Company: IPHYF
Filing Date: 2025-04-30
Form Type: 20-F
Source: 0001598599-25-000042
Chunk: 113

Company: Innate Pharma SA
Filing Date: 2025-04-30
Form: 20-F
Item: Item 4
Chunk 113
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AML) is the most common acute leukemia in adults, mostly affecting elderly patients, with a median age at diagnosis of 65-70 years. AML is a heterogeneous cancer characterized by the clonal expansion of myeloid precursors in the bone marrow and peripheral blood. Despite significant progress in the care of AML patients in the past decade, there is still a clear unmet medical need in AML, as up to 50% of patients relapse after initial chemotherapy, and the prognosis for older patients remains poor.

Cytotoxic antibodies targeting CD123 displayed limited antileukemic activity in several clinical trials, even when tested in the form of Fc-engineered antibodies designed specifically to increase antibody-dependent cell cytotoxicity (ADCC). By contrast, T cell engager molecules and CAR-T cell therapies have some clinical efficacy, but are also highly toxic, confirming the need for alternative targeted approaches for the treatment of AML. NK cell-based therapies may provide new treatment perspectives and a safer alternative for targeting tumor cells in this context.

c. Preclinical Development

In its preclinical studies, Innate and Sanofi investigated whether NKp46-based NKCE technology could provide more effective antitumor activity than regular IgG antibodies for AML treatment by generating a NKCE molecule targeting CD123. Innate and Sanofi evaluated the ex vivo antitumor activity of this molecule, comparing it with a regular IgG1 antibody derived from clone 7G3 (CD123-IgG1+) with an engineered Fc domain for enhanced ADCC.

The anti-CD123 antibody-mediated killing of primary blasts from AML patients (AML#1 to AML#4) was evaluated ex vivo with NK cells from healthy donors as effectors. The anti-CD123 antibody (CD123-IgG1+) mediated the killing of blasts from half the patient samples (AML#1 and AML#2) but was barely active against blasts from the other half of the primary samples (AML#3 and AML#4). The patient samples could therefore be separated into two distinct groups: CD123-IgG1+- responders and CD123-IgG1+- non-responders.

Innate and Sanofi observed that trifunctional CD123-ANKET® displayed killing activity against all primary malignant AML cells, promoting significant antitumor activity in CD123-IgG1+- non-responders samples from AML patients against which the regular anti-CD123 cytotoxic antibody was completely inactive.

The