Complexa Announces Presentation of Phase 1 Data Evaluating Lead Candidate CXA-10 as a Disease-Modifying Therapy in Pulmonary Arterial Hypertension at PHA’s 2018 International PH Conference
- Data demonstrate favorable safety and pharmacological profile of oral CXA-10 and confirm recommended dose range for Phase 2 development -
BERWYN, PA, June 28, 2018 – Complexa Inc., announced today the presentation of data evaluating the pharmacology of the company’s lead candidate, CXA-10, as a disease-modifying agent in pulmonary arterial hypertension (PAH) at the Pulmonary Hypertension Association’s 2018 International PH Conference, which was held from June 28-July 1, 2018 in Orlando. CXA-10 is the first drug of a novel pharmacological class of oral compounds called nitro fatty acids (NFAs) in development for PAH, a progressive disorder characterized by high pressure in the arteries of the lungs without a known cause.
The PHA International Conference Abstract titled “Use of an Obese Population in Phase 1 to Evaluate the Pharmacology of Oral CXA-10, an Endogenous Nitrated Fatty Acid Signaling Agent as a Disease-Modifying Therapy in Pulmonary Arterial Hypertension” was presented in a poster session on June 28, 2018. The primary objective of the study was to evaluate the pharmacology of CXA-10 in an obese population as a surrogate for diseases with activated inflammatory and impaired metabolic pathways like PAH and to identify a dose range for Phase 2 clinical development. Key inﬂammatory and metabolic biomarkers selected for this study were serum MCP-1, IL-6, leptin and lipids (e.g. triglycerides, cholesterol), which have been shown to be highly prevalent in obese individuals.
“We are encouraged by the results from this Phase 1 study of our novel NFA compound CXA-10. They support further clinical development and evaluation of CXA-10’s potential as a disease-modifying therapy in PAH,” said Francisco Salva, President and Chief Executive Officer of Complexa. “Based on the favorable pharmacological findings from this study, we identified the recommended dose range for a Phase 2 clinical trial of oral CXA-10 for which patient recruitment is underway.”
In this Phase 1 randomized, double-blind, placebo-controlled study of multiple ascending doses of oral CXA-10, male patients who were considered obese according to their body mass index (BMI ≥ 27 and ≤ 40 kilograms/meters squared) were treated with CXA-10 once daily for 14 days. The study involved three treatment cohorts in doses ranging from 25 mg, 150 mg and 450 mg. Pharmacokinetics and biomarkers were assessed prior to dosing and at various times throughout the study. The study demonstrated consistent decreases on several relevant biomarkers including MCP-1, IL-6, leptin, cholesterol and triglycerides at a dose of 150 milligrams (mg) of CXA-10, administered orally once daily. These changes were observed as early as two weeks after dosing. For MCP-1 and triglycerides, the changes from placebo were statistically significant in the 150 mg dose group while the mean change from baseline in IL-6 concentrations showed a decreasing trend.
CXA-10 was safe and tolerated up to a 450 mg dose. Dose-limiting tolerability of diarrhea and nausea was observed at the 450 mg dose but was reduced with food. There were no changes in vital signs, physical examinations or weight and no electrocardiogram (ECG or EKG) or heart rate abnormalities.
More information about the Phase 2 trial in PAH, called PRIMEx, is available at www.clinicaltrials.gov, identifier NCT03449524.
Complexa Inc. is a patient-focused, science-driven, clinical stage biopharmaceutical company developing a novel class of compounds, nitro fatty acids (NFAs), for the safe and effective treatment of debilitating fibrotic and inflammatory diseases. NFAs have demonstrated broad potential to be effective therapeutic agents in multiple disease indications in which oxidative stress, inflammation, fibrosis and/or direct tissue toxicity play significant roles. This class of molecules has the potential to be disease-modifying in many disorders, given NFAs’ broad activity. An experienced consortium of investors, including Andera Partners, HBM Healthcare Investments, JAFCO, New Enterprise Associates (NEA) and Pfizer Venture Investments have committed funding to advance a platform of NFA agents across multiple orphan disease indications. Complexa’s lead candidate, CXA-10, is currently in Phase 2 development for focal segmental glomerulosclerosis (FSGS) and pulmonary arterial hypertension (PAH). For more information, visit www.complexarx.com.
CXA-10 is an oral NFA compound which impacts the fibrotic and inflammatory pathways. CXA‑10 acts through key reparative, metabolic and inflammatory pathways, including upregulation of the Nrf2 pathway and inhibition of Nuclear factor-kappa B and Toll-Like Receptor 4 pathways. In addition, CXA-10 increases the expression of heat shock proteins, which act as chaperones during cellular stress, and inhibits xanthine oxidoreductase to reduce oxidative stress. In five Phase 1 clinical trials, CXA-10 demonstrated target engagement at the specific doses being used in Phase 2, and was shown to be tolerable and safe in more than 100 subjects. Importantly, CXA-10 has demonstrated impact on relevant biomarkers of pharmacological action as well as inhibition of key biomarkers of disease-related inflammation and fibrosis.
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