Bimatoprost grenod

这周生物医药有几条主线。并购端，Ipsen一周内谈下两笔交易，收购 Kartos 拿下三期的navtemadlin，收购 Memo Therapeutics 拿下二期的potravitug，方向都在后期的血液和罕见病；Zymeworks、Lonza、达纳赫的交易也在同步推进。临床端，罗氏的 divarasib 在KRAS G12C 肺癌里头对头击败两款已获批的第一代抑制剂，总生存和无进展生存双双达标，是本周最重要的一条数据。监管端，FDA一周内批准了 Orca Bio 的首个 Treg 细胞疗法、Viridian 的甲状腺眼病新药，并把 Casgevy 的适用年龄下探到 2 岁。和前几周一致，买家和资金仍然集中流向后期项目或生产设施，监管则在细胞治疗、甲状腺眼病、镰状细胞病和专科免疫几个方向继续扩展。并购与合作：Ipsen 一周两笔交易补强后期管线，工具与产能交易同步推进 本周并购的主角是 Ipsen。它先宣布收购 Kartos Therapeutics，首付 4.5 亿美元，里程碑最高再加 13 亿美元，交易总额最高约 17.5 亿美元，拿到的是已进入三期的navtemadlin（一种口服 MDM2 抑制剂），主攻骨髓纤维化。紧接着又宣布收购瑞士的Memo Therapeutics，潜在总额最高约 8 亿美元，核心是二期的potravitug，针对移植后 BK 病毒感染这类并发症。两笔交易方向一致，都是后期、面向血液和罕见病的项目，给Ipsen 在现有罕见病和肿瘤组合之外补上两条接近关键数据、面向注册的后期管线。 其余交易也保持活跃。Zymeworks 同意以约 9.29 亿美元收购 Theravance Biopharma；Lonza 以约 12 亿美元收购罗氏位于加州 Vacaville 的生物制药生产基地，扩大代工产能；达纳赫（Danaher）完成对Masimo 交易的交割。买家这一周覆盖了后期项目、生产设施和工具几类，选择的仍是靠近商业化或能补强现有能力的标的。 晚期临床：罗氏 divarasib 头对头击败已获批KRAS G12C 抑制剂，双抗与 BTK 联合方案再添阳性数据 本周最重要的临床数据来自罗氏。divarasib（研发代号 GDC-6036）的三期 Krascendo-1 公布顶线：在既往治疗过的 KRAS G12C 突变非小细胞肺癌里，divarasib头对头对比两款已获批的第一代抑制剂，安进的 Lumakras（sotorasib）和 BMS 的 Krazati（adagrasib），总生存和无进展生存都取得有统计学意义、也有临床意义的改善。这是第一个直接在 KRAS G12C 抑制剂之间做的头对头三期，入组 338 例。第一代两款药在二线相对化疗主要改善的是无进展生存，总生存的获益一直不明显；divarasib直接跟已获批药比、还把总生存做到显著，是这条数据的关键。具体数值罗氏没有公布，称完整数据留待后续学术会议。 血液肿瘤这一周也有两条阳性数据。艾伯维与 Genmab 的 epcoritamab（商品名 Epkinly，一种 CD3×CD20 双特异性抗体）联合来那度胺，在 EPCORE DLBCL-4 三期对比R-GemOx 化疗，把复发或难治弥漫大B细胞淋巴瘤患者的疾病进展或死亡风险，在美国和美国以外人群分别降低60%（HR 0.40）和 56%（HR 0.44），两者 p 值都小于0.0001，针对的是做不了移植、也用不了 CAR-T 的这类人群。BeOne（原百济神州）的百悦泽（Brukinsa，泽布替尼）联合利妥昔单抗，在套细胞淋巴瘤三期把疾病进展风险降低43%。两条数据都把已获批的药往更前线或新的联合方案推进。 其他晚期项目还有几条。赛诺菲的 Nexviazyme（avalglucosidase alfa）在 Baby-COMET 三期达到主要终点，面向婴儿型庞贝病；Viatris的 VR-205 在日本的 IgA 肾病三期达标；艾伯维的 upadacitinib（Rinvoq）在新适应症上再添阳性数据。受挫的一条来自 Vistagen，其针对社交焦虑障碍的PALISADE-4 三期失败。整体看，本周晚期临床阳性偏多，但个别项目也提示后期数据仍有不确定性。 监管准入：FDA 批准首个 Treg 细胞疗法与甲状腺眼病新药，Casgevy 扩龄至 2 岁 FDA 这一周批准了 Orca Bio 的 Tregzi（研发代号 Orca-T），用于成人血液肿瘤患者的配型相合供体造血干细胞移植。这是第一个使用高纯度调节性T 细胞（Treg）的获批细胞疗法。支持批准的三期Precision-T 里，一年的慢性移植物抗宿主病无病生存为 78%，传统移植为38%（HR 0.26，p<0.00001），慢性 GVHD 发生率从 44% 降到13%。定价方面，批发采购价为 42.8 万美元。 另有两项获批扩大了适应人群。Viridian 的 Lumvoa（veligrotug）获批用于甲状腺眼病，给这一适应症新增一个选项。Vertex与 CRISPR Therapeutics 的 Casgevy（exa-cel）把适用年龄从 12 岁下探到2 岁及以上，成为首个用于幼儿镰状细胞病的基因疗法，这次从递交到批准只用了 53 天。加上此前的细胞和基因疗法准入，监管端在细胞治疗和罕见病方向继续扩展。 融资与 AI：资金选择性投向平台与三期项目，AI 合作走向研究与实验室环节 资本市场这一周只对部分项目开放。Scribe Therapeutics 递交纳斯达克 IPO 申请，核心是体内CRISPR 编辑 PCSK9 的心血管项目，属于较早期的基因编辑公司尝试上市；Celea与 PureTech 相关的一笔融资募集 1.8 亿美元，推进特发性肺纤维化的三期；Beeline 把 A 轮扩大到 4.263 亿美元，围绕从 BMS 授权来的免疫项目；Nuvectis 完成 1 亿美元公开增发。能拿到大额资金的，仍是有平台基础或有明确三期计划的项目。 AI 这一周继续从会议主题转向具体合作。英矽智能（Insilico Medicine）与 SK Biopharmaceuticals、阿布扎比与MIT 的 Koch 研究所、Tecan 与英伟达 BioNeMo、Edison Scientific 与 Population Health Partners、Sword Health，以及 Anthropic 的 Claude Science，把 AI 从通用工具推向药物发现、肿瘤研究、实验室运营和医疗交付几个具体环节。重点要看的仍是，这些合作能否转化成具体项目、真实客户或临床证据，只有框架还不够。 学术端这一周偏转化和临床实用。来自公开文献的信号里，口内光生物调节降低了造血干细胞移植后的重度口腔黏膜炎；AQP4 和 MOG 抗体谱有助于判断免疫检查点抑制剂相关的视神经炎；UK Biobank 的数据厘清了肥胖发生时间对心血管风险的影响；还有胰腺癌复发与治疗相关的标志物，以及类器官可重复性方面的工作。这些结果更贴近临床和实验判断，不直接影响市场。 风险与政策：Tavneos 面临撤市建议，多起药价与支付争议同步进行 监管风险这一周也不少。欧洲药品管理局（EMA）的顾问在 ADVOCATE 试验出现数据完整性问题后，建议撤销 Tavneos（avacopan，用于 ANCA 相关血管炎）的上市许可；Newron 正在争取解除 evenamide 的临床暂停；Capricor 的 deramiocel（用于杜氏肌营养不良相关心肌病）拿到 7 月的 FDA 咨询委员会日期；Enspryng、NCX 470、obefazimod 也各自有临近的审评问题要回答。一批产品能否获得准入、能否继续留在市场上，都还要过监管这一关。 药价和支付这一周同样活跃。本周包括 340B 医院支付争议再起、科罗拉多州围绕 Enbrel 限价的诉讼、礼来医院折扣受到审查、医疗补助（Medicaid）工作要求相关的诉讼，以及Elevance 就医保优势（Medicare Advantage）星级评定支付发起的挑战。这些都说明定价和报销端的压力还在持续。整体来看，本周的结论和前几周一致：靠近商业化、终点明确的项目拿到了较好的结果，越依赖政策和支付环境的环节，暴露的问题越具体。下一周看什么 下周需要关注以下几件事：Ipsen 收购 Kartos 和Memo 之后的整合与管线推进；罗氏 divarasib 完整数据（总生存和无进展生存的具体幅度、风险比）在学术会议上的披露；FDA对 Capricor deramiocel 咨询委员会和幼儿基因疗法标签的后续动作；Scribe这类较早期的 CRISPR 公司能否顺利完成 IPO 定价；以及英矽智能与 SK、阿布扎比与 MIT、Tecan 与英伟达、Edison 与Population Health、Sword、Anthropic等 AI 合作能否落到具体项目、客户或临床证据上。 www.polaristerminal.com

