First Publication from OSE Immunotherapeutics on the Role of SIRPα in the Induction and Maintenance of Immune Tolerance in the American Journal of Transplantation

Regulatory News:

OSE Immunotherapeutics (Paris:OSE) (ISIN: FR0012127173; Mnemo: OSE) announces a scientific publication in the American Journal of Transplantation⁽¹⁾. This publication is the first from the Company’s R&D team on SIRPα, a receptor expressed by myeloid lineage cells, and the target of its immuno-oncology program asset BI 765063 (OSE-172).

This article, entitled "SIRPα/CD47 axis controls the maintenance of transplant tolerance sustained by myeloid‐derived suppressor cells" describes the important role of the SIRPα/CD47 axis in the induction and maintenance of acquired immune tolerance. Based on a transplant model, the OSE R&D team demonstrated that blockade of the inhibitory SIRPα molecule breaks allograft immune tolerance, in part by modifying both the phenotype and the function of regulatory MDSC (myeloid-derived suppressive cells) and the macrophage response.

MDSC and macrophages being key cells in the tumor microenvironment and as a result, the OSE team first evaluated the role of SIRPα myeloid checkpoint blockade in breaking abnormal tolerance to cancer cells. These findings subsequently helped guide development of myeloid checkpoint inhibitor BI 765063, a selective SIRPα antagonist.

BI 765063 is currently in a Phase 1 clinical trial initiated in March 2019. This first-in-class checkpoint inhibitor is being evaluated as a single agent and in combination with Boehringer Ingelheim’s monoclonal antibody PD-1 antagonist BI 754091, a lymphocyte T checkpoint inhibitor, in patients with advanced solid tumors. The trial aims to characterize safety, pharmacokinetics, pharmacodynamics and preliminary efficacy in this patient population. The study is conducted by OSE Immunotherapeutics as part of a collaboration and license agreement with Boehringer Ingelheim under which Boehringer Ingelheim obtained exclusive rights to BI 765063, signed in April 2018.

“OSE’s expertise in preclinical research capitalizes on our strong knowledge of the pathways controlling immune activation and regulation, which have been leveraged to develop technologies that target master switch receptors of immune cells. Our findings, initially from transplantation immunology, and our discoveries on mechanisms regulating or reinforcing immune tolerance could be directly translated oppositely to applications in immuno-oncology to re-instate efficient immune responses. This highlights a differentiated and innovative R&D model of thinking implemented by OSE, which has provided a number of first-in-class developmental products in immuno-oncology and autoimmune diseases,” said Nicolas Poirier, chief scientific officer of OSE Immunotherapeutics. “First-in-class BI 765063 myeloid checkpoint inhibitor illustrates this original research approach in the very attractive and competitive field of myeloid suppressive cells and tumor associated macrophages. That is how the development of selective SIRPα antagonist BI 765063 has progressed until the ongoing Phase 1 clinical study in advanced solid tumors, conducted in collaboration with partner Boehringer Ingelheim.”