- IPH5401, an anti-C5aR antibody, potentially reverses tumor immuno-suppressive microenvironment and overcomes tumor resistance; preclinical data suggest that combined C5aR and PD-1 blockade synergistically reduce tumor growth;
- New preclinical data further reinforce the rationale for combination treatment with monalizumab (anti-NKG2A) and anti-PD-L1 checkpoint inhibitors;
- Data were presented at the International Cancer Immunotherapy conference 2017 in Frankfurt.
Innate Pharma SA (the “Company” - Euronext Paris: FR0010331421 – IPH) today announces that new preclinical data for its first-in-class clinical stage antibodies IPH5401 and monalizumab, were presented at the 3rd CRI-CIMT-EATI-AACR International Cancer Immunotherapy conference, September 6 – 9, 2017, in Frankfurt, Germany.
Poster #B184 shows the selective expression of C5aR on myeloid-derived suppressor cells (MDSC) and neutrophils. These cells accumulate within the tumor microenvironment and secrete pro-angiogenic factors which promote tumor progression. They also inhibit NK and T cells and suppress anti-tumor immunity.
In this poster, the data demonstrate that IPH5401 selectively inhibits the activation of neutrophils. Moreover, the data show that the combined administration of anti-C5aR with anti-PD-1 reduced tumor growth. Taken together, these data suggest that C5aR blockade may result in a more permissive environment for immune-mediated tumor killing and treatment with checkpoint inhibitors.
Poster #A130 demonstrates that blocking both NKG2A/HLA-E and PD-1/PD-L1 pathways enhance anti-tumor efficacy of CD8+ T cells. The data show that the deletion of either NKG2A (Qa-1b) or PD-L1 significantly delays tumor growth, suggesting that both receptors are involved in the immune-escape of tumors. Combined PD-L1 and NKG2A blockade achieved a complete response of 82%, compared to 54% for anti-PD-L1 and 36% for anti-NKG2A alone. CD8+ tumor infiltrated lymphocytes (TILs) expressing high levels of PD-1 co-expressed high levels of NKG2A, raising the possibility that NKG2A blockade may potentiate PD-1/PD-L1 blockers by directly enhancing CD8+ T cell-mediated killing of tumors.
Yannis Morel, Executive Vice President Products Portfolio Strategy of Innate Pharma, said: “We are encouraged by the preclinical data for IPH5401, which further support the development of this first-in-class anti-C5aR antibody especially in combination with PD‑1/PD‑L1 checkpoint inhibitors. We look forward to start clinical trials in oncology with IPH5401 in 2018.
In addition, preclinical data indicate that NKG2A blockade in conjunction with PD-L1 blockade enhances anti-tumor efficacy of CD8+ T cells and provide further evidence to support the ongoing clinical trial evaluating monalizumab, Innate’s first-in-class NKG2A checkpoint inhibitor, in combination with durvalumab, AstraZeneca/Medimmune’s PD-L1 checkpoint inhibitor.”