pariceract (BIA 28-6156) / BIAL - LARVOL DELTA

Efficacy and Safety of the GCase Activator BIA 28-6156 in GBA-Associated Parkinson’s Disease: Results from the Phase 2b ACTIVATE Trial (MDS Congress 2026) - No abstract available

Clinical • Late-breaking abstract • P2b data • CNS Disorders • Movement Disorders • Parkinson's Disease

Mass balance and metabolism of BIA 28-6156, an allosteric activator of beta-glucocerebrosidase, in humans (MDS Congress 2026) - No abstract available

CNS Disorders • GBA

Clinical and Genetic Profile of the ACTIVATE Population: A Phase 2 Trial of BIA 28-6156 in GBA-PD (MDS Congress 2026) - No abstract available

Clinical • P2 data • CNS Disorders

Clinical Drug-Drug Interaction Profile Of BIA 28-6156: Results From Three Independent Phase I Studies (MDS Congress 2026) - No abstract available

Clinical • P1 data • CNS Disorders

Mass balance and metabolism of BIA 28-6156, an allosteric activator of beta-glucocerebrosidase, in humans (EAN 2026) - No abstract available

GBA

Clinical Drug-Drug Interaction Profile of BIA 28-6156: Results from Three Phase I Studies (EAN 2026) - No abstract available

Clinical • P1 data

BIA-28-6156-111: Phase I, Open-Label Study to Evaluate the Pharmacokinetics, Safety and Tolerability of BIA 28-6156 in Participants with Varying Degrees of Renal Impairment (clinicaltrialsregister.eu) - P1 | N=40 | Completed | Sponsor: Bial R&D Investments S.A. | Recruiting ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease • Renal Disease

Bial Reports Topline Results From ACTIVATE Phase 2b Study in GBA‑Associated Parkinson’s (Businesswire) - "Bial...announced today that the Phase 2b ACTIVATE study of BIA 28-6156 (pariceract) in patients with Parkinson’s who have a pathogenic variant in the GBA1 gene (GBA-PD) did not meet its primary, nor the key secondary efficacy endpoints, meaning that BIA 28-6156 failed to slow the progression of GBA-PD versus placebo. BIA 28-6156 proved to be generally well tolerated in the study, with no unexpected safety concerns arising...While the study data provide valuable scientific information and contribute to a broader understanding of Parkinson’s biology, BIA 28-6156 did not demonstrate significant differentiation from placebo on the primary or key secondary endpoints measured. Based on the lack of demonstrated efficacy in this study, Bial has made the decision to discontinue further development of BIA 28-6156 for this indication."

Discontinued • P2b data • Parkinson's Disease

Bial Announces Completion of Phase 2b ACTIVATE Study with BIA 28-6156 in GBA1-Associated Parkinson’s (Businesswire) - "Upon completion of the 78-week double-blind treatment period and all scheduled safety follow-ups, data cleaning and analysis are currently ongoing. Topline results will be released around the end of Q2...A status report on the ACTIVATE study was presented in an oral presentation at the 3rd International GBA1 Meeting 2026. The team is currently attending the 7th World Parkinson Congress, taking place in Phoenix from 24 to 27 May 2026....Translating Bial’s focus on Parkinson's Disease research and development, the company is also presenting two posters at the 7th World Parkinson Congress, highlighting patient perspectives on treatment routines and adherence, and new insights from a Phase IV study on opicapone’s effects on sleep and non-motor symptoms in Parkinson’s."

P2b data • P4 data • Trial completion • Parkinson's Disease

Compassionate Use for BIA 28-6156 in Patients With Parkinson's Disease (PD) Who Have a Pathogenic Variant in the GBA1 Gene (GBA-PD) and Completed the ACTIVATE Study (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Bial R&D Investments, S.A.

