Lirilumab: First-in-class anti-KIR mAb licensed to Bristol-Myers Squibb

About this program

Lirilumab (IPH2102/BMS-986015) is a fully human monoclonal antibody that is designed to act as a checkpoint inhibitor by blocking the interaction between KIR2DL-1,-2,-3 inhibitory receptors and their ligands.

Blocking these receptors facilitates activation of NK cells and, potentially some subsets of T cells, ultimately leading to destruction of tumor cells.

Lirilumab has been or is currently being tested in several indications and combination settings:



Patients (planned)




Randomized Phase II


Acute Myeloid Leukemia Maintenance setting

LFS expected 2Q 2016

Combination nivolumab

Phase I with dose escalation and cohort expansion


Selected solid tumors: MEL, NSCLC, GI, SCCHN, HCC

Enrollment close to completion

Combination nivolumab

Phase I with dose escalation


Selected hematologic tumors: R/R NHL, HL, MM or CML

Started in October 2014

Combination elotuzumab

Phase I with dose escalation and randomized cohort expansion


Multiple myeloma: R/R MM Post autologous transplant

Started in October 2014

Combination 5-azacytidine (Vidaza)

Phase II with dose escalation


Acute Myeloid Leukemia Relapsed/refractory

Started in April 2015

Combination rituximab

Phase II


Chronic Lymphocytic Leukemia R/R or High-risk Untreated

Started June 2015

Combination nivolumab & 5-azacytidine

Phase II


Myelodysplastic Syndromes


Started in November 2015

R/R: relapsed / refractory 

* Three arms (nivo, nivo + ipi, nivo + liri)

** Two arms (elo + liri, elo + ure)

To see all trials with lirilumab, please visit


About the agreement with Bristol-Myers Squibb

Lirilumab and related compounds blocking KIR receptors are licensed to Bristol-Myers Squibb Company (NYSE:BMY), for all indications.

Innate Pharma received an upfront payment of $35 million at the signing of the agreement in July 2011. The Company is eligible to additional payments of up to $430 million, depending on the achievement of pre-specified milestones during the development and commercialization period, as well as pre-specified tiered double-digit royalty payments on worldwide net sales.

Bristol-Myers Squibb funds the development of lirilumab. Innate Pharma is conducting the development of lirilumab through Phase II in AML and provides pre-clinical support to the program.


A new mechanism of action, potentiating the activation of Natural Killer cells

NK cells (Natural Killer) are non conventional lymphocytes, belonging to the innate immunity compartment. They are able to:

  • Directly and selectively kill « stressed » cells (cancerous, infected or over-activated cells);
  • Participate in the set up of a global immune reaction against a selected target, notably via the production of cytokines (the communicating agents of the immune system)
  • Bind one of the two ends of cytotoxic antibodies, and then kill cells recognized by these antibodies. This property is known as antibody-dependent cellular cytotoxicity (ADCC)


The mechanism behind NK cells activation depends on a balance between activatory and inhibitory signals, ie. signals of abnormality sent by the target:

  • Normal cells send “normality” signals and are thus spared by NK cells;
  • Cells undergoing a stress (infection, cancerous transformation, over activation) can send normality as well as danger signals at the same time. This can result in the “blinding” of NK cells.


Lirilumab, an anti-KIR monoclonal antibody, aims at “unblinding” NK cells and facilitating their activation by blocking their inhibitory receptors.  

The therapeutic potential of NK cells was strikingly illustrated in 2002 by the results of a study performed on patients with acute myeloid leukemia (a rapidly growing cancer that affects immature blood cells) having received a bone marrow allograft (i.e. transplantation of bone marrow cells from a donor and not from their own marrow).

In this study (see bibliography: Ruggeri et al, Science, 2002) grafted NK cells reacted and attacked the host cancer cells in about one third of the patients. In such cases, the likehood of relapse was dramatically reduced, even in patients with late stage diseases.

The results of this study have been confirmed in several other studies.

The anti-KIR approach aims at mimicking this situation with a drug.

NK cells are actives in numerous liquid and solid tumors, which allows to consider a comprehensive development in cancer.