Phase 3 ALTO trial designed to demonstrate superiority of KSI-501 versus aflibercept in patients with diabetic macular edema

旨在证明KSI-501在糖尿病性黄斑水肿患者中优于阿柏西普的3期ALTO试验

PALO ALTO, Calif.

加利福尼亚州帕洛阿尔托

,

，

Aug. 10, 2026

2026年8月10日

/PRNewswire/ -- Kodiak Sciences Inc. (Nasdaq:

/美通社/ -- Kodiak Sciences Inc.（纳斯达克：

KOD

柯达

), a precommercial retina-focused biotechnology company committed to researching, developing and commercializing transformative therapeutics, today announced that the first patients have been enrolled in the global Phase 3 ALTO trial evaluating KSI-501 in patients with diabetic macular edema (DME). KSI-501 is an investigational, first-in-class bispecific therapy built on Kodiak's ABC.

），一家专注于视网膜领域、致力于研发和商业化变革性疗法的临床前生物技术公司，今日宣布，全球评估KSI-501治疗糖尿病性黄斑水肿（DME）患者的III期ALTO试验已完成首批患者入组。KSI-501是一种基于Kodiak公司ABC平台开发的在研首创双特异性疗法。

®

®

Platform and designed to potently inhibit two complementary pathways implicated in retinal vascular disease: interleukin (IL)-6-mediated inflammation and vascular endothelial growth factor (VEGF)-mediated vascular permeability and neovascularization.

该平台旨在强效抑制与视网膜血管疾病相关的两条互补通路：白细胞介素（IL）-6介导的炎症，以及血管内皮生长因子（VEGF）介导的血管通透性和新生血管形成。

The ALTO trial is designed to demonstrate the superiority of bispecific (anti-VEGF, anti-IL-6) KSI-501 versus monospecific (anti-VEGF) aflibercept in patients with DME. ALTO is the second registrational Phase 3 trial of KSI-501, following the DAYBREAK study in patients with wet AMD.

ALTO 试验旨在证明双特异性（抗 VEGF、抗 IL-6）药物 KSI-501 在糖尿病性黄斑水肿（DME）患者中优于单特异性（抗 VEGF）药物阿柏西普。继在湿性年龄相关性黄斑变性（wet AMD）患者中开展的 DAYBREAK 研究之后，ALTO 是 KSI-501 的第二项注册性 III 期临床试验。

ALTO explores whether dual inhibition of immune and vascular pathways can deliver deeper and more sustained disease control for patients with DME and evaluates two dosing regimens, one regimen with intensive dosing and a second regimen with individualized dosing intervals of up to every six months.

ALTO研究旨在探索同时抑制免疫和血管通路是否能为糖尿病性黄斑水肿（DME）患者带来更深入且更持久的疾病控制，并评估两种给药方案：一种为强化给药方案，另一种为个体化给药间隔方案，给药间隔最长可达每六个月一次。

'Initiating ALTO is an important next step for KSI-501 and for our broader effort to advance multifunctional retinal medicines that address disease biology beyond VEGF alone,' said Victor Perlroth, M.D., Chief Executive Officer of Kodiak. 'Anti-VEGF therapies have transformed the treatment of DME, yet many patients continue to live with persistent retinal fluid, incomplete visual recovery and the burden of frequent ongoing injections.

“启动ALTO研究是KSI-501项目的重要下一步，也是我们推动超越单一VEGF靶点、针对疾病生物学机制的多功能视网膜药物更广泛努力的关键一步，”Kodiak公司首席执行官Victor Perlroth医学博士表示。“抗VEGF疗法已彻底改变了糖尿病性黄斑水肿（DME）的治疗格局，但许多患者仍面临持续性视网膜下积液、视力恢复不完全以及频繁反复注射带来的负担。”

We believe that inhibiting the immune-focused IL-6 pathway alongside the vessel-focused VEGF pathway, further enhanced with the durability of our ABC Platform, may achieve deeper and more sustained control of this disease.'.

