Technology

Hyleukin-7

Hyleukin-7, a homodimeric IL-7 based growth factor for T cells, is engineered to serve as a stable, long lasting factor for T cell production, maturation, expansion, trafficking, functioning and survival, in multiple levels of T cell production. Hyleukin-7 is designed with the end-goal of inducing persistent and long-lasting anti-tumor T cell response, as it controls white blood cell production and peripheral homeostasis.

Hyleukin-7 (Top part): The effector part of Hyleukin-7 is a stabilized form of Interleukin-7 (IL-7). IL-7, as a therapeutic protein, exhibits poor structural stability and low productivity, that act as intrinsic technical barriers to commercialization. Using advanced protein engineering techniques, we created a stabilized, more effective form of IL-7

Hyleukin-7 (Bottom part) – Hyleukin-7 is built on the hyFc® platform technology, originating from NIT’s related company, Genexine. hyFc® was used to construct a long-acting fusion protein comprising the engineered IL-7 moiety, hybridized with IgD and IgG4 Fc fragments that serve as a non-cytolytic and non-immunogenic carrier. hyFc® increases the half-life, minimizes the loss of bioactivity of drug candidates, and prevents cell killing effect by ADCC and CDC reactions. For more information about hyFc® technology — http://www.genexine.com/m21.php

Mode of Action in Diseases

Hyleukin-7 is designed to increase the number of naïve and memory T cells and to enhance T cell functionality. In addition, it is predicted to broaden T cell receptor (TCR) diversity, and consequentially prepare T cells to respond to even subdominant epitopes. Moreover, Hyleukin-7 will enhance T cell homing and infiltration to tumor by increasing homing chemokine activity and antagonizing various inhibitory networks.

NIT is developing Hyleukin-7 in the clinic for diseases where a shortage of T cells and T cell functionality is not only a symptom, but a major part of the disease, focusing on clinical development of three key indication areas – cancer, lymphopenia, and HPV-induced diseases. NIT is working in collaboration with major cancer centers and universities in the US and South Korea, pursuing combination trials with leading immunotherapeutics such as immune checkpoint inhibitors, cancer vaccines and more.

Cancer

NIT aims at developing Hyleukin-7 as an enabling drug for cancer therapeutics, by harnessing T cell immunity. Hyleukin-7 may substantially enhance the efficacy of cancer treatments such as the conventional chemo/radiotherapy, and/or state-of-the-art novel immunotherapies including immune checkpoint inhibitors, cancer vaccines, and more.

The mode of action of Hyleukin-7 effectively overlaps with cancer immunity cycles, especially at the sites of antigen presentation and tumor microenvironment. Therefore, Hyleukin-7 could work in a complementary or synergetic means with various cancer treatments targeting a specific immunity cycle or mechanism, such as novel immunotherapeutics.

Lymphopenia

Lymphopenia, or lymphocytopenia is the condition of having an abnormally low level of lymphocytes. It causes lowered immune responses to cancer and increased risk of life-threatening infections. About 25% of cancer patients have lymphopenia at the time of diagnosis, and up to 95% of patients receiving chemotherapy and/or radiotherapy may suffer lymphopenia after multiple treatments of certain regimens.

Lymphopenia is an independent prognostic marker to predict unfavorable overall survival of cancer patients. Recent publications in the immune-oncology field indicate that cancer patients with lymphopenia exhibit substantially shorter survival time and low response rate to chemo/radiotherapy or immunotherapy.

HPV

Among many HPV-induced diseases, NIT is primarily aiming at treating HPV persistent infection, for which there is no standard of care. Although there are approved prophylactic HPV vaccines, they cannot treat established chronic infections, nor can they prevent progression to harsher conditions such as precancer or cancer. Intravaginal formulation of Hyleukin-7 highly enhances the expansion and function of T cells in chronic cervical HPV infection and has efficient mucosal delivery by FcRn-mediated transcytosis mechanism in animal experiments, and co-delivery of HPV DNA vaccine (GX-188E by Genexine, Inc.) and Hyleukin-7 substantially enhances the vaccine induced CD8 T cell response, CD8 T cell-mediated anti-tumor effect and survival rate in mice.