Company: IPHYF
Filing Date: 2025-04-30
Form Type: 20-F
Source: 0001598599-25-000042
Chunk: 120

Company: Innate Pharma SA
Filing Date: 2025-04-30
Form: 20-F
Item: Item 4
Chunk 120
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3, including experiments on non-human primates and samples from R/R B-NHL patients. In preclinical settings, IPH6501 was shown to induce NK cell proliferation and to trigger high NK cell cytoxicity against CD20+ target cells in in vitro assays, in ex vivo assays with relapse/refractory (R/R) B-NHL patient samples who received at least one prior treatment, as well as in in vivo studies in non-human primates. A surrogate of IPH6501 mediated a potent anti-tumor activity in vivo in CD20+ tumor models in mice. In addition, in ex vivo assays with R/R B-NHL patient samples, IPH6501 was shown to be more efficient than a T cell engager targeting CD20.

•Non-human primates

In non-human primates, a well-tolerated dose of IPH6501 resulted in NK cell expansion, with minimal increase in systemic cytokine levels, and to the depletion of CD20+ B cells in circulation and lymphoid tissues.

•Analysis from samples from R/R B-NHL patients

Flow cytometric analysis of samples from R/R B-NHL patients revealed that NK cell numbers in blood were within normal range values, and NKp46 expression was maintained in blood and tumor-involved lymph nodes. Of note, in contrast to NKp46, cell surface expression of CD16 was down-regulated on NK cells in B-NHL patient’s lymph nodes, suggesting a potential therapeutic advantage of targeting NKp46 with IPH6501 in B-NHL compared with classical monoclonal antibodies. IPH6501 stimulated NK cell

proliferation and CD20+ cell depletion ex vivo in PBMC samples from R/R B-NHL patients, which compared favourably with acontrol CD3xCD20 T cell engager.

In 2024, new preclinical data supporting the development of IPH6501 were presented at the SITC, EHA, and EHA conferences with the following key messages:

• IPH6501 expand and mobilize peripheral NK cells for tumor killing: IPH6501 mouse surrogate potently induces NK cells activation, proliferation and recruitment from the periphery to the tumor microenvironment in mouse models

•IPH6501 advantage over antibody-based CD20- T cell engagers:

◦ Higher efficacy in depleting autologous CD20 B cells in PBMC from HD and from R/R B-NHL patients (leukemic phase disease)

◦ Reduced induction of