Biogen Inc.: New Data from Biogen's Investigational Antisense Oligonucleotide (ASO) Targeting Tau Shows Promise for Potential New Generation of Treatments in Early Alzheimer's Disease

• In the Phase 1b study, favorable trends were reported for the high-dose groups on multiple measures of cognition and function.
  
• First study of a tau targeting drug that shows reduction of aggregated tau pathology and favorable trends on clinical outcomes.
• Recruitment is underway for the Phase 2 CELIA study further investigating clinical efficacy and safety.
  

CAMBRIDGE, Mass., Oct. 25, 2023Inc.which showed a reduction of tau protein in the cerebral spinal fluidat the 2023 Clinical Trials on Alzheimer's Disease (CTAD) meeting held in Boston, MA from October 24-27.

In AD, both tau and amyloid beta are linked to disease progression.¹ Tau protein can form tangles which progressively accumulate in brain regions involved in cognition.² The accumulation of pathological tau tangles has been shown to lead to neuronal loss. ASO therapies are seen as promising tools for modulating production of disease-associated proteins. Currently, the ASO approach underpins more than 60 treatments approved or in clinical trials for a variety of disease areas including a range of cancers, viral illnesses, and genetic conditions.³

"This is the first time we've seen both strong target engagement and favorable trends on clinical outcomes with a novel mechanism targeting tau," said Priya Singhal, M.D., M.P.H., Head of Development at Biogen. "While these are preliminary findings, we are excited about these results and continue to enroll the Phase 2 CELIA study. We believe defeating Alzheimer's disease will take different approaches and we are committed to exploring the targeting of tau as a new generation of treatment."

In results presented at CTAD, favorable trends were observed on the global Clinical Dementia Rating Sum of Boxes (CDR-SB), Mini-Mental State Exam (MMSE) cognitive scales and Functional Activities Questionnaire (FAQ) at week 100 in groups treated with a high-dose of BIIB080 (n=16). The results build on data presented at the International Conference on Alzheimer's and Parkinson's Disease (ADPD^TM 2023) which showed that direct targeting of tau protein production had a substantial impact on tau biomarkers, reducing total and phosphorylated tau in the CSF and aggregated tau pathology as measured by PET across all brain regions assessed. The favorable trends suggest a potential link between a reduction in tau PET pathology and clinical outcomes.

Treatment was generally well tolerated throughout the study. The majority of adverse events were mild or moderate in severity, of which the most common were headache, back pain, pain in extremity, post-lumbar puncture syndrome and procedural pain.

BIIB080 is designed to target microtubule-associated protein tau (MAPT) mRNA and reduce production of tau protein. The Phase 1b trial and its long-term extension study (LTE) were designed to assess the safety and tolerability of multiple doses in patients with mild dementia due to AD. Participants were randomized to placebo or to four dose cohorts receiving 10mg once every 4 weeks [Q4W], 30mg Q4W, 60mg Q4W or 115mg Q12W. In the LTE, all participants received 60mg or 115mg every 12 weeks.

Recruitment for the Phase 2 CELIA study (NCT05399888), evaluating the potential for this ASO targeting tau to slow the worsening of mild cognitive impairment or mild dementia due to AD, is ongoing at sites across North America, Europe and Asia Pacific.

In December 2019, Biogen exercised a license option with Ionis and obtained a worldwide, exclusive, royalty-bearing license to develop and commercialize BIIB080.

About Antisense Therapies
Antisense therapies are designed to seek out, bind to and destroy a mRNA in a highly specific manner, so that the amount of disease-causing protein is dramatically decreased. Antisense therapies can also treat diseases caused by too little protein by increasing the production of the protein, thereby restoring the protein to normal levels.

About Biogen
Founded in 1978, Biogen is a leading global biotechnology company that has pioneered multiple breakthrough innovations including a broad portfolio of medicines to treat multiple sclerosis, the first approved treatment for spinal muscular atrophy, and two co-developed treatments to address a defining pathology of Alzheimer's disease. Biogen is advancing a pipeline of potential novel therapies across neurology, neuropsychiatry, specialized immunology and rare diseases and remains acutely focused on its purpose of serving humanity through science while advancing a healthier, more sustainable and equitable world.

We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media - X, LinkedIn, Facebook, YouTube.

Biogen Safe Harbor
This news release contains forward-looking statements, about the potential of BIIB080, including related to the Phase 2 CELIA study; the potential of Biogen's commercial business and pipeline programs; and risks and uncertainties associated with drug development and commercialization. These statements may be identified by words such as "aim," "anticipate," "believe," "could," "estimate," "expect," "forecast," "intend," "may," "plan," "possible," "potential," "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 studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. You should not place undue reliance on these statements.
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References:

1. BrightFocus Foundation. Tau Protein and Alzheimer's Disease: What's the Connection? https://www.brightfocus.org/alzheimers/article/tau-protein-and-alzheimers-disease-whats-connection (https://www.brightfocus.org/alzheimers/article/tau-protein-and-alzheimers-disease-whats-connection). Accessed September 2023.
2. Moumné (https://pubmed.ncbi.nlm.nih.gov/?term=Moumn%C3%A9%20L%5BAuthor%5D) et al. Oligonucleotide Therapeutics: From Discovery and Development to Patentability. Pharmaceutics 2022, 14(2), 260; https://doi.org/10.3390/pharmaceutics14020260 (https://doi.org/10.3390/pharmaceutics14020260)
3. Alzheimer's Association. Tau Topic Sheet. https://www.alz.org/media/Documents/alzheimers-dementia-tau-ts.pdf (https://www.alz.org/media/Documents/alzheimers-dementia-tau-ts.pdf). Accessed October 2023.
   

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