OGA

Biogen has two clinical-stage Alzheimer's disease assets behind Leqembi, both of which target tau proteins or their dysfunction. “What does it mean to be a leader in Alzheimer’s disease?” That’s the question Biogen is asking itself, and the question many of the company’s peers are working fervently to answer as the heated race to differentiate from the first batch of Alzheimer’s treatments turns to a simmer.  Adam Keeney, Ph.D., corporate development chief for the Leqembi co-maker, said in an interview with Fierce Biotech that Biogen is "not only just satisfied with [amyloid] beta" and instead "looking at the different pillars of disease." Keeney says the first stop on the portfolio-building circuit is tau. The company’s phase 2 antisense drug, BIIB-080, targets the protein buildup that accompanies amyloid beta in patients with Alzheimer’s. It’s an intrathecal injection—an injection into the spinal cord to bypass the blood-brain barrier— which Keeney described as “not ideal” though probably satisfactory for a first-generation option. But Biogen is planning for and think-tanking easier methods, like IV delivery and even oral compounds.  “We're thinking about degraders and molecular glues and different technologies that we can use,” Keeney said. Biogen already has one oral option in the clinic, the O-GlcNACase inhibitor BIIB-131, a small molecule that looks to block the enzyme research has tied to tau’s dysfunction in Alzheimer’s patients.  Keeney described oral delivery as a goal that’s on a “longer time horizon” routing the work back to the original question: What does it mean to be a leader in the space?  Biogen has experienced the ups and downs of Alzheimer's drug discovery more acutely than probably any company. Its well-documented Aduhelm failure came to a much-expected conclusion earlier this year, when Biogen wound down all work on the approved med. Not only was it made obsolete by Leqembi, but the therapy was a corporate representation of time wasted. Meanwhile, Eli Lilly pressed on from behind, raising up donanemab, which is expected to get an FDA ruling any day now.  The amyloid beta battle may not ultimately be an automatic reflection of tomorrow’s tau contest, or other options that may be discovered. Deeper into Biogen’s research work, the company is tinkering with novel anti-inflammatory targets, Keeney says. Targeting rogue tau buildup has proven difficult, just like amyloid. Lilly cut a phase 2 large-molecule zagotenemab in October 2021 after it failed to hit phase 2 endpoints. This followed phase 1 data showing four cases of brain bleeding (ARIA-H) across three patients, representing 19% of treated patients. Kenney says it remains to be seen whether that’s a genuine signal tied to tau-busting treatments—but it's certainly been an issue with Leqembi and donanemab.  “I think it's probably too early to say there's a signal or not in that,” he said. “We have no signal that is preventing us to move forward.”  Beyond drug development, critical advancements are happening in the Alzheimer’s diagnostic sector, with companies working to improve the tests that could detect amyloid buildup. There’s been such improvement in this area that a working group convened by the Alzheimer’s Association and the National Institute on Aging recently revised its criteria for diagnosing Alzheimer’s to include blood-based biomarkers. Keeney says those tests may not immediately be a primary diagnosis, but a negative result could preclude someone from an additional PET scan.  “So we're also investing and working with collaborators because there are blood-brain barrier biomarkers that are out there,” Keeney said, noting they aren’t yet 100% predictive. “We're helping also get the predictive validity improved.”  Despite the blood-based tests needing refinement, authors of the new testing criteria made clear that the future is now, and some tests provide “excellent diagnostic performance.” “The field is now in a transition phase during which plasma biomarkers are being integrated with traditional CSF and PET biomarkers,” the guidance states. 

