The US Food and Drug Administration (FDA) has granted clearance to Generon Corporation's Investigational New Drug (IND) application for a phase IIa study, entitled "Recombinant Human Interleukin-22-IgG2-Fc (F-652) in combination with systemic corticosteroids for the treatment of newly diagnosed grade II-IV lower gastrointestinal acute graft-versus-host disease in hematopoietic stem cell transplantation recipients.

F-652 was demonstrated to be safe in a phase I study conducted in Australia in healthy volunteers in 2013. In addition, F-652 showed good pharmacokinetic (PK) and biomarker profiles. The current phase II clinical programme is sponsored by Generon in collaboration with the Memorial Sloan-Kettering Cancer Center (MSKCC), New York, in which F-652 will be used to treat patients with acute graft versus host disease (aGvHD). The Phase IIa study is a single arm, open-label study to investigate the safety, tolerability, and PK of F-652 in combination with systemic corticosteroids in subjects who have undergone hematopoietic stem cell transplantation (HSCT) and have newly diagnosed with grade II-IV lower GI aGvHD.

F-652 will be administered once per week for four weeks. Subjects will be evaluated for safety and efficacy through day 180 and their survival status will be collected at day 365. The primary efficacy endpoint is to assess the lower GI aGvHD response rate at day 28. The study will also be conducted at MD Anderson Cancer Center in Houston, Texas and possibly expanded to other cancer centers in the US at a later time.

Dr Marcel RM van den Brink, head, Division of Hematologic Oncology of MSKCC said “Acute GvHD is a serious complication after allogeneic bone marrow transplantation and very difficult to treat. F-652 represents a novel approach focusing on the regeneration of the intestines rather than additional immune suppression. We are very excited to collaborate with Generon in the development of what promises to be a novel and exciting approach to acute GvHD.”

Dr David Lacey, chairman of Generon’s Scientific Advisory Board said “F-652 has previously shown that it is both potent and biologically active in healthy subjects. In the setting of acute GvHD, Generon will test whether this novel, IL-22-based molecule can provide clinical benefit to those suffering from this serious condition that can follow allogeneic bone marrow transplantation. This is the second molecule that Generon has placed into phase II clinical studies and this achievement further exemplifies both the power and successful deployment of the company’s DiKineTM platform.”

Dr Tom Tang, chief medical officer of Generon said “This is a true first-in-class molecule developed by a China-based biopharmaceutical company. The collaboration with the best cancer centers in the world sets a benchmark for the innovative biotech industry in China. This is the first clinical study with F-652 in patients. F-652 has multiple therapeutic potentials, we will continue to work with the top institutions to seek solutions for other unmet medical needs. ”

Generon has filed an IND in China to treat acute pancreatitis. It is currently under review by CFDA.

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 contrast to the current therapeutic approaches to treat aGvHD patients, F-652 mediated via STAT3 activation driven through IL-22 may protect gastric intestinal stem cells (ISCs) from dying during aGvHD, concurrent with the stimulation of intestinal epithelial regeneration. Therefore, F-652 may provide a novel and effective therapy, fulfilling an unmet medical need for patients with aGvHD.