PORT-77 / GondolaBio - LARVOL DELTA

Rapid, Dose-Dependent Reduction of Plasma Protoporphyrin IX With PORT-77 in Adults with Erythropoietic Protoporphyria: Results from the Phase 2a GATEWAY Study (EADV 2026) - "Clinical Relevance EPP is characterized by extreme light intolerance that profoundly impacts daily life. By substantially lowering circulating PPIX, the central mediator of phototoxic injury, PORT-77 has the potential to translate biochemical improvements into meaningful dermatologic benefit, including reduced pain, increased light exposure tolerance, and improved quality of life for patients with severe photodermatosis."

Clinical • P2a data • Genetic Disorders • Metabolic Disorders • ABCG2

Diagnostic Pivot in Porphyria: Subacute Liver Injury Revealing Underlying Erythropoietic Protoporphyria (ACG 2026) - "Case Description/ A 37 year old man with non-blistering photosensitivity since age 5 was diagnosed with PCT in 2021 on urinary porphyrins alone and started on hydroxychloroquine...Allogeneic HSCT, the curative option, was precluded by clinical instability; compassionate-use PORT-77 (ABCG2 transport inhibitor) was pursued as a porphyrin-lowering bridge...Liver transplant cannot correct the marrow defect; allograft recurrence is near-universal without HSCT. Bridging therapies, such as PLEX, RBC exchange, erythropoiesis-suppressing transfusion, and ABCG2 inhibition, reduce hepatic burden until HSCT is feasible."

Bone Marrow Transplantation • Cholestasis • Genetic Disorders • Hematological Disorders • Hepatology • Liver Failure • Metabolic Disorders • Rare Diseases • ABCG2

PATHWAY: A Study to Investigate PORT-77 Oral Dosing Compared With Placebo in Participants With Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP) (clinicaltrials.gov) - P2/3 | N=225 | Recruiting | Sponsor: Portal Therapeutics, Inc.

New P2/3 trial • Genetic Disorders • Metabolic Disorders

EPP: GATEWAY: A Phase 2a Study of PORT-77 in Adults With Erythropoietic Protoporphyria (clinicaltrials.gov) - P2 | N=28 | Completed | Sponsor: Portal Therapeutics, Inc. | Enrolling by invitation ➔ Completed | N=14 ➔ 28

Enrollment change • Trial completion • Genetic Disorders • Metabolic Disorders

RAPID, DOSE-DEPENDENT REDUCTION OF PLASMA PROTOPORPHYRIN IX WITH PORT-77 IN ADULTS WITH ERYTHROPOIETIC PROTOPORPHYRIA: RESULTS FROM THE PHASE 2A GATEWAY STUDY (EHA 2026) - "Figure 1. Mean Percent Reduction in Plasma PPIX Rapid, dose-dependent reductions in plasma PPIX, with greater lowering at 300 mg BID than 180 mg QD, consistent with dose-proportional PK and on-target suppression of plasma PPIX."

Clinical • P2a data • Cholestasis • Genetic Disorders • Hepatology • Metabolic Disorders • ABCG2 • FECH

Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study of PORT-77 Administered to Healthy Adult Participants (clinicaltrials.gov) - P1 | N=156 | Completed | Sponsor: Portal Therapeutics, Inc. | Recruiting ➔ Completed | N=108 ➔ 156 | Trial completion date: Aug 2025 ➔ Jan 2026 | Trial primary completion date: Aug 2025 ➔ Dec 2025

Enrollment change • First-in-human • Trial completion • Trial completion date • Trial primary completion date

PORT-77 is a potent inhibitor of ABCG2 that reduces efflux of protoporphyrin IX from erythrocytes of patients with protoporphyria and reduces plasma protoporphyrin IX levels in healthy human subjects (ASH 2025) - P1, P2 | "These in vitro studies using RBCs from EPP and XLP patients and in vivo observations in healthy humanvolunteers provide the first-ever human evidence that PORT-77-mediated inhibition of ABCG2 is sufficientto reduce efflux of PPIX from RBCs and lower plasma PPIX levels, respectively. These data in healthyhuman volunteers and patient-derived RBCs support further investigation of PORT-77 in the ongoingPhase 2 study (NCT06971900) of individuals with EPP."

Clinical • Cholestasis • Dermatology • Genetic Disorders • Hepatology • Metabolic Disorders • ABCG2

PORT-77, a Novel and Potent Inhibitor of ABCG2, Protects Against Skin Photo Toxicity and Liver Damage in a Mouse Model of Erythropoietic Protoporphyria (EPP) (ASH 2024) - "Conclusions In summary, in vitro pharmacology data and in vivo efficacy data in a mouse model of EPP provide a strong biological rationale for developing PORT-77 for the treatment of the patients with EPP. The safety and PK of PORT-77 are currently being evaluated in a phase 1 study."

Preclinical • Dermatology • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • ABCG2 • FECH

GondolaBio Receives U.S. FDA Orphan Drug and Fast Track Designations for PORT-77 for the Treatment of Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP) (Yahoo Finance) - "In preclinical and Phase 1 healthy volunteer studies, PORT-77 has demonstrated the ability to significantly lower plasma PPIX...PORT-77 is currently being investigated in the Phase 2A proof-of-concept trial, GATEWAY, with the primary endpoint of plasma PPIX reduction."

Fast track • Orphan drug • Genetic Disorders

EPP: GATEWAY: A Phase 2a Study of PORT-77 in Adults With Erythropoietic Protoporphyria (clinicaltrials.gov) - P2 | N=14 | Enrolling by invitation | Sponsor: Portal Therapeutics, Inc.

New P2 trial • Genetic Disorders • Metabolic Disorders

Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study of PORT-77 Administered to Healthy Adult Participants (clinicaltrials.gov) - P1 | N=108 | Recruiting | Sponsor: Portal Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2024 ➔ Aug 2025 | Trial primary completion date: Dec 2024 ➔ Aug 2025

Enrollment open • Trial completion date • Trial primary completion date