Osugacestat

--Independent data monitoring committee (IDMC) determined the trial unlikely to meet primary endpoint – --Alector remains focused on advancing its pipeline of novel ABC-enabled candidates, including an anti-Aβ antibody for Alzheimer’s disease (AD), a GCase enzyme replacement therapy (ERT) for Parkinson’s disease (PD), a tau siRNA for AD, an α-synuclein siRNA for PD, and an NLRP3 siRNA for multiple neurological and metabolic disorders, alongside several first-in-class discovery programs— SOUTH SAN FRANCISCO, Calif., April 29, 2026 (GLOBE NEWSWIRE) -- Alector, Inc. (Nasdaq: ALEC), a biotechnology company focused on developing therapies to counteract the devastating progression of neurodegeneration, today confirmed that the Phase 2 PROGRESS-AD trial of nivisnebart (AL101/GSK4527226) in individuals with early Alzheimer’s disease (AD) will be discontinued. The decision follows a pre-specified futility analysis conducted by an IDMC, which concluded that the trial was unlikely to meet its primary endpoint of slowing disease progression at completion. “This outcome is disappointing for patients and families affected by Alzheimer’s disease and underscores the complexity of developing effective treatments for this devastating disease,” said Arnon Rosenthal, Ph.D., Chief Executive Officer of Alector. “We are deeply grateful to the patients, caregivers, investigators and study staff who participated in the PROGRESS-AD trial and contributed to advancing the scientific understanding of progranulin biology in neurodegeneration. We remain committed to progressing our broader pipeline of programs targeting neurodegenerative disease, including multiple wholly owned candidates enabled by our ABC platform.” Alector and GSK have been co-developing nivisnebart. The companies will work closely with study investigators to inform participants enrolled in the PROGRESS-AD trial. Full results will be shared at a future medical meeting or congress. Alector Pipeline Outlook Alector remains focused on advancing a pipeline of programs designed to treat neurodegenerative diseases through mechanisms that remove toxic proteins, replace deficient proteins, and restore immune and neuronal function. A key pillar of this strategy is Alector Brain Carrier (ABC), the company’s proprietary blood-brain barrier technology platform, which has been developed over the last seven years to enhance brain delivery and enable peripheral dosing across multiple modalities, including antibodies, enzymes, and siRNA. Alector continues to advance AL037/AL137, its ABC-enabled anti-amyloid beta antibody program for the treatment of Alzheimer’s disease, through investigational new drug (IND)-enabling studies, and is targeting an IND submission in Q1 2027. AL037/AL137 is engineered for robust brain uptake, potency, and safety, incorporating ABC with tuned transferrin receptor binding to facilitate brain penetration and plaque removal while minimizing hematologic effects. In addition, Alector is advancing its ABC-enabled siRNA platform, which is designed to allow peripheral dosing and potentially more convenient administration compared with traditional intrathecal delivery. AL064/AL164, an ABC-enabled tau-targeting siRNA for Alzheimer’s disease and other tauopathies, is progressing towards IND-enabling studies, while other siRNA programs, ADP062-ABC (alpha synuclein) and ADP065-ABC (NLRP3), continue to move toward lead selection. The company is also progressing AL050, its ABC-enabled engineered glucocerebrosidase enzyme replacement therapy for Parkinson’s disease, toward an IND application targeted for 2027. About AL101 / GSK4527226 AL101/GSK4527226 is an investigational human monoclonal antibody designed to block and downregulate the sortilin receptor to elevate progranulin (PGRN) levels in the brain. PGRN, a protein encoded by the GRN gene, regulates lysosomal function, neuronal survival, and inflammation. The protein is genetically linked to multiple neurodegenerative disorders. Alector and GSK have been co-developing AL101 for the potential treatment of early Alzheimer’s disease (AD). About Alector Alector is a biotechnology company focused on developing therapies to counteract the devastating progression of neurodegenerative diseases. Leveraging the principles of genetics, immunology, and neuroscience, the company is advancing a portfolio of programs that aim to remove toxic proteins, replace missing proteins, and restore immune and nerve cell function. Supported by biomarkers, Alector’s product candidates seek to treat a range of indications, such as Alzheimer’s disease and Parkinson's disease. The company is also developing Alector Brain Carrier (ABC), a proprietary blood-brain barrier platform, which is being applied to its preclinical and research pipeline. ABC aims to enhance the delivery of therapeutics, achieve deeper brain penetration and efficacy at lower doses, and ultimately improve patient outcomes while reducing costs. Alector is headquartered in South San Francisco, California. For more information, please visit www.alector.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this press release include, but are not limited to, statements regarding our business plans, business strategy, product candidates, research and preclinical pipeline, blood-brain barrier technology platform, planned and ongoing preclinical studies, expected milestones, and expectations of our collaborations. Such statements are subject to numerous risks and uncertainties, including but not limited to risks and uncertainties as set forth in Alector’s Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q, with the Securities and Exchange Commission (“SEC”), as well as the other documents Alector files from time to time with the SEC. These documents contain and identify important factors that could cause the actual results for Alector to differ materially from those contained in Alector’s forward-looking statements. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alector specifically disclaims any obligation to update any forward-looking statement, except as required by law. Alector Contacts: Argot Partners (media) David Rosen (646) 461-6387 alector@argotpartners.com Argot Partners (investors) Laura Perry (212) 600-1902 alector@argotpartners.com Source: Alector, Inc.