Press Release Nicox and Vester Finance Sign Shareholder Loan Agreement to Support Strategic Activities for the Company Shareholder loan agreement for up to €6.0 million over 3 yearsCompany is currently well-financed, and this shareholder operation provides additional flexibility to support its strategic activitiesNo obligation for Nicox to draw down any amount and maximum potential dilution is cappedIf drawn down, loans are repayable in new shares or in cash. In the event of a drawdown of the maximum amount, a full repayment in shares would represent up 16% of to the Company’s share capital June 23, 2026 – release at 7:30 am CET Sophia Antipolis, FranceNicox SA (Euronext Growth Paris: FR0013018124, ALCOX), an international ophthalmology company, today announced the establishment of a straight shareholder loan agreement with Vester Finance, repayable in new shares or in cash. No advance has been made under this facility as of the date of this announcement, and Nicox has no obligation to draw down any amount. Without this optional facility the Company believes it is financed beyond 2027, as communicated on 30 April 2026.“Having optimised our corporate structure for current activities, our operating costs are expected to be covered beyond 2027. This is thanks to the expected milestone payments and recurrent sales revenue from NCX 470. This puts us in a unique position as we look at future strategic opportunities for the company. To provide additional flexibility in those strategic discussions, we are pleased to have secured the support of our shareholder and long-term financing partner, Vester Finance, through a shareholder loan of up to €6 million.” said Gavin Spencer, Chief Executive Officer of Nicox. “As we continue the dual-focus of NCX 470’s New Drug Application submission, expected this summer, and future value creation for the company, this loan facility offers us access to additional financing, if needed, on a non-dilutive or capped-dilution basis with a trusted partner.”Key Future Milestones NCX 470 NDA submission in the United States: expected summer 2026NCX 470 NDA submission in China: expected shortly after submission in the U.S.NCX 470 Phase 3 clinical program in Japan: initiated summer 2025. Main Terms of the Shareholder Loan AgreementIn accordance with the terms of the agreement signed on 22 June 2026, Vester Finance has agreed to provide the Company with shareholder loans up to a limit of €6.0 million over a period of 36 months, subject to certain customary contractual conditions, at an interest rate of 7.0% per annum payable in fine. The Company may, under certain usual conditions, request advances of up to €0.5 million each, at its own discretion. The shareholder loans may be repaid either at any time by way of subscription of newly issued shares of the Company, in accordance with the 13th resolution of the General Meeting of Shareholders of the Company of 27 June 2025 (the “General Meeting”) and in accordance with the applicable market rules, or