Significant appointments of industry and academic experts to support Phase II development of ASN51 in Alzheimer's disease LAUSANNE, Switzerland and SAN FRANCISCO, March 6, 2024 /PRNewswire/ -- Asceneuron SA, a clinical stage biotech company dedicated to targeting the root causes of neurodegenerative diseases, today announces the appointments of neurodegenerative disease experts to its Scientific Advisory Board (SAB). These include Dr Samantha Budd Haeberlein, PhD, Henrik Zetterberg, MD, PhD, Rik Ossenkoppele, PhD, and Christopher van Dyck, MD. Asceneuron is advancing development of its lead asset ASN51 into Phase II clinical development targeting Alzheimer's disease. This compound is a potential best-in-class, orally administered, OGA inhibitor targeting tau aggregation. The Scientific Advisory Board members have vast experience in clinical trial design and biomarkers and will help support this promising program through Phase II clinical development. ASN51 has demonstrated its potential as a pathbreaker to halt disease progression in tau-mediated neurodegenerative diseases with its safe and well tolerated profile and sustained high central enzyme occupancy. In the field of Alzheimer's disease, ASN51 has the potential to change the treatment paradigm for patients when it commences a Phase II clinical trial in the second half of 2024. Ryan Schubert, Senior Vice President Research and Development at Asceneuron, said: "There is strong momentum in the Alzheimer's disease field, driven by recent progress and developments. This is an exciting stage for Asceneuron as tau is now clinically validated as a target. Our once daily, orally administered anti-tau O-GlcNAcase inhibitor, ASN51, has the potential to be best in class based on its unique pharmacology. I am honored to have these stellar neurodegenerative experts join our SAB at a fundamental time of development. Their deep knowledge and expertise will be invaluable as we move ASN51 into Phase II development." Dr Samantha Budd Haeberlein, PhD, is an esteemed figure in neurological drug development with international experience at research and executive levels in the discovery and development of therapeutics and biomarkers for neurodegenerative diseases. She was previously Senior Vice President and Head of Neurodegeneration at Biogen, where she led and co-led the development of two FDA approved treatments for Alzheimer's disease, ADUHELM and LEQEMBI. Samantha currently serves as the Chief Medical Officer at Enigma Biomedical Group, developing solutions for the treatment of neurodegenerative diseases, is on the Board of Directors at Vigil Neuro, and is a Senior Advisor to the ICG Life Sciences Investment team. Henrik Zetterberg, MD, PhD, is a decorated researcher in the field of neurodegenerative diseases. Henrik is a Professor of Neurochemistry at the University of Gothenburg, Sweden, and University College London (UCL), UK, and is a Clinical Chemist at Sahlgrenska University Hospital in Gothenburg, Sweden. He is Head of the Department of Psychiatry and Neurochemistry at the University of Gothenburg, leads the UK DRI Fluid Biomarker Laboratory at UCL, and is a Key Member of the Hong Kong Center for neurodegenerative diseases. He is also a Visiting Professor in the UW Department of Medicine, School of Medicine and Public Health, Madison, Wisconsin. Henrik has developed and researched new diagnostic tests and new preclinical models for Alzheimer's disease and has been recognised for his influential discoveries as a recipient of numerous prizes such as the Erik K. Fernström Prize for Junior Scientists and the Inga Sandeborg Prize for Research on Alzheimer's Disease. Rik Ossenkoppele, PhD, is a renowned academic in neuroscience, working at the intersection of neuroimaging, biomarkers, and cognition in Alzheimer's disease. Rik is an Associate Professor in Translational Neuroscience and is a Principal Investigator both at the Alzheimer center Amsterdam of the Amsterdam UMC and at Lund University in Sweden. Rik received the European Grand Prix for Research on the Foundation of Alzheimer's Disease in 2019, the Young Investigator Research award from Alzheimer Nederland in 2020, and the Queen Silvia Research prize in 2021. Christopher van Dyck, MD, is a leading clinical researcher focusing on neuroimaging and therapeutic studies of Alzheimer's disease and brain aging. He is a Professor of Psychiatry, Neurology, and Neuroscience and serves as Director of the Alzheimer's Disease Research Unit, the Alzheimer's Disease Research Center, and the Division of Aging and Geriatric Psychiatry at Yale School of Medicine. Alongside his academic positions, Christopher has extensive experience in leading and participating in more than 100 therapeutic trials in Alzheimer's disease, which include prodromal/ preclinical and brain aging stages. He serves on the Steering and Executive Committee and Co-Chairs the Protocol Evaluation Committee at the Alzheimer's Clinical Trials Consortium (ACTC). His extensive research has culminated in the lead authorship of the publication of the first disease-modifying treatment for AD (lecanemab) in 2023. About Asceneuron Asceneuron is a clinical stage biotech company focused on the development of orally bioavailable therapeutics for debilitating neurodegenerative disorders with high unmet medical need. The company's pipeline reflects its ambition and commitment to developing treatments for a wide a range of neurodegenerative diseases including Alzheimer's and Parkinson's disease, as well as orphan tauopathies. Asceneuron has two clinical-stage small molecule O-GlcNAcase inhibitors in development for the treatment of proteinopathies: OGA inhibitor ASN90 (licensed to Ferrer Pharmaceuticals) for the treatment of progressive supranuclear palsy (PSP) and a potential best-in-class OGA inhibitor, ASN51 for Alzheimer's disease. Asceneuron is backed by a renowned syndicate of investors consisting of Sofinnova Partners, M Ventures, SR One, Johnson & Johnson Innovation – JJDC, Inc. (JJDC) and Kurma Partners. For more information, please visit . SOURCE Asceneuron

