Pete Schmidt, MD, MSc, Chief Medical Officer of Portal Therapeutics, discusses data from the phase 2a GATEWAY trial testingPORT-77, an ABCG2 inhibitor, in patients with erythropoietic protoporphyria (EPP).
EPP is a rare congenital metabolic disorder characterized by an inborn error of porphyrin-heme biosynthesis. Signs and symptoms include painful cutaneous photosensitivity leading to blistering and scarring of the exposed skin areas, erythrodontia, red discoloration of urine, hemolytic anemia, and splenomegaly.
The phase 2a GATEWAY clinical trial (NCT06971900) was a blinded, randomized, placebo-controlled crossover trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamic effects on plasma protoporphyrin IX (PPIX) of PORT-77 in adults with EPP.
PORT-77 is a novel investigational oral, small molecule ABCG2 inhibitor designed to modify efflux of PPIX from the red blood cell to the plasma and from hepatocytes to the biliary tract.
A total of 19 patients enrolled and received placebo followed by 180 mg of PORT-77 oral suspension once daily (QD) or 300 mg twice daily (BID) for four days.
Results presented at the European Hematology Association (EHA) 2026 Congress highlighted the potential of PORT-77 in causing rapid, dose-dependent reductions in plasma PPIX. A mean decrease of 79% in plasma PPIX was observed in participants receiving 300 mg BID and 63% for those receiving 180 mg QD. These reductions were observed within hours of treatment in both dose groups with no rebound effect after dosing cessation. Additionally, these reduction rates were consistent across a broad range of baseline PPIX levels.
PORT-77 was well tolerated, with no serious adverse events, treatment discontinuations, or tolerability signals observed.
Based on these results, initiation of the global phase 2b/3 PATHWAY trial evaluating the safety and efficacy of PORT-77 in patients with EPP and XLP is expected in Q3 2026.
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To learn more about EPP and other rare metabolic conditions, visit https://checkrare.com/diseases/metabolic-disorders/
