Systematic and sequential development for pipeline from biosimilar to novel drugs
ISU104 is a fully human antibody targeting ErbB3 for refractory cancer treatment.
Members of the epidermal growth factor receptor family (ErbB family) are known as potent mediators in the development and progression of cancer. Activated ErbBs recruit various adaptors and signaling molecules through the phosphorylated cytoplasmic domain, which further leads to activation of downstream oncogenic signaling pathways.
Of them, ErbB3 is noted as one of the major causes of treatment failure in human cancers. The activation of alternative signaling pathways that bypass the original target and sustained PI3K/AKT activation by ErbB3 are associated with resistance to anti-ErbB-targeted therapies and several chemotherapies.
ISU104 is anti-ErbB3 antibody isolated from phage library, and evaluated for the preclinical safety. ISU104 is designed to inhibit ligand-dependent/independent dimerization of ErbB3 with other ErbBs and induces internalization of ErbB3, and subsequently inactivates the downstream signaling. ISU104 shows potent inhibition of tumor growth in multiple xenograft tumor models including head and neck, breast, lung, and pancreatic cancers. Especially in cetuximab-resistant head and neck cancer model, ISU104 manifests tumor regression activity. We have received IND for ISU104 Phase 1 clinical study approval from MFDS in 2017, and is currently being tested in patients with head and neck cancer.
ISU304 (CB 2679d) is a modified recombinant Factor IX protein being developed for the treatment of Hemophilia B patients. Hemophilia B is a rare genetic disorder that occurs in one out of every 25,000 men. Blood coagulation is defective in patients due to low level of Factor IX, a key protein necessary for hemostasis. Accordingly, Hemophilia B patients suffer from not only accidental but also spontaneous bleeding and concomitant side effects such as long term joint damage. Currently approved plasma-derived and recombinant Factor IX proteins are administered intravenously in patients upon bleeding or in advance to prevent spontaneous bleeding. Current Hemophilia B medical unmet needs are normalizing (i.e. >40%) Factor IX trough levels and improving patient administration convenience for example by allowing for subcutaneous dosing.
ISU304 (CB 2679d) was originally developed by Catalyst Biosciences, Inc. (San Francisco, USA – Nasdaq: CBIO) and rationally designed for superior activity and increased potency. ISU304’s superior subcutaneous activity and potency have been demonstrated in multiple in vitro and in vivo studies and has completed GLP toxicology studies. We have completed a Phase 1/2 clinical trial in 2018.
We and Catalyst Biosciences, Inc. have been collaborating on ISU304 (CB1679d) since 2013. We are responsible for pre-clinical development and the Phase 1/2 study after which Catalyst Biosciences is responsible for global commercial manufacturing and late-stage clinical development.
ISU 305 is an antibody biosimilar for PNH (Paroxysmal Nocturnal Hemoglobinuria) therapy, Soliris (Alexion Pharmaceuticals). PNH is a rare disease in which red blood cells break apart because of mutation of protein on membrane of red blood cells and defect in bone marrow. PNH patients’ red blood cells which are easily destructed by complement system, a protective mechanism of body for virus, bacteria and other pathogens. Breakage of red blood cells can result in disabling fatigue, difficulty in swallowing and painful abdomen contractions. Furthermore, patients are susceptible to developing life-threatening blood clots and some may develop kidney disease.
The only curative therapy is bone marrow transplantation, but, it is reserved to severe patients with serious bone marrow failure or life-threatening blood clot formation because of the high risk of morbidity and mortality. Soliris is an antibody against C5 molecule, a pivotal component of complement system, preventing destruction of red blood cells and improving quality of life dramatically. However, it is very hard for patients to access because Soliris is one of the most expensive medicines in the world. In 2020, we have completed ISU305 Phase I clinical trial in Australia and New Zealand.
ISU106 is a biosimilar for cancer immunotherapy, Opdivo(Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb Company). Opdivo is a treatment for cancers including malignant melanoma, non-small cell lung cancer, and other types of cancer. Cancer immunotherapy is a treatment that stimulates the body’s immune system to attack cancer cells and it works for most types of cancers. In 2019, we have done for a process development for ISU106.