09/30/2025 - 08:30 AM

2025年9月30日- 上午 8:30

VANCOUVER, Washington, Sept. 30, 2025 (GLOBE NEWSWIRE) --

华盛顿温哥华，2025年9月30日（GLOBE NEWSWIRE）--

Dear Shareholders,

亲爱的股东们，

As this pivotal year continues to take shape for CytoDyn Inc. (“CytoDyn” or the “Company”), I am pleased to share the progress we have made in advancing leronlimab as an innovative treatment in oncology. We remain confident that addressing critical unmet needs in this field is the best way to build value while improving the lives of patients. The foundation of our conviction in leronlimab rests on both preclinical and clinical evidence. From laboratory insights to encouraging patient survival observations, our story is compelling and one of consistent validation. The data presented over the past several months marks a watershed moment for both patients and our Company, providing evidence that leronlimab has the potential to reshape treatment paradigms in solid tumor oncology. With multiple clinical trials advancing, we are moving with discipline and urgency along a well-defined path forward.

随着这一关键年份的不断发展，我很高兴与大家分享我们在推进 leronlimab 作为肿瘤学创新治疗方面所取得的进展。我们坚信，解决这一领域的关键未满足需求是创造价值并改善患者生活的最佳途径。我们对 leronlimab 的信心基础建立在前临床和临床证据之上。从实验室的见解到令人鼓舞的患者生存观察，我们的故事引人注目，并且得到了持续的验证。在过去几个月中呈现的数据标志着患者和我们公司的一个重要时刻，提供了 leronlimab 有潜力重塑实体肿瘤肿瘤学治疗范式的证据。随着多个临床试验的推进，我们正沿着一条明确的道路，以严谨和紧迫感向前迈进。

Strengthening Our Leadership

加强我们的领导力

To support this next chapter, we welcomed Robert E. Hoffman as our new Chief Financial Officer. An industry veteran with decades of financial and leadership experience, holding various executive and board positions in his biotech career, Robert has already brought significant value to CytoDyn. His expertise in capital markets and strategic planning strengthens our ability to execute, network, and expand our pipeline. We are delighted to have him aboard.

为了支持这一新篇章，我们欢迎罗伯特·E·霍夫曼（Robert E. Hoffman）担任我们的新首席财务官。他是一位拥有数十年财务和领导经验的行业老将，在生物技术职业生涯中担任过多个高管和董事会职位，罗伯特已经为 CytoDyn 带来了显著的价值。他在资本市场和战略规划方面的专业知识增强了我们执行、网络和扩展管道的能力。我们很高兴他能加入我们。

Scientific Progress and Clinical Development

科学进展与临床发展

At the heart of leronlimab’s promise is a novel mechanism of action (“MOA”) associated with prolonged survival observed in a group of patients with Metastatic Triple-Negative Breast Cancer (“mTNBC”). Supporting data, presented at a poster session at the European Society for Medical Oncology (“ESMO”) breast cancer meeting in Munich, suggest that leronlimab induces PD-L1 expression, creating synergy with immune checkpoint inhibitors (ICIs), a potential breakthrough in solid tumor treatment. This finding not only opens new therapeutic opportunities for leronlimab, but also represents a significant market opportunity for the Company. For additional information on this novel MOA and the status of our clinical initiatives and publications, please see the science update included with this letter.

leronlimab 的承诺核心在于其与观察到的转移性三阴性乳腺癌（mTNBC）患者延长生存相关的新机制。支持数据在慕尼黑的欧洲医学肿瘤学会（ESMO）乳腺癌会议的海报环节中展示，表明 leronlimab 诱导 PD-L1 表达，与免疫检查点抑制剂（ICIs）产生协同作用，这在实体肿瘤治疗中可能是一个突破。这一发现不仅为 leronlimab 开辟了新的治疗机会，也为公司代表了一个重要的市场机会。有关这一新机制及我们临床计划和出版物状态的更多信息，请参见随信附上的科学更新。

One indication that carries the potential for significant value return is leronlimab in mTNBC, the most aggressive form of breast cancer, with 5-year survival rates around 15%. Based on the positive data presented at ESMO, we will shortly submit a follow-up Phase II proof of concept (POC) protocol for PD-L1-negative patients with mTNBC. These patients, currently ineligible for ICI therapy, will receive leronlimab plus standard chemotherapy, followed by a regimen of leronlimab with an ICI. We look forward to sharing more details after the FDA review of the protocol and briefing package that provides a complete summary of CytoDyn’s oncology data.

一个具有显著价值回报潜力的适应症是 mTNBC，这是一种最具侵袭性的乳腺癌，5 年生存率约为 15%。基于在 ESMO 上展示的积极数据，我们将很快提交针对 PD-L1 阴性 mTNBC 患者的后续 II 期概念验证（POC）方案。这些患者目前不符合 ICI 治疗资格，将接受 leronlimab 加标准化疗，随后进行 leronlimab 与 ICI 的联合治疗。我们期待在 FDA 审查该方案和提供 CytoDyn 肿瘤学数据的简报材料后分享更多细节。

In parallel, we will be submitting an Expanded Access Protocol (“EAP”) to enable treatment for patients with second-line, or later, mTNBC, who are ineligible or otherwise unable to participate in our Phase II study. I am pleased to announce that we will be working with an individual benefactor to fund the launch of this compassionate-use program. This benefactor has also expressed interest in supporting an investigator-initiated study in patients with recurrent glioblastoma with an anticipated start date in 2026.

