- 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.
- Immune responses were generated toward the MHC-I negative tumors by combining CTX-009 with CTX-471. This combination was surprisingly synergistic. The proposed mechanism for this effect suggests the involvement of NK-cells, which can generate potent cell killing independent of MHC-I.
- By blocking DLL4 and VEGF, CTX-009 may increase the trafficking and penetration of NK Cells into the tumor microenvironment where CTX-471 may augment the activity of these cells. This activity against the tumor does not require MHC-I integrity.
- The combination of CTX-009 and CTX-471 has the potential to be an effective therapeutic regimen in patients who have previously progressed on checkpoint blockers, such as anti-PD-1 and anti-PD-L1 antibodies.
“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
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 www.compasstherapeutics.com 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. (https://www.handok.co.kr/eng/) and rights in China, which were out-licensed to Elpiscience Biopharma, Ltd. (https://www.elpiscience.com/).
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.
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