Medicenna Presents Updated Preclinical Data on MDNA113, a First-in-Class, Targeted and Masked Bi-functional Anti-PD1-IL2 Superkine, at the 2024 Annual Meeting of the American Association for Cancer Research (AACR)
Medicenna Presents Updated Preclinical Data on MDNA113, a First-in-Class, Targeted and Masked Bi-functional Anti-PD1-IL2 Superkine, at the 2024 Annual Meeting of the American Association for Cancer Research (AACR)
MDNA113 is targeted to the tumor site where it is activated to simultaneously deliver two immunotherapies, an IL-2 superkine and anti-PD1 antibody, to the same cancer fighting immune cells in the tumor micro-environment (TME) to maximize efficacy and minimize systemic toxicity
MDNA113 靶向肿瘤部位，激活该部位，可同时向肿瘤微环境 (TME) 中的同一个抗癌免疫细胞提供两种免疫疗法，即 IL-2 超因子和抗 PD1 抗体，以最大限度地提高疗效并最大限度地减少全身毒性
MDNA113 is our most advanced pre-clinical candidate that targets IL-13Rα2, a tumor associated antigen, which is overexpressed by immunologically "cold" tumors with high unmet needs in pancreatic, prostate, ovarian, breast and brain cancer affecting over two million patients every year
MDNA113 是我们最先进的临床前候选药物，它靶向肿瘤相关抗原IL-13Rα2，这种抗原被免疫学 “冷” 肿瘤过度表达，胰腺癌、前列腺癌、卵巢癌、乳腺癌和脑癌的需求未得到满足，每年影响超过200万名患者
TORONTO and HOUSTON, April 09, 2024 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. ("Medicenna" or the "Company") (TSX: MDNA), a clinical-stage immunotherapy company focused on the development of Superkines, today announced new preclinical data on MDNA113, the Company's novel T-MASK (Targeted Metallo/protease Activated SuperKine) candidate, an IL-13R⍺2 (Interleukin-13 receptor alpha2) specific superkine featuring unique masking and tumor targeting characteristics, were presented at the 2024 Annual Meeting of the American Association for Cancer Research (AACR) held in San Diego, CA, on April 9th, 2024.
多伦多和休斯顿，2024年4月9日（GLOBE NEWSWIRE）——专注于开发Superkines的临床阶段免疫疗法公司Medicenna Therapeutics Corp.（“MDINA” 或 “公司”）（多伦多证券交易所股票代码：MDNA）今天公布了该公司的新型T-MASK（靶向金属/蛋白酶活化SuperKine）候选药物 IL-13R2（在美国癌症研究协会（AACR）2024年年会上发布了具有独特掩盖和肿瘤靶向特性的白介素-13受体（α2）特异性超因子 MDNA113于 2024 年 4 月 9 日在加利福尼亚州圣地亚哥举行。
"We are pleased to show preclinical data demonstrating the ability of Medicenna's first T-MASK candidate, MDNA113 to enhance tumor accumulation and tolerability of our potent bi-functional immune modulator, anti-PD1-IL-2SK," said Fahar Merchant, Ph.D., President and Chief Executive Officer of Medicenna. "MDNA113 has novel features, including the tunable blockade of the IL-2R agonism to reduce peripheral immune stimulation for enhanced tolerability, and tumor targeting to IL-13R⍺2 which is linked to aggressive cancers that annually affect over 2 million patients world-wide. The cleavage and release of the IL-13 tumor-targeting/masking domain by matrix metalloproteases restores IL-2R signaling within the tumor microenvironment, thereby benefiting from the simultaneous and synergistic activity of IL-2R agonism and immune checkpoint blockade at the tumor site."