我们相信，通过ABC平台的持久性增强作用，联合抑制以免疫为核心的IL-6通路和以血管为核心的VEGF通路，或许能够实现对这种疾病更深入且更持久的控制。

'It has long been believed that there is more to be gained for patients with DME by targeting mechanisms beyond VEGF, and in particular by addressing the chronic, low-grade inflammatory state that often persists in patients who have suboptimal response to anti-VEGF monotherapy,' said Margaret Chang, M.D., M.S., Co-Director of Clinical Research at Retina Consultants Medical Group.

“长期以来，人们一直认为，通过靶向VEGF以外的机制，尤其是解决在对抗VEGF单药治疗反应不佳的患者中常常持续存在的慢性、低度炎症状态，可以为糖尿病性黄斑水肿（DME）患者带来更多获益。”视网膜咨询医疗集团临床研究联合主任Margaret Chang博士表示。

'Recent results from the Phase 2 ALLUVIUM study demonstrated that IL-6 inhibition alone can lead to clinically meaningful functional and anatomic benefits in DME patients, providing evidence that the IL-6 pathway is biologically active in diabetic eye diseases and operates independently of VEGF-driven pathology.

二期ALLUVIUM研究的最新结果表明，单独抑制IL-6可为糖尿病性黄斑水肿（DME）患者带来具有临床意义的功能和解剖学获益，这为IL-6通路在糖尿病眼病中具有生物活性且独立于VEGF驱动的病理机制提供了证据。

Importantly, the recent Phase 2 BARDENAS study further suggested that dual inhibition of VEGF and IL-6 may offer synergistic effects, with the potential to deliver superior vision gains and improved fluid control versus targeting either pathway alone.'.

重要的是，近期的BARDENAS II期研究进一步表明，联合抑制VEGF和IL-6可能产生协同效应，与单独靶向任一通路相比，有望带来更优的视力获益和更好的液体控制。

'DME is a multifactorial disease in which vascular leakage, blood-retinal barrier dysfunction and immune signaling together drive retinal edema and vision loss,' said J. Pablo Velazquez-Martin, M.D., Chief Medical Officer of Kodiak. 'Our ALTO study is designed to rigorously evaluate whether dual inhibition of IL-6 and VEGF translates into meaningful benefit for patients, including the potential for better vision gains and greater fluid control, and through Kodiak's ABC biopolymer conjugate platform the potential for superior durability.

“糖尿病性黄斑水肿（DME）是一种多因素疾病，其中血管渗漏、血-视网膜屏障功能障碍和免疫信号传导共同导致视网膜水肿和视力丧失，”Kodiak公司首席医疗官J. Pablo Velazquez-Martin博士表示。“我们的ALTO研究旨在严格评估IL-6和VEGF的双重抑制是否能为患者带来具有临床意义的获益，包括实现更好的视力提升和更佳的液体积聚控制，并且借助Kodiak公司的ABC生物聚合物偶联平台，有望实现更优的持久性。”

Alongside the primary visual acuity endpoint, the study is powered for a key secondary endpoint of two-step or greater improvement on the Diabetic Retinopathy Severity Scale (DRSS), and it evaluates a regimen with dosing intervals extending to six months. Our objective is to characterize efficacy, anatomic response and durability in a single Phase 3 program.'.

除了主要视力终点外，该研究还针对糖尿病视网膜病变严重程度量表（DRSS）改善两步或以上的关键次要终点进行了效能设计，并评估了一种给药间隔延长至六个月的方案。我们的目标是在一项单一的III期临床试验项目中表征其疗效、解剖学反应和持久性。

About the ALTO Study

关于ALTO研究

The ALTO Study (KSMP002-S1) is a global, multicenter, randomized, double-masked, active comparator-controlled Phase 3 study evaluating the efficacy and safety of intravitreal KSI-501 5 mg compared with intravitreal aflibercept 2 mg in patients with visual impairment secondary to center-involved DME..

