Major Histocompatibility Complex Class I (MHC-I) negative tumors are refractory to immune-oncology therapies, including resistance to checkpoint blockers, due to the loss of the fundamental recognition of the tumor by CD8+ T-Cells, which drive the adaptive immune attack on the tumor.
BOSTON, April 09, 2024 (GLOBE NEWSWIRE) -- Compass Therapeutics, Inc. (Nasdaq: CMPX), a clinical-stage, oncology-focused biopharmaceutical company developing proprietary antibody-based therapeutics to treat multiple human diseases, today presents a poster on the combination of its bispecific antibody, CTX-009, and its agonistic anti-CD137 antibody, CTX-471, on anti-tumor activity in preclinical models at the 2024 American Association for Cancer Research (AACR) Annual Meeting taking place at the San Diego Convention Center in San Diego, California on April 9.
"We are very excited to see the anti-tumor activity of our bispecific DLL4/VEGF-A antibody, CTX-009, in multiple preclinical tumor models," said Thomas Schuetz, MD, PhD, Co-Founder and President of Research & Development at Compass. "The post-Checkpoint Inhibitor (CPIs, either PD-1 or PD-L1) patient population is one of the most significant unmet medical needs in medical oncology today. When a tumor is MHC-I negative, it is effectively invisible to the immune system; however, importantly, in these models the combination of CTX-009 and CTX-471 eliminated tumors, suggesting that the combination of CTX-009 and CTX-471 could be considered as a viable alternative where previous immunotherapy has failed."
Data highlights from the poster presentation include:
The combination of mCTX-009 and mCTX-471 demonstrated superior efficacy in both Checkpoint Inhibitor (CPI)-sensitive and CPI-refractory models with markedly enhanced anti-tumor activity compared with either monotherapy.
Following mCTX-009 and mCTX-471 combination treatment, superior efficacy was observed in MHC Class I negative tumors. Deletion of B2m produced MHC-I null phenotypes in two colorectal cancer cell lines. Tumor elimination was in part mediated by NK cells.
These preclinical data suggest that the combination of CTX-009 and CTX-471 could re-establish anti-tumor immunity in patients whose tumors have either downregulated or lost MHC-I expression by way of NK-cell mediated tumor cell killing.
A copy of the presentation materials can be accessed on the News & Events section under "Presentations" of the Company's website at once the presentation has concluded.
About CTX-009
CTX-009 is a bispecific antibody that simultaneously blocks Delta-like ligand 4/Notch (DLL4) and vascular endothelial growth factor A (VEGF-A) signaling pathways, which are critical to angiogenesis and tumor vascularization. Preclinical and early clinical data of CTX-009 suggest that blockade of both pathways provides robust anti-tumor activity across several solid tumors, including colorectal, gastric, cholangiocarcinoma, pancreatic and non-small cell lung cancer. Partial responses to CTX-009 as a monotherapy have been observed in heavily pre-treated patients with cancer who were resistant to currently approved anti-VEGF therapies. Compass holds the global rights to CTX-009 (also known as ABL001) with the exception of rights in Korea, held by Handok, Inc. () and rights in China, which were out-licensed to Elpiscience Biopharma, Ltd. ().
About CTX-471
CTX-471 is a fully human monoclonal antibody that binds and activates a novel epitope of the co-stimulatory receptor CD137, also known as 4-1BB, a member of the tumor necrosis factor receptor superfamily. The antibody is currently being evaluated in a Phase 1b clinical trial in patients with solid tumors that have progressed after at least three months on an approved PD-1 or PD-L1 inhibitor. Initial results reported from a monotherapy cohort of the study included partial responses in melanoma, small cell lung cancer, and mesothelioma, and CTX-471 has been generally well tolerated. In preclinical studies, CTX-471 has demonstrated potent monotherapy activity against multiple syngeneic tumor models, including the generation of long-term functional immunological memory.
波士頓，2024年4月9日（GLOBE NEWSWIRE）——Compass Therapeutics, Inc.（納斯達克股票代碼：CMPX）是一家臨床階段、專注於腫瘤學的生物製藥公司，正在開發專有的抗體療法來治療多種人類疾病，該公司今天在臨床前模型中發佈了一張關於其雙特異性抗體 CTX-009 及其激動性抗CD137抗體 CTX-471 組合的海報 2024年美國癌症研究協會（AACR）年會將於4月9日在加利福尼亞州聖地亞哥的聖地亞哥會議中心舉行。
康帕思聯合創始人兼研發總裁托馬斯·舒茨說：“我們很高興看到我們的雙特異性DLL4/VEGF-A抗體 CTX-009 在多個臨床前腫瘤模型中具有抗腫瘤活性。”“檢查點後抑制劑（CPI，PD-1或 PD-L1）患者群體是當今醫學腫瘤學中最重要的未滿足的醫療需求之一。當腫瘤爲 MHC-I 陰性時，免疫系統實際上是看不見的；但是，重要的是，在這些模型中，CTX-009 和 CTX-471 的組合消除了腫瘤，這表明 CTX-009 和 CTX-471 的組合可以被視爲先前免疫療法失敗的可行替代方案。”
海報演示的數據亮點包括：
MCTX-009和mcTX-471的組合在檢查點抑制劑（CPI）敏感型和CPI難治型模型中均顯示出卓越的療效，與任何一種單一療法相比，抗腫瘤活性明顯增強。
在MCTX-009和mcTX-471聯合治療後，在MHC I類陰性腫瘤中觀察到卓越的療效。缺失 B2m 在兩種結直腸癌細胞系中產生 MHC-I 空表型。腫瘤消滅在一定程度上是由NK細胞介導的。
這些臨床前數據表明，CTX-009 和 CTX-471 的組合可以在腫瘤通過 NK-Cell 介導的腫瘤細胞殺滅而下調或喪失 MHC-I 表達的患者中重建抗腫瘤免疫力。
演示結束後，可以在公司網站 “演示文稿” 下方的新聞與活動部分訪問演示材料的副本。
關於 CTX-009
CTX-009 是一種雙特異性抗體，可同時阻斷 Delta 樣配體 4/Notch (DLL4) 和血管內皮生長因子 A (VEGF-A) 信號通路，這些通路對血管生成和腫瘤血管形成至關重要。CTX-009 的臨床前和早期臨床數據表明，阻斷兩種途徑可爲多種實體瘤提供強大的抗腫瘤活性，包括結直腸癌、胃癌、膽管癌、胰腺癌和非小細胞肺癌。在對目前批准的抗血管內皮生長因子療法產生耐藥性的嚴重預治療的癌症患者中，已觀察到對作爲單一療法的 CTX-009 有部分反應。康帕思擁有 CTX-009（也稱爲 ABL001）的全球版權，但由Handok, Inc. 持有的韓國的版權和已外包給科望生物製藥有限公司的中國版權除外。
關於 CTX-471
CTX-471 是一種全人源單克隆抗體，可結合並激活共刺激受體 CD137（也稱爲 4-1BB）的新表位，是腫瘤壞死因子受體超家族的成員。該抗體目前正在一項針對實體瘤患者進行的 1b 期臨床試驗中進行評估，這些患者在服用經批准的 PD-1 或 PD-L1 抑制劑至少三個月後出現進展。該研究的單一療法組報告的初步結果包括黑色素瘤、小細胞肺癌和間皮瘤的部分反應，而且 CTX-471 的耐受性總體良好。在臨床前研究中，CTX-471 已顯示出針對多種同源腫瘤模型的強大單一療法活性，包括生成長期功能免疫記憶。
