GBA3

PORTO, Portugal, May 25, 2023 /PRNewswire/ -- 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 (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: 1 BIAL R&D (data on file) Logo: SOURCE Bial

Study results support the disease-modifying potential of GCase-targeting small molecule therapy for neuronopathic Gaucher disease BETHESDA, Md., Feb. 27, 2023 (GLOBE NEWSWIRE) -- Gain Therapeutics, Inc. (Nasdaq: GANX) (“Gain”, or the “Company”), a biotechnology company transforming drug discovery with its proprietary computational discovery platform identifying novel allosteric binding sites and creating small molecule treatments, presented new pre-clinical data from its Gaucher disease program in a poster presentation at the 19th Annual WORLDSymposium held February 22–26, 2023, in Orlando, Florida. The data generated in an animal model of neuronopathic Gaucher disease (nGD) show that GT-02329 restores β-glucocerebrosidase (GCase) activity, depletes accumulation of toxic lipid substrates, reduces neuroinflammation and improves neuromuscular function. “These data are a further validation of the disease-modifying potential of our GCase-targeting small molecule compounds in diseases caused by mutations of the GBA1 gene, including for the treatment of nGD and GBA1 Parkinson’s disease,” said Matthias Alder, Chief Executive Officer of Gain. “The consistency of the extensive preclinical data package we have generated with our GCase-targeting drug candidates is encouraging, and we remain on track to submit the dossier for the start of the Phase 1 clinical study with our lead GCase-targeting compound GT-02287 in mid-2023.” The effect of Gain’s small molecule structurally targeted allosteric regulators of GCase that act on lysosomal function was shown in studies conducted in the conduritol beta epoxide (CBE) mouse model. CBE is a covalent inhibitor that causes a reduction in GCase activity by reacting with the catalytic site of GCase and inactivating the GCase enzyme, which results in neurological features that occur in nGD patients, including the accumulation of the toxic lipid substrate glucosylsphingosine. The data presented in the poster titled “GT-02329, a structurally targeted allosteric regulator of GCase, restores GCase activity, reduces microgliosis and improves fine locomotor skills in the CBE model of neuronopathic Gaucher’s disease” demonstrated that: GT-02329 is orally bioavailable and brain penetrant, restored GCase activity, reduced accumulation of GCase substrates glucosylceramide and glucosylsphingosine, reduced a marker of inflammation (Iba-1), and improved neuromuscular function in a dose-dependent manner in CBE-injured mice treated with the compound. A PDF of the poster presented at the WORLDSymposium is available on the Science & Technology section of the Company’s website at . About Gaucher Disease Gaucher disease (GD) is a lysosomal storage disease characterized by deficiency in the β-glucocerebrosidase (GCase) enzyme encoded by mutated forms of the GBA1 gene. This causes the accumulation of toxic lipid substrates in the liver, spleen and bone marrow and, in neuronopathic GD (nGD), also in the nervous system. Current standard of care for GD, namely enzyme replacement therapy, does not cross the blood-brain barrier, leaving an unmet medical need for the development of novel therapies for nGD patients. Gain Therapeutics has applied its proprietary computational drug discovery platform, Site-directed Enzyme Enhancement Therapy (SEE-Tx®), to the development of small-molecule structurally targeted allosteric regulators (STARs) that bind to GCase, stabilize it, and restore its function. SEE-Tx® is a fast and cost-effective solution that has allowed us to discover STARs of the GCase enzyme that are orally bioavailable and brain-penetrant. About Gain Therapeutics, Inc. Gain Therapeutics, Inc. is transforming drug discovery with its proprietary computational discovery platform identifying novel allosteric binding sites and creating small molecule treatments to address unmet medical needs. The ability to identify never-seen-before allosteric targets on proteins involved in diseases across the full spectrum of therapeutic areas provides opportunities for a range of drug-protein interactions, including protein stabilization, protein destabilization, targeted protein degradation, allosteric inhibition, and allosteric activation. Gain’s pipeline spans neurodegenerative diseases, lysosomal storage disorders (LSDs), metabolic disorders, as well as other diseases that can be targeted through protein degradation, such as oncology. Gain’s lead program in Parkinson’s disease has been awarded funding support from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and The Silverstein Foundation for Parkinson’s with GBA, as well as from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and Innosuisse. For more information, please visit Cautionary Note Regarding Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify these statements by forward-looking words such as "may," "might," "will," "should," "expect," "plan," "anticipate," "believe," "estimate," "predict," "goal, " "intend," "seek, " "potential" or "continue," the negative of these terms and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. All statements, other than historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, statements regarding: the development of the Company’s current or future product candidates; expectations regarding timing for reporting data from ongoing preclinical studies or the initiation of future clinical trials, including the timing for completion of IND-enabling toxicology studies and submission of the dossier requirement for commencement of a Phase 1 clinical program for GT-02287 for GBA1 Parkinson’s disease and the potential therapeutic and clinical benefits of the Company’s product candidates; the selection and development, and timing thereof, of future programs, or any potential business development opportunities for product candidates; the Company’s financial position and ability to execute on the next phase of its strategy; and the Company’s anticipated cash runway guidance, including the ability for the Company’s current and projected cash to allow the Company to meet value inflection points. 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These statements are not historical facts but instead represent the Company's belief regarding future results, many of which, by their nature, are inherently uncertain and outside the Company's control.Many factors may cause differences between current expectations and actual results, including the impacts of the COVID-19 pandemic and other global and macroeconomic conditions on the Company’s business; clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials, clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; and unexpected litigation or other disputes. Other factors that may cause the Company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified in the sections titled “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in the Company’s Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission from time to time. New risks and uncertainties arise over time, and it is not possible for us to predict all such factors or how they may affect us. You should not place undue reliance on forward-looking statements. All information in this press release is as of the date of the release, and we are under no duty to update this information after the date of this release, except as required by law. You should not rely on it as representing our views as of any date subsequent to the date of this press release. Investor & Media Contact: Argot Partners (212) 600-1902 Gain@argotpartners.com