inflammatory disorders. We believe our ability to efficiently discover and develop differentiated drug candidates will allow us to address important unmet medical need with novel oral therapies that can shift immunology markets from injectable to oral drugs. Our current pipeline includes three clinical-stage internally discovered programs targeting TYK2, S1P1R and NLRP3, positioning us to become a leader in the development of oral immunology therapies. Ventyx is headquartered in Encinitas, California. Forward-Looking Statements Ventyx cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on Ventyx’s current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding management’s beliefs regarding the company’s cash runway following the closing of the private placement. The inclusion of forward-looking statements should not be regarded as a representation by Ventyx that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Ventyx’s business, including, without limitation, market risks and other market conditions; the risk that the conditions to the closing of the private placement are not satisfied; potential delays in the commencement, enrollment and completion of clinical trials; disruption to our operations from the ongoing global outbreak of the COVID-19 pandemic, or from the ongoing military conflict in Ukraine, including clinical trial delays; Ventyx’s dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing, which may be impacted by disruptions in the supply chain, including raw materials needed for manufacturing, animals used in research, delays in site activations and enrollment of clinical trials; the results of preclinical studies and early clinical trials are not necessarily predictive of future results; the success of Ventyx’s clinical trials and preclinical studies for its product candidates; interim results not necessarily being predictive of final results; the potential of one or more outcomes to materially change as the trial continues and more patient data become available and following more comprehensive audit and verification procedures; regulatory developments in the United States and foreign countries; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; Ventyx’s ability to obtain and maintain intellectual property protection for its product candidates; the use of capital resources by Ventyx sooner than expected; and other risks described in Ventyx’s prior press releases and Ventyx’s filings with the Securities and Exchange Commission (SEC), including in Part II, Item 1A (Risk Factors) of Ventyx’s Quarterly Report on Form 10-Q filed on August 15, 2022, and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Ventyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investor Relations Contact Patti BankManaging DirectorWestwicke Partners(415) 513-1284IR@ventyxbio.com

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2026-08-24

·etherna.be

Valerio Therapeutics announces signing of definitive agreements for the acquisition of Etherna Immunotherapies, building a leading platform in targeted RNA, and €40.25 million PIPE financing from new and existing investors Definitive share purchase agreement signed for the acquisition of 100% of Etherna Immunotherapies NV (“Etherna“), and the related contribution agreement, based on an enterprise value of €30 million, to be settled through a combination of a cash consideration and a share consideration (the “Contributions“) €40.25 million PIPE financing successfully priced with support from new and existing investors, to finance the cash consideration of the Acquisition and support the development of the combined company Shareholder approval of the Contributions, at an extraordinary general meeting to be convened for that purpose, with approval already secured through irrevocable voting undertakings from existing shareholders representing more than 70% of the voting rights of the Company The Acquisition marks a major milestone in Valerio’s strategy to build a leading platform in the development of next-generation precision-guided RNA therapeutics Villejuif, August 24, 2026, 8:00 a.m. CET— Valerio Therapeutics (FR0010095596 – ALVIO), a biotechnology company pioneering next-generation precision-guided RNA therapeutics (“Valerio” or the “Company“), today announces the signing of a definitive share purchase agreement (the “SPA“) and of the related contribution agreement (the “Contribution Agreement“) for the acquisition of 100% of the share capital and voting rights of Etherna Immunotherapies NV (“Etherna“) (the “Acquisition“), based on an enterprise value of €30 million, and a €40.25 million private investment in public equity (PIPE) financing supported by existing shareholders and new investors (the “Financing“). “The acquisition of Etherna marks a decisive step in Valerio’s strategy: to build a leading player in RNA therapeutics. By combining Etherna’s RNA and LNP platforms with our proprietary cell-targeting technologies, we are creating a powerful innovation engine designed to accelerate the development of next-generation RNA medicines. Most