Bial Achieves Key Milestone in Phase 2b ACTIVATE Study of
BIA 28-6156 in GBA1-Associated Parkinson’s Disease

• 75% of patients have completed the Week 78 Last Study Visit
• Topline results expected in mid-2026

Bial, an innovation-driven biopharmaceutical company focused on neurosciences and rare diseases, today announced that 75% of patients currently enrolled in its ongoing Phase 2b clinical study ACTIVATE (ClinicalTrials.gov identifier: NCT05819359) have completed the double-blind treatment
period through week 78.

This operational milestone represents a significant step toward the completion of the ACTIVATE study, which is evaluating the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics of BIA 28-6156 in patients with Parkinson’s disease (PD) who have a pathogenic mutation in the glucocerebrosidase 1 (GBA1) gene
(GBA-PD).

The date of the Last Patient, Last Visit (LPLV) is anticipated in April 2026, with topline results on track to be released in mid-2026.

“We look forward to presenting data from our Phase 2b study. BIA 28-6156 is the leading asset in GBA-PD, and clinical outcomes are just around the corner,” said António Portela, CEO of Bial. “We are witnessing growing enthusiasm across the Parkinson’s community and are truly excited to be at the forefront of a potential and much-needed diseasemodifying treatment for people living with GBA-PD.”

The study is reporting strong patient retention, despite its long duration and complexity. This reflects the commitment of participating patients, as well as the high quality and robustness of study conduct across sites. As part of its commitment to transparency and patient engagement, Bial has maintained regular communication with trial participants through newsletters distributed via clinical sites every three to four months or upon achievement of key milestones.

“We are deeply grateful to the patients and their families for their extraordinary commitment, and to the global clinical community whose efforts continue to drive progress for people living with GBA-PD,” added António Portela.

Recruitment for the ACTIVATE study was completed ahead of expectations, with 273 genetically confirmed GBA-PD patients enrolled over approximately 18 months across 85 clinical sites in 11 countries throughout Europe and North America. This rapid recruitment underscores the strong engagement of the global Parkinson’s disease
community and highlights the substantial unmet medical need for disease-modifying therapies targeting GBA1-associated Parkinson’s disease.

PD is the second most common neurodegenerative disorder affecting more than 10 million people worldwide.⁽¹⁾ Between 5-15% of PD patients have mutations in the GBA1 gene, making it the largest genetic risk factor for PD.⁽²⁾

^{References
1- APDA, www.apdaparkinson.org/what-is-parkinsons, accessed October 30 2024
2- Smith L, Schapira AHV. Cells. 2022 Apr 8;11(8):1261
3- Gan-Or et al., 2015; Grabowski, 2008
4- den Heijer JM et al. Br J Clin Pharmacol. 2021 Sep;87(9):3561-3573;
5- Guedes L. et al. Integrated safety analysis of BIA-28-6156 phase 1 clinical trials (a novel allosteric activator of beta-glucocerebrosidase). Presented at the International Congress of Parkinson’s Disease and Movement Disorders (MDS), Copenhagen, Denmark. August 27–31, 2023}