GondolaBio Reports Positive Phase 2a Results for PORT-77 in EPP

GondolaBio has reported positive results from the Phase 2a GATEWAY trial (NCT06971900) evaluating PORT-77 in patients with erythropoietic protoporphyria (EPP), with the investigational therapy meeting its primary endpoint and producing rapid, substantial reductions in plasma protoporphyrin IX (PPIX) levels. The findings support continued development of PORT-77 as a potential disease-modifying treatment for EPP and X-linked protoporphyria (XLP).

The data were presented at the European Hematology Association (EHA) 2026 Congress and will support the planned initiation of the global Phase 2b/3 PATHWAY trial in the third quarter of 2026.

Trial Meets Primary Endpoint

The blinded, randomized, placebo-controlled crossover Phase 2a GATEWAY study enrolled 19 adults with EPP to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of PORT-77. Participants received placebo followed by either PORT-77 180 mg once daily or 300 mg twice daily for four days.

PORT-77 met the study’s primary endpoint, achieving rapid and dose-dependent reductions in plasma PPIX, a key biomarker of disease activity in EPP and XLP. Mean plasma PPIX levels decreased by 79% in participants receiving the 300 mg twice-daily regimen and by 63% in those receiving the 180 mg once-daily regimen.

According to GondolaBio, plasma PPIX reductions were observed within hours of treatment initiation, remained consistent across a broad range of baseline levels, and showed no rebound after treatment cessation.

Pete Schmidt, M.D., M.Sc., Chief Medical Officer of Portal Therapeutics, said the findings highlight PORT-77’s potential as a disease-modifying therapy for EPP and XLP, noting the rapid reductions in plasma PPIX and the possibility of improved sunlight tolerance and quality of life for patients.

Favorable Safety Profile

PORT-77 was generally well tolerated, with no serious adverse events, treatment discontinuations, or significant tolerability concerns reported during the study. The company also reported a lower rate of treatment-emergent adverse events during PORT-77 treatment periods compared with placebo.

The safety findings were consistent with previous clinical experience and support advancement into later-stage development.

Potential Disease-Modifying Approach

PORT-77 is an oral small-molecule ABCG2 inhibitor designed to address the underlying biology of EPP and XLP by modifying the transport of PPIX. The company believes the rapid and substantial reductions in plasma PPIX observed in the study may ultimately translate into improved sunlight tolerance and quality of life, although these outcomes will require confirmation in larger clinical trials.

Advancing Toward Registrational Development

Following the Phase 2a results and recent End-of-Phase 2 discussions with the U.S. Food and Drug Administration, GondolaBio reported general alignment with the agency on the development strategy for PORT-77.

The company plans to initiate the global Phase 2b/3 PATHWAY trial in patients with EPP and XLP in Q3 2026. In parallel, GondolaBio is conducting the stEPP observational study to further characterize disease burden, phototoxicity, sunlight exposure, and plasma PPIX variability in affected patients.

EPP and XLP are rare genetic disorders characterized by the accumulation of PPIX, resulting in severe photosensitivity, debilitating pain following sunlight exposure, and an increased risk of liver complications. According to GondolaBio, more than 25,000 people across the United States and European Union are affected by these conditions, for which no approved disease-modifying therapies currently exist.

What This Means for Patients

For people living with erythropoietic protoporphyria (EPP) and X‑linked protoporphyria (XLP), the Phase 2a results for PORT‑77 provide early evidence of a therapy that addresses the root cause of disease rather than only managing symptoms. By rapidly lowering plasma protoporphyrin IX (PPIX) the compound that drives painful reactions to sunlight and liver complications PORT‑77 may expand sunlight tolerance and ease daily limitations. Larger studies are still needed to confirm long‑term benefits, but the positive findings and planned Phase 2b/3 trial mark an important step toward a disease‑modifying option for patients who currently lack treatments that directly target the biology of EPP and XLP.

Reference

GondolaBio Announces Positive Phase 2a Results Demonstrating 79% Plasma Protoporphyrin IX Reduction and Disease-Modifying Potential of PORT-77 for Erythropoietic Protoporphyria • Gondola Bio