ImmunOs has developed a proprietary human leukocyte antigen (HLA)-based platform to generate a novel class of biologic therapeutics for the treatment of cancer and autoimmune disease. These novel therapies target both the adaptive and innate immune systems, including myeloid-derived cells, T cells, and NK cells. The Company has identified specific HLA molecules known to activate the immune system of patients with autoimmune disorders. ImmunOs is utilizing these HLA molecules as the backbone of novel therapies capable of stimulating the immune system of cancer patients to eliminate tumor cells. ImmunOs is also developing antibodies to block the activation of specific HLA molecules associated with autoimmune diseases.
Cancer
ImmunOs’ platform utilizes specific HLA molecules known to activate the immune system of patients with autoimmune disorders to create novel human-derived treatments. In contrast to other immuno-oncology therapies, the product candidates developed by ImmunOs’ platform address multiple targets of the innate immune system – specific leukocyte immunoglobulin-like receptors (LILRBs, which are also known as ILTs, i.e., immunoglobulin-like transcripts) and killer cell immunoglobulin-like receptors (KIRs) – via a single molecule. Therefore, ImmunOs´ product candidates target a broader range of immune cells than other competing innate immunity approaches. In addition, the multitasking nature of the candidates enables targeting of the adaptive immune system, initiating a cascade of immune responses against tumor cells. The ability of ImmunOs’ product candidates to engage both the innate and adaptive immune systems is a key advantage over clinically approved checkpoint inhibitors which focus only on modulating the adaptive immune system.
ImmunOs’ approach of using a single therapeutic to target a broader range of cell types in the tumor microenvironment than competing technologies has the potential to transform the immune-suppressing tumor microenvironment to allow the eradication of tumor cells.
Autoimmune disease
To treat autoimmune diseases and reduce pro-inflammatory immune responses, ImmunOs is developing antibodies blocking the activation of specific HLA protein molecules associated with a broad set of autoimmune diseases, including ankylosing spondylitis, lupus, psoriasis, and IBD.
Background: HLA-based Therapeutics
Origin of ImmunOs’ immuno-oncology product candidates
ImmunOs’ immuno-oncology product candidates are fusion proteins based on specific HLA molecules discovered in patients with certain autoimmune diseases and known to hyper-activate the immune system, including providing protection against viral infections. Using these molecules to create novel immunotherapies can activate the patient’s immune system to attack and eliminate tumor cells.
The Company´s HLA-based technology platform provides carefully screened HLA variants from patients with severe autoimmune diseases to identify and develop the most promising molecules for the treatment of cancer. As these HLA variants are derived from humans, ImmunOs’ cancer immunotherapies have the potential to demonstrate a significantly enhanced safety profile.
Open Formats
The HLA molecules that ImmunOs is using are called HLA open formats. Classic HLA molecules, known as HLA heterotrimers, bind and present antigen peptides to the immune system. HLA open formats are HLA molecules that are peptide-free and bind to innate and adaptive immune cell receptors. Naturally occurring variants of certain HLA open formats are overexpressed in specific autoimmune diseases. The Company´s lead compound, IOS-1002 (formerly iosH2), utilizes an HLA open format variant derived from psoriasis patients. It binds to three receptors expressed on innate and adaptive immune cells, i.e., LILRB1 (also known as ILT2), LILRB2 (also known as ILT4), and KIR3DL1, which are checkpoint receptors that suppress immune responses when activated. By blocking this activation, IOS-1002 alters the tumor microenvironment to induce tumor infiltration of M1 macrophages, T cells and NK cells resulting in the killing of tumors.
MECHANISM OF ACTION
Cancer
The Company’s multi-targeting approach for cancer remodels the tumor microenvironment – a key prerequisite for effective immunotherapy – to enhance anti-tumor immunity resulting in the killing of tumor cells. By binding to and blocking the activation of three different immunosuppressive receptors (also known as checkpoints) on innate and adaptive immune cells (LILRB1 / ILT2, LILRB2 / ILT4, KIR3DL1), ImmunOs’ lead product candidate, IOS-1002 (formerly iosH2), alters the tumor microenvironment by:
- Directly stimulating the innate immune system by activating M1-type macrophages and suppressing M2-type macrophages. Shifting from the M2 to M1-type in the tumor microenvironment is vital as the M1-type facilitates a robust immune response to tumors.
- Blocking the activation of immuno-suppressive myeloid-derived suppressor cells (MDSCs), resulting in the expansion of killer CD8+ T cells which can directly destroy tumor cells.
- Directly activating T cells and enhancing their cytotoxicity against tumor cells.
- Directly activating NK cells to enhance a potent anti-tumor effect.
By remodeling the tumor microenvironment to enhance anti-tumor immunity and induce the killing of tumor cells, IOS-1002 and ImmunOs’ additional product candidates in development can be used as monotherapy treatments and as part of combination therapy regimens. IOS-1002 has demonstrated strong anti-tumor responses in multiple solid and liquid cancer models in combination with checkpoint inhibitors such as PD-1, PD-L1, CD47, SIRPα and agonist antibodies such as 4-1BB.