New trial • CNS Disorders • Movement Disorders • Parkinson's Disease

A Randomized, Double-Blinded, Placebo-Controlled QTc Study to Evaluate BIA 28-6156 Effect on Cardiac Repolarization in Healthy Volunteers. (PubMed, Clin Pharmacol Drug Dev) - "Participants received single doses of 60 or 150 mg BIA 28-6156, 400 mg moxifloxacin, or placebo in a cross-over design. No clinically significant effects on ECG parameters were observed, and BIA 28-6156 was generally well tolerated, with no deaths or serious AEs. This study concluded that BIA 28-6156 has no clinically relevant impact on ECG parameters, confirming a negative thorough QT/QTc study."

Clinical • Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • GBA • GBA1

BIA-28-6156-111: Phase I, Open-Label Study to Evaluate the Pharmacokinetics, Safety and Tolerability of BIA 28-6156 in Participants with Varying Degrees of Renal Impairment (clinicaltrialsregister.eu) - P1 | N=40 | Recruiting | Sponsor: Bial R&D Investments S.A.

New P1 trial • CNS Disorders • Movement Disorders • Parkinson's Disease • Renal Disease

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

P2b data • Trial status • Parkinson's Disease

Trial of BIA 28-6156 for GBA1 Parkinson’s patients hits milestone (Parkinson's News Today) - "More than 80% of the people with Parkinson’s disease caused by GBA1 gene mutations who are enrolled in a Phase 2 clinical trial have completed one year of treatment with Bial’s experimental candidate BIA 28-6156...The study, called ACTIVATE (NCT05819359), is assessing the treatment’s safety and efficacy at slowing the clinical progression of motor symptoms in people with Parkinson’s and GBA1 mutations compared with a placebo....The last participant is expected to complete their final visit by April 2026, with top-line results anticipated by June."

P2 data • Trial status • Parkinson's Disease

Key Milestone in ACTIVATE Phase 2 Clinical Trial of BIA 28-6156 (Businesswire) - "The ACTIVATE study has enrolled 273 genetically confirmed GBA-PD patients across 85 sites in Europe and North America. Seventy-three patients have already completed the double-blind treatment period of 78 weeks, and more than 80% of participants have now reached the one-year treatment milestone....The last visit of the last patient in the trial is expected by April 2026, with topline results anticipated in the second quarter of the same year."

P2 data • Trial status • Parkinson's Disease

HOW THE THERAPEUTIC APPROACH TO EARLY PARKINSON'S DISEASE WILL CHANGE IN THE NEXT FUTURE (ADPD 2025) - "Levodopa remains the most efficacious drug, a better preparation of levodopa like IPX 203 can ensure more stable plasma levels of Levodopa...Tavapadon is a new dopamine agonist stimulating D1-D5 receptors which concluded the phase III. Other compounds such as CVN424 (Cerevance) orally active and selective GPR6 inverse agonist, piperamat (IRLAB 752) a cortical enhancer to improve balance, Clenbuterol/Nadolol for cognition, mesdopetam a D3 antagonist are under investigation...These include the monoclonal antibody prasinezumab, UCB0599 and buntanetap small-molecules α-synuclein aggregation inhibitor, the vaccine ACI-7104.056 by AC immune...The LRKK2 kinase inhibitor BIIB122/DNL151 is in phase IIb in PD. BIAL BIA 28-6156 activator of the GCase enzyme is under investigation in patients with GBA mutation. The combination of symptomatic and disease modifying therapy, the use of accurate biomarkers and more precise treatment will be the future in the treatment of PD."

CNS Disorders • Movement Disorders • Parkinson's Disease • GBA

BIAL Announces First Patient Out in its Phase 2 Clinical Trial of BIA 28-6156 - a Novel Therapy for GBA1 Parkinson’s Disease (PRNewswire) - "BIAL...announced that the first patient has completed the full dose regimen in the ACTIVATE Phase 2 study....The ACTIVATE study...is a Phase 2, multicenter, randomised, double-blind, placebo-controlled study evaluating the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics of two fixed-dose levels (10mg/day and 60mg/day) of BIA 28-6156. Topline data from this Phase 2 study is expected to be released in mid-2026."

