• 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 3 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.'

Poster #B184 and Poster A#130 are available on Innate Pharma's website.

Innate Pharma SA published this content on 11 September 2017 and is solely responsible for the information contained herein.
Distributed by Public, unedited and unaltered, on 11 September 2017 05:03:11 UTC.

Original documenthttp://www.innate-pharma.com/en/news-events/press-releases/ici-conference-2017-new-preclinical-data-further-strengthen-rationale-iph5401-and-monalizumab-cancer-treatments-and-combination-anti-pd-1/pd-l1

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