Company: IPHYF
Filing Date: 2025-04-30
Form Type: 20-F
Source: 0001598599-25-000042
Chunk: 106

Company: Innate Pharma SA
Filing Date: 2025-04-30
Form: 20-F
Item: Item 4
Chunk 106
---
 combination strategy in this clinical indication.

• The Phase 2 KILT (anti-KIR in T Cell Lymphoma) trial, an investigator-sponsored, randomized trial led by the Lymphoma Study Association (LYSA) to evaluate lacutamab in combination with chemotherapy GEMOX (gemcitabine in combination with oxaliplatin) versus GEMOX alone in patients with KIR3DL2-expressing relapsed/refractory PTCL is ongoing.

Monalizumab, a Dual Checkpoint Inhibitor Targeting T Cells and NK Cells

a. Mechanism & Rationale

Monalizumab (IPH2201) is a potentially first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells. NKG2A is an inhibitory receptor for HLA-E (Human Leukocyte Antigen-E). HLA-E is a non-classical MHC class I molecule that plays a in immune regulation. In cancer, HLA-E is frequently overexpressed allowing tumor cells to evade immune attack by engaging NKG2A and suppressing the activity of cytotoxic immune cells. Monalizumab may reestablish a broad anti-tumor response mediated by NK and T cells, and may enhance the cytotoxic potential of other therapeutic antibodies (André et al., Cell 2018).

b. Rationale for combinations with monalizumab

The Company is primarily focused on investigating monalizumab in combination with durvalumab, which is an antibody directed against PD-L1 (Programmed Death-Ligand 1). PD-L1 is an immune checkpoint protein expressed on the surface of many cancer cells that binds to PD-1 on T cells, suppressing their activity and preventing an effective immune response. By inhibiting PD-L1, durvalumab restores T cell function, enhancing the immune system’s ability to recognize and attack tumor cells. Both PD-L1 and HLA-E are frequently overexpressed on cancer cells and contribute to immune evasion by binding to their respective inhibitory receptors, PD-1 and NKG2A. Innate Pharma's preclinical data support its hypothesis that a monalizumab and durvalumab combination therapy may result in a greater anti-tumor immune response than durvalumab alone by blocking both the PD-1/PD-L1 and the NKG2A/HLA-E inhibitory pathways.

The following illustration depicts the