Complexa Inc., a biopharmaceutical company developing therapies to treat fibrosis and inflammation-related diseases, announced the successful completion of a Phase 1 clinical program of its lead drug candidate CXA-10, and the beginning of preparations for Phase 2 clinical trials for focal segmental glomerulosclerosis (FSGS) and pulmonary arterial hypertension (PAH) in 2016.
The announcement builds on a growing trend in PAH drug development that targets inflammation. Data on the cardiovascular and renal benefits obtained by administering CXA-10 to patients was recently presented at the 2015 American Society of Nephrology’s Kidney Week.
CXA-10 is described by the company as an endogenous nitro-fatty acid (NFA) modulator of Nrf2 and NF-κB, which has been shown in early studies to impact the core of fibrotic and inflammatory pathways. It modulates the activity of two key inflammatory signaling pathways, blocking the activity of NF-κB (nuclear factor kappa B), the body’s main pro-inflammatory pathway that is chronically active in many inflammatory diseases (such as PAH), and inducing Nrf2 activity, a key pathway in the cellular defense against inflammation and oxidative stress.
The recently completed Phase 1 program included four studies, a Phase 1b trial of intravenous (IV) CXA-10 and a Phase 1b trial of oral CXA-10 in obese patients with inflammation. The lead candidate demonstrated safety and tolerability in all 97 participants, with both oral and intravenous administrations. The therapy was also shown to be effective in targeting gene expression and inhibition of inflammatory, oxidative, and fibrotic molecular pathways without any serious adverse side effects.
The promising results obtained in the Phase 1 trials, along with previous substantial animal model studies and the demonstrated endogenous mechanism of the drug, support the development of Phase 2 trials for CXA-10. Complexa has designed three Phase 2 clinical trials that will focus on orphan diseases with key dysregulation of the Nrf2 and NF-κB: a trial studying the effect of oral CXA-10 in FSGS, a study of oral CXA-10 in PAH, and a Phase 1B/2A study of CXA-10 in sickle cell crisis (IV administration) and sickle cell disease (oral).
Joshua Tarnoff, President and Chief Executive Officer of Complexa, said in a press release, “We and our investigators are impressed by the translational preclinical and Phase 1 data we have seen for CXA-10 as well as the differentiated therapeutic profile that the endogenous mechanism appears to provide. Our multi-pronged development program is focused on orphan indications with the potential for disease modification outcomes and rapid development paths.”