Medicenna总裁兼首席执行官法哈尔·默特博士表示：“我们很高兴展示临床前数据，表明Medicenna的首款T-MASK候选药物 MDNA113 能够增强我们的强效双功能免疫调节剂抗PD1-IL-2SK的肿瘤积累和耐受性。”“MDNA113 具有新特征，包括可调阻断 IL-2R 激动作用以减少外周免疫刺激以增强耐受性，以及靶向 IL-13R2 的肿瘤，后者与侵袭性癌症有关，侵袭性癌症每年影响全球超过 200 万名患者。基质金属蛋白酶分裂和释放 IL-13 肿瘤靶向/掩盖结构域可恢复 IL-2R 在肿瘤微环境中的信号，从而受益于肿瘤部位的 IL-2R 激动作用和免疫检查点阻断的同步协同活性。”
The Company selected MDNA113, a novel, first-in-class tumor-targeted and tumor-activated bi-functional anti-PD1-IL-2 superkine with high selectivity and affinity for IL-13Rα2, a tumor associated antigen expressed in many aggressive solid tumors. The IL-13 Superkine (MDNA213) is a highly specific tumor-targeting/masking domain which is fused via a protease sensitive linker to a bi-functional immunotherapy domain (MDNA223) containing an IL-2 Superkine fused to an anti-PD1 antibody.
该公司选择了 MDNA113，这是一种新型、同类首创的肿瘤靶向和肿瘤激活的双功能抗PD1-IL-2超因子，对IL-13Rα2具有高选择性和亲和力，IL-13Rα2是一种在许多侵袭性实体瘤中表达的肿瘤相关抗原。IL-13 Superkine（MDNA213）是一种高度特异的肿瘤靶向/屏蔽结构域，它通过蛋白酶敏感的连接剂融合到包含与抗PD1抗体融合的IL-2超级因子的双功能免疫治疗结构域（MDNA223）。
Key findings presented at the conference include:
会议上提出的主要发现包括：
When not activated, MDNA113 shows reduced IL-2R agonism with no change to PD-1/PDL-1 blockade activity.
Cleavage and activation of MDNA113 by cancer specific enzymes (metalloproteases) releases the T-MASK domain (MDNA213), restoring activity of the IL-2 Superkine at the tumor site.
MDNA113 shows attenuated systemic lymphocyte expansion compared to non-masked version (MDNA223), consistent with design of MDNA113.
MDNA113 is better tolerated than non-masked counterpart (MDNA223), supporting higher and more efficacious dosing schedule.
MDNA113 selectively binds IL-13R⍺2 positive tumor cells in vitro, and durably accumulates (>7 days) in IL-13R⍺2 positive tumors in mice.
Cleavable MDNA113 shows similar efficacy as non-masked MDNA223 in mouse tumor models by either localized (intra-tumoral) or systemic (intra-peritoneal) delivery, consistent with proteolytic activation within TME.
Single neoadjuvant treatment with MDNA113 in a highly invasive orthotopic 4T1.2 breast cancer model significantly increases survival by preventing metastasis.
In summary, the T-MASK platform exemplified by MDNA113, facilitates tumor targeting and minimizes systemic toxicity while maximizing therapeutic activity at the tumor site.
未激活时，MDNA113 显示出 IL-2R 激动作用降低，PD-1/PDL-1 的阻断活性没有变化。
通过癌症特异性酶（金属蛋白酶）分解和激活 MDNA113 会释放 T-MASK 结构域（MDNA213），恢复 IL-2 超因子在肿瘤部位的活性。
与非掩膜版本（MDNA223）相比，MDNA113 的全身淋巴细胞扩张减弱，与 MDNA113 的设计一致。
MDNA113 的耐受性优于非掩膜对应物 (MDNA223)，支持更高、更有效的给药时间表。
MDNA113 在体外选择性结合 IL-13R2 阳性肿瘤细胞，并在小鼠体内 IL-13R2 阳性肿瘤中持久积累（>7 天）。
Cleavable MDNA113 通过局部（肿瘤内）或全身（腹膜内）递送，在小鼠肿瘤模型中表现出与非掩膜 MDNA223 相似的疗效，这与 TME 内的蛋白水解激活一致。
在高侵入性原位 4T1.2 乳腺癌模型中使用 MDNA113 进行单一新辅助治疗可防止转移，从而显著提高存活率。
总而言之，以 MDNA113 为例的 T-MASK 平台可促进肿瘤靶向并最大限度地减少全身毒性，同时最大限度地提高肿瘤部位的治疗活性。
The poster, "Characterization of MDNA113, a Tumor-Targeting Anti-PD1-IL-2SK Immunocytokine with Conditional Activation to Increase Tolerability and Maximize Efficacy" can be found on the AACR website for conference registrants. It will be also available on the Scientific Presentations page of Medicenna's website following the conclusion of the 2024 Annual Meeting of AACR.
海报 “MDNA113 的表征，一种靶向肿瘤的抗 PD1-IL-2SK 免疫细胞因子，具有条件激活，可提高耐受性并最大限度地提高疗效”，可在AACR网站上为会议注册者找到。2024年AACR年会结束后，它还将在Medicenna网站的科学演示页面上公布。
About the T-MASK Platform
关于 T-MASK 平台
Medicenna's novel T-MASK (Targeted Metallo/protease Activated SuperKine) platform involves fusion of a dual tumor-targeting/masking domain to an immune modulator (such as a Superkine or a BiSKIT) via a matrix metalloprotease (MMP) sensitive linker to (i) reduce and fine-tune the potency of the immune modulator, (ii) increase its systemic tolerability (iii) prolong its retention in the TME and (iv) to maximize and restore full potency at the intended target site. The T-MASK platform offers opportunity to target and fine-tune immune cell stimulation in the TME to improve the therapeutic index of Medicenna's Superkine and BiSKIT platforms.
Medicenna 的新型 T-MASK（靶向金属/蛋白酶活化 SuperKine）平台涉及通过基质金属蛋白酶（MMP）敏感连接剂将双肿瘤靶向/屏蔽结构域与免疫调节剂（例如 Superkine 或 BisKit）融合，以（i）降低和微调免疫调节剂的效力，（iii）提高其全身耐受性（iii）延长其全身耐受性（iii）延长其耐受性保留在 TME 中，以及（iv）最大限度地发挥和恢复预期目标部位的全部效力。T-MASK平台为靶向和微调TME中的免疫细胞刺激提供了机会，以提高Medicenna的Superkine和BisKit平台的治疗指数。
About MDNA113
关于 MDNA113
MDNA113 is a novel, first-in-class tumor-targeted and tumor-activated bi-functional anti-PD1-IL-2 Superkine with high affinity for IL-13Rα2 without binding to the functional IL-13R⍺1. IL-13Rα2 is overexpressed in a wide range of solid tumors, including cold tumors. IL-13Rα2 is a tumor-associated antigen with minimal to no expression in normal tissues but is highly expressed by a wide range of tumors including "cold" tumors. IL-13Rα2 expressing tumors also have abundant MMPs in the TME that may efficiently activate MDNA113. IL-13Rα2 expression is associated with poor clinical outcome in multiple tumor types with an annual world-wide incidence of over 2 million in different tumor types including prostate cancer, pancreatic cancer, ovarian cancer, liver cancer, breast cancer and brain cancer, and among others.
MDNA113 是一种新型、同类首创的肿瘤靶向和肿瘤激活的双功能抗PD1-IL-2 Superkine，对白细胞介素13Rα2具有很高的亲和力，不会与功能性IL-13R1结合。IL-13Rα2在各种实体瘤中过度表达，包括感冒性肿瘤。IL-13Rα2 是一种肿瘤相关抗原，在正常组织中几乎没有表达，但它在包括 “冷” 肿瘤在内的各种肿瘤中高度表达。表达 IL-13Rα2 的肿瘤在 TME 中也含有丰富的 MMP，可以有效激活 MDNA113。IL-13Rα2的表达与多种肿瘤类型的临床效果不佳有关，全球每年在不同类型的肿瘤中发病率超过200万例，包括前列腺癌、胰腺癌、卵巢癌、肝癌、乳腺癌和脑癌等。