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LARKSPUR, Calif.--( BUSINESS WIRE )--Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of potentially best-in-class IL-2 therapeutics, today shared positive results from its Phase 1/2 dose escalation and cohort expansion study of AU-007. The data will be presented in a poster session at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting in Houston, Texas. Preliminary Phase 2 data reveal that a combination of AU-007 and low-dose, subcutaneous aldesleukin is clinically active in melanoma, a finding consistent with Phase 1 data demonstrating clinical activity in a range of patients whose tumors had progressed through prior checkpoint inhibitors. Data from all 77 patients show durable reductions in immunosuppressive Treg cells – a result unprecedented in the IL-2 class – with a correlation between longer progression-free survival outcomes as Treg reduction deepens. “ We believe these data represent preliminary clinical proof of concept for our unique monoclonal antibody, AU-007, and we are confident in its emerging profile as a potential best-in-class therapeutic,” said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer . “ We look forward to presenting a fuller and more mature set of Phase 2 data for melanoma, renal cell carcinoma and non-small cell lung cancer in the first half of next year.” Key findings from preliminary results of the Phase 1/2 dose escalation and cohort expansion study of AU-007, with data available on 77 patients as of the data cutoff date of September 28, 2024, are as follows: A tolerable and manageable safety profile was observed at all doses evaluated in Phase 1 dose escalation. No dose-limiting toxicity occurred throughout Phase 1 dose escalation. Most drug-related adverse events were Grade 1 or 2 except for: Grade 3 anemia in one patient who entered the study with Grade 2 anemia, had rapid disease progression and received only two doses of the study drug. Grade 4 cytokine release syndrome (CRS) in one patient that resolved with steroids, IV fluids and brief vascular pressor support, and did not require tocilizumab. This patient was noted retrospectively to have subclinical elevated IL-6 (5x upper limit of normal) serum levels, likely due to an active case of gout at baseline. Transient Grade 3 elevated lipase in one patient that was not associated with clinical symptoms and resolved without intervention. Transient (3-7 days) Grade 3 or 4 lymphopenias in six patients. The lymphopenias were not associated with adverse outcomes. Transient lymphopenia is a known effect of IL-2 treatment as lymphocytes traffic out of blood and into tissue. Strong evidence of anti-tumor activity was observed in heavily pre-treated patients, particularly in melanoma. Two patients with melanoma refractory to prior anti-CTLA-4 and anti-PD-1 therapy were treated with AU-007 every two weeks (Q2W) and one administration of low-dose, subcutaneous aldesleukin (recombinant human IL-2), and experienced deep and durable tumor shrinkages of 