in cash 18 months following their release, and at the latest at the term of the agreement. The Company can, under certain circumstances, and at its discretion, repay the advances early in cash. Interest would only apply in the event of repayment in cash.In case of reimbursement in shares, new shares will be issued on the basis of the average market price preceding each issue1, reduced by a maximum discount of 6.5%, subject to the pricing and ceiling rules set by the General Meeting2, and up to a maximum of 15,000,000 newly issued shares of the Company, representing up to 16.00% of its issued share capital3 as of 31 May 2026. If the Company used the entirety of this facility, Vester would own 14.5% of the issued share capital and 11.3% on a fully-diluted basis. To the Company’s knowledge, no shareholder holds more than 5% of the issued share capital. The Company has no obligation to use this facility. Once an advance has been drawn down and reimbursed, the Company will have the option to suspend or terminate this agreement at any time and at no cost. This transaction was approved by the Chief Executive Officer acting pursuant to the sub-delegation of authority granted by the Company’s Board of Directors, itself acting pursuant to the delegation of authority granted to it by the 13th resolution of the General Meeting4 to grant Vester Finance the right to subscribe for a maximum of 15,000,000 new shares under the terms set out in this press release. This transaction is not subject to the preparation of a prospectus requiring an approval by the Autorité des Marchés Financiers (AMF), pursuant to Article 1 of Regulation (EU) 2017/1129 as amended (Prospectus Regulation), nor to the filing with the AMF of a document containing the information set out in Annex IX of the Prospectus Regulation. The number of shares issued under this agreement and admitted to trading will be announced on the Company’s website. Theoretical Impact of the OperationAssuming that all of the 15,000,000 new shares are issued, the Company's share capital would amount to €1,087,625.06, divided into 108,762,506 ordinary shares with a par value of €0.01 each. A shareholder holding 1.00% of the Company's share capital before the operation would see his stake decrease to 0.86% of the share capital on a non-diluted basis5, and 0.67% of the share capital on a diluted basis6. This transaction will have no impact on the Company’s governance. This facility operates in parallel with the unsecured bond financing announced on 5 January 2026.Risk FactorsThe risk factors affecting the Company are detailed in section 3 of the Company's 2025 Annual Report which is available on the Company's website (www.nicox.com).Vester Finance, acting here in its capacity as both shareholder and financier, may be required to sell all or part of the shares subscribed for in connection with this transaction within a shorter or longer timeframe. The sale of the shares on the market may have an impact on the volatility and liquidity of the security, as well as on the Company’s share price.About NicoxNicox SA is an international ophthalmology company developing innovative solutions to help maintain vision and improve ocular health. Nicox’s lead late-stage development program is NCX 470 (bimatoprost grenod), a novel nitric oxide-donating bimatoprost eye drop, for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension, licensed