ALTO研究（KSMP002-S1）是一项全球性、多中心、随机、双盲、活性对照的III期临床试验，旨在评估玻璃体腔注射5 mg KSI-501与玻璃体腔注射2 mg阿柏西普相比，在治疗因累及黄斑中心的糖尿病性黄斑水肿（DME）所致视力损害患者中的有效性和安全性。

Approximately 910 patients, treatment-naïve or previously treated, will be randomized 5:3:5 to one of three arms:

约910名初治或经治患者将以5:3:5的比例随机分配至三个组别之一：

Arm A:

A组：

KSI-501 5 mg every 8 weeks, with monthly assessment for additional individualized dosing, following six monthly loading doses

KSI-501 每8周给药5 mg，在完成六次每月负荷剂量后，每月评估以进行额外的个体化剂量调整

Arm B:

B组：

KSI-501 5 mg on an individualized regimen of every 4 to 24 weeks, following six monthly loading doses

在给予六次每月负荷剂量后，采用每4至24周一次的个体化给药方案，每次给予KSI-501 5 mg

Arm C:

C组：

aflibercept 2 mg every 8 weeks, following five monthly loading doses

在完成五次每月负荷剂量后，每8周给予2 mg阿柏西普

The primary endpoint is the mean change in best-corrected visual acuity from baseline to the average of Week 48 and Week 52. The key secondary endpoint is the proportion of patients improving two or more steps on the DRSS from baseline at Week 48. Additional secondary and exploratory endpoints evaluate visual function, retinal anatomy, treatment burden and durability, and safety..

主要终点指标为从基线到第48周和第52周平均值期间，最佳矫正视力（BCVA）的平均变化。关键次要终点指标为在第48周时，糖尿病视网膜病变严重程度量表（DRSS）较基线改善两步或以上的患者比例。其他次要终点和探索性终点评估视觉功能、视网膜解剖结构、治疗负担与持久性以及安全性。

Participants will be treated and followed for approximately 96 weeks. Additional information about ALTO, also known as Study KSMP002-S1, is available at

参与者将接受治疗和随访，持续约96周。有关ALTO（也称为研究KSMP002-S1）的更多信息可在以下网址获取：

https://clinicaltrials.gov/study/NCT07734844

https://clinicaltrials.gov/study/NCT07734844

.

。

The Potential of Dual IL-6 and VEGF Inhibition in DME

双靶点抑制IL-6和VEGF在糖尿病性黄斑水肿中的潜力

VEGF is an established driver of vascular permeability and abnormal vessel growth in retinal vascular disease, and anti-VEGF therapy has revolutionized the treatment of DME by reducing retinal fluid and delivering meaningful vision gains for the majority of patients. Yet significant room for improvement remains.

血管内皮生长因子（VEGF）是视网膜血管疾病中血管通透性增加和异常血管生成的明确驱动因素，而抗VEGF疗法通过减少视网膜积液并为大多数患者带来有临床意义的视力提升，彻底改变了糖尿病性黄斑水肿（DME）的治疗格局。然而，仍存在显著的改进空间。

Across pivotal DME trials, a substantial proportion of patients have persistent edema despite ongoing treatment, and most patients do not achieve 20/20 vision. While recent intravitreal biologics have extended dosing intervals, many patients still require frequent injections to sustain their best possible visual outcome..

在关键的糖尿病性黄斑水肿（DME）临床试验中，尽管接受持续治疗，仍有相当比例的患者存在持续性水肿，且大多数患者未能达到20/20的视力。尽管最近的玻璃体内生物制剂延长了给药间隔，但许多患者仍需要频繁注射以维持最佳可能的视力结果。

IL-6 is a pro-inflammatory cytokine and immune growth factor implicated in inflammatory signaling, endothelial dysfunction and disruption of the blood-retinal barrier. Ocular IL-6 is elevated in patients with DME, and higher intraocular IL-6 levels have been associated with poorer visual outcomes in patients treated with anti-VEGF monotherapy..

IL-6是一种促炎性细胞因子和免疫生长因子，参与炎症信号传导、内皮功能障碍以及血-视网膜屏障的破坏。糖尿病性黄斑水肿（DME）患者眼内IL-6水平升高，且在接受抗VEGF单药治疗的患者中，较高的眼内IL-6水平与较差的视力预后相关。

KSI-501 is designed to address these complementary mechanisms in a single intravitreal medicine. The VEGF-trap component mimics the native VEGF receptors and is designed to inhibit VEGF-mediated vascular permeability and neovascularization. The anti-IL-6 antibody component is designed to inhibit IL-6-mediated inflammatory signaling and normalize the blood-retinal barrier.

