Centre for Human Drug Research

VQ-101 is the first small molecule to demonstrate > 75% activation of the lysosomal enzyme glucocerebrosidase (GCase) in humansIn healthy volunteers, VQ-101 was well tolerated and achieved peripheral and cerebrospinal fluid (CSF) exposures supporting once daily dosingVanqua has initiated the Phase 1b portion of the study in patients with Parkinson’s disease (PD) with and without GBA mutations; data are expected in 2025Vanqua announces the expansion of its development team with the appointment of Maurizio Facheris, M.D., as Chief Medical Officer CHICAGO, Oct. 09, 2024 (GLOBE NEWSWIRE) -- Vanqua Bio, a clinical-stage biopharmaceutical company dedicated to discovering and developing next-generation medicines for the treatment of neurodegenerative diseases, announced positive results from its Phase 1 clinical trial of VQ-101, an orally administered, brain-penetrant, allosteric activator of GCase. The Phase 1a portion of the study evaluated safety, pharmacokinetics, and pharmacodynamics across single and multiple ascending doses in healthy volunteers. “We are excited to announce that VQ-101 demonstrated robust activation of lysosomal GCase and high levels of CSF exposure at doses that were safe and well tolerated in healthy volunteers. These data reflect the considerable efforts of an experienced team that is passionate about making a difference in the lives of people living with PD,” said Jim Sullivan, Ph.D., CEO of Vanqua Bio. “These results, paired with data from our preclinical patient-derived neuronal models, support the potential for VQ-101 to stop the accumulation of alpha synuclein in Parkinson’s patients and slow or stop disease progression. We are pleased to advance to the Phase 1b portion of the study in patients with PD.” The Phase 1a portion of the clinical trial, conducted at the Centre for Human Drug Research (CHDR) in the Netherlands, consisted of randomized, double-blind, placebo-controlled single and multiple ascending doses in healthy volunteers. The Phase 1b portion of the trial will include 28-day, randomized, double-blind, placebo-controlled treatment with multiple ascending doses of VQ-101 in patients with PD with and without GBA mutations. In healthy volunteers, VQ-101 activated lysosomal GCase by more than 75% in single dose cohorts, and activation was sustained following multiple doses. This exceeded the study’s target engagement goal of 50% activation, which was informed by human genetics and Vanqua’s preclinical studies in patient-derived dopaminergic neurons in which 50% activation of GCase resulted in significant blockade of the accumulation of insoluble alpha synuclein, the pathologic hallmark of PD. In addition to robust target engagement, VQ-101 achieved significant levels in the CSF; the mean CSF:unbound plasma ratios were ≥1, indicating full central nervous system penetrance. Lastly, in both the single and multiple ascending dose cohorts of this Phase 1a study, VQ-101 was well-tolerated, with no dose-limiting or serious adverse events reported. All treatment-emergent adverse events were mild or moderate in nature and there were no study discontinuations due to adverse events. Detailed data from the Phase 1 study will be presented at a future medical conference. In anticipation of advancing VQ-101 into later stage clinical studies, Vanqua also announced the appointment of Dr. Maurizio Facheris as the company’s CMO. Vanqua’s acting CMO, Dr. Jesse Cedarbaum, will continue to support the company as a senior clinical advisor. “We are grateful for Jesse’s contributions to Vanqua’s progress and are pleased that he will remain a key part of the Vanqua team,” said Jim Sullivan, Ph.D. “Maurizio brings first-hand experience of taking PD therapies from early phase development to approval and will be an excellent addition to our team.” Before joining Vanqua, Dr. Facheris was Senior Medical Director in Neuroscience Development at AbbVie, where he oversaw the clinical development of therapeutic approaches for PD, including successfully bringing foslevodopa/foscarbidopa for subcutaneous infusion to approval. Prior to that, he was Senior Associate Director