与此同时，我们将提交扩展使用协议（EAP），以便为第二线或更晚期的 mTNBC 患者提供治疗，这些患者不符合或无法参与我们的 II 期研究。我很高兴地宣布，我们将与一位个人捐助者合作，资助这一同情使用项目的启动。这位捐助者还表示有兴趣支持一项针对复发性胶质母细胞瘤患者的研究，该研究预计将在 2026 年开始。

Beyond breast cancer, leronlimab continues to advance in the treatment of metastatic Colorectal Cancer (mCRC). Enrollment in our Phase II study is underway with five sites initiated and several more onboarding in the next several weeks. The enrollment of our fifth patient in the trial will trigger the Data Safety Monitoring Board (DSMB) safety review, which could then open study randomization to include the 700 mg dose. Importantly, we will be closely tracking PD-L1 levels of enrolled patients to further validate our MOA across solid tumors. With that in mind, we have prepared a rollover protocol to ensure that CRC patients who remain stable can continue leronlimab treatment beyond 48 weeks and to allow patients with disease progression the opportunity to receive leronlimab at a dose of 700 mg in combination with an ICI.

除了乳腺癌，leronlimab 在转移性结直肠癌（mCRC）的治疗中也在不断推进。我们的 II 期研究正在进行中，目前已启动五个研究中心，未来几周还将有更多中心加入。我们在试验中招募的第五位患者将触发数据安全监测委员会（DSMB）的安全审查，这可能会开启研究随机化，以包括 700 毫克剂量。重要的是，我们将密切跟踪入组患者的 PD-L1 水平，以进一步验证我们在实体肿瘤中的机制。考虑到这一点，我们已准备好一个滚动协议，以确保稳定的 CRC 患者可以在 48 周后继续接受 leronlimab 治疗，并允许病情进展的患者有机会以 700 毫克的剂量与 ICI 联合接受 leronlimab 治疗。

Finally, I am happy to share a very promising announcement as it relates to a patient who prospectively upregulated PD-L1 after having obtained access to leronlimab through an eIND application submitted by her treating physician. In early 2025, we received a compassionate access request for a patient with mTNBC who was previously unresponsive to treatment with Keytruda. This particular patient had two prior tissue biopsies, both of which were PD-L1 negative. In April, the patient started treatment with leronlimab, and in July blood tests confirmed an increase in PD-L1 levels. Our past clinical observations have shown that upregulating PD-L1 is the first step towards prolonged survival in this patient population and we are encouraged by this readout, which supports our working theory. This is the first of hopefully many PD-L1 upregulation readouts across our CRC and TNBC trial(s) in the coming year. I continue to have high hopes for our upcoming Phase II trials, as well as our expanded access program, as we look to reshape treatment paradigms in solid tumor oncology.

最后，我很高兴分享一个非常有希望的消息，涉及一位在通过其治疗医生提交的 eIND 申请获得 leronlimab 后，前瞻性上调 PD-L1 的患者。在 2025 年初，我们收到了针对一名之前对 Keytruda 治疗无反应的 mTNBC 患者的同情使用请求。这位患者之前进行了两次组织活检，均为 PD-L1 阴性。在 4 月，该患者开始接受 leronlimab 治疗，7 月的血液检测确认 PD-L1 水平上升。我们过去的临床观察表明，上调 PD-L1 是这一患者群体延长生存的第一步，我们对这一结果感到鼓舞，这支持了我们的工作理论。这是希望在未来一年内我们 CRC 和 TNBC 试验中许多 PD-L1 上调结果的第一例。我对我们即将进行的 II 期试验以及扩展使用项目充满信心，因为我们希望重塑实体肿瘤肿瘤学的治疗范式。

Update on Regulatory Matters, Resolution of SEC and DOJ Investigations

关于监管事务的更新，SEC 和 DOJ 调查的解决

I am also pleased to share that we recently received confirmation from both the Securities and Exchange Commission (“SEC”) and Department of Justice (“DOJ”) that their respective investigations have now closed, and nothing further is required of the Company. I believe this positive conclusion for the Company is a reflection of our team here and our collective commitment to compliance and cooperation.

我也很高兴地分享，我们最近收到了来自证券交易委员会（SEC）和司法部（DOJ）的确认，表示他们各自的调查现已结束，公司无需再做进一步的事情。我相信这一积极的结论反映了我们团队的努力和我们对合规与合作的共同承诺。

I remain confident that our collaborative relationship with the FDA has placed us on a productive trajectory. To accelerate progress in oncology, we established an oncology advisory board focused on pursuing the fastest and most responsible pathway(s) forward. The FDA recently granted our request for a meeting, and we look forward to discussing our retrospective data set and related observations in TNBC, as well as the next steps in our TNBC development plan. Maintaining strong relationships and credibility with the FDA and industry partners remains a top priority as we move forward.

