A Phase One, Open Label, Multi-Dose Study To Evaluate the Safety, Tolerability, and Biologic Effects of Three Doses of IW001 in Patients with Idiopathic Pulmonary Fibrosis (IPF)

Purpose IW001, an oral solution of Type V collagen (col(V)), is a therapeutic agent in clinical development for IPF by ImmuneWorks. ImmuneWorks scientists believe that lung injury might result in the exposure of a normally hidden protein to the immune system, such as col(V). The immune system may recognize this sequestered protein as foreign, initiating an autoimmune cascade, resulting in an attack on the lung. As the autoimmune response expands, a fibrotic response would follow in an attempt to heal the lung. Lung transplantation is the only viable treatment that has shown survival benefit for IPF patients but the survival benefit is still complicated by significant early mortality rates, especially within the first year. High incidence of col(V) autoreactivity was found with IPF patients and associated with a higher incidence of PGD. Pre-clinical studies showed that col(V)-induced immune tolerance abrogated acute rejection in a rat lung transplant model. Methods and Materials ImmuneWorks conducted an open label, multicenter, Phase I clinical trial in IPF patients who tested positive for anti-col(V) antibodies. Study was designed to evaluate the safety, tolerability, and biological/clinical effects of a three doses (0.1mg, 0.5mg, 1.0mg) of IW001, when administered once daily orally for 24 weeks. Results About 40% of IPF patients screened for this study tested positive for anti-Col(V) IgG. A total of 30 IPF patients were enrolled in one of three IW001 dose treatment groups. Absolute changes in %FVC pred from baseline to week 24 were determined and showed a trend toward the stabilization of the lung function with IW001 doses at both 0.5mg and 1.0mg/day. Additional biomarkers will be discussed. Conclusions Our phase I results have demonstrated that IW001 is safe and well tolerated with no unexpected adverse events. IW001 may lead to a possible stabilization of lung function, underscoring the potential of col(V)-induced tolerance to be an effective therapeutic strategy in IPF.