WTX-518, a conditionally activated IL-18 INDUKINETM molecule that resists suppression by IL-18BP, led to complete tumor regressions in preclinical models
WTX-712, a conditionally activated IL-21 INDUKINETM molecule has potent antitumor activity in preclinical models with a differentiated immune activation mechanism
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.
"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."
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:
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.
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:
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).
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
Werewolf plans to develop WTX-518 and WTX-712 as potential immunotherapies in refractory and/or immunologically unresponsive tumors.
WTX-518 是一種條件激活的 IL-18 INDUKINETM 分子,可抵抗 IL-18BP 的抑制,在臨床前模型中實現了完整的腫瘤回歸
WTX-712 是一種條件激活的 IL-21 INDUKINETM 分子,在具有差異化免疫激活機制的臨床前模型中具有強大的抗腫瘤活性
馬薩諸塞州沃特敦,2024年4月5日(GLOBE NEWSWIRE)——Werewolf Therapeutics, Inc.(“公司” 或 “狼人”)(納斯達克股票代碼:HOWL)是一家率先開發旨在刺激人體免疫系統治療癌症的條件激活療法的創新生物製藥公司,將在美國癌症研究協會的海報中展示有關開發候選物 WTX-518 和 WTX-712 的臨床前數據(AACR) 年會將於4月5日至10日在加利福尼亞州聖地亞哥舉行。
狼人總裁兼首席執行官丹尼爾·希克林博士說:“我們很高興與大家分享,WTX-518 和 WTX-712 在臨床前模型中都表現出強大的免疫治療作用。”“WTX-518 表現出顯著的腫瘤選擇性激活、對 IL-18BP 的耐藥性和強大的免疫激活性,克服了在癌症治療中使用這種有前途的細胞因子的關鍵障礙。WTX-712 通過一種獨特的機制起作用,該機制通過在 TME 中選擇性釋放野生型 IL-21 來強力激活腫瘤特異性 T 淋巴細胞,從而擴大治療窗口。這些數據共同凸顯了我們爲進一步擴展抗擊癌症的獨特免疫刺激細胞因子機制所追求的創新策略。”
一張標題爲 “WTX-518 的發現,這是一種在腫瘤微環境中有條件激活並誘發小鼠腫瘤模型回歸的 IL-18 前藥” 的海報中總結了突出 WTX-518 發現的結果(摘要 #4074)。關鍵要點表明,WTX-518:
一張海報總結了 WTX-712 的數據,標題爲 “WTX-712 是一種有條件活性的 IL-21 INDUKINE 分子,通過差異化機制誘導強大的抗腫瘤表型”(摘要 #4078)。關鍵要點表明:
WTX-712 在 MC38 小鼠腫瘤模型中表現出誘導性和抗腫瘤活性;
在對抗PD-1/PD-L1治療具有高度耐藥性的小鼠腫瘤模型中,與IL-2 HLE療法相比,IL-21 HLE(半衰期延長)具有卓越的抗腫瘤功效,部分原因是激活了I型干擾素通路;以及
IL-21 HLE 促進腫瘤浸潤 CD8 T 細胞的持續擴張和激活,增加多功能性,並誘導細胞毒效應分子(Granzyme A、Granzyme B 和穿孔素)的表達。
兩張海報均可在太平洋夏令時間4月9日星期二上午 9:00 至下午 12:30 在海報第 4 部分的 “免疫學” 會議類別中親自觀看,並將在我們的網站上公佈
狼人計劃開發 WTX-518 和 WTX-712 作爲難治性和/或免疫學無反應腫瘤的潛在免疫療法。