iStock, wildpixel Following the hard-won success of early anti-amyloid drugs, a new generation of Alzheimer’s modalities—from tau-targeting gene silencers to blood-brain barrier delivery platforms—is entering the pipeline to anchor future combination therapies. The development of treatments for Alzheimer’s disease has been marked by consistent disappointment, with a demoralizing 99% candidate failure rate . However, recent market entrants—beginning with Biogen and Eisai’s ill-fated Aduhelm , then their more prosperous Leqembi and Eli Lilly’s Kisunla —have defied these odds. With proof that progress is possible in this space, a new wave of treatments has emerged in the early-stage pipeline. Many of these candidates are taking novel approaches to the disease, whether through gene silencing, antisense platforms or improved drug-delivery technologies. Having various modalities with different targets coming through the pipeline could be especially important as the treatment landscape matures, with a combination of approaches likely to be key to managing Alzheimer’s disease, Patrick Trucchio, managing director of Equity Research at H.C. Wainwright, told BioSpace . Several companies, including Eisai, Bristol Myers Squibb and Merck, are working on another common Alzheimer’s target: the tau protein. “KOLs . . . expect it will take a combination of anti-amyloid, anti-tau and then some sort of neuroinflammatory drug to address the disease,” he said. “In terms of tau-targeting, I think the next two years will determine which candidates and which type of approach is going to be paired with the amyloid drugs.” Against this backdrop, attention is turning to the next generation of Alzheimer’s drugs that could form the backbone of future combination therapies. Alzheimer’s disease Eisai Still Confident in Anti-Tau Asset as J&J Becomes Latest Victim in Spiraling Space Days after Johnson & Johnson’s posdinemab failed to slow clinical decline in patients with Alzheimer’s disease, Eisai Chief Clinical Officer Lynn Kramer expressed unwavering conviction in his company’s own anti-tau asset, while others suggest the Alzheimer’s field is heading in a completely different direction. December 5, 2025 · 4 min read · Heather McKenzie Biogen’s BIIB080 Antisense oligonucleotide Biogen was there in the beginning, and the company remains in the thick of the next generation of Alzheimer’s R&D. BIIB080, a tau-targeting antisense oligonucleotide (ASO) granted FDA Fast Track designation last year, is currently being evaluated in Phase II trials. A popular target, the tau protein forms into toxic tangles in the brains of individuals living with Alzheimer’s. Phase Ib data presented at the International Conference on Alzheimer’s and Parkinson’s Diseases in 2023 showed BIIB080 reduced soluble tau protein in cerebrospinal fluid (CSF) in patients with early-stage Alzheimer’s. The clinical study was the first to show a reduction of this magnitude in tau PET across brain regions, Biogen said in its press release at the time. The ASO therapy reduced biomarkers of tau in all dose groups by approximately 60% compared to baseline. Biogen announced in April 2025 that the Phase II CELIA trial of BIIB080 was fully enrolled. The study’s completion date is set for May , with readouts expected this year. This readout will be one of the most significant for Alzheimer’s in 2026, Laura Nisenbaum, executive director of drug development at the Alzheimer’s Drug Discovery Foundation (ADDF), told BioSpace . “So far, the drug appears to be safe and to reduce tau levels in the brain,” she said. “What we’re looking to see next is whether this holds across more individuals, continues to be safe and possibly has an impact on cognitive symptoms.” Arrowhead Pharmaceuticals’ ARO-MAPT RNA interference therapy California-based Arrowhead is also working on a tau-targeting asset, an investigational RNA interference therapeutic called ARO-MAPT. Arrowhead launched a Phase I/IIa trial of the treatment in Alzheimer’s and other tauopathies last month. Traditional methods of targeting tau, such as antibodies and small molecules, have had difficulty in modulating the protein, which makes it ideal for a siRNA-mediated knockdown approach, James Hamilton, chief medical officer at Arrowhead, told BioSpace in an email. The primary reason for the other approaches’ struggles, Hamilton said, is that “tau monoclonals do not adequately target intracellular tau neurofibrillary tangles, which are one of the key drivers of disease biology.” ARO-MAPT, on the other hand, “targets tau mRNA expression in neurons and is administered by a subcutaneous injection,” he explained. Arrowhead is hoping its study will show reductions in CSF translating into lower levels of regional brain tau, Hamilton said. He noted that the study will also include cognitive measures and other disease-relevant rating scales but cautioned that the trial is likely too small to show an effect on cognition, with this set to be assessed in