importantly, our combined platforms enable us to overcome a bottleneck that has held the field back for decades: reaching tissues beyond the liver and, in doing so, opening the way to the treatment of a broad range of diseases that have so far been beyond the reach of conventional mRNA delivery.” said Gilles Besin, Ph.D., CEO of Valerio. “Signing this agreement is a defining moment for Etherna, and I could not be prouder of what our team has built with the support of our investors. Over the past years, we have turned a decade of mRNA and LNP expertise into platforms capable of reaching far beyond what conventional mRNA and delivery and manufacturing technologies could ever achieve. Joining forces with Valerio gives that platform the scale, the targeting capabilities and the resources to move faster and further than we could alone. I want to thank our shareholders, partners and, above all, our people for their trust and dedication in getting us here. Together with Valerio, Etherna’s science and manufacturing will deliver transformative medicines to patients who need them most.”, said Bernard Sagaert, CEO of Etherna. Terms and Conditions of the Acquisition The Acquisition marks a major milestone in Valerio’s strategy to build a leading platform in targeted nucleic acid medicines. By uniting three complementary technology platforms – nucleic acid chemistry, LNP delivery and targeted moiety engineering – within a fully integrated biotech supported by in-house manufacturing capabilities, the Acquisition aims to position Valerio to accelerate the development of next-generation RNA medicines targeting tissues beyond the liver. The Acquisition will be settled through (i) a cash consideration, fully funded by the Financing, and (ii) a share consideration through contributions in kind of Etherna shares (the “Contributions“) to the Company. The Contributions remain subject to Valerio shareholders approval at an extraordinary general meeting to be convened for that purpose expected to be held on or about October 6, 2026. Approval is secured by irrevocable voting undertakings from existing shareholders representing more than 70% of the voting rights of the Company. Shares issued as consideration for the Contributions will be valued at the same Subscription Price as the New Shares issued in the Financing. A contribution auditor (commissaires aux apports) has been appointed to assess the valuation of the Contributions and issue a fairness report. Certain lenders and managers of Etherna will also subscribe to new Valerio shares through the set-off of their receivables owed by Etherna at the same subscription price. The consideration for the Acquisition is based on an enterprise value of €30 million (on a debt-free, cash-free basis) subject to customary purchase price adjustments and contingent earn-out payments. Main Terms of the Financing The Financing was carried out through the issuance of 68,220,333 new ordinary shares (the “New Shares”), at a subscription price of €0.59 per share (i.e., a par value of €0.01 and an issuance premium of €0.58 per New Share) (the “Subscription Price”), representing a discount of 25% to the 3-day VWAP prior to pricing. The New Shares are issued through a capital increase without shareholders’ preferential subscription rights by way of an offering referred to in paragraph 1 of article L. 411-2 of the French Monetary and Financial Code (Code monétaire et financier), and pursuant to the decisions of the Company’s Chief Executive Officer on August 21, 2026, acting upon sub-delegation of the Company’s Board of Directors on July 30, 2026, in accordance with the delegations granted pursuant to the 15th resolutions and within the limits set by the 22nd resolution of the Company’s combined shareholders’ meeting held on June 16, 2026 (the “General Meeting”). The issuance of the 68,220,333 New Shares will result in a capital increase of €40.25 million (i.e., a nominal amount of €682,203.33 and a total issuance premium of €39,567,793.14), representing approximately 13.7% of the Company’s share capital and voting rights outstanding before the Financing. Existing shareholders Artal International SCA, Financière de la Montagne and Saint James Luxembourg subscribed for €18.0 million, €7.0 million and €1.0 million respectively. Artal International SCA and Financière de la Montagne, who are also members of or represented on Valerio’s Board of Directors, did not take participate in the vote on the Financing at the Board of Directors’ meeting held on July 30, 2026. Following the settlement-delivery of the New Shares expected on August 26, 2026, the Company’s share capital will be €5,676,686.34 divided into 567,668,634 ordinary shares. Impact of the Financing on Cash Flow and Use of Proceeds The Company intends to use the net proceeds from the Financing, together with its existing cash and cash equivalents, to: (i) fund the cash component of the consideration payable in connection with the Acquisition; (ii) advance its proprietary pipeline, including VTX-001, VTX-002 and VTX-003, as well as