of Research Programs at the Michael J. Fox Foundation for Parkinson’s Research. Dr. Facheris received his M.D. from the University of Brescia, Italy and attended his residency in Neurology at the University of Milano, Italy. About VQ-101 VQ-101 is a novel brain-penetrant small molecule allosteric activator of GCase. VQ-101 activates lysosomal GCase in a live-cell assay in vitro, ex vivo, and in vivo, and blocks the accumulation of insoluble alpha synuclein, which is the pathological hallmark of PD, in patient-derived neurons. About Vanqua Bio Founded in 2019 and headquartered in Chicago, Vanqua Bio is a biopharmaceutical company dedicated to discovering and developing next-generation medicines that have the potential to transform the lives of patients with neurodegenerative diseases. Our technology platform utilizes human genetics and patient-derived neuronal cells to identify, validate, and clinically translate novel disease pathways associated with lysosomal dysfunction or aberrant activation of the innate immune system. Initially, we are targeting glucocerebrosidase (GCase) as a potential treatment for Parkinson’s disease (PD). Additional programs address overactivation of the innate immune system in central and peripheral neurodegenerative disorders, including Alzheimer’s disease. For more information, go to www.vanquabio.com. Media Contact Alyssa PaldoFINN Partnersalyssa.paldo@finnpartners.com

CHICAGO, Sept. 18, 2024 (GLOBE NEWSWIRE) -- Vanqua Bio, a biopharmaceutical company dedicated to discovering and developing next-generation medicines for the treatment of neurodegenerative diseases, announced today that it will participate in the following scientific conferences: Grand Challenges in Parkinson’s Disease Symposium, September 23-24, Grand Rapids, MIVanqua Bio Poster Presentation Information: Title: A Validated Glucocerebrosidase Activity Assay Enables Measurement of in Vivo Target Engagement of Allosteric GCase Activators Session date and time: Monday, September 23, 12:30-2:30 p.m. ETPresenter: Daniel Ysselstein, Ph.D., Vice President, Biology, Vanqua Bio The International Congress of Parkinson's Disease and Movement Disorders®, September 27-October 1, Philadelphia, PACentre for Human Drug Research (CHDR) and Leiden University Medical Centre (LUMC), Leiden, the Netherlands and Vanqua Bio Presentation Information: Title: Inter- and Intra-day Variability in β-Glucocerebrosidase Activity and Pathway Biomarkers in Healthy Volunteers and Patients with Parkinson’s Disease with a GBA1 MutationSession date and time: Sunday, September 29, 1-3 p.m. ETPresenter: Jurrian van der Valk, CHDR, LUMC About Vanqua BioFounded in 2019 and headquartered in Chicago, Vanqua Bio is a biopharmaceutical company dedicated to discovering and developing next-generation medicines that have the potential to transform the lives of patients with neurodegenerative diseases. Our technology platform utilizes human genetics and patient-derived neuronal cells to identify, validate, and clinically translate novel disease pathways associated with lysosomal dysfunction or aberrant activation of the innate immune system. Initially, we are targeting glucocerebrosidase (GCase) as a potential treatment for Parkinson’s disease (PD). Additional programs address overactivation of the innate immune system in central and peripheral neurodegenerative disorders, including Alzheimer’s disease. For more information, go to www.vanquabio.com. Media ContactAlyssa PaldoFINN Partnersalyssa.paldo@finnpartners.com

Media Release IMP761 is designed to enhance the “brake” function of LAG-3 on T cells to restore balance to the immune system and address the underlying cause of many autoimmune diseasesSafety data from this first-in-human study anticipated by year-end and pharmacokinetics and pharmacodynamics data in first half CY2025 SYDNEY, AUSTRALIA, Aug. 14, 2024 (GLOBE NEWSWIRE) -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep” or “the Company”), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, today announces that the first participant has been successfully dosed in the first-in-human Phase I trial of IMP761. This first-in-class agonist