IL-22 is produced by CD4 T-cell subsets, Th17/Th22 cells, NK cells and LTi-like cells. IL-22 levels in serum samples are up-regulated during inflammation in human disease settings. IL-22 plays an important role in controlling bacteria infection, homeostasis, and tissue repair by binding a cell surface receptor IL-22 receptor complex and subsequently activating the STAT3 signaling pathways. IL-22 receptor complex consists of IL-22 R2, or IL-10 R2 which is ubiquitously expressed, and IL-22 R1 which restrictedly expressed on epithelial cells such as keratinocytes, bronchial and intestinal epithelial cells and hepatocytes.
F-652 is a recombinant protein containing human interleukin 22 (IL-22) and produced in Chinese Hamster Ovary (CHO) cells in serum-free culture. In pre-clinical studies, F-652 demonstrated expected bioactivity in vitro and in vivowith excellent pharmacokinetics and safety profile. The company is conducting a first-in-man (FIM) trial in healthy volunteers to evaluate the safety and PK properties of F-652. F-652 could potentially address unmet medical needs in several inflammatory diseases. For example, F-652 helps liver regenerate after injury by promoting hepatocyte survival and proliferation. A phase I clinical study in healthy volunteers was successfully completed in Australia.
Generon is the first company to develop IL-22 for multiple therapeutic indications such as acute pancreatitis, acute alcoholic hepatitis and GvHD, etc.
Mechanism of action of F-652 in tissue repair and regeneration during inflammation.
F-652 development highlights:
Molecular modality: An innovative rhIL-22 dimer expressed in CHO cells with strong IP positions. Sixteen global patents have been granted regarding the use of IL-22 and IL-22 dimer.
Clinical indications: Acute pancreatitis (AP), alcoholic hepatitis (AH), fatty-liver diseases, graft vs host disease (GvHD) after allogeneic bone marrow transplantation, organ failure, colitis and respiratory diseases. Both AP and GvHD fit into orphan drug category with unmet medical need.
Preclinical studies summary: In pre-clinical studies, F-652 demonstrated expected bioactivity in vitro and in vivowith excellent pharmacokinetics and safety profile. A number of biomarkers were established in the preclinical models.
Phase I study in healthy subjects: A Ph I clinical study was conducted in Australia in healthy subjects. F-652 was well tolerated with a good safety profile and a very long half-life (> 200 hrs). F-652 showed potent bioactivity in human with induction of a number of biomarkers in a dose-dependent manner.
Phase I study in acute pancreatic patients: An IND was filed to the China FDA (CFDA). The Ph I clinical study is to evaluate the safety, PK and biomarkers in patients with acute pancreatitis.