IND-enabling activities for VTX-001; (iii) integrate Etherna into Valerio, including by investing in and scaling Etherna’s GMP manufacturing capabilities at its Niel facility to support the Company’s clinical supply requirements and build internal capacity for mRNA and LNP production, and by combining the two organizations’ research, technical operations and quality functions on a single platform; and (iv) fund working capital and other general corporate purposes. The expected use of net proceeds reflects the Company’s current intentions, based on its present plans and business condition. The amounts and timing of the Company’s actual expenditures will depend on numerous factors, including the progress of its development programs, the timing and outcome of the integration of Etherna, and any unforeseen cash needs. Based on its current operating plan and forecasted expenses, and taking into account its cash and cash equivalents together with the net proceeds from the Financing, the Company believes it has sufficient resources to fund its planned operating expenses and capital expenditure requirements for at least 18 months following the closing of the Financing. This estimate is based on assumptions that may prove to be incorrect, and the Company may use its capital resources sooner than currently expected. Shareholding Structure after the Financing On an illustrative basis, a shareholder holding 1% of the Company’s share capital before the Financing and who did not participate in the Financing will hold 0.88% of the Company’s share capital after the issuance of the New Shares. To the Company’s knowledge, the shareholding structure, on a non-diluted basis, before and after the Financing, breaks down as follows: Lock-up Agreements In connection with the Financing, the Company has entered into a lock-up agreement restricting the issuance of additional ordinary shares for a period ending ninety (90) calendar days following the date of settlement-delivery, subject to customary exceptions. In addition, the investors subscribing to the Financing, have agreed to a sixty (60) calendar days lock-up on the New Shares, following the date of settlement-delivery, subject to customary exceptions. Settlement-delivery of the Financing The admission of the New Shares to trading on the Euronext Growth market in Paris is scheduled for the time of settlement and delivery, which is expected to take place on August 26, 2026. The New Shares will be immediately assimilated to the Company’s existing shares already traded on Euronext Growth in Paris, and will be able to be traded, from their issuance, on the same listing line (ISIN code: FR0010095596). The Financing has not given rise to a prospectus submitted for approval by the AMF, nor to an information document containing the information set out in Annex IX of Regulation (EU) 2017/1129, as amended. Risk Factors The Company draws the public’s attention to the risk factors related to the Company and its activities presented in the 2025 annual financial report published on April 28, 2026, which is available free of charge on the website of the Company (https://valeriotx.com/). In addition, investors are invited to consider the following risks: (i) shareholders’ stake in the Company will be diluted further to the issuance of the New Shares for the shareholders who did not participate in the Financing, (ii) the market price for the Company’s shares may fluctuate and fall below the subscription price of the shares issued pursuant to the Financing, (iii) the volatility and liquidity of the Company’s shares may fluctuate significantly, (iv) sales of the Company’s shares may occur on the market and have a negative impact on the market price of the shares, and (v) the Company’s shareholders could undergo a potentially material dilution resulting from any future capital increases that are needed to finance the Company. Advisors Van Lanschot Kempen NV is acting as exclusive financial advisor for the Acquisition and as Sole Placement Agent in connection with the Financing. Goodwin Procter LLP is acting as legal counsel to Valerio Therapeutics. Moelis & Company is acting as financial advisor to Etherna. Deloitte (Belgium) and August Debouzy (France) are acting as legal counsels to Etherna. ****** About Valerio Therapeutics Valerio Therapeutics (FR0010095596 – ALVIO) is a pioneering biotechnology company specialized in the discovery and development of innovative targeted RNA therapeutics. The Company is listed on Euronext Growth Paris. For more information: https://valeriotx.com/. About Etherna Immunotherapies, a Valerio company Etherna is a leading technology platform company pioneering the development of mRNA and lipid nanoparticle (LNP) technologies, including manufacturing up to GMP grade. With over a decade of expertise, the company provides pharma and biotech partners with an integrated suite of proprietary platforms, including customizable lipid nanoparticles (cLNPs) and advanced mRNA chemistry to enable the delivery of high-quality and efficacious Nucleic Acid based therapeutics.

