Blue Bees Therapeutics addresses the field of immune modulators to treat cancers, using revolutionary immune response potentiation technology

Blue Bees Therapeutics i.Ther technology has led to the validation of its first lead product, intended to be used a stand alone drug (as monotherapy or combined therapy), and to the establishment of a biobetter and new product discovery platform.

Blue Bees Therapeutics technology consists of protein complexes combining an L1 ligand of a receptor selectively expressed on the surface of immune cells, with an L2 ligand of Heparan Sulfate Proteoglycans (HSPGs). HSPGs represent a family of molecules ubiquitously expressed by most cells. They often act as co-receptors potentializing cell signaling and can thus modify receptor-mediated activation (Xie et al., 2019, Cell Signal., 54:115-121). Our L1-L2 complexes take advantage of these co-receptor properties.

This body of information and findings led to the development of our i-Ther technology. Indeed, it consists of engineered dual-targeting molecules, associating a L1 Ab specific for a receptor expressed selectively on the surface of immune cells, with an L2 ligand of HSPGs. The L1-L2 complexes exhibit increased cellular activity as compared to free L1 Ab and appear to be more effective immunomodulators, i.e. they boost the specific immune response in vitro and in vivo and improve tumor control (Knittel et al., 2016, Vaccine, 34(27):3093-3101).

Blue Bees Therapeutics first lead candidate, BB10x, targets Fc-gamma receptors (FcgR). 

FcgR was selected as our first target since it is expressed by cells derived from the myeloid lineage as well as NK cells and B-lymphocytes. Thus, it allows us to impact a large panel of immune cells involved in tumor control or progression. As FcgR-mediated cell-regulation proceeds through Ab binding via its Fc domain, BB10x lead candidate contains a Fc fragment of human IgG1 fused to a HSPG-binding ligand, or pHSL.

BB10x showed its ability to impact tumor-growth as assessed using different syngeneic models. Furthermore,  immune profiling of the tumor mivro-environment in syngeneic models showed that BB10x treatment impacts the MDSC/T-cell ratio, shifting it from a MDSC-high/T-cell-low immunosuppressive content to a MDSC-low/T-cell-high characteristic of an inflamed immunotype more prone to tumor control.

Blue Bees Therapeutics technology platform allows to produce a variety of first-in class immune modulators

Immune cells express a wide array of receptors that might contribute to immune cell activation and thus might behave as immune regulators. However, L1 antibody ligands that bind to these receptors do not always trigger a sufficient signaling for an appropriate activation. This limitation is waived by associating the L1 antibody ligands with the L2 HPSG ligand that increases signaling.

Blue Bees Therapeutics technology allows to easily create a variety of L1-L2 complexes against a wide array of receptors. These L1-L2 complexes can be used to screen receptor-mediated activation of different immune cell types as well as the impact on tumor control. This selection process leads to the definition of new first-in class immune regulators immunotherapies.