Therabest and Glycotope to assess Therabest’s iPSC-derived NK cell product TB-100 in combination with Glycotope’s GT-00AxIL15 immuno-cytokine for development in triple negative breast cancerSan Diego, U.S.A., Seoul, Korea and Berlin, Germany, 13 December 2022 – Therabest USA. Inc, Therabest Korea (Therabest) and Glycotope GmbH (Glycotope) have signed an agreement to assess the clinical development of Therabest’s EiNKTM (Enhanced iPSC-derived NK) cell therapy, TB-100, in combination with Glycotope’s immuno-cytokine, GT-00AxIL15 in triple-negative breast cancer (TNBC) patients.NK cell therapies from various cell sources have demonstrated exciting results in early clinical trials and are rapidly becoming powerful alternatives to conventional treatments. However, for solid tumors, NK cell therapies are still hampered by the low persistency and homing of NK cells. The combination of Therabest’s iPSC derived NK cell therapy TB-100 and Glycotope’s tumor-targeted immuno-cytokine GT-00AxIL15 challenges the current NK cell therapy paradigm by converging a two-component platform in which the dosage of an immuno-cytokine improves the activity of TB-100.“We look forward to maximizing the strengths of TB-100 and GT-00AxIL15 to challenge solid tumors with enhanced cytotoxicity, specificity, persistency, and safety through this collaboration. We expect serial killing of MUC1 positive TNBC tumor cells by TB-100 redirected with GT-00AxIL15,” said Sung Chang Lee, CEO, Therabest USA and adjunct CDO, Therabest.“The collaboration underlines the attractivity of our tumor targeted immuno-cytokine GT-00AxIL15 and its suitability for combination therapies. We are excited by the potential of combining two highly innovative technologies to explore the treatment of TNBC here,” added Henner Kollenberg, CEO, Glycotope.Therabest's EiNKTM platform is a next-generation allogeneic NK cell therapy manufacturing technology that covers all processes from iPSC gene editing to iPSC-derived NK cell differentiation and proliferation. TB-100, a highly active NK cell therapy development candidate from EiNKTM platform, can recognize and remove heterogeneous cancer cells very effectively. TB-100 is an off-the-shelf and uniform cell therapy without donor-dependent batch-to-batch variation with minimal risk of current cell therapies.Glycotope’s antibodies target specific tumor-associated carbohydrate structures or protein/carbohydrate combined glyco-epitopes (GlycoTargets). Targeting these specific antigens enables broad indication range, long-term treatment potential and reduced on-target/off tumor toxicity, key elements of highly potent therapies. Based on this unrivalled tumor-specificity, Glycotope’s antibodies are highly suitable for a multi-function platform approach with independent modes of action to provide a tailored therapy format for as many patients as possible.Contact Information:Therabest, Therabest USASung Chang Lee (CDO, Therabest Korea and CEO, Therabest USA)Phone: +1 619-614-2966Email: sunglee@therabest-usa.comGlycotope GmbHHenner Kollenberg (CEO)Phone: +49 30 9489 2600Email: contact@glycotope.comMedia Contact:Chris Gardner, Chris WelshConsillium Strategic CommunicationsPhone: +44 20 3709 5700Email: glycotope@consillium-comms.comAbout TB-100Therabest’s TB-100 is an allogeneic iPSC-derived NK cell therapy produced from Therabest’s EiNKTM (Enhanced iPSC-derived NK) platform. TB-100 is the next generation cell therapy consisting of highly specialized cytotoxic NK cells which can recognize and removes heterogeneous cancer cells very effectively because they have high expressions of various activation receptors, including IL-15R and NKG2D, and low expressions of inhibitory receptors. TB-100 is an off-the-shelf and uniform cell therapy without donor-dependent batch-to-batch variation with minimal risk of CRS (cytokine release syndrome) and neurotoxicity, which are known challenges in current CAR-T cell therapy.About GT-00A x IL15GT-00A x IL15 is a TA-MUC1 targeting IL-15 immuno-cytokine fusion antibody. Cytokines have long been used for cancer therapy to activate the immune system, but side effects and short half-life limit their therapeutic application. The concept of specific targeting to the tumor and tumor microenvironment to exploit the full potential of IL-15 biology is unique within the competitive field of IL-15 (super)agonists. The Immuno-cytokine attracts and activates immune cells (e.g., T and NK cells) directly at the tumor site thereby turning an “immune desert” into a “hot” tumor and inducing tumor cell lysis. A comprehensive non-clinical data package is available.About TherabestTherabest is a discovery/clinical-stage biotech company focusing on developing immunotherapy for allogeneic adoptive transfer and biologics that improve well-being. Programs include Off-the-Shelf production of immune cells for universal cell therapy products as well as precision biologics to educate the immune system to target/attack specific abnormal cells as well as to enhance the immune response to eliminate hematological and solid cancer. Visit www.therabest.co.kr/en/.About GlycotopeGlycotope is a biotechnology company utilizing a proprietary technology platform to develop uniquely tumor-specific monoclonal antibodies. Our antibodies target specific tumor-associated carbohydrate structures or protein/carbohydrate combined glyco-epitopes (GlycoTargets). Glycotope has to date discovered in excess of 200 GlycoTargets with antibodies against several of these targets currently under development.Based on their superior tumor-specificity, our antibodies are suitable for development in an array of different modes of action including naked antibodies, bispecifics, antibody-drug-conjugates, cellular therapies or fusion-proteins. Visit www.glycotope.com

