LRRK1

–Preclinical data for ARV-393 presented at the European Hematology Association 2024 Annual Congress showed anti-tumor activity in models of B-cell lymphoma – – Preclinical data presented at the Biennial International LRRK2 Meeting highlighted the promise of PROTAC®-induced leucine-rich repeat kinase 2 (LRRK2) degradation as a potential treatment for neurodegenerative diseases – NEW HAVEN, Conn., June 21, 2024 (GLOBE NEWSWIRE) -- Arvinas Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, today announced it presented new preclinical data from its investigational BCL6 PROTAC® degrader ARV-393 at the European Hematology Association (EHA) 2024 Annual Congress that took place June 13-16, 2024 in Madrid, Spain, and presented new preclinical data from its PROTAC LRRK2 degrader program at the Biennial International LRRK2 Meeting that took place June 18-21, 2024 in Crete, Greece. Data presented at EHA showed anti-tumor activity for the company’s investigational PROTAC BCL6 degrader, ARV-393, in preclinical models of B-cell lymphoma. In these preclinical models, ARV-393 potently and rapidly degraded the BCL6 protein and inhibited cell growth in diffuse large B-cell lymphoma (DLBCL) and Burkitt cell lines. ARV-393 showed tumor growth inhibition, including tumor regression, in various DLBCL cell line-derived xenograft (CDX) models and in multiple patient-derived xenograft (PDX) models of non-Hodgkin lymphoma (NHL), including germinal center B-cell-like (GCB), activated B-cell (ABC), GCB/ABC, BCL not otherwise specified (BCL/NOS) subtypes of DLBCL, and Burkitt lymphoma. “These new preclinical data for ARV-393 demonstrate that in these models it can effectively target and induce the degradation of the BCL6 protein that is commonly deregulated in DLBCL,” said John Houston, Ph.D., Chairperson, President, and Chief Executive Officer at Arvinas. “These encouraging results suggest that ARV-393 could be developed into a potential new treatment for patients with certain types of non-Hodgkin lymphoma, particularly those who have not responded to other treatments." Preclinical data presented at the Biennial LRRK2 Meeting highlighted the potential of the company’s oral PROTAC LRRK2 degraders to treat neurodegenerative diseases. Preclinical studies in mice demonstrated full target engagement of LRRK2 kinase inhibitor and near-complete LRRK2 degradation with PROTAC LRRK2 degraders, but substantially less Type II pneumocyte enlargement compared to an experimental LRRK2 kinase inhibitor. In addition, the more noticeable Type II pneumocyte enlargement phenotype observed with the experimental LRRK2 kinase inhibitor was substantiated by the accumulation of surfactant protein C in lung, which was not observed after treatment with a PROTAC LRRK2 degrader. “Nonclinical findings presented this week suggest the potential for a wide therapeutic index and manageable safety pro PROTAC degraders versus experimental LRRK2 kinase inhibitors,” said Angela Cacace, Ph.D., Chief Scientific Officer at Arvinas. “In earlier preclinical studies, Arvinas’ PROTAC LRRK2 degraders have been shown to cross the blood-brain barrier and degrade LRRK2, a large multidomain scaffolding kinase, in deep brain regions.” Arvinas’ oral PROTAC BCL6 degrader ARV-393 is currently in a phase 1 clinical trial in patients with NHL, and Arvinas also has an oral PROTAC LRRK2 degrader, ARV-102, currently being investigated in a phase 1 clinical trial in healthy volunteers. About ARV-393 ARV-393 is an investigational PROTAC designed to degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. The BCL6 protein facilitates B cell tolerance of rapid proliferation and somatic gene recombination via repressing cell cycle checkpoints, terminal differentiation, apoptosis, and the DNA damage response. PROTAC-mediated degradation has the potential to address the traditional undruggable nature of BCL6. ARV-393 is currently in a phase 1 clinical trial in patients with non-Hodgkin lymphoma. About ARV-102 ARV-102 is an investigational PROTAC designed to degrade Leucine-rich repeat kinase 2 (LRRK2) which is a large multidomain scaffolding kinase. Human genetics, increased activity and expressions of LRRK2 is genetically involved in the pathogenesis of neurological diseases including Parkinson’s Disease and progressive supranuclear palsy. Arvinas is developing oral, blood-brain-barrier penetrant PROTAC degraders of LRRK2. About Arvinas Arvinas (Nasdaq: ARVN) is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases. Through its PROTAC (PROteolysis Targeting Chimera) protein degrader platform, the Company is pioneering the development of protein degradation therapies designed to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. Arvinas is currently progressing multiple investigational drugs through clinical development programs, including vepdegestrant, targeting estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-102, targeting LRRK2 for neurodegenerative disorders; and ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin Lymphoma. Arvinas is headquartered in New Haven, Connecticut. For more information about Arvinas, visit us on , which does not form part of this release, and connect with us on LinkedIn and X. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the potential for Arvinas’ investigational BCL6 PROTAC degrader ARV-393 as a new treatment for patients with certain types of non-Hodgkin lymphoma, particularly those who have not responded to other treatments and its potential to address the traditional undruggable nature of BCL6; and the potential for Arvinas’ investigational PROTAC LRRK2 degraders (including ARV-102) to treat neurodegenerative diseases , and the potential for a wide therapeutic index and manageable safety profile. All statements, other than statements of historical facts, contained in this press release, including statements regarding Arvinas’ strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Arvinas may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on such forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements Arvinas makes as a result of various risks and uncertainties, including but not limited to: whether Arvinas will be able to successfully conduct and complete development for its product candidates, including ARV-393 and ARV-102, including whether Arvinas initiates and completes clinical trials for its product candidates and receives results from its clinical trials on its expected timelines or at all; Arvinas’ ability to protect its intellectual property portfolio; whether Arvinas’ cash and cash equivalent resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements; and other important factors discussed in the “Risk Factors” section of Arvinas’ Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent other reports on the U.S. Securities and Exchange Commission. The forward-looking statements contained in this press release reflect Arvinas’ current views with respect to future events, and Arvinas assumes no obligation to update any forward-looking statements, except as required by applicable law. These forward-looking statements should not be relied upon as representing Arvinas’ views as of any date subsequent to the date of this release. Contacts Investor Contact: Jeff Boyle, Arvinas Investor Relations +1 (347) 247-5089 Jeff.Boyle@arvinas.com Media Contact: Kirsten Owens, Arvinas Communications +1 (203) 584-0307 Kirsten.Owens@arvinas.com

This technology will support the development of Halia's new Alzheimer's disease drug, HT-4253, targeting a mediator of neuroinflammation called Leucine-rich repeat kinase 2 (LRRK2) LEHI, Utah, Feb. 6, 2024 /PRNewswire/ -- Halia Therapeutics, a pharmaceutical company at the forefront of developing neuroinflammation-targeting drugs, and Canary Speech, a leader in artificial intelligence vocal biomarker technology, today announced a collaboration to revolutionize the way Alzheimer's disease can be monitored and treated. This collaboration leverages Canary Speech's state-of-the-art AI vocal biomarker platform which utilizes advanced AI algorithms to analyze subtle changes in voice patterns and monitor cognitive function changes in Alzheimer's patients. This non-invasive, efficient method offers a revolutionary approach to tracking the progression of Alzheimer's disease and the effectiveness of treatments. Halia will integrate these insights to enhance the development and efficacy of its new Alzheimer's drug, HT-4253, targeting a mediator of neuroinflammation called Leucine-rich repeat kinase 2 (LRRK2), known for playing a critical role in driving pathogenesis in Alzheimer's disease progression. By focusing on this component, Halia aims to slow or even halt the progression of the disease, offering new hope to patients and families. "This collaboration is a significant step forward in our mission to address the challenges of Alzheimer's disease and advance the clinical development of HT-4253, which targets a unique component of neuro-inflammation," said David Bearss, CEO of Halia Therapeutics. "Canary AI-driven Speech technology will provide invaluable data to help us tailor our therapies more effectively and improve outcomes for patients with this debilitating neurodegenerative disease". "We are thrilled to be combining our pioneering AI technology with Halia's' expertise in drug development targeting neuro-inflammation," said Henry O'Connell, CEO and Co-founder of Canary Speech. "Our goal is to transform Alzheimer's patient care and provide a more nuanced understanding of how treatments impact cognitive function over time". About Canary Speech Canary Speech is the global leader in the speech digital biomarker industry by achieving real time vocal analysis on as little as 40 seconds of speech using smart devices. Canary Speech is seeking to advance speech and language applications for the hospital, health and wellness, and pharmaceutical markets. The Utah-based company enhances patient care and outcomes by improving access to care, quality of care and management of health conditions with its patented AI speech technology. Canary Speech technology also provides the opportunity to enhance telemedicine and remote medical services. For more information, visit . About HT-4253 HT-4253 is an orally administered small molecule with excellent brain penetration that targets a mediator of neuroinflammation called LRRK2. Chronic inflammation in the brain is a driver of several neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Halia scientists have shown that LRRK2 is an essential regulator of neuroinflammation. LRRK2 inhibition by HT-4253 could represent a new way to treat neurodegenerative diseases with an inflammation component by changing how the disease progresses. Halia Therapeutics plans to file for an IND with HT-4253 this year, with the goal of initiating a first-in-human phase 1 clinical trial by the end of 2024. About Halia Therapeutics, Inc. Halia Therapeutics is discovering and developing a pipeline of novel therapeutics to improve patients' lives with chronic inflammatory disorders and neurodegenerative diseases, with its initial programs targeting NEK7 and LRRK2. Halia's lead candidate, HT-6184, a novel NEK7/NLRP3 inhibitor, has completed a Phase 1 study ( NCT05447546) evaluating the safety and tolerability of HT-6184 when administered as single or multiple oral doses at escalating dose levels in healthy volunteer subjects. The company is headquartered in Lehi, Utah. For more info, visit or follow us on LinkedIn and Twitter (X). Company Contact: James Dye +1.385.355.4315 [email protected] Media Contact: Ignacio Guerrero-Ros, Ph.D. Russo Partners, LLC +1 (646) 942-5604 [email protected] SOURCE Halia Therapeutics