New data presented at AACR support the rationale for combination treatment with monalizumab and durvalumab

• Preclinical data demonstrate enhanced anti-tumor efficacy by combining PD-1/PD-L1 pathway blockade and NKG2A checkpoint inhibitor;

• Resistance to PD-1 pathway blockers is associated with upregulation of NKG2A;

• Provides in vivo preclinical validation of the rationale for the ongoing clinical trial investigating this combination.

Innate Pharma SA (the “Company” - Euronext Paris: FR0010331421 – IPH) today presented data demonstrating enhanced anti-tumor efficacy and survival by combining anti-NKG2A with PD-1/PD-L1 pathway inhibitors in murine models at the American Association for Cancer Research (AACR) Annual Meeting 2016 in New Orleans, Louisiana, USA.

The NKG2A checkpoint receptor is expressed on a subset of NK cells. Similar to the PD-1 receptors, NKG2A can also be induced on tumor-infiltrating CD8 T cells. Therefore, PD-1 and NKG2A may both inhibit anti-tumor immune responses in situations where cancers express the ligands of both these checkpoint receptors. Conversely, anti-tumor immune responses might be enhanced by combined NKG2A and PD-1 pathway blockade. 

Poster #2342 reports preclinical data based on an in vivo model of PD-L1 expressing solid tumors. In this model, treatment with either an antibody blocking PD-1 or NKG2A as single agents resulted in modest anti-tumor efficacy. The frequency of tumor-infiltrating NKG2A+ CD8 T cells was increased in anti-PD-1 resistant mice, suggesting that NKG2A is a pathway involved in adaptive PD-1 resistance. Treatment with combination of NKG2A and PD-1 checkpoint inhibitors resulted in significantly enhanced anti-tumor responses. Nearly twice as many mice achieved complete tumor cell regression compared to treatment with anti PD-1 alone.

Nicolai Wagtmann, CSO of Innate Pharma, said: “We are very excited by these data showing that the NKG2A pathway acts as a major mechanism of tumor escape in this model. Considering the high frequency of patients who respond inadequately to PD-1 pathway blockade, we are intrigued by the observations that NKG2A expression on CD8 T cells was increased in PD-1 resistant mice”.  He added: “These data and the striking efficacy of the combination treatment in this model provide strong support for the clinical trial that was just initiated, testing the combination of monalizumab, Innate’s first-in-class NKG2A checkpoint inhibitor, and durvalumab, AstraZeneca/Medimmune’s investigational PD-L1 checkpoint inhibitor”.

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Reminder:

Nicolai Wagtmann, Chief Scientific Officer of Innate Pharma, will hold a conference call to the attention of analysts and portfolio managers to discuss the data published and Company’s innovative pipeline.
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