Complexa Inc., a biopharmaceutical company developing therapies for fibrosis and inflammation-associated orphan conditions, recently announced the conclusion of a broad Phase 1 clinical development program for its drug candidate CXA-10, as well as plans to initiate three new clinical trials, including one that will address pulmonary arterial hypertension (PAH).
CXA-10 is an endogenous Nitro Fatty Acid (NFA) and Keto Fatty Acid (KFA) Anti-Fibrosis and Anti-Inflammation Cell Signaling modulator that targets the Nrf2 and NF-κB signaling pathways. Its promising anti-inflammation properties make it a potentially effective treatment for PAH, which is characterized by inflammation in the pulmonary vessels, leading to increased blood pressure in the lungs.
The four recently completed Phase 1 clinical trials assessing the safety of CXA-10 given to 97 patients in oral and intravenous formulations revealed that the compound was well tolerated. Results from these trials also showed that the therapy exhibited activation of objective gene expression and consequent inhibition of key fibrosis and inflammation biomarkers.
Based on the results observed in early trials, Complexa has initiated plans for Phase 2 clinical trials in pulmonary arterial hypertension (PAH) and focal segmental glomerulosclerosis (FSGS) — both targeted orphan diseases that involve the Nrf2 and NF-κB signaling pathways.
“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,” said Joshua Tarnoff, President and Chief Executive Officer of Complexa in a press release. “Our multi-pronged development program is focused on orphan indications with the potential for disease modification outcomes and rapid development paths.”
The Phase 1 clinical development program included a Phase 1b clinical trial featuring the application of CXA-10 via intravenous formulation in renal patients, which confirmed composite target gene activation. In a second Phase 1b clinical trial of CXA-10 given orally to patients with obesity, the composite exhibited positive clinical effects on key protein as well as in other biomarkers following repeat dosing.
In all four clinical trials, the composite was well tolerated and did not cause patients to experience serious adverse events, which demonstrates a favorable therapeutic index for the drug. Based on these results, the composite reached its human translational proof of concept and can now be evaluated in Phase 2 trials.
“To have this degree of pharmacological proof of concept in humans after only two weeks of dosing and to demonstrate these effects at predicted doses provides great confidence for the robust conduct of Phase 2 trials in FSGS and PAH,” said Complexa’s Chief Medical Officer, Diane Jorkasky, MD.
During the 2015 American Society of Nephrology Kidney Week that took place recently in San Diego, Complexa presented new data showing that CXA-10 demonstrated clinical benefits in cardiovascular and renal conditions. These results were determined in a DOCA model of cardiovascular and inflammatory oxidative stress mimicking the FSGS, an orphan renal condition.
The researchers established that the composite offered clinical benefit by acting on anti-oxidant, anti-inflammatory, and anti-fibrotic signaling pathways. As a result of these findings, the company believes that CXA-10 may offer a unique therapeutic benefit to treating those with PAH.