Complexa Presents Data Evaluating the Pharmacological
Action of CXA-10 on Drug-metabolizing Transport Proteins at 2018 American College of Clinical Pharmacology Annual Meeting
- Data demonstrate the pharmacological activity of CXA-10 at 150 mg daily dose -
BERWYN, PA, September 24, 2018 – Complexa Inc., announced today the presentation of data evaluating the pharmacological action of the company’s lead candidate, CXA-10, on drug-metabolizing transport proteins at the 2018 Annual Meeting of the American College of Clinical Pharmacology (ACCP), taking place September 23–25, 2018 in Bethesda, Maryland. CXA-10 is the first drug of a novel pharmacological class of oral compounds called nitro fatty acids (NFAs) in development for the treatment of focal segmental glomerulosclerosis (FSGS) and pulmonary arterial hypertension (PAH).
The ACCP Abstract titled “A Study to Explore the Effects of CXA-10 on the Pharmacokinetics of a Cocktail of Transport Protein Substrates via the Pharmacological Action of CXA-10 on Nrf2” was presented in a poster session on September 24. The primary objective of the study was to assess CXA-10’s pharmacological action on nuclear factor erythroid-derived 2 (Nrf2)-related transport proteins by evaluating a potential pharmacokinetic interaction of CXA-10 with a cocktail of cholesterol-lowering drugs. CXA-10 has been shown to activate Nrf2 through post-translation modification.
“The data presented at ACCP are important because they provide an understanding about how the pharmacological activity of CXA-10 affects the metabolism of certain cholesterol-lowering drugs to help guide dose adjustments and ensure safety of concomitant administration,” said Francisco Salva, President and Chief Executive Officer of Complexa. “We are especially pleased that our poster was named winner of the ACCP New Member Abstract Award and we look forward to sharing the results of this study which demonstrate the pharmacological activity of a 150 mg daily dose of CXA-10.”
The mechanism of action of CXA-10 involves Nrf2 activation. Nrf2 activation has been shown to affect several drug metabolizing enzymes and transport proteins. Statins and cholesterol absorption inhibitors, which are commonly prescribed in patients with FSGS and PAH, are known substrates for Nrf2‑related transport proteins and enzymes. Therefore, the study involved a cocktail of the cholesterol-lowering drugs, Vytorin® (20 mg simvastatin/10 mg ezetimibe) and pravastatin (40 mg), to investigate the effects of Nrf2 activation following steady-state administration of CXA-10.
In this single-center, randomized, open-label study, ten healthy male participants received a 40 mg dose of pravastatin on Day 1 and Vytorin® (20 mg simvastatin/10 mg ezetimibe) on Day 2. Subjects then received a once-daily, oral dose of 150 mg CXA-10 for seven days (Days 4 -10). On Day 11, subjects received CXA-10 (150 mg) with pravastatin (40 mg) and on Day 12, subjects received CXA-10 (150 mg) with Vytorin® (20 mg simvastatin/10 mg ezetimibe). Plasma concentrations were measured before and after steady-state administration of CXA-10 for pravastatin, simvastatin, and ezetimibe. Although conclusions about the potential for drug-drug interactions could not be definitively made, the study showed that mean Cmax and AUC levels (measurements of drug exposure) increased or decreased following co-administration with CXA-10. These effects of CXA-10 on a cocktail of cholesterol lowering drugs were supportive of the pharmacological of action of CXA-10 on Nrf2 and confirmed that CXA-10 at a once daily dose of 150 mg is pharmacologically active in humans.
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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