Founded in 2015 and based in Seoul, South Korea, Eutilex is a biotechnology company focused on the research and development of innovative T cell, chimeric antigen receptor (CAR) T cell and antibody therapies for cancer and autoimmune diseases. Eutilex is developing preclinical and clinical-stage immunotherapeutics using its three in-house platform technologies.
Eutilex’s CEO, Byoung S. Kwon, is a leading immuno-oncology researcher responsible for the discovery of the human 4-1BB, an inducible costimu-latory receptor expressed on activated T cells. The Eutilex T cell platform is based on 4-1BB, which is expressed on cancer-specific T cells. Increased signaling through the 4-1BB receptor enhances cancer-specific T cell activation, which has shown to lead to high antitumor efficacy and an excellent safety profile in humans. The platform has the potential to provide a personalized therapy for individual patients with cancer.
The patented manufacturing process begins with the patient’s own blood cells. Using Eutilex’s 4-1BB proprietary technology, technicians select cancer-specific memory T cells on the basis of their induced expression of 4-1BB (Fig. 1), and amplify the cells before infusing them back into patients. The standardized manufacturing process is simple and efficient, and results in a cell suspension containing about 95% pure cancer-specific killer T cells. The platform has the potential to treat all cancers, certainly including solid tumor applications.
Eutilex is conducting various clinical trials to further confirm and expand the efficacy and safety data for its 4-1BB platform technology. EBViNT, which targets Epstein–Barr virus (EBV)-positive cancers, is in phase 2 for the treatment of natural killer/T cell (NK/T cell) lymphoma. This follows a phase 1 study (Fig. 1) that demonstrated a 50% overall response rate in patients with late-stage EBV-positive cancers, including two patients with NK/T lymphomas who had 100% complete responses. Preparations are underway for clinical trials in the US. Eutilex plans to gain US Food and Drug Administration approval by approximately 2023.
4-1BB cytotoxic T lymphocytes have also shown encouraging efficacy in solid tumors, including breast cancer. TERTiNT, which targets telomerase reverse transcriptase-positive cancers, and WTiNT, which targets Wilms tumor protein-positive cancers, are both in phase 1 in patients with late-stage solid tumors. Clinical data so far have shown a reduction in tumor burden, with a significant improvement in symptoms and quality of life. One of the key challenges of solid tumors is their heterogeneity. To overcome this, Eutilex is developing a personalized T cell therapy, known as TAST (tumor antigen-specific T cell), employing multiple cancer antigens, including neoantigens.
Fig. 1 | 4-1BB CTL mechanism and cases of clinical trials. The 4-1BB cytotoxic T lymphocyte (CTL) platform has demonstrated high efficacy in several clinical trials, has produced complete responses (CRs) in 100% (2/2) of patients with natural killer/T cell (NK/T) lymphoma and has even shown efficacy in solid cancers. The procedure is simple, standardized and applicable to most hematologic and solid cancers. hTERT, telomerase reverse transcriptase; MHC I, major histocompatibility complex class I; NSCLC, non-small-cell lung cancer; TCR, T cell receptor; WT1, Wilms tumor protein.
Using an antibody approach to treat cancer
Eutilex has used its knowledge-based COSTIM (co-stimulatory) platform technology to create a pipeline of more than 15 monoclonal and bispecific immuno-oncology antibodies. These antibodies activate T cells by binding to costimulatory receptors. Eutilex has gathered preclinical data and plans to license out its antibody pipelines.
The lead antibody candidate, EU101, targets 4-1BB and promotes the activation and proliferation of killer T cells, with no signs of liver toxicity. In human cancer mouse models, EU101 was more effective than approved checkpoint inhibitors and has also shown excellent efficacy in combination with these drugs. In September 2017, Eutilex licensed exclusively the Chinese rights to Zhejiang Huahai Pharmaceutical.
EU102 is a fully human monoclonal antibody against the activation-inducible tumor necrosis factor family receptor (AITR; also known as CD357), another costim-ulatory factor discovered by Kwon in the 1990s. EU102 is a real game-changer, because it both activates killer T cells and is the first therapy in the world to convert regulatory T cells to T helper 1-like cells while retaining cytotoxic abilities and fighting cancer. EU102’s dual function has already demonstrated high anticancer efficacy. Animal studies have shown complete regression of cancers with greater efficacy and safety than Keytruda or other AITR-targeted antibodies from other companies. Eutilex plans to further develop the use of EU102 in solid tumors and is discussing potential licensing options with various global companies.
Harnessing the immune system against cancer
Eutilex is also developing CAR Ts based on its next-generation technology. The malignancy variant receptor CAR T program, for relapsed and refractory hematologic malignancy, targets human leukocyte antigen-DR (HLA-DR), which is highly overexpressed on malignant B cells, rather than CD1 9, which is expressed also on healthy B cells. This reduces the possibility of potentially fatal side effects associated with the CD19-targeting CAR T therapies, such as cytokine release syndrome, neurological toxicities and B cell aplasia. Other CAR T approaches in development include a CAR T designed specifically for treating solid tumors and a universal, allogeneic CAR T that will be used as an ‘off-the-shelf’cancer therapy.
Eutilex is developing its immuno-oncology pipeline in collaboration with a number of Korean and global biotechnology companies and research institutes and is looking to expand its network of partnerships. The company also plans to add additional pipelines to its portfolio in the future.
Agustin de la Calle, Business
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