48% and 100% in target lesions. One patient in dose escalation with acral melanoma that progressed rapidly on prior anti-PD-1 therapy received AU-007 Q2W and one loading dose of subcutaneous aldesleukin. This patient remained on AU-007 therapy for 11 months with disease control. Anti-tumor activity was also observed in heavily pre-treated patients with renal cell carcinoma (RCC), bladder cancer, head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) whose tumors had progressed through checkpoint inhibitors. AU-007 and low-dose, subcutaneous aldesleukin continues to demonstrate a unique pharmacodynamic (PD) profile in the IL-2 class. A decrease in Tregs appears to be a critical determinant of observed efficacy, with greater median decreases observed in patients receiving one loading dose of low-dose, subcutaneous aldesleukin compared to low-dose, subcutaneous aldesleukin administered Q2W. Based on the Treg reduction levels and other PD findings, the company has made the decision to use the loading dose rather than the Q2W schedule of subcutaneous aldesleukin going forward. Greater decreases in Tregs on treatment is associated with longer progression-free survival (PFS) across the Phase 1 and Phase 2 portions of the AU-007 trial. Patients with a Treg cell reduction greater than the median of 43% had longer PFS outcomes than those with a Treg cell reduction less than the median of 43%. The Phase 2 expansion cohorts evaluating AU-007 and low-dose, subcutaneous aldesleukin continue to enroll patients, with a focus on melanoma and non-small cell lung cancer. An additional Phase 2 cohort will evaluate AU-007 and low-dose, subcutaneous aldesleukin combined with avelumab (checkpoint inhibitor; anti-PD-L1) in NSCLC. The company anticipates presenting updated clinical data in the first half of 2025. The poster, “ A phase 1/2 dose escalation and cohort expansion study of AU-007, a human monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, plus low-dose aldesleukin in advanced solid tumors,” (Abstract 685) is available to meeting registrants as an electronic poster on the SITC 2024 virtual meeting platform. It will be presented in a poster session on Friday, November 8, 2024, 9:00 a.m.-7:00 p.m. CST in Exhibit Halls AB. The poster presentation is also available on the Aulos Bioscience website in the Abstracts and Publications section. To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626 ). For patients and providers in the U.S., please visit www.solidtumorstudy.com . For patients and health professionals in Australia, please visit www.solidtumourstudy.com . About AU-007 AU-007 is a human IgG1 monoclonal antibody designed by leveraging artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 redirects IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy. About Aulos Aulos Bioscience is an immuno-oncology company working to revolutionize cancer patient care through best-in-class IL-2 therapeutics that direct patients’ immune systems toward killing tumor cells. Matching world-class machine learning