Kringle Pharma, Inc. announced the publication of a peer-reviewed article in the international scientific journal Inflammation and Regeneration online edition issued on October 16, 2023, presenting preclinical results generated from the collaborative research between KRINGLE and Keio University regarding the dual therapeutic intervention for the treatment of acute to subacute severe spinal cord injury. KRINGLE is currently conducting a Phase III clinical trial of recombinant human hepatocyte growth factor ("HGF") in subjects with acute spinal cord injury. In parallel, KRINGLE launched a collaborative research program with Professors Hideyuki Okano and Masaya Nakamura at Keio University School of Medicine in 2021, aiming to create next-generation therapies for spinal cord injury. In this research, administering HGF developed by KRINGLE in the acute phase, followed by transplantation of human induced pluripotent stem cell-derived neural stem/progenitor cell ("hiPSC-NS/PC") owned by Keio University in the sub-acute phase, substantially enhanced motor functional recovery in the rat model of severe spinal cord injury compared to each single treatment group. The finding led to the patent application claiming a priority, jointly filed by KRINGLE and Keio University as announced in the KRINGLE news release dated
September 8, 2023. The research results published in the journal demonstrated that pretreatment with HGF in the acute phase of spinal cord injury improved the spinal cord microenvironment by promoting tissue regeneration including angiogenesis, neuronal regeneration and myelination, as well as suppressing inflammation. In addition, the survival rate of hiPSC-NS/PC transplanted in the sub-acute phase was improved in this favorable environment, leading to further acceleration of neuronal regeneration. Consequently, locomotor function was substantially restored in rats with severe spinal cord injury that had not shown sufficient recovery with cell transplantation alone. This research opens the door to the promising combination therapy of HGF and hiPSC- NS/PC transplantation to treat the acute and subacute phases of spinal cord injury. Clinical development and practical application of the combined therapeutic approach is expected in the future. HGF was originally discovered as an endogenous mitogen for mature hepatocytes. Subsequent studies demonstrated that HGF exerts multiple biological functions based on its mitogenic, motogenic, anti-apoptotic,
morphogenic, anti-fibrotic, and angiogenic activities, and facilitates regeneration and protection of a wide variety of organs. HGF exerts neurotrophic effects and enhances neurite outgrowth, and the therapeutic effect of HGF on spinal cord injury has been demonstrated in animal models by Professors Hideyuki Okano and Masaya Nakamura at Keio University School of Medicine. Expectations for HGF as a novel therapeutic agent are increasing for spinal cord injury. A group led by Professor Shigeru Hirano of the Department of Otolaryngology and Head and Neck Surgery, Kyoto Prefectural University of Medicine, focused on the anti-fibrotic effects of HGF and demonstrated its pharmacological effects on vocal cord scar. HGF is also expected to have the potential to be an effective therapeutic agent for various fibrotic diseases including vocal fold scar. Human Induced Pluripotent Stem Cell-derived Neural Stem/Progenitor Cell (hiPSC-NS/PC): hiPSC-NS/PC is derived from human induced pluripotent stem cells and has the self-renewal capability, enabling proliferation maintaining undifferentiated state, as well as pluripotency, enabling differentiation into cells constituting the central nervous system such as neurons, astrocytes, and oligodendrocytes.