Reyon Pharmaceutical said on Thursday that it signed a memorandum of understanding (MOU) with Therabest on business cooperation based on the supply of plasmid DNA (pDNA) samples for the development of natural killer (NK) cell therapy. Under the MOU, Therabest will exchange information with Reyon to produce and supply pDNA samples and K-562 cell lines for the development of NK cell therapies. Both companies will also discuss participation in strategic investment and a joint partnership for NK cell therapies, said a Reyon official.Therabest is a drug R&D company that develops next-generation NK cell therapy derived from induced pluripotent stem cells (iPSCs) for intractable diseases. It also has current good manufacturing practices (cGMP) facilities specializing in cell therapies and plans to register its products for clinical trials in 2023.The collaboration aims to enable next-generation NK cell therapies, which can constantly produce NK cells in iPSCs without requiring blood samples.They plan to make them as “ready-made chimeric antigen receptor-natural killer (CAR-NK) products” homogeneously from gene-edited iPSCs."We will do our best to successfully develop the next-generation NK cell therapies through close cooperation with Therabest," Reyon Pharmaceutical CEO Yoo Yong-hwan said. "We will also continue expanding into various bio-business areas based on our pDNA production capabilities.”Therabest CEO Ki Pyung-suk said, "We will secure key samples optimized for major processes such as gene editing and culturing of next-generation NK cell therapies through close cooperation with Reyon Pharmaceutical.”Ki added that the combination of the core competencies of the two companies is expected to accelerate the entire process from clinical trials to commercialization for a stable supply of samples. 

THERABEST Co., Ltd. plans to release its pre-clinical results of immune-modulatory NK (imNK) cells on Alzheimer’s disease for the first time at an international conference. These research findings on the therapeutic effect and mode of action of imNK cells will be presented at the Alzheimer’s Accociation International Conference (AAIC), taking place in San Diego, USA from July 31 to August 4. The upcoming AAIC presentation will showcase the company’s aim to shift the therapeutic paradigm to address Alzheimer’s disease with potential NK cell therapy. The human gene mutant transgenic Alzheimer’s disease animal model showed improvement in cognitive function and significant reduction of beta amyloid plaque aggregation. Spatial transcriptomic techniques, which allow the simultaneous examination of entire gene expression in individual brain regions and changes of a variety of brain cell types, was introduced to investigate the underlying mode of action analysis of Alzheimer’s disease treatment, revealing significant decrease in dysfunctional microglial cells inducing neuroinflammation in a certain brain region and increase in gene signatures associated with cellular respiration and immune metabolism.Do Won Hwang, CTO of THERABEST, said “over the last three years, we’ve witnessed that imNK cells, which secrete immunomodulatory cytokines and neurotropic factors, can promote a decrease in pathological protein aggregate level and recovery of cognitive function in various Alzheimer’s disease models. Thanks to the joint research with Seoul National University, spatial transcriptome analysis clearly elucidated a new mode of action of imNK cell therapy by observing the recovery of inhibitory neurons in specialized brain region involved in emotion control”. THERABEST is planning for a clinical trial of EiNK, an “off-the-shelf” iPSC-derived NK cell therapeutics allowing mass production with low cost, on Alzheimer’s disease.  

Our CTO Do Won Hwang and CSO Shin-Il Kim, along with CSO Nick Boyd-Gibbins at Therabest Japan, published an article "iPSCs in NK Cell Manufacturing and NKEV Development" in Frontiers in Immunology (IF: 8.786). This review explores the advantages of using iPSCs (induced Pluripotent Stem Cells) for NK cell manufacturing and translation, and how these trends can extend into the next generation of enhanced NK cell therapies and the emerging field of NK cell-derived extracellular vesicles / exosomes (NKEVs). Please refer to the following link. https://www.frontiersin.org/articles/10.3389/fimmu.2022.890894/full

▲     Koichi Seriu, CEO of Therabest JapanTHERABEST Japan, a subsidiary of South Korea’s THERABEST, is moving into Japan’s largest medical cluster to begin full-scale iPSC technology exchange.   THERABEST (CEO Pyung-Suk Ki), a company specializing in iPSC (induced Pluripotent Stem Cell)-derived immune cell therapy, announced on 29th, June that its subsidiary, THERABEST Japan (CEO Koichi Seriu), became a resident company for the Kobe Biomedical Innovation Cluster (hereafter ‘KBIC’), a medical industry city located in Kobe, Japan.   KBIC, built on an island in Kobe Port called "Port Island", is Japan's largest medical cluster. Japan's leading pharmaceutical companies, research institutes and specialized hospitals have come together to carry out the entire translational process, from basic research to clinical trials, to develop new drugs and advanced medical devices. To move into SCL (Startup Creative Lab) within CLIK (Creative Lab for Innovation in Kobe) in KBIC, companies have to pass rigorous screening.   A company official explained, “In order to move into SCL we had to pass a total of five stages of screening, with interviews at three KBIC-related organizations.” He said, “At a time when interest in iPSC application technologies is growing around the world, our company recieved a very positive evaluation based on our potential for synergy with local companies, universities, and research institutes.”   THERABEST, leading the iPSC-derived immune cell therapy field in South Korea, is an innovative bio company that develops safe, efficient, and scalable off-the-shelf allogeneic cell therapy products that can provide more patients with access to effective medical care. In February of this year, the subsidiary THERABEST Japan was established to promote joint research, partnerships, and the expansion of iPSC application technologies.   THERABEST Japan was under review since March to move into the SCL, which is the main base of KBIC. SCL is located in CLIK, which is about 12,200 m2, and hosts laboratories that meet diverse needs, from startups to large corporations as well as research institutes.   THERABEST Japan is the only Korean or Korean affiliate company participating at KBIC. KBIC is where the world's first clinical trials using iPS cells were approved. The RIKEN and foundation for biomedical research and innovation at Kobe have together been conducting clinical trials for retinal regeneration using iPS cells.   Pyung-Suk Ki, CEO of Therabest, said, “Based on the technologies and manufacturing facilities we have established so far, we are in full swing to discuss cooperations such as the joint development of new drugs with domestic and foreign companies.” Adding, "In KBIC we plan to actively engage in joint research exchanges not only with global pharmaceutical companies in Japan, but also with local research institutes including Kyoto University’s CiRA, the birthplace of iPSC technology."   THERABEST plans to implement its EiNK (Enhanced iPSC-derived NK cell) platform technology through their Anyang GMP manufacturing center (Thera-Cell Center), which will start full-scale operation from the second half of this year. The Thera-Cell Center was estabilished to produce global clinical products. It was designed to meet international clinical standards from design to facility construction and validation.

Our CSO Shin-Il Kim, along with Peter Karagiannis at Center for iPS Cell Research and Application (CiRA), Kyoto University, Japan, published an article "iPSC-Derived Natural Killer Cells for Cancer Immunotherapy" in Molecules and Cells (IF: 4.250).  This review describes the importance and future vision of Therabest’s main focus, iPSC (induced Pluripotent Stem Cells)-derived NK cells in cancer immunotherapy.   Please refer to the following link. https://www.molcells.org/journal/view.html?pn=mostread&uid=4317&vmd=Full