我仍然对我们与 FDA 的合作关系充满信心，这使我们走上了一条富有成效的轨道。为了加快肿瘤学领域的进展，我们成立了一个专注于追求最快和最负责任的前进路径的肿瘤学顾问委员会。FDA 最近批准了我们的会议请求，我们期待讨论我们的回顾性数据集及在 TNBC 方面的相关观察，以及我们 TNBC 开发计划的下一步。维护与 FDA 和行业合作伙伴的良好关系和信誉仍然是我们前进的首要任务。

Commitment to our Shareholders

对股东的承诺

Your support has carried the Company through the last several years and we remain committed to acting in your best interests. I want to thank you all again for your perseverance and patience. Your questions and feedback are always appreciated and best received through the Company’s IR email account: ir@cytodyn.com. In the coming months, we will be engaging in critical conversations with our key opinion leaders, potential industry partners and regulators. In support of these efforts, we ask our shareholders to be mindful of the process and respectful of our counterparties. Excessive outreach to these third parties can inadvertently hinder our progress. Our recent results and the novel MOA have attracted the attention of numerous patients, treating physicians, and others across the industry. Please know that we are actively pursuing collaborations to maximize the potential of leronlimab.

你们的支持使公司度过了过去几年，我们仍然致力于以你们的最佳利益为行动准则。再次感谢大家的坚持和耐心。你们的问题和反馈总是受到欢迎，最好通过公司的投资者关系电子邮件账户：ir@cytodyn.com 进行反馈。在接下来的几个月里，我们将与我们的关键意见领袖、潜在行业合作伙伴和监管机构进行重要对话。为了支持这些努力，我们要求我们的股东关注这一过程，并尊重我们的对方。对这些第三方的过度接触可能会无意中阻碍我们的进展。我们最近的结果和新颖的作用机制吸引了众多患者、治疗医生和行业其他人士的关注。请知道，我们正在积极寻求合作，以最大化 leronlimab 的潜力。

A Human Reminder of Our Mission

我们使命的人性提醒

In closing, I’d like to share a brief personal anecdote. As the Company has worked to confirm the mTNBC survival observations and arranged for related follow-up testing, I’ve had the opportunity to speak with several of the surviving patients who accessed leronlimab during the Company’s prior oncology studies. These are individuals who had exhausted all other options yet are now enjoying more time with their families. I had the privilege of sharing a meal with one survivor and her spouse and it is difficult to put into words the emotions we all felt when reflecting on the remarkable sequence of events that brought us together that night, but I can name the most prominent – hope. Encounters like these remind us why our work matters and fuel our determination to accelerate progress for patients everywhere.

最后，我想分享一个简短的个人轶事。随着公司努力确认 mTNBC 生存观察并安排相关的后续测试，我有机会与几位在公司之前的肿瘤学研究中获得 leronlimab 的幸存患者交谈。这些人曾经用尽所有其他选择，但现在能够与家人享受更多的时光。我有幸与一位幸存者及其配偶共进晚餐，难以用言语表达我们在回顾那晚将我们聚集在一起的非凡事件时所感受到的情感，但我可以说最突出的情感是——希望。这样的遭遇提醒我们为什么我们的工作是重要的，并激励我们加快为患者带来进展的决心。

With Gratitude,

怀着感激之情，

Jacob Lalezari, MD

CEO

首席执行官

Note Regarding Forward-Looking Statements

关于前瞻性声明的说明

This news release contains forward-looking statements relating to, among other things, mechanism of action, clinical trial results, product development, market position, future operating and financial performance, and business strategy. The reader is cautioned not to rely on these statements, which are based on current expectations of future events. For important information about these statements and our Company, including the risks, uncertainties and other factors that could cause actual results to vary materially from the assumptions, expectations and projections expressed in any forward-looking statements, the reader should review our Annual Report on Form 10-K for the fiscal year ended May 31, 2025, including the section captioned “Forward-Looking Statements” and in Item 1A, and in subsequent reports filed with the Securities and Exchange Commission. CytoDyn Inc. does not undertake to update any forward-looking statement as a result of new information or future events or developments other than as required by law.

本新闻稿包含与机制、临床试验结果、产品开发、市场地位、未来运营和财务表现以及商业战略等相关的前瞻性声明。读者应谨慎对待这些声明，因为它们基于对未来事件的当前预期。有关这些声明和我们公司的重要信息，包括可能导致实际结果与任何前瞻性声明中表达的假设、预期和预测显著不同的风险、不确定性和其他因素，读者应查阅我们截至2025年5月31日的年度报告（Form 10-K），包括标题为 “前瞻性声明” 的部分以及第 1A 项，以及随后向证券交易委员会提交的报告。CytoDyn Inc.不承担因新信息或未来事件或发展而更新任何前瞻性声明的义务，除非法律要求。

Corporate Contact

公司联系方式

CytoDyn Inc.

ir@cytodyn.com

Media Contacts

媒体联系人

Rob Haney, Ph.D., or Ignacio Guerrero-Ros, Ph.D.

Rob Haney, Ph.D.，或 Ignacio Guerrero-Ros, Ph.D.