Phase II trials. The company is anticipating initial data from the first parts of the study in the second half of this year, Hamilton said in the December press release announcing the trial’s launch. With Arrowhead’s and other significant readouts expected this year, Trucchio referred to 2026 as “the year of tau,” adding that 2027 will also be crucial. The data from these trials will be important because they will help confirm the most appropriate approach, Trucchio said, likening the different methods of tau reduction to either “a chisel or a sledgehammer.” Weight Loss Arrowhead Enters Obesity Chat by Doubling Tirzepatide’s Weight Loss in Combo Study Arrowhead heralded the results as proof of concept that inhibiting the Activin E pathway can improve body composition and enhance weight loss as compared to tirzepatide alone, particularly in patients with type 2 diabetes. January 6, 2026 · 3 min read · Annalee Armstrong Alnylam’s Mivelsiran RNA interference therapy Alnylam’s mivelsiran, also an siRNA therapy, is being tested in Phase I trials for Alzheimer’s disease. Plans were underway to initiate a Phase II trial during the fourth quarter of 2025, according to the biotech’s third-quarter 2025 earnings report , but as of publication no such trial was listed on ClinicalTrials.gov . While part of the same class as ARO-MAPT, mivelsiran is delivered via intrathecal rather than subcutaneous injection. Alnylam is targeting amyloid in its Phase I trial, while a further asset, ALN-5288, also a siRNA, is being explored to target tau. “With RNAi, we can target amyloid-beta and tau at their genetic source, addressing both intracellular and extracellular pools of these problematic proteins,” Tim Mooney, program lead for mivelsiran at Alnylam, told BioSpace in an email. “This upstream approach may be able to more comprehensively address drivers of Alzheimer’s progression compared to other modalities.” Echoing Trucchio, Mooney said Alnylam expects the future of Alzheimer’s treatment to comprise a variety of approaches and combinations to provide “a more comprehensive effect.” This includes looking at approaches that extend beyond targeting amyloid and/or tau proteins, he added, with Alnylam “exploring multiple mechanisms” to address the disease. “Looking further into the future, we anticipate that diagnostic screening with blood-based biomarkers may eventually play a role in helping to identify individuals at risk of developing AD who could benefit from treatment with targeted therapeutic approaches like ours to prevent the onset of dementia altogether,” Mooney said. Alector Therapeutics’ AL137 Next-gen antibody paired with brain carrier technology Alector suffered two setbacks to its neurodegenerative pipeline, experiencing clinical trial failures in its partnerships with both AbbVie and GSK in a 13-month span. The biotech is still developing AL101 alongside GSK for Alzheimer’s but has pivoted its approach in its earlier-stage pipeline. AL137, a preclinical anti-amyloid beta antibody, is being paired with Alector’s “brain carrier” (ABC) delivery technology to target Alzheimer’s disease. This design is intended to counter one of the major barriers to administering treatments for Alzheimer’s by navigating the blood-brain barrier (BBB). Alector’s ABC technology uses receptor-mediated transcytosis to cross the BBB, targeting specific receptors of endothelial cells to facilitate the delivery of therapeutics. This delivery technology is designed to improve drug delivery and also to reduce dose levels whilst maintaining efficacy, according to the company’s website. Navigating the BBB could help to prevent one of the key known side effects of the anti-amyloid antibody class: amyloid-related imaging abnormalities (ARIA), Trucchio said. Last July, Lilly’s Kisunla received a label update for its dosing schedule to reduce the likelihood of ARIA. ARIA prevention is now becoming a key differentiator that companies in this space hope to achieve, Trucchio said, adding that analysts will be looking to the next-generation anti-amyloid therapies or delivery platforms to deliver this. As the potential for improved delivery of Alzheimer’s treatments becomes clear, companies emerging later into the space—or those on the rebound, such as Roche with its antibody trontinemab —are leveraging this as a means to catch up to the early frontrunners. The progress currently being seen in the Alzheimer’s space is lifting the negativity that existed in the field five years ago, Nisenbaum said. “With the success of anti-amyloid therapies and the development and approval of blood-based biomarker tests, we’ve seen renewed excitement and a greater willingness from drug developers to enter this space.” Neuropsychiatric disorders Alector Scraps Dementia Drug After Phase III Flop, Lays Off 49% of Staff This represents Alector’s second failed neurodegenerative asset in a year, after an AbbVie-partnered asset missed in Alzheimer’s last November. On latozinemab for frