Werewolf Therapeutics Presents Preclinical Results Demonstrating Anti-Tumor Effects of Pro-Inflammatory Cytokine Therapeutics WTX-518 and WTX-712 at AACR 2024 Annual Meeting
Werewolf Therapeutics Presents Preclinical Results Demonstrating Anti-Tumor Effects of Pro-Inflammatory Cytokine Therapeutics WTX-518 and WTX-712 at AACR 2024 Annual Meeting
WTX-518, a conditionally activated IL-18 INDUKINETM molecule that resists suppression by IL-18BP, led to complete tumor regressions in preclinical models
WTX-518 是一种条件激活的 IL-18 INDUKINETM 分子,可抵抗 IL-18BP 的抑制,在临床前模型中实现了完整的肿瘤回归
WTX-712, a conditionally activated IL-21 INDUKINETM molecule has potent antitumor activity in preclinical models with a differentiated immune activation mechanism
WTX-712 是一种条件激活的 IL-21 INDUKINETM 分子,在具有差异化免疫激活机制的临床前模型中具有强大的抗肿瘤活性
WATERTOWN, Mass., April 05, 2024 (GLOBE NEWSWIRE) -- Werewolf Therapeutics, Inc. (the "Company" or "Werewolf") (Nasdaq: HOWL), an innovative biopharmaceutical company pioneering the development of conditionally-activated therapeutics engineered to stimulate the body's immune system for the treatment of cancer, is presenting preclinical data on development candidates WTX-518 and WTX-712 in posters at the American Association for Cancer Research (AACR) Annual Meeting, taking place April 5-10 in San Diego, California.
马萨诸塞州沃特敦,2024年4月5日(GLOBE NEWSWIRE)——Werewolf Therapeutics, Inc.(“公司” 或 “狼人”)(纳斯达克股票代码:HOWL)是一家率先开发旨在刺激人体免疫系统治疗癌症的条件激活疗法的创新生物制药公司,将在美国癌症研究协会的海报中展示有关开发候选物 WTX-518 和 WTX-712 的临床前数据(AACR) 年会将于4月5日至10日在加利福尼亚州圣地亚哥举行。
"We are excited to share that both WTX-518 and WTX-712 demonstrate powerful immunotherapeutic effects in preclinical models," said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf. "WTX-518 exhibits remarkable tumor-selective activation, resistance to IL-18BP and robust immune activation, overcoming key hurdles in the use of this promising cytokine in cancer therapy. WTX-712 acts through a unique mechanism that robustly activates tumor-specific T lymphocytes with an expanded therapeutic window through its selective release of wild-type IL-21 in the TME. These data collectively highlight the innovative strategies we are pursuing to further expand the repertoire of unique immune stimulating cytokine mechanisms in the fight against cancer."
狼人总裁兼首席执行官丹尼尔·希克林博士说:“我们很高兴与大家分享,WTX-518 和 WTX-712 在临床前模型中都表现出强大的免疫治疗作用。”“WTX-518 表现出显著的肿瘤选择性激活、对 IL-18BP 的耐药性和强大的免疫激活性,克服了在癌症治疗中使用这种有前途的细胞因子的关键障碍。WTX-712 通过一种独特的机制起作用,该机制通过在 TME 中选择性释放野生型 IL-21 来强力激活肿瘤特异性 T 淋巴细胞,从而扩大治疗窗口。这些数据共同凸显了我们为进一步扩展抗击癌症的独特免疫刺激细胞因子机制所追求的创新策略。”
Results highlighting WTX-518 findings are summarized in a poster titled, "Discovery of WTX-518, an IL-18 pro-drug that is conditionally activated within the tumor microenvironment and induces regressions in mouse tumor models" (Abstract #4074). Key takeaways reveal that WTX-518:
一张标题为 “WTX-518 的发现,这是一种在肿瘤微环境中有条件激活并诱发小鼠肿瘤模型回归的 IL-18 前药” 的海报中总结了突出 WTX-518 发现的结果(摘要 #4074)。关键要点表明,WTX-518:
is inducible, and its in vitro activity is not impeded by IL-18BP;
selectively delivers active binding protein resistant (BPR) IL-18 to the tumor microenvironment (TME); and
promotes increased influx and activation of NK cells and polyfunctional CD8 T cells in the TME, and demonstrates complete tumor regression in the MC38 mouse tumor model.
可诱导,其体外活性不受 IL-18BP 阻碍;
选择性地向肿瘤微环境 (TME) 输送抗活性结合蛋白 (BPR) IL-18;以及
促进 TME 中 NK 细胞和多功能 CD8 T 细胞的涌入和激活增加,并在 MC38 小鼠肿瘤模型中显示肿瘤完全消退。
The WTX-712 data are summarized in a poster titled, "WTX-712, a conditionally active IL-21 INDUKINE molecule, induces a strong anti-tumor phenotype through a differentiated mechanism" (Abstract #4078). Key takeaways reveal that:
一张海报总结了 WTX-712 的数据,标题为 “WTX-712 是一种有条件活性的 IL-21 INDUKINE 分子,通过差异化机制诱导强大的抗肿瘤表型”(摘要 #4078)。关键要点表明:
WTX-712 demonstrates inducibility and antitumor activity with regressions in the MC38 mouse tumor model;
IL-21 HLE (half-life extended) has superior anti-tumor efficacy compared to IL-2 HLE therapy in mouse tumor models that are highly resistant to anti-PD-1/PD-L1 treatment, in part due to the activation of type-I IFN pathways; and
IL-21 HLE promotes sustained expansion and activation of tumor infiltrating CD8 T cells with increased polyfunctionality and induces expression of cytotoxic effector molecules (Granzyme A, Granzyme B, and perforin).
WTX-712 在 MC38 小鼠肿瘤模型中表现出诱导性和抗肿瘤活性;
在对抗PD-1/PD-L1治疗具有高度耐药性的小鼠肿瘤模型中,与IL-2 HLE疗法相比,IL-21 HLE(半衰期延长)具有卓越的抗肿瘤功效,部分原因是激活了I型干扰素通路;以及
IL-21 HLE 促进肿瘤浸润 CD8 T 细胞的持续扩张和激活,增加多功能性,并诱导细胞毒效应分子(Granzyme A、Granzyme B 和穿孔素)的表达。
Both posters can be viewed in person from 9:00 a.m. to 12:30 p.m. PDT on Tuesday, April 9, during the session category "Immunology" at Poster Section 4, and will be available on our website
两张海报均可在太平洋夏令时间4月9日星期二上午 9:00 至下午 12:30 在海报第 4 部分的 “免疫学” 会议类别中亲自观看,并将在我们的网站上公布
Werewolf plans to develop WTX-518 and WTX-712 as potential immunotherapies in refractory and/or immunologically unresponsive tumors.
狼人计划开发 WTX-518 和 WTX-712 作为难治性和/或免疫学无反应肿瘤的潜在免疫疗法。