KSI-501 旨在通过一种单一的玻璃体内注射药物来应对这些互补机制。其 VEGF 陷阱成分模拟天然 VEGF 受体，旨在抑制 VEGF 介导的血管通透性和新生血管形成。其抗 IL-6 抗体成分旨在抑制 IL-6 介导的炎症信号传导，并使血视网膜屏障恢复正常。

The ABC Platform-based design, with its signature 20-day intraocular half-life, is intended to support sustained intraocular activity and extended durability..

基于ABC平台的设计，凭借其标志性的20天眼内半衰期，旨在支持持久的眼内活性和延长的耐久性。

In preclinical models, KSI-501 was shown to be a potent inhibitor of both VEGF and IL-6 and to normalize the blood-retinal barrier, opening the possibility that KSI-501 may be a disease-modifying therapy for retinal vascular diseases.

在临床前模型中，KSI-501 被证明是 VEGF 和 IL-6 的强效抑制剂，并能使血视网膜屏障正常化，从而为 KSI-501 可能成为视网膜血管疾病的疾病修饰疗法提供了可能性。

About KSI-501

关于 KSI-501

KSI-501 is an investigational anti-IL-6, VEGF-trap bispecific therapy built on the ABC platform and is being developed for high prevalence retinal vascular diseases to address the leading unmet needs of extended durability and targeting disease biology beyond VEGF for differentiated efficacy. KSI-501 is designed to provide high immediacy/efficacy, driven by the enhanced formulation, and high durability, driven by the ABC platform and our science of durability..

KSI-501 是一种基于 ABC 平台开发的在研抗 IL-6/VEGF 陷阱双特异性疗法，旨在治疗高患病率的视网膜血管疾病，以满足延长作用持久性以及针对 VEGF 以外的疾病生物学机制以实现差异化疗效这两大尚未满足的关键需求。KSI-501 的设计旨在通过增强型制剂提供快速起效/高效力，并依托 ABC 平台及我们的作用持久性科学实现高持久性。

Kodiak has advanced KSI-501 into the registrational Phase 3 study DAYBREAK to evaluate its efficacy and safety in wet AMD. DAYBREAK uses KSI-501's enhanced 50 mg/mL formulation containing both conjugated and unconjugated antibody that is intended to balance immediacy and durability. DAYBREAK has completed enrollment.

Kodiak 已推进 KSI-501 进入注册性 III 期研究 DAYBREAK，以评估其在湿性年龄相关性黄斑变性（wet AMD）中的疗效和安全性。DAYBREAK 研究采用 KSI-501 的增强型 50 mg/mL 制剂，该制剂同时含有结合型和未结合型抗体，旨在平衡起效速度与持久性。DAYBREAK 研究已完成受试者入组。

Topline data for the one-year primary endpoint in DAYBREAK are expected in September 2026..

DAYBREAK 研究一年主要终点的顶线数据预计将于2026年9月公布。

Kodiak has also advanced KSI-501 into the registrational Phase 3 ALTO study designed to demonstrate the superiority of bispecific KSI-501 (anti-VEGF, anti-IL-6) versus monospecific aflibercept (anti-VEGF) in patients with diabetic macular edema. The ALTO study is now enrolling patients.

Kodiak 还推进了 KSI-501 进入注册性 III 期 ALTO 研究，该研究旨在证明双特异性 KSI-501（抗 VEGF、抗 IL-6）在糖尿病性黄斑水肿患者中优于单特异性阿柏西普（抗 VEGF）。ALTO 研究目前正在招募患者。

About Kodiak Sciences Inc.

关于科迪亚克科学公司

Kodiak Sciences (Nasdaq:

科迪亚克科学公司（纳斯达克：

KOD

柯达

) is a pre-commercial retina-focused biotechnology company committed to researching, developing and commercializing transformative therapeutics. We are focused on bringing new science to the design and manufacture of next-generation retinal medicines to prevent and treat the leading causes of blindness globally.

）是一家处于商业化前阶段的专注于视网膜领域的生物技术公司，致力于研究、开发和商业化变革性疗法。我们专注于将新科学应用于下一代视网膜药物的设计与制造，以预防和治疗全球导致失明的主要原因。

We are developing a portfolio of three late-stage clinical programs. Zenkuda™ (tarcocimab tedromer) has a BLA-ready profile in diabetic retinopathy, retinal vein occlusion and wet AMD, and, together with KSI-501, is being explored in the BLA-facing Phase 3 DAYBREAK wet AMD study, with topline data expected in September 2026.