Russo Partners, LLC

CytoDyn@russopartnersllc.com

Science Supplement

科学补充

– September 2025–

– 2025 年 9 月–

History of leronlimab in mTNBC

leronlimab 在 mTNBC 中的历史

Dr. Richard Pestell, our Lead Consultant – Preclinical and Clinical Oncology, has published preclinical data demonstrating that leronlimab both prevented the metastatic spread of TNBC and caused reversal of established metastases in mice. These important observations speak to two different mechanisms by which leronlimab's blockade of the CCR5 receptor appears to impact cancer: the first involves the role that CCR5 plays in cell migration and how that receptor is hijacked by cancer cells to promote the spread of distant metastases; the second speaks to the direct anti-cancer activity of leronlimab on an established tumor itself and, in particular, the surrounding microenvironment.

我们的首席顾问——临床前和临床肿瘤学的 Richard Pestell 博士，已发表临床前数据，证明 leronlimab 既能防止 TNBC 的转移扩散，又能导致小鼠中已建立的转移逆转。这些重要观察结果表明了 leronlimab 通过阻断 CCR5 受体影响癌症的两种不同机制：第一种涉及 CCR5 在细胞迁移中的作用，以及癌细胞如何劫持该受体以促进远处转移的扩散；第二种则涉及 leronlimab 对已建立肿瘤本身 的 直接抗癌活性，尤其是周围的微环境。

To follow up on these preclinical observations, CytoDyn conducted three clinical studies in patients with mTNBC and other solid tumors starting in 2019. Analysis of pooled follow-up data from the 28 patients with mTNBC enrolled across these studies formed the basis for our presentation at ESMO and provided evidence of leronlimab’s stand-alone activity in three important ways:

为了跟进这些临床前观察，CytoDyn 于 2019 年在 mTNBC 和其他实体瘤患者中进行了三项临床研究。对这三项研究中 28 名 mTNBC 患者的汇总随访数据的分析为我们在 ESMO 的演示提供了基础，并提供了 leronlimab 在三个重要方面的独立活性的证据：

Promising survival rates: Overall survival rates at years 1, 2, 3, and 4 (35.7%, 21.4%, 17.9%, and 17.9%) compare favorably with previous studies of patients with advanced mTNBC. In particular, the long-term survival rates of 17.9% at both years 3 and 4 are very exciting, considering other studies exploring potential mTNBC treatments typically don’t even report survival rates out to three years. Moreover, the survival rate of 17.9% at year 4 was calculated without removing or “censoring” patients who dropped out for any reason, meaning it is presented in the most conservative way possible.
Impact on advanced disease: Patients in our study population had failed a median of two prior lines of treatment after developing metastatic disease, and a majority had cancer in other organs (64% had visceral metastases and 29% had brain metastases at entry into the studies). Despite that, the median overall survival (“mOS”) of 6.8 months for all 28 patients (9.7 months for the 18 patients receiving >525 mg) appears comparable to the current standard of care. This makes our results especially promising, given our study population had, generally speaking, more advanced disease than typical clinical populations. Given our survival observations and working theory on the mechanism of action, we are excited to explore leronlimab as an earlier line of therapy with the idea that earlier treatment could serve to save more lives.
Decreased CTC levels: The decline in circulating tumor cells (“CTCs”) observed in most patients after as little as one dose of leronlimab was significantly associated with both progression-free and overall survival. Leronlimab’s rapid and prognostically significant impact on CTCs, which appears to reflect activity within the primary tumor itself, provides important evidence of leronlimab’s activity as a stand-alone agent. Confirming the full extent of leronlimab’s activity on the primary tumor is on our short list of clinical priorities in the coming months.

令人鼓舞的生存率： 在 1 年、2 年、3 年和 4 年的总体生存率分别为 35.7%、21.4%、17.9% 和 17.9%，与以往对晚期转移性三阴性乳腺癌（mTNBC）患者的研究结果相比，表现良好。特别是，3 年和 4 年的长期生存率均为 17.9%，这令人振奋，因为其他研究探索潜在的 mTNBC 治疗时，通常甚至不报告三年的生存率。此外，4 年时的 17.9% 生存率是在没有剔除或 “审查” 因任何原因退出的患者的情况下计算得出的，这意味着它以尽可能保守的方式呈现。
对晚期疾病的影响： 我们研究人群中的患者在发展转移性疾病后，平均接受了两条之前治疗方案的失败，大多数患者在其他器官也有癌症（64% 的患者有内脏转移，29% 的患者在入组时有脑转移）。尽管如此，28 名患者的中位总体生存期（“mOS”）为 6.8 个月（接受>525 毫克治疗的 18 名患者为 9.7 个月），这与当前的标准治疗相当。考虑到我们的研究人群通常比典型临床人群的疾病更为晚期，这使得我们的结果特别令人期待。基于我们的生存观察和对作用机制的工作理论，我们很高兴探索 leronlimab 作为早期治疗方案，认为早期治疗可能有助于挽救更多生命。
CTC 水平降低： 在大多数患者中，观察到在仅接受一剂 leronlimab 后循环肿瘤细胞（“CTCs”）的下降与无进展生存期和总体生存期显著相关。Leronlimab 对 CTCs 的快速且具有预后意义的影响，似乎反映了其在原发肿瘤内的活性，为 leronlimab 作为单一药物的活性提供了重要证据。确认 leronlimab 对原发肿瘤的全部活性是我们在未来几个月的临床优先事项之一。