New data advances understanding of new approaches to treating Alzheimer’s disease Research on disease progression could help inform future clinical trials CAMBRIDGE, Mass., March 04, 2024 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) announced it will present new data from its Alzheimer’s disease (AD) portfolio at the upcoming International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD™ 2024), taking place March 5-9 in Lisbon, Portugal and virtually. The presentations include new data for its oral small molecule inhibitor of tau aggregation (BIIB113), as well as presentations providing insights into the underlying mechanisms of Alzheimer’s disease. “These data reflect our approach of exploring multiple pathologies and modalities in Alzheimer’s disease to create a leading portfolio that can transform the course of Alzheimer’s care,” said Priya Singhal, M.D., M.P.H., Executive Vice President, Head of Development at Biogen. “Our ongoing investments in areas of Alzheimer’s research reinforce our commitment to push the boundaries of innovation and make a real difference in the lives of those affected by this complex disease.” Biogen presentations will provide new data on brain target engagement and the safety pro healthy volunteers of an oral small molecule O-GlcNAcase (OGA) enzyme inhibitor intended to reduce tau aggregation (BIIB113). In addition to BIIB113, Biogen is researching the potential of tau reduction in AD with its investigational antisense oligonucleotide targeting the microtubule associated protein tau (MAPT) gene (BIIB080). Other presentations will discuss the long-term efficacy of lecanemab as well as the presence of alpha-synuclein pathology in AD which could inform future research on its role in AD clinical progression. Key presentations include: Oral presentation: Results of the first in-human, randomized, blinded, placebo-controlled, single- and multiple-ascending dose study of BIIB113 in healthy volunteers. Friday, March 8, 9:55-10:10 AM GMT / 4:55-5:10 AM ET. Oral presentation: Distribution of Alpha-Synuclein co-pathology in MCI, mild Alzheimer’s disease and progressive supranuclear palsy clinical trial cohorts. Friday, March 8, 6:55-7:10 PM GMT / 1:55-2:10 PM ET. Oral presentation: Treatment with lecanemab disrupts tau accumulation across brain regions in early Alzheimer’s disease. Presented by Eisai. Thursday, March 7, 1:50-2:05 PM GMT / 8:50-9:05 AM ET. Oral presentation: Lecanemab for the treatment of early Alzheimer’s disease; the extension of efficacy results from Clarity AD. Presented by Eisai. Saturday, March 9, 9:10-9:25 AM GMT / 4:10-4:25 AM ET. On-demand oral presentation: A Neuro-Dynamic Quantitative Systems Pharmacology (QSP) Model for Alzheimer’s disease Incorporating Amyloid and Tau Pathophysiology, online. Poster presentation: Minimum Inclusion Criteria and Relation to Subsequent Cognitive Decline, P#0250, Wednesday, March 6, 9:00 AM GMT. E-poster presentation: Occupancy of BIIB113, an inhibitor of the enzyme O-GlcNAcase (OGA) in the human brain. BIIB080 is licensed from Ionis. About Biogen Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patient’s lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth. We routinely post information that may be important to investors on our website at . Follow us on social media - Twitter, LinkedIn, Facebook, YouTube. Biogen Safe Harbor This news release contains forward-looking statements, the potential clinical effects of lecenamab, BIIB113 and BIIB080; the potential benefits, safety and efficacy of lecenamab, BIIB113 and BIIB080; the clinical development program for lecenamab, BIIB113 and BIIB080; the identification and treatment of Alzheimer’s and Parkinson’s Diseases; our research and development program for the treatment of ALS; the potential of our commercial business and pipeline programs, including lecenamab, BIIB113 and BIIB080; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “potential,” “possible,” “will,” “would” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on our forward-looking statements. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation, uncertainty of success in the development and potential commercialization of lecenamab, BIIB113 and BIIB080; the risk that we may not fully enroll our clinical trials or enrollment will take longer than expected; unexpected concerns may arise from additional data, analysis or results obtained during our clinical trials; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of our drug candidates, including BIIB113 and BIIB080; the occurrence of adverse safety events; the risks of unexpected hurdles, costs or delays; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements. MEDIA CONTACT: Biogen Jack Cox + 1 781 464 3260 public.affairs@biogen.com INVESTOR CONTACT: Biogen Chuck Triano +1 781 464 2442 IR@biogen.com