Alnylam Highlights Progress with Neuroscience Programs at AAIC 2026, Showcasing Potential of RNAi in Neurological Disease

− Initiates Global Phase 2 APPlauDS Study of Mivelsiran in Down Syndrome–Associated Alzheimer’s Disease (DS-AD) −

− Announces Completion of Enrollment in the Phase 2 cAPPricorn-1 Study of Mivelsiran in Cerebral Amyloid Angiopathy (CAA) −

− Presents Updated Phase 1 Data on Mivelsiran in Early Onset Alzheimer’s Disease (EOAD) Showing Low Incidence of Amyloid-Related Imaging Abnormalities (ARIA) −

− Shares Preclinical Data and Design of Ongoing Phase 1 Study of Tau-Targeting ALN‑5288 in Alzheimer’s Patients –

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today shared advances across its growing neuroscience portfolio at the Alzheimer’s Association International Conference (AAIC) 2026. This scientific progress underscores the potential of RNAi therapeutics to address the needs of patients with debilitating neurological diseases.

Mivelsiran: An investigational RNAi therapeutic targeting amyloid precursor protein (APP) in development for Cerebral Amyloid Angiopathy (CAA) and Alzheimer’s disease (AD)

The company announced the initiation of a Phase 2 study of mivelsiran in people with Down syndrome-associated AD and presented a poster detailing the design and rationale. The APPlauDS Study (evaluating APP-lowering to reduce amyloid accumulation in Down syndrome) will be recruiting people with Down syndrome with early-stage AD across approximately 30 global sites.

“People with Down syndrome have a genetically determined form of Alzheimer’s disease that is now the leading cause of death among adults over age 35 years,” said Michael S. Rafii, M.D., Ph.D., Professor of Neurology at the Keck School of Medicine of USC and presenting author. “APPlauDS is the first clinical trial to evaluate whether an RNAi approach can reduce APP overexpression caused by trisomy 21, where the APP gene is located. By lowering APP expression early in the disease process, this approach has the potential to slow or prevent the progression of Alzheimer’s disease in people with Down syndrome.”

An additional presentation included updated data from the Phase 1 trial of mivelsiran in patients with early-onset Alzheimer’s disease. An analysis of safety data from single- and multiple-doses of mivelsiran showed no evidence of increased risk of amyloid-related imaging abnormality (ARIA) events. Results also showed robust, durable reductions in cerebrospinal fluid (CSF) soluble amyloid beta precursor protein (sAPPβ) and amyloid beta 42 (Aβ42), with up to 30 months of treatment exposure. The mean maximum reductions in the highest dose group were -89.9% and -70.2% change from baseline for sAPPβ and Aβ42, respectively. The most common adverse events (AEs) were procedural pain and procedural headache, and no serious or severe AEs were deemed related to study drug. CSF safety labs showed no significant elevations of CSF total protein or white blood cells.

Alnylam also announced today that it has completed enrollment in the Phase 2 cAPPricorn-1 study of mivelsiran in CAA, a leading cause of hemorrhagic stroke. CAA is defined by progressive deposition of Aβ in blood vessels of the brain. Reducing APP production reduces downstream Aβ accumulation and could potentially slow CAA progression and CAA-related bleeds in the brain. cAPPricorn-1’s primary endpoint is rate of new lobar microbleeds measured by magnetic resonance imaging (MRI) with initial results expected in 2028.

ALN-5288: An investigational RNAi therapeutic targeting Microtubule-Associated Protein Tau (MAPT) in development for Alzheimer’s disease and tauopathies

Alnylam also highlighted progress with ALN-5288 – an investigational asset in development in collaboration with Regeneron Pharmaceuticals – in presentations of preclinical data and of the design of the ongoing first-in-human Phase 1 trial (NCT07214727), which initiated in the fourth quarter of 2025.

With mivelsiran and ALN-5288, Alnylam has two RNAi therapeutics targeting AD in clinical development, and, together with its collaboration partner Regeneron, a total of seven clinical programs for neuroscience indications.