CytoDyn’s Presentation at ESMO – Outlining a Novel Mechanism of Action

CytoDyn 在 ESMO 的演示 – 概述一种新颖的作用机制

As announced leading up to the ESMO presentation, the survival observations and related retrospective data collectively suggest a potential paradigm shift in solid tumor oncology involving leronlimab’s novel mechanism of action in conjunction with Immune Checkpoint Inhibitors (“ICIs”). To help understand this new paradigm, the following is an explanation of the basic steps and the Company’s working theory at this time:

正如在 ESMO 演示之前所宣布的，生存观察和相关的回顾性数据共同表明，涉及 leronlimab 的新颖作用机制与免疫检查点抑制剂（“ICIs”）结合，可能会在实体肿瘤肿瘤学中引发潜在的范式转变。为了帮助理解这一新范式，以下是对基本步骤和公司目前工作理论的解释：

For a cancerous tumor to establish itself and grow in the body, it attempts to avoid detection and an immune response. One way a cancer can do this is by hijacking CCR5, a protein receptor on the surface of certain immune cells. Through CCR5 signaling, the tumor commandeers host macrophages, a type of white blood cell that would otherwise attack the cancer cells, to help the tumor build a surrounding area or “microenvironment” to support its growth, including a blood supply that provides necessary nutrients. The growing tumor also uses CCR5 signaling to recruit immunosuppressive cells to the local environment that keep the microenvironment “cold” and the host immune system at bay.

为了使癌肿瘤在体内建立并生长，它试图避免被检测和免疫反应。癌症可以通过劫持 CCR5（一种在某些免疫细胞表面的蛋白质受体）来实现这一点。通过 CCR5 信号传导，肿瘤指挥宿主巨噬细胞，这是一种本应攻击癌细胞的白血球，帮助肿瘤建立一个支持其生长的周围区域或 “微环境”，包括提供必要营养的血液供应。生长中的肿瘤还利用 CCR5 信号传导招募免疫抑制细胞到局部环境中，使微环境保持 “冷” 并抑制宿主免疫系统。

As to the above processes, it appears leronlimab has the ability to disrupt the CCR5 signaling that both promotes the cancer tumor’s growth and protects its microenvironment from the host immune response. By disrupting CCR5 signaling, leronlimab allows the host immune system (CD8+ cells) to identify the cancer cells as a threat and attack them in what has now become a “hot” or inflamed microenvironment (expressing various inflammatory cytokines).

关于上述过程，leronlimab 似乎具有干扰 CCR5 信号传导的能力，这种信号传导既促进癌肿瘤的生长，又保护其微环境免受宿主免疫反应的影响。通过干扰 CCR5 信号传导，leronlimab 使宿主免疫系统（CD8+ 细胞）能够将癌细胞识别为威胁并攻击它们，从而使微环境变为 “热” 或发炎状态（表达各种炎性细胞因子）。

To counter the pressure of an attack from the host immune system, the cancer, at least as evidenced on the CTCs, has a secondary line of defense: expressing a protein called PD-L1 and hijacking its relationship to its receptor, PD-1. Ordinarily, PD-1 acts as the immune system’s “off switch”, binding with PD-L1 on functioning immune cells and preventing them from being so strong that they kill healthy cells in the body. Cancer cells capitalize on this system by expressing PD-L1 and binding to the “off switch” on the invading host immune cells, in turn slowing an immune response, thereby protecting the tumor.

为了应对宿主免疫系统攻击的压力，癌症至少在 CTCs 的证据上，具有第二道防线：表达一种称为 PD-L1 的蛋白质，并劫持其与受体 PD-1 的关系。通常，PD-1 作为免疫系统的 “关闭开关”，与功能性免疫细胞上的 PD-L1 结合，防止它们过于强大而杀死体内的健康细胞。癌细胞利用这一系统，通过表达 PD-L1 并与侵入的宿主免疫细胞上的 “关闭开关” 结合，从而减缓免疫反应，保护肿瘤。

As observed in patients who were fortunate enough to receive a PD-L1 antibody called an ICI in our prior studies, this “secondary defense” of the tumor can be thwarted. The antibody prevents the PD-L1 protein from binding to the “off switch” (PD-1), keeping the immune system “on” and allowing the host immune system’s attack on the cancer to continue. Typically, patients who have tumors with higher levels of PD-L1 expression derive the most benefit from treatment with an ICI, given there are more opportunities for the antibody to block connections to the “off” switch and allow the immune system to fight the cancer cells.

在我们之前的研究中，幸运地接受了名为 ICI 的 PD-L1 抗体的患者观察到，这种肿瘤的 “第二道防线” 可以被破坏。该抗体阻止 PD-L1 蛋白与 “关闭开关”（PD-1）结合，使免疫系统保持 “开启”，并允许宿主免疫系统继续攻击癌症。通常，具有较高 PD-L1 表达水平的肿瘤患者从 ICI 治疗中获益最大，因为抗体有更多机会阻止与 “关闭” 开关的连接，从而允许免疫系统对抗癌细胞。

As to this process, preliminary data indicate that leronlimab has the ability to induce higher levels of PD-L1 expression in solid tumor cancer cells. This opens potential new treatment pathways for patients with low PD-L1 levels who would have otherwise been unable to derive benefit from an ICI.