P2 data • Trial status • CNS Disorders • Parkinson's Disease

ACTIVATE: Efficacy, Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of BIA 28-6156 in GBA-PD (clinicaltrials.gov) - P2 | N=237 | Active, not recruiting | Sponsor: Bial R&D Investments, S.A. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Movement Disorders • Parkinson's Disease • LRRK2

A Randomized, Double-Blinded, Placebo-Controlled QTc Study to Evaluate BIA 28­6156 Effect On Cardiac Repolarization (EAN 2024) - "A single dose of 60 mg or 150 mg BIA 28-6156, 400 mg moxifloxacin or placebo was administered in fed state (Table 1). BIA-28-6156 doses were well tolerated, with a favorable safety profile. These results showed no clinically relevant effects on ECG parameters, constituting a negative thorough QT/QTc study."

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease • GBA

ACTIVATE: Efficacy, Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of BIA 28-6156 in GBA-PD (clinicaltrials.gov) - P2 | N=237 | Recruiting | Sponsor: Bial R&D Investments, S.A. | Trial completion date: Mar 2026 ➔ Jul 2026 | Trial primary completion date: Dec 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease • LRRK2

A structural perspective on the interaction between glucocerebrosidase and the positive allosteric modulator BIA 28-6156 (Neuroscience 2023) - "This residue is located in an unfolded loop of GCase structure that undergoes a conformational change and is stabilized by BIA 28-6156. A model for GCase with BIA 28-6156 in complex with Sap C is reported suggesting a role played by BIA 28-6156 in the interaction between both proteins and provides insights on the mechanism underling the observed positive allosteric modulation of GCase."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Parkinson's Disease

Design of a time-to-event study in GBA Parkinson’s Disease patients: Efficacy and safety of BIA 28- 6156, an allosteric activator of beta-glucocerobridase (GCase) (MDS Congress 2023) - "This time-to-event study will evaluate the efficacy and safety of a once-daily GCase activator, BIA 28-6156, as a disease-modifying therapy for GBA-PD patients."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Parkinson's Disease

Integrated safety analysis of BIA-28-6156 phase 1 clinical trials (a novel allosteric activator of beta- glucocerebrosidase) (MDS Congress 2023) - "BIA-28-6156 was well-tolerated and presented a favorable safety profile in healthy subjects and in GBA-PD patients. No relevant safety concerns were identified in completed phase I clinical studies."

Clinical • P1 data • CNS Disorders • Parkinson's Disease • GBA

BIAL R&D Announces First Patient Dosed in its Phase 2 Clinical Trial of BIA 28-6156 to Treat Parkinson's Disease Patients With a Pathogenic Variant in the Glucocerebrosidase (GBA1) Gene (PRNewswire) - "BIAL...announced the dosing of the first patient in its Phase 2 clinical trial...to evaluate the efficacy, safety, and tolerability of BIA 28-6156....The ACTIVATE study is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics of two fixed dose levels of BIA 28-6156 (10mg and 60mg/day). The trial will randomize approximately 237 genetically confirmed GBA-PD subjects to one of the three treatment arms, either 10mg, 60mg or placebo. This is a time to event study to assess the delay of meaningful clinical progression as assessed by the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II and Part III up to 78 weeks of double-blind treatment period. The ACTIVATE study is currently screening patients across sites in North America and planned to start in Q3.2023 in EU."

Trial status • CNS Disorders • Parkinson's Disease

A Phase 1B Trial in GBA1-Associated Parkinson's Disease of BIA-28-6156, a Glucocerebrosidase Activator. (PubMed, Mov Disord) - "These first-in-patient studies demonstrated that LTI-291 was well tolerated when administered orally for 28 consecutive days to patients with GBA-PD. Plasma and CSF concentrations that are considered pharmacologically active were reached (ie, sufficient to at least double GCase activity). Intracellular GluCer elevations were detected. Clinical benefit will be assessed in a larger long-term trial in GBA-PD."

Clinical • Journal • P1 data • CNS Disorders • Movement Disorders • Parkinson's Disease