“The updates we’re sharing at AAIC 2026 mark an important step forward for Alnylam as we continue to build our leadership in neuroscience,” said Toby Ferguson, M.D., Ph.D., Senior Vice President and Head of the Neuroscience Therapeutic Area at Alnylam. “Our RNAi platform is demonstrating strong potential across neurological diseases, with a favorable safety profile and the possibility to reach broad patient populations. By targeting disease-driving proteins like amyloid and tau at their genetic source, we aim to deliver the kind of transformative, disease-modifying therapies patients and families have long awaited.”

To view Alnylam’s AAIC 2026 presentations please visit Capella.

About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common neurodegenerative disease and the most common form of dementia, affecting over 30 million people worldwide. Amyloid and tau are widely viewed as the two principal biological drivers of AD, together contributing to the cascade of neurodegeneration and cognitive decline. Disease progression results in progressive loss of independence, increased caregiver burden, institutionalization and premature death. Early-onset Alzheimer’s disease (EOAD), the leading cause of dementia in younger individuals, refers to a subgroup of AD with symptom onset prior to the age of 65, representing approximately 4% to 6% of all AD. People with Down syndrome (DS) have a near-complete risk of developing Alzheimer’s disease (AD) in late adulthood; AD has become the leading cause of death in adults with DS. DS-AD is caused by overexpression of amyloid precursor protein (APP) due to an additional copy of chromosome 21 (Trisomy 21), the locus of the APP gene.

About Cerebral Amyloid Angiopathy
Cerebral amyloid angiopathy (CAA) is the second most-common cause of hemorrhagic stroke. CAA is defined by progressive deposition of amyloid beta (Aβ) into the walls of small arteries, arterioles and capillaries in the brain, causing impaired vascular reactivity, focal tissue damage and increased risk for intracerebral hemorrhage. CAA has also been shown to be an independent contributor to cognitive impairment. There are currently no available treatment options for CAA.

About Alnylam Pharmaceuticals
Alnylam (Nasdaq: ALNY) is a leading global biopharmaceutical company and the pioneer of the RNA interference (RNAi) revolution. The Company is focused on developing transformative therapies with the potential to prevent, halt or reverse disease. For more than two decades, Alnylam has advanced the Nobel-Prize-winning science of RNAi, delivering critical breakthroughs and six approved medicines. Alnylam has medicines available in more than 70 countries and a rapidly expanding and robust pipeline, in addition to consistently being recognized as an exceptional workplace and socially responsible organization. The Company is executing on its Alnylam 2030 strategy to accelerate innovation and scale impact to transform human health.

Alnylam Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects, including, without limitation, statements regarding the potential of RNAi therapeutics to address the needs of patients with neurological diseases; the potential efficacy or safety of any of Alnylam’s product candidates; the potential for mivelsiran to slow or prevent the progression of Alzheimer’s disease in people with Down syndrome; the timing of the publication of results from any of Alnylam’s clinical trials; the potential for Alnylam’s RNAi platform to treat neurological diseases with a favorable safety profile and the possibility to reach broad patient populations; Alnylam’s ability to deliver transformative, disease-modifying therapies patients and families have long awaited; and Alnylam’s ability to execute on its Alnylam 2030 strategy to accelerate innovation and scale to transform human health, should be considered forward-looking statements. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to: Alnylam’s ability to successfully execute on its “Alnylam 2030” strategy; Alnylam’s ability to successfully launch, market and sell Alnylam’s approved products globally; Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; delays, interruptions or failures in the manufacture and supply of Alnylam’s marketed products or its product candidates; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations; Alnylam’s ability to maintain strategic business collaborations; Alnylam’s dependence on third parties for the development and commercialization of certain products; the outcome of litigation and government investigations; the risk of future litigation and government investigations; and unexpected expenditures; as well as those risks and uncertainties more fully discussed in the “Risk Factors” filed with Alnylam’s 2025 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q, and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

Alnylam Pharmaceuticals, Inc.
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(Media)
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(Investors)
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