关于这一过程，初步数据显示，leronlimab 具有诱导实体肿瘤癌细胞中更高 PD-L1 表达水平的能力。这为 PD-L1 水平较低的患者打开了潜在的新治疗途径，否则他们将无法从 ICI 中获益。

The foregoing sequence is a novel working theory; however, our data, first presented at ESMO, suggest that this is what happened in the five patients who are alive today, 48 months after diagnosis.

上述序列是一种新颖的工作理论；然而，我们的数据首次在 ESMO 上展示，表明这就是在诊断 48 个月后仍然存活的五名患者所发生的情况。

The key findings from our presentation at ESMO included the following:

我们在 ESMO 演示中的关键发现包括以下内容：

PD-L1 Upregulation:16/21 (76%) of patients showed a significant increase in PD-L1 expression on CTCs within 30-90 days after starting leronlimab, regardless of dose. This suggests that the tumor microenvironment was turned from “cold” to “hot” (from being protected against host immune invasion to being under host immune attack). Even more remarkably, this shift from “cold” to “hot” occurred in 15/17 (88%) patients who received weekly leronlimab doses of 525 mg or higher. Turning “cold” tumors “hot” means that far more patients with TNBC (and potentially other solid tumors) may become eligible for a class of drugs known as anti-PD-1/anti-PD-L1 treatments and collectively referred to as ICIs.
Long Term Survival:The clinical significance of the increase in PD-L1 observed on the CTCs was driven home by the confirmation that 5/5 (100%) of patients who demonstrated a significant increase in PD-L1 expression while receiving leronlimab and received any ICI are alive today, 4+ years later. More remarkably, three of these individuals (60%) are currently identified as having no ongoing evidence of disease. Underscoring the clinical significance of these results is the unfortunate finding that none of the 23 patients who didn’t induce significant PD-L1 expression or didn’t receive an ICI with leronlimab are alive today.

PD-L1 上调：在开始使用 leronlimab 后的 30-90 天内，16/21（76%）的患者在循环肿瘤细胞（CTCs）上显示出 PD-L1 表达显著增加，无论剂量如何。这表明肿瘤微环境从 “冷” 转变为 “热”（从抵御宿主免疫侵袭转变为受到宿主免疫攻击）。更值得注意的是，这种从 “冷” 到 “热” 的转变发生在接受每周 525 毫克或更高剂量 leronlimab 的 15/17（88%）患者中。将 “冷” 肿瘤转变为 “热” 意味着更多的三阴性乳腺癌（TNBC）患者（以及潜在的其他实体瘤患者）可能有资格接受一类称为抗 PD-1/抗 PD-L1 治疗的药物，统称为免疫检查点抑制剂（ICIs）。
长期生存：在 CTCs 上观察到的 PD-L1 增加的临床意义得到了确认，5/5（100%）在接受 leronlimab 治疗时表现出显著 PD-L1 表达增加并且接受了任何 ICIs 的患者至今仍然存活，已经超过 4 年。更值得注意的是，这三名患者（60%）目前被认定为没有持续的疾病证据。这些结果的临床意义被一个不幸的发现所强调，即在 23 名没有诱导显著 PD-L1 表达或没有与 leronlimab 一起接受 ICIs 的患者中，没有一人今天仍然存活。

Update(s) on Colorectal Cancer and Pending Trial

结直肠癌的更新及待定试验

While generating the TNBC dataset, we documented outcomes in patients with other solid tumors previously enrolled in the CD09 “Basket Study.” The results from five such patients with colorectal cancer (“CRC”) were presented at the ESMO GI meeting in Barcelona this past July by the Principal Investigator for our current CRC study, Dr. Ben Weinberg from the Lombardi Comprehensive Cancer Center at Georgetown University. Additional updates on our CRC trial and how we will be using the CRC trial to further establish our working theory on the mechanism of action driving improved survival are included below.

在生成 TNBC 数据集的过程中，我们记录了在 CD09“篮子研究” 中先前入组的其他实体瘤患者的结果。来自五名结直肠癌（“CRC”）患者的结果在今年 7 月的巴塞罗那 ESMO GI 会议上由我们当前 CRC 研究的首席研究员、乔治城大学隆巴尔迪综合癌症中心的 Ben Weinberg 博士进行了介绍。关于我们 CRC 试验的更多更新以及我们将如何利用 CRC 试验进一步建立我们关于改善生存机制的工作理论的信息如下。

The timing of the TNBC observations, data set, and working mechanism of action theory creates a unique opportunity for CytoDyn to evaluate this “cold to hot” paradigm shift in the context of a second solid tumor during our CRC study. Up to 85% of patients with CRC are not currently candidates for ICI therapy because their tumors are “cold” and do not express PD-L1. Our mCRC study design provides leronlimab in both arms of the study. As such, we have amended the protocol to include close monitoring of PD-L1 levels on the CTCs in all enrolled patients. In addition, we are submitting a new rollover protocol to the FDA, which will provide ongoing access to leronlimab for those patients with CRC who continue to do well after 48 weeks on the parent study and will now offer leronlimab plus an ICI to those patients who progress on the parent study. These amendments will allow us to achieve multiple critical goals, including:

