PORTO, Portugal I May 25, 2023 I BIAL – R&D Investments S.A (BIAL R&D), a subsidiary of BIAL Holding, S.A., today announced the dosing of the first patient in its Phase 2 clinical trial (ACTIVATE study) to evaluate the efficacy, safety, and tolerability of BIA 28-6156.

BIA 28-6156 is an allosteric activator of the enzyme beta-glucocerebrosidase (GCase) for the treatment of patients with Parkinson’s disease (PD) who have a mutation in the glucocerebrosidase 1 (GBA1) gene (GBA-PD).

Parkinson’s disease is the second most common neurodegenerative disorder and the GBA1 gene mutations are identified as the most common genetic risk factor of the disease.

Dosing of the first patient in our Phase 2 clinical trial represents a major milestone in the clinical development of BIA 28-6156 for the treatment of Parkinson’s disease patients with a genetic validated risk factor as GBA1 gene mutation. Activation of GCase enzymatic activity via allosteric modulation with BIA 28-6156 offers a novel potential treatment for patients with GBA-PD as well as a promising new approach to delay clinical motor progression. Data from nonclinical settings, including data from human cells, suggest that activation of GCase enzymatic activity could provide therapeutic benefit to patients with PD who carry a GBA-PD risk-associated variant in the GBA1 gene.1“, commented Nuno Mendonça, Chief Medical Officer of BIAL

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 trial will enrol subjects with PD diagnosed between 1 to 7 years before genetic screening, a modified Hoehn and Yahr score ≤2.5, and a score of ≥22 on the Montreal Cognitive Assessment. Subjects must be receiving a stable dose of PD medication and will continue to receive it throughout the study.

The ACTIVATE study is currently screening patients across sites in North America and planned to start in Q3.2023 in EU.

For more information regarding the trial design, please see www.clinicaltrials.gov  (identifier: NCT05819359).

About BIA 28-6156

BIA 28-6156 (formerly called LTI-291 or LTI-00291) is a novel allosteric activator of beta-glucocerebrosidase (GCase) that is being developed by BIAL R&D for the proposed indication of treatment of Parkinson’s disease (PD) in patients with a mutation in the glucocerebrosidase 1 (GBA1) gene (GBA-PD).

BIA 28-6156 is a small molecule, for oral administration, once-daily that has been designed to have a low toxicity profile with the ability to cross the blood brain barrier, features that were validated in vitro and in vivo experiences and extensive toxicology studies.

About BIAL R&D

BIAL – R&D Investments S.A. (BIAL R&D), a Portuguese Company, is a subsidiary of BIAL Holding, S.A. and part of the BIAL Group (BIAL), dedicated to the conduction and management of research projects with the objective of discovering new drugs for human use.

BIAL – R&D is also the owner of intellectual property relating to proprietary pharmaceutical compounds for neurodegenerative diseases, namely Parkinson’s disease, at various stages of clinical development, such as, a small molecule activator of GCase enzyme referred to internally as BIA 28-6156; BIAL – R&D, as part of BIAL, benefits from the BIAL expertise, knowledge, and long experience, namely, in discovery, development and clinical activities.

About BIAL

BIAL is an innovation-driven pharmaceutical company aiming to improve people’s lives worldwide. With 99 years of experience, BIAL is strongly committed to therapeutic innovation, consistently investing over 20% of its annual turnover in R&D, in which neurosciences is its major area of research.

Based on its own innovative medicines and with a consistent partnering program, BIAL has extended its presence worldwide. The company has ten affiliates in three different continents – Europe, America and Africa – and its products are present in fifty countries, fulfilling its purpose of making a real difference in the lives of people all over the world.

For more information about BIA28-6156, please click here

For more information about BIAL, please visit: www.bial.com

1 BIAL R&D (data on file)