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100 项与他木兹莫德相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D12897	-	-	-

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
溃疡性结肠炎	临床2期	美国	Oppilan Pharma Ltd.	2021-11-30
溃疡性结肠炎	临床2期	保加利亚	Oppilan Pharma Ltd.	2021-11-30
溃疡性结肠炎	临床2期	捷克	Oppilan Pharma Ltd.	2021-11-30
溃疡性结肠炎	临床2期	法国	Oppilan Pharma Ltd.	2021-11-30
溃疡性结肠炎	临床2期	德国	Oppilan Pharma Ltd.	2021-11-30
溃疡性结肠炎	临床2期	匈牙利	Oppilan Pharma Ltd.	2021-11-30
溃疡性结肠炎	临床2期	印度	Oppilan Pharma Ltd.	2021-11-30
溃疡性结肠炎	临床2期	意大利	Oppilan Pharma Ltd.	2021-11-30
溃疡性结肠炎	临床2期	立陶宛	Oppilan Pharma Ltd.	2021-11-30
溃疡性结肠炎	临床2期	波兰	Oppilan Pharma Ltd.	2021-11-30

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05156125 (Pubmed \| Lancet Gastroenterol Hepatol) 人工标引	临床2期	活动性中度溃疡性结肠炎 \| 活动性重度溃疡性结肠炎	213	Tamuzimod 60 mg	簾淵鹹鑰膚獵憲衊齋廠(糧衊網鏇繭選夢積廠簾) = 遞製襯獵淵鬱顧艱醖夢顧淵夢範範窪餘壓艱壓 (鹽廠齋糧鏇鏇簾餘獵壓 ) 更多	积极	2025-03-01
				Tamuzimod 30 mg	簾淵鹹鑰膚獵憲衊齋廠(糧衊網鏇繭選夢積廠簾) = 餘網餘壓範艱夢壓範廠顧淵夢範範窪餘壓艱壓 (鹽廠齋糧鏇鏇簾餘獵壓 ) 更多
NCT05156125 (CTgov)	临床2期	溃疡性结肠炎	213	VTX002 (VTX002 60 mg Once Daily)	製繭廠簾鏇網鑰鹹窪築 = 廠網壓選顧艱襯選醖蓋淵膚膚壓廠積鏇膚窪淵 (觸膚鹽鏇餘網鑰醖淵願, 願鹽觸夢鹹觸範遞壓遞 ~ 築鹽範築獵夢網顧築壓) 更多	-	2024-11-13
				VTX002 (VTX002 30 mg Once Daily)	製繭廠簾鏇網鑰鹹窪築 = 構襯糧鏇衊鬱構遞觸醖淵膚膚壓廠積鏇膚窪淵 (觸膚鹽鏇餘網鑰醖淵願, 糧蓋夢願網淵鑰簾觸衊 ~ 鑰蓋鑰鬱夢鏇構衊壓齋) 更多
NCT05156125 (UEGW2024) 人工标引	临床2期	活动性中度溃疡性结肠炎 \| 活动性重度溃疡性结肠炎	85	Placebo	選鏇淵願廠鏇膚壓艱夢(窪選顧範襯壓鬱壓築繭) = 範齋衊構廠鏇壓構餘顧膚廠繭鏇齋窪蓋網鹽衊 (糧艱壓膚鹹簾願鬱簾鹽 ) 更多	积极	2024-10-17
				TamuzimodTamuzimod 30 mg	選鏇淵願廠鏇膚壓艱夢(窪選顧範襯壓鬱壓築繭) = 襯製簾遞鬱製襯觸獵窪膚廠繭鏇齋窪蓋網鹽衊 (糧艱壓膚鹹簾願鬱簾鹽 ) 更多
NCT05156125 (ECCO2024)	临床2期	溃疡性结肠炎	213	VTX002 60 mg	鹽壓襯鹹蓋壓窪簾遞製(糧餘膚製夢鹹醖製鬱壓) = 憲鏇鏇鹽窪廠壓壓廠醖艱選衊簾窪衊艱築夢夢 (餘繭壓襯膚繭衊築遞鏇 ) 更多	积极	2024-02-21
				Placebo	鹽壓襯鹹蓋壓窪簾遞製(糧餘膚製夢鹹醖製鬱壓) = 製積願顧製遞築艱膚願艱選衊簾窪衊艱築夢夢 (餘繭壓襯膚繭衊築遞鏇 ) 更多
NCT05156125 (Corporate Publications) 人工标引	临床2期	溃疡性结肠炎	213	VTX002VTX002 30 mg	簾願憲簾齋窪網簾網築(範醖衊艱願蓋築餘鏇鹹) = 築簾壓遞蓋鑰鏇繭艱淵鹹製觸鹽壓廠繭壓餘製 (顧顧襯壓壓鬱鑰淵艱蓋 ) 达到更多	积极	2023-10-09
				VTX002VTX002 60 mg	簾願憲簾齋窪網簾網築(範醖衊艱願蓋築餘鏇鹹) = 齋製憲構醖鑰顧觸願願鹹製觸鹽壓廠繭壓餘製 (顧顧襯壓壓鬱鑰淵艱蓋 ) 达到更多
NCT05156125 (ECCO2023)	临床1期	-	12	VTX002 20 mg tablet	顧鑰構夢醖齋選廠範構(壓夢構築製壓願襯積築) = A total of 23 AEs were reported; of which 19 were considered mild, and 4 were moderate 選蓋鹽餘觸艱簾選鹹蓋 (選淵憲糧積衊願窪觸膚 ) 更多	积极	2023-03-01
				VTX002 20 mg SDD suspension