TNBC 观察、数据集和工作机制理论的时机为 CytoDyn 在我们的 CRC 研究中评估这一 “冷到热” 的范式转变创造了独特的机会。高达 85% 的 CRC 患者目前不符合 ICI 治疗的候选资格，因为他们的肿瘤是 “冷” 的且不表达 PD-L1。我们的 mCRC 研究设计在研究的两个组中提供 leronlimab。因此，我们已修订协议，以包括对所有入组患者 CTCs 上 PD-L1 水平的密切监测。此外，我们正在向 FDA 提交新的滚动协议，该协议将为在母研究中经过 48 周后继续表现良好的 CRC 患者提供持续的 leronlimab 使用，并将为在母研究中进展的患者提供 leronlimab 加 ICI。这些修订将使我们能够实现多个关键目标，包括：

Evaluate leronlimab as a stand-alone agent (in combination with Standard of Care) in a second solid tumor type;
Prospectively evaluate the ability of 2 different leronlimab dose levels to induce PD-L1 expression on CTCs in a solid tumor that is typically “cold” and not usually associated with PD-L1 expression;
Obtain biopsy tissue from patients with disease progression enrolling in the rollover protocol to correlate PD-L1 levels and changes in the tumor microenvironment on tumor tissue with PD-L1 expression on concurrently drawn CTCs; and
Evaluate the possibility of treating patients with a common and typically “cold” cancer with the combination of leronlimab and an ICI, the same regimen that demonstrated long-lasting remission in 5/5 patients with mTNBC who significantly induced PD-L1, as reported at ESMO.

评估 leronlimab 作为单独药物（与标准护理结合）在第二种实体瘤类型中的效果；
前瞻性评估两种不同 leronlimab 剂量水平在通常 “冷” 且通常不与 PD-L1 表达相关的实体瘤中诱导 PD-L1 表达的能力；
从在滚动协议中入组的疾病进展患者中获取活检组织，以将 PD-L1 水平和肿瘤组织中肿瘤微环境的变化与同时抽取的 CTCs 上的 PD-L1 表达进行关联；
评估用 leronlimab 和 ICI 的组合治疗一种常见且通常 “冷” 的癌症的可能性，这一方案在 5/5 名显著诱导 PD-L1 的 mTNBC 患者中显示出持久的缓解，如在 ESMO 上报告的那样。

It is fortuitous that we launched the CRC study just as the PD-L1 data came to light, as it allows us to immediately commence efforts to collect certain prospective confirmatory data. Five trial sites have been initiated. It is our hope that the ESMO CRC data, together with the option of receiving leronlimab and an ICI during the rollover protocol, will generate interest among both patients and caregivers and help to expedite enrollment efforts.

我们在 PD-L1 数据浮出水面时启动 CRC 研究是非常幸运的，因为这使我们能够立即开始收集某些前瞻性确认数据。五个试验站点已启动。我们希望 ESMO CRC 数据，加上在滚动协议中接受 leronlimab 和 ICI 的选项，将在患者和护理人员中产生兴趣，并帮助加快入组工作。

Investigator-Initiated Study in Glioblastoma

在胶质母细胞瘤中的研究

In addition to mTNBC and CRC, we are continuing our investigation into a possible role for leronlimab in the treatment of glioblastoma, a third solid tumor type. We have found an individual who has agreed to fund this venture, and we have reached a tentative agreement with two medical centers to support their investigator-initiated pilot study in patients with recurrent glioblastoma. These patients will receive leronlimab in advance of their pending surgery and then start an ICI after surgery. This study is predicated on the prior observation of CNS penetration of leronlimab in macaques, as well as the potentially peripheral site of activity of ICI on T Cells in patients who had their protected tumor microenvironment disrupted while receiving leronlimab prior to surgery.

除了 mTNBC 和 CRC，我们还在继续研究 leronlimab 在胶质母细胞瘤治疗中的潜在作用，这是一种第三种实体瘤类型。我们找到了一位同意资助这一项目的个人，并与两个医疗中心达成了初步协议，以支持他们在复发性胶质母细胞瘤患者中的研究者发起的试点研究。这些患者将在待进行手术前接受 leronlimab 治疗，然后在手术后开始接受 ICI。这项研究基于之前观察到的 leronlimab 在猕猴中的中枢神经系统穿透能力，以及在接受 leronlimab 治疗后其保护的肿瘤微环境被破坏的患者中，ICI 在 T 细胞上的潜在外周作用。

Other Pre-Clinical and Clinical Projects

其他前临床和临床项目

We are pleased to share that the Alzheimer’s study at Cornell University Medical Center in New York has received both FDA and IRB approval, a “kickoff meeting” was just conducted, and enrollment will begin in the coming weeks. As previously noted, this study has been funded by an outside foundation to whom we are very grateful, but that wishes to remain anonymous at this time.

