15 October 2021 - - The first patient has been dosed in US-based cancer immunotherapy company Immune-Onc Therapeutics, Inc's first-in-human clinical trial of IO-108, a novel antagonist antibody targeting the myeloid checkpoint Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2, also known as ILT4) for the treatment of solid tumors, the company said.

The Phase 1, multicenter, dose-escalation study will consist of a monotherapy cohort and a combination therapy cohort to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IO-108 alone and in combination with pembrolizumab, an anti-PD-1 antibody.

Biomarkers will be assessed to enable a mechanistic understanding of clinical data and inform future trials.

This study may also provide an opportunity to identify preliminary efficacy signals. After determination of the recommended Phase 2 dose, Immune-Onc plans to evaluate the efficacy, safety, and tolerability of IO-108 in combination with pembrolizumab and as monotherapy in indication-specific expansion cohorts.

IO-108 binds to LILRB2 with high affinity and specificity and blocks the interaction of LILRB2 with multiple ligands that are involved in cancer-associated immune suppression, including HLA-G, ANGPTLs, SEMA4A, and CD1d.

In preclinical studies, treatment of various primary human immune cell systems containing myeloid cells with IO-108 results in enhanced pro-inflammatory responses to multiple stimuli that are relevant to anti-tumor immunity.

As a single agent, IO-108 reverses the anti-inflammatory myeloid cell phenotype that results from "tumor conditioning" and promotes the differentiation of monocytes into pro-inflammatory dendritic cells.

Moreover, IO-108 potentiates the effect of PD-1 blocking antibodies on CD4+ T cell activation in co-cultures with allogeneic macrophages. In mouse models IO-108 inhibits the growth of solid tumors, which is associated with enhanced T cell responses.

Together these data demonstrate that IO-108 has the potential to provide additive or synergistic benefit in combination with standard-of-care immunotherapies and/or immunogenic therapies for solid tumors that are both resistant and sensitive to T-cell checkpoint inhibitors.

LILRB2, also known as ILT4, is expressed mostly on myeloid cells, including monocytes, dendritic cells, macrophages, and neutrophils. In solid tumors, interaction of LILRB2 with tumor microenvironment relevant ligands, including HLA-G, ANGPTLs, SEMA4A, and CD1d, makes myeloid cells pro-tumorigenic (tolerating or promoting tumor growth) and promotes tumor immune evasion.

Immune-Onc Therapeutics is a clinical-stage cancer immunotherapy company dedicated to the discovery and development of novel myeloid checkpoint inhibitors for cancer patients.

The company aims to translate unique scientific insights in myeloid cell biology and immune inhibitory receptors to discover and develop first-in-class biotherapeutics that disarm immune suppression in the tumor microenvironment.

Immune-Onc has a pipeline with a current focus on targeting the Leukocyte Immunoglobulin-Like Receptor subfamily B (LILRB) of myeloid checkpoints.