Technologies | IMMUNE FX (IFx): Innate Immune Agonists
Harnessing The Power Of The Innate Immune Response
We have developed Immune Fx, or IFx, as an innate immune agonist technology designed to “trick” the body’s immune system to attack tumor cells by making tumor cells look like bacteria and to thereby harness the natural power of innate immunity by leveraging natural mechanisms conserved throughout evolution to recognize threats from foreign pathogens like bacteria or viruses. Our innate immune agonist product candidates are delivered either via intratumoral injection (in the case of the Company’s pDNA innate immune agonist) or tumor targeted via intravenous or autologous whole-cell administration (in the case of our mRNA innate immune agonist).
Our IFx-2.0 innate immune agonist, our company’s lead product candidate, is comparatively simple to administer and involves only the injection into a patient’s tumor, or lymph node, of a relatively small amount of pDNA that is designed to encode for an immunogenic gram-positive bacterial protein that gets expressed on the surface of the patient’s tumor, so that the surface of the tumor looks like a bacterium.
Bacteria, like all pathogens, have molecular patterns or motifs that are conserved through evolution and that are recognized by specific pattern-recognition receptors on immune cells of our innate immune system. This is an individual’s primary line of defense against pathogens that the individual is born with, and the innate immune system has no choice but to recognize the tumor as it would a gram-positive bacteria or any pathogen. Gram-
positive bacterial proteins are recognized by Toll Like Receptor-2 (TLR-2) on antigen presenting cells, or APCs, which engulf and ingest the entire intact tumor cell packaging all the foreign tumor neoantigens presenting them to and educating tumor killing T cells and B cells. In doing so, IFx-2.0 harnesses the power of the innate immune response to produce activated tumor-specific T cells where they previously didn’t exist overcoming primary resistance to checkpoint inhibitor therapy.
Checkpoint Inhibitors Dominate the Oncology Market, However There Remains Significant Need to Overcome Tumor Resistance to Checkpoint Inhibitors
Resistance to Checkpoint Inhibitors (CPIs) Remains a Significant Unmet Need
CPIs have revolutionized the treatment of cancer replacing chemotherapy in some types of cancer. However, despite their success in certain cancer types, approximately 70% to 80% of cancers will exhibit primary resistance and not respond to immune checkpoint inhibitors. Agents that can overcome primary resistance to immune checkpoint inhibitors would address a major unmet medical need, expanding the potential benefits of immune checkpoint inhibitors to a wider population of patients across more cancer types.
Overall, only 20% of patients respond because tumors escape immune recognition and attack by not appearing foreign to the immune system.* For checkpoint inhibitors to work they require activated T cells, resulting from activation of an immune response against the tumor. The goal of immunotherapy is to activate an immune response against tumor antigens resulting in the activation of tumor specific T cells to allow checkpoint inhibitors to work in tumors where they would otherwise fail.
IFx-2.0, by priming and activating a tumor specific innate immune response leading to the production, activation and proliferation of tumor specific T cells (and B cells), may allow immune checkpoint inhibitors like Keytruda® to potentially work in more patients where they would otherwise not.
Checkpoint Inhibitor Market Expected To Reach WW Sales Of $148 Billion By 2030**