我们很高兴地分享，位于纽约的康奈尔大学医学中心的阿尔茨海默病研究已获得 FDA 和 IRB 的批准，刚刚召开了 “启动会议”，并将在接下来的几周内开始入组。如前所述，该研究得到了一个外部基金会的资助，我们对此非常感激，但该基金会希望此时保持匿名。

Additionally, the LATCH study with Dr. Jonah Sacha and his team at Oregon Health & Science University has been updated and is now ready for IRB and FDA submission. The study will further explore the role of leronlimab in the potential cure of HIV+ patients who receive a stem cell transplant from CCR5+ donors. We were also able to work with Dr. Sacha to arrange for commitments from outside foundation(s) to fund the costs of this study.

此外，Oregon Health & Science University 的 Jonah Sacha 博士及其团队的 LATCH 研究已更新，并准备提交 IRB 和 FDA。该研究将进一步探讨 leronlimab 在接受 CCR5+ 供体的干细胞移植的 HIV+ 患者潜在治愈中的作用。我们还与 Sacha 博士合作，安排外部基金会资助该研究的费用。

Pending Publications

待发表的文献

Our top publication priority remains a comprehensive TNBC manuscript that includes the clinical and PD-L1 data presented at ESMO, as well as recent laboratory data generated by Dr. Richard Pestell that appears to reinforce our belief in leronlimab as a paradigm shift in solid tumor oncology. The initial draft of the manuscript will be ready for internal review in the coming weeks.

我们最重要的出版优先事项仍然是一个全面的三阴性乳腺癌（TNBC）手稿，其中包括在 ESMO 上展示的临床和 PD-L1 数据，以及由 Richard Pestell 博士生成的最新实验室数据，这些数据似乎进一步强化了我们对 leronlimab 作为实体肿瘤肿瘤学范式转变的信念。手稿的初稿将在接下来的几周内准备好进行内部审查。

The Company has also prepared a case report of a patient with mTNBC whose cancer had spread to both brain and lungs,but who is alive today without evidence of disease, almost 5 years after receiving fourth-line treatment with leronlimab plus atezolizumab. That manuscript will be submitted for peer review shortly.

公司还准备了一份关于一名转移性三阴性乳腺癌（mTNBC）患者的病例报告，该患者的癌症已扩散至大脑和肺部，但在接受 leronlimab 加阿特珠单抗的第四线治疗近 5 年后，今天仍然存活且没有疾病证据。该手稿将很快提交同行评审。

The company is also preparing a safety manuscript summarizing the safety data in almost 1,600 patients who have now been treated with leronlimab in CytoDyn-sponsored studies.

公司还在准备一份安全性手稿，总结近 1600 名在 CytoDyn 赞助的研究中接受 leronlimab 治疗的患者的安全性数据。

The company’s manuscript describing the results of CytoDyn’s prior study in patients with Metabolic Dysfunction-Associated Steatohepatitis was recently accepted for publication.

公司关于 CytoDyn 之前在代谢功能障碍相关脂肪肝炎患者中研究结果的手稿最近已被接受发表。

Finally, we have recently submitted two additional manuscripts for peer-review, including:

最后，我们最近提交了另外两份手稿进行同行评审，包括：

A manuscript of a preclinical study of CRC performed at the Cleveland Clinic, which demonstrated a significant reduction in lung metastasis in mice treated with leronlimab.
A manuscript summarizing results from SMC Laboratories detailing the effects of leronlimab on liver fibrosis, inflammation, and fat.

一份在克利夫兰诊所进行的结直肠癌（CRC）预临床研究的手稿，显示接受 leronlimab 治疗的小鼠肺转移显著减少。
一份总结 SMC 实验室结果的手稿，详细说明 leronlimab 对肝纤维化、炎症和脂肪的影响。

Note Regarding Forward-Looking Statements

关于前瞻性声明的注意事项

This September 2025 Science Supplement contains forward-looking statements relating to, among other things, mechanism of action, clinical trial results, product development, market position, future operating and financial performance, and business strategy. The reader is cautioned not to rely on these statements, which are based on current expectations of future events. For important information about these statements and our Company, including the risks, uncertainties and other factors that could cause actual results to vary materially from the assumptions, expectations and projections expressed in any forward-looking statements, the reader should review our Annual Report on Form 10-K for the fiscal year ended May 31, 2025, including the section captioned “Forward-Looking Statements” and in Item 1A, and in subsequent reports filed with the Securities and Exchange Commission. CytoDyn Inc. does not undertake to update any forward-looking statement as a result of new information or future events or developments other than as required by law.

本 2025 年 9 月的科学补充材料包含与作用机制、临床试验结果、产品开发、市场地位、未来运营和财务表现以及商业战略等相关的前瞻性声明。读者被警告不要依赖这些声明，因为它们基于对未来事件的当前预期。有关这些声明和我们公司的重要信息，包括可能导致实际结果与任何前瞻性声明中表达的假设、期望和预测显著不同的风险、不确定性和其他因素，读者应查看我们截至2025年5月31日的 10-K 表格年度报告，包括标题为 “前瞻性声明” 的部分和第 1A 项，以及随后向证券交易委员会提交的报告。CytoDyn Inc.不承担因新信息或未来事件或发展而更新任何前瞻性声明的义务，法律另有要求的除外。

2025 年 9 月致股东信 | CYDY 股票新闻