LAG-3 antibody is designed to restore balance to the immune system by enhancing the “brake” function of LAG-3 to silence dysregulated self-antigen-specific memory T cells that cause many autoimmune diseases. The single and multiple ascending dose, placebo-controlled, double-blind Phase I study is being conducted by the Centre for Human Drug Research (CHDR), a world-class institute in Leiden, the Netherlands, specializing in cutting-edge early-stage clinical drug research. The study aims to enrol 49 healthy volunteers, to assess safety, pharmacokinetics (PK) and pharmacodynamics (PD). CHDR will implement its unique keyhole limpet haemocyanin (KLH) challenge model allowing for the evaluation of IMP761’s pharmacodynamic activity at the earliest stages of clinical development. Immutep anticipates the first safety data from the Phase I study to be available before end of the year with assessment of PK/PD relationships to follow in the first half of CY2025. The immune checkpoint LAG-3 has been identified as a promising target for agonist LAG-3 immunotherapy to treat rheumatoid arthritis, Type 1 diabetes, and multiple sclerosis, among other autoimmune diseases.1,2,3 In preclinical studies, IMP761 has led to a large decrease in inflammatory cytokines and demonstrated its effectiveness in suppressing antigen-specific T cell–mediated immune responses.4,5 About IMP761IMP761, a first-in-class immunosuppressive LAG-3 agonist antibody, has the potential to address the root cause of many autoimmune diseases by specifically silencing autoimmune memory T cells that accumulate at disease sites and restoring balance to the immune system. As published in the Journal of Immunology, encouraging pre-clinical in vivo and in vitro studies show IMP761 inhibits peptide-induced T cell proliferation, activation of human primary T cells, and an antigen-specific delayed-type hypersensitivity (DTH) reaction. Additional preclinical data in oligoarticular juvenile idiopathic arthritis (o-JIA) published in Pediatric Research details how IMP761 led to a decrease in a broad spectrum of effector cytokines in just 48 hours. This study also showed children with o-JIA have a skewed LAG-3 metabolism and suggested they can benefit from agonistic LAG-3 activity. About ImmutepImmutep is a clinical-stage biotechnology company developing novel LAG-3 immunotherapy for cancer and autoimmune disease. We are pioneers in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and our diversified product portfolio harnesses its unique ability to stimulate or suppress the immune response. Immutep is dedicated to leveraging its expertise to bring innovative treatment options to patients in need and to maximise value for shareholders. For more information, please visit www.immutep.com. Australian Investors/Media:Catherine Strong, Morrow Sodali+61 (0)406 759 268; c.strong@morrowsodali.com U.S. Investors/Media:Chris Basta, VP, Investor Relations and Corporate Communications+1 (631) 318 4000; chris.basta@immutep.com 1. Pedersen, J.M., Hansen, A.S., Skejø, C. et al. Lymphocyte activation gene 3 is increased and affects cytokine production in rheumatoid arthritis. Arthritis Res Ther 25, 97 (2023). https://doi.org/10.1186/s13075-023-03073-z2. Jones BE, Maerz MD et al. Fewer LAG-3+ T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes. J Immunol. 2022 Feb 1;208(3):594-602. doi: 10.4049/jimmunol.2100850. Epub 2022 Jan 12. PMID: 35022272; PMCID: PMC8820445.3. Zhou X, Gu Y et al. From bench to bedside: targeting lymphocyte activation gene 3 as a therapeutic strategy for autoimmune diseases. Inflamm Res. 2023 Jun;72(6):1215-1235. doi: 10.1007/s00011-023-01742-y. Epub 2023 Jun 14. PMID: 37314518.4. Mathieu Angin, Chrystelle Brignone, Frédéric Triebel; A LAG-3–Specific Agonist Antibody for the Treatment of T Cell–Induced Autoimmune Diseases. J Immunol 15 February 2020; 204 (4): 810–818. https://doi.org/10.4049/jimmunol.19008235. Sag, E., Demir, S., Aspari, M. et al. Juvenile idiopathic arthritis: lymphocyte activation gene-3 is a central immune receptor in children with oligoarticular subtypes. Pediatr Res 90, 744–751 (2021). https://doi.org/10.1038/s41390-021-01588-2