Company: IPHYF
Filing Date: 2025-04-30
Form Type: 20-F
Source: 0001598599-25-000042
Chunk: 119

Company: Innate Pharma SA
Filing Date: 2025-04-30
Form: 20-F
Item: Item 4
Chunk 119
---
 CD20-targeting agents, new alternatives and strategies are still required for patients, which are relapsing or refractory after several lines of treatment. High circulating NK cell numbers have been associated with better clinical responses

to anti-CD20-targeting monoclonal antibodies, supporting the role of NK cells in efficacy of these treatments.

c. Preclinical Development

IPH6501 preclinical activity was explored both in vitro and in vivo. In vitro studies established that IPH6501´s main modes of action were NK cell proliferation and antibody-dependent cell cytotoxicity (ADCC) against CD20-expressing cells.

• In vitro

Non-saturating doses of IPH6501 on NK cells and on CD20+ cells were sufficient to promote maximal killing activity. Furthermore, IPH6501 promoted NK cell cytotoxicity against tumor cells expressing very low levels of CD20. IPH6501 also demonstrated superiority to control tumor cell growth in vitro, as compared to the CD20-targeting clinical benchmark antibodies rituximab and the Fc-optimized obinutuzumab.

IPH6501 alone without NK cells did not induce direct killing of CD20+ cells. Culturing human purified NK cells with CD20+B-lymphoma cell lines and IPH6501 induced the specific lysis of tumoral CD20+ cells. Alternatively, culturing human PBMCs with IPH6501 induced the specific depletion of normal CD20+ B lymphocytes without affecting other lymphocyte population numbers, as well as cytokine production in line with NK cell activation. Incubation of human PBMC with IPH6501 induced a preferential NK cell proliferation that occurred at lower doses as compared to the proliferating effect of IPH6501 on other CD8+ or CD4+ T lymphocytes (expressing the IL-2R).

• In vivo

In vivo treatment with a mouse surrogate of IPH6501 induced peripheral NK cell proliferation and activation, and demonstrated potent antitumor efficacy in a xenograft mouse model using the aggressive human B-lymphoma CD20+RAJI cell line engrafted subcutaneously. Surrogate moIPH6501 also showed

a dose dependent and significant control of tumor growth in a model of CD20-expressing B16F10 cells injected intravenously (IV) in immunocompetent mice, as shown in figure below.

Updated preclinical data were presented at the European Hematology Association (EHA) congress in June 202