to Ocumension Therapeutics for the Chinese, Korean and Southeast Asian markets and to Kowa in the rest of the world. Nicox also has a preclinical research program on NCX 1728, a nitric oxide-donating phosphodiesterase-5 inhibitor, with Glaukos. Nicox’s first product, VYZULTA® in glaucoma, licensed exclusively worldwide to Bausch + Lomb, is available commercially in the U.S. and over 15 other territories. Nicox generates revenue from ZERVIATE® in allergic conjunctivitis, licensed in multiple geographies, including to Harrow, Inc. in the U.S., and Ocumension Therapeutics in the Chinese and in the majority of Southeast Asian markets.Nicox, headquartered in Sophia Antipolis, France, is listed on Euronext Growth Paris (Ticker symbol: ALCOX). For more information www.nicox.com Analyst coverageH.C. Wainwright & Co Yi Chen New York, U.S. The views expressed by analysts in their coverage of Nicox are those of the author and do not reflect the views of Nicox. Additionally, the information contained in their reports may not be correct or current. Nicox disavows any obligation to correct or to update the information contained in analyst reports. Contacts NicoxGavin SpencerChief Executive OfficerT +33 (0)4 97 24 53 00communications@nicox.com DisclaimerThe information contained in this document may be modified without prior notice. This information includes forward-looking statements. Such forward-looking statements are not guarantees of future performance. These statements are based on current expectations or beliefs of the management of Nicox S.A. and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Nicox S.A. and its affiliates, directors, officers, employees, advisers or agents, do not undertake, nor do they have any obligation, to provide updates or to revise any forward-looking statements.Risks factors which are likely to have a material effect on Nicox’s business are presented in section 3 of the “Rapport Annuel 2025” which are available on Nicox’s website (www.nicox.com).Finally, this press release may be drafted in the French and English languages. If both versions are interpreted differently, the French language version shall prevail.Nicox S.A.Sundesk Sophia Antipolis, Bâtiment C, Emerald Square, Rue Evariste Galois, 06410 Biot, FranceT +33 (0)4 97 24 53 00 1 Lower of the two daily volume-weighted average prices over the period immediately preceding each issue.2 At least equal to the volume-weighted average of the share prices over the three trading sessions immediately preceding the setting of the issue price, subject to a discount of up to 30%.3 The number of shares that may be issued under the agreement will be specified in the monthly information on the number of shares and voting rights posted on the Company's website.4 Delegation of competence to the Board of Directors to increase the share capital for the benefit of a category of investors (physical or moral persons, trusts, investment funds or other financial placement vehicles; strategic partners of the Company; or all other creditors) without preferential right of subscription of the shareholders.5 On the basis of the 93,762,506 shares comprising the share capital, as of 31 May 2026.6 On a fully diluted basis, including 30,372,852 shares that may be issued upon exercise of all the outstanding dilutive instruments as of 31 May 2026. Attachment EN_VesterShareholderLoanJune2026_PR_FINAL