我们正在开发包含三个后期临床项目的产品组合。Zenkuda™（tarcocimab tedromer）在糖尿病视网膜病变、视网膜静脉阻塞和湿性年龄相关性黄斑变性（wet AMD）方面已具备提交生物制品许可申请（BLA）的条件，并与KSI-501一同在面向BLA的3期DAYBREAK湿性AMD研究中进行探索，预计将于2026年9月公布顶线数据。

Zenkuda and KSI-501 target the $15 billion anti-VEGF market across retinal vascular diseases. KSI-101 is a bispecific protein being explored in two BLA-facing Phase 3 studies in Macular Edema Secondary to Inflammation (MESI). Topline data for Pivotal Analysis 1 (PEAK) are expected in December 2026 and Pivotal Analysis 2 (PEAK+PINNACLE) in 2Q 2027..

Zenkuda 和 KSI-501 瞄准的是视网膜血管疾病领域高达 150 亿美元的抗 VEGF 市场。KSI-101 是一种双特异性蛋白，目前正在两项针对生物制品许可申请（BLA）的 III 期临床试验中进行探索，适应症为炎症继发性黄斑水肿（MESI）。关键分析 1（PEAK）的顶层数据预计将于 2026 年 12 月公布，关键分析 2（PEAK+PINNACLE）的顶层数据预计将于 2027 年第二季度公布。

Forward-Looking Statements

前瞻性陈述

This press release contains 'forward-looking statements' within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934, and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include, but are not limited to, statements regarding: the ability to demonstrate the superiority of KSI-501 over aflibercept in patients with DME; the potential for dual inhibition of the IL-6 and VEGF pathways to deliver deeper and more sustained disease control for patients with DME; the possibility that KSI-501 may be a disease-modifying therapy for retinal vascular diseases.

本新闻稿包含1933年《证券法》第27A条、1934年《证券交易法》第21E条以及1995年《私人证券诉讼改革法》所定义的“前瞻性陈述”。这些前瞻性陈述并非基于历史事实，包括但不限于以下方面的陈述：证明KSI-501在糖尿病性黄斑水肿（DME）患者中优于阿柏西普的能力；双重抑制IL-6和VEGF通路为DME患者提供更深入且更持久的疾病控制的潜力；KSI-501可能成为视网膜血管性疾病疾病修饰疗法的可能性。

Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as 'may,' 'will,' 'should,' 'would,' 'could,' 'expect,' 'plan,' 'believe,' 'intend,' 'pursue,' 'anticipate,' and other similar expressions, among others.

前瞻性陈述通常包括具有预测性质的陈述，这些陈述依赖于或提及未来事件或条件，并包含“可能”、“将”、“应该”、“会”、“可以”、“预期”、“计划”、“相信”、“打算”、“追求”、“ anticipate ”等词语及其他类似表述。

Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that the Phase 3 ALTO trial may not achieve its primary or key secondary endpoints or may not do so on the anticipated timeline; the risk that dual inhibition of IL-6 and VEGF may not translate into the clinical benefits observed or suggested in earlier studies, including the Phase 2 ALLUVIUM and BARDENAS studies; as well as the other risks identified in the section entitled 'Risk Factors' in Kodiak's most recent Annual Report on F.

任何前瞻性陈述均基于管理层对当前未来事件的预期，并受多种风险和不确定性的影响，这些风险和不确定性可能导致实际结果与前瞻性陈述中明确表述或暗示的结果产生重大且不利的差异。这些风险和不确定性包括但不限于：III期ALTO试验可能无法达到其主要终点或关键次要终点，或无法按预期时间表实现的风险；IL-6和VEGF双重抑制可能无法转化为早期研究（包括II期ALLUVIUM和BARDENAS研究）中观察到的或提示的临床获益的风险；以及Kodiak最新年度F表报告中“风险因素”一节所识别的其他风险。

SOURCE Kodiak Sciences Inc.

来源：Kodiak Sciences Inc.

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