from co-founder Biolojic Design with an in-depth understanding of the immune system, Aulos’ initial clinical candidate, AU-007, is a human antibody designed by leveraging artificial intelligence that harnesses the power of IL-2 to induce tumor killing while limiting the immunosuppression and toxicities typically associated with this validated pathway. The company was founded by Biolojic Design and Apple Tree Partners ( ATP ) and is led by pioneers in the field of artificial intelligence, antibody development and cancer immunotherapies. For more information, visit www.aulosbio.com , X ( @AulosBioscience ) and LinkedIn .

欢迎关注凯莱英药闻 2024年10月23日，Aulos Bioscience（“Aulos”）在西班牙巴塞罗那举行的第 36 届 EORTC-NCI-AACR 分子靶点和癌症治疗研讨会上，分享了其主要候选药物 AU-007 的 1/2 期临床试验中2 期扩展队列的部分临床研究数据。 AU-007是一款新型的白细胞介素 2 (IL-2)治疗抗体，是第一个利用人工智能设计的进入人体临床试验的人类 IgG1 单克隆抗体，具有同类最佳的治疗潜力；公司计划于今年晚些时候展示新的 2 期临床疗效和安全性数据，特别是在黑色素瘤和肾细胞癌方面。 关于最新研究数据 本次研讨会上，主要披露了AU-007的药效学、药代动力学、安全性和临床疗效的数据，结果显示： 使用该药物后调节性T细胞（Treg）减少；在不同剂量水平、肿瘤类型和治疗线的患者中，外周血Treg计数的下降与更长的无进展生存（PFS）相关。 随着皮下给药剂量的增加，观察到干扰素-γ(IFN-γ)和效应T细胞（Teffs）的增加。 在安全性上，低剂量时毒性可控，在评估的所有剂量水平下均无血管泄漏综合征或肺水肿。 药代动力学数据显示，没有证据表明它具有中和抗药物抗体（ADA）的活性，半衰期大约超过15天。 关于AU-007 AU-007 由 Biolojic Design 创建，对IL-2的CD25结合部分具有高度选择性。 不同于其它IL-2治疗药物，AU-007通过阻止外源性或由T细胞分泌的IL-2与T细胞上的三聚体受体结合，同时仍允许IL-2结合并扩增T细胞和NK细胞。这可以防止由其他基于IL-2的治疗引起的负反馈回路，并使免疫系统偏向于激活而不是抑制。 此外，AU-007 还可阻止 IL-2与嗜酸性粒细胞、血管和肺内皮上的含 CD25 受体结合，从而显著减少与高剂量 IL-2 治疗相关的血管渗漏综合征和肺水肿。 根据2024年5月披露其在晚期实体瘤患者中的研究显示： 一名接受抗 PD-1 治疗后病情进展的鼻咽癌患者出现确认的部分缓解（减少 32%）； 非小细胞肺癌、膀胱癌、头颈癌、结直肠癌 (CRC) 和肾癌患者的肿瘤出现萎缩； 一名接受抗 CTLA-4 + 抗PD-1 治疗后病情进展的黑色素瘤患者，靶肿瘤减少了 48%； 一名微卫星稳定性 CRC 患者在第一个周期治疗后肿瘤萎缩了 26%； 患者血清 Treg 和嗜酸性粒细胞减少，而 NK 和 CD8 细胞计数呈上升趋势。 所有药物相关不良事件 (AE) 均为1 级或 2 级。最常见的药物相关不良事件是发热（18%）、疲劳（16%）、恶心（14%）、淋巴细胞减少（8%）和发冷（6%）。两名患者出现一过性 2 级药物相关严重不良反应：发热和细胞因子释放综合征；两名患者均继续治疗。 此外，公司于2024年5月与默克的瑞士子公司Ares Trading签署了一项新的合作与供应协议；根据协议条款，默克将向Aulos免费提供Bavencio（PD-L1抗体），用于在Aulos的AU-007治疗实体瘤癌症的1/2期临床试验的额外2期队列中，评估Bavencio与AU-007和低剂量皮下注射醛固酮的联合用药情况。公司称，Bavencio可与AU-007产生独特的机理协同作用，通过称为ADCC的过程调动自然杀伤细胞杀伤肿瘤细胞，同时还能干扰抑制效应T细胞的PD-L1/PD-1检查点，有望创造出一种强大的联合治疗方案，可根除多种癌症类型的肿瘤细胞。 关于IL-2药物 IL-2也称为T 细胞生长因子，是一种主要由活化的T 细胞，尤其是CD4+T 辅助细胞产生的多功能细胞因子，IL-2 通过与不同细胞上IL-2 受体的结合，在免疫反应中介导多重作用：1）IL-2 具有免疫系统刺激作用，可以刺激T 细胞和天然杀伤（NK）细胞增殖和分化；2）IL-2 能够促进免疫抑制性CD4+CD25+调节性T 细胞（Treg）的维持，在患者中引起由激活的Treg 细胞导致的免疫抑制。 功能性IL-2 受体（IL-2R）的3 种亚基具有不同的亲和力和信号传导功能。其中，IL-2Rα又称为CD25， IL-2Rβ 又称为CD122，IL-2Rγ 又称为CD132。IL-2Rβ/γ异源二聚体复合物具备中等亲和力（ Kd=1nmol/L ）， IL-2α/β/γ 异源三聚体复合物具备最高亲和力（Kd=10pmol/L），以上复合物主要启动JAK/STAT5、PI3K/Akt/mTOR 和MAPK 三种信号通路，在细胞生长、存活、分化和免疫中起着关键角色。 目前，IL-2 药物开发历程不断进阶，主要的开发类型包括：1）免疫调节剂，例如重组IL-2、突变IL-2、受体偏向性IL-2 和靶向CD-25 抗体被开发出来调节IL-2 信号；2）递送细胞毒素，例如抗CD25 RIC，抗CD25 IT 及ADC 药物。 在交易上，早在2018 年，BMS 以36.5 亿美元拿下Nektar 的偏向性IL-2 候选药物的部分权益；2019 年赛诺菲以25 亿美元收购Synthrox，其中核心资产包括重组IL-2 THOR-707；2020-2023 年，国内外陆续有多家企业针对IL2 药物进行交易。尽管各家开发思路不同，但是针对IL-2偏向剂，企业开发思路多为降低IL-2Rα结合力，目前临床数据并不乐观。 关于Aulos Aulos是一家免疫肿瘤学公司，致力于通过一流的IL-2疗法引导患者的免疫系统杀死肿瘤细胞，从而彻底改变癌症患者的治疗。该公司由Biolojic Design和Apple Tree Partners (ATP)创立，由人工智能、抗体开发和癌症免疫疗法领域的先驱领导。 参考资料 1、公司官网 2、国联证券 3、智药邦 感谢关注、转发，转载授权、加行业交流群，请加管理员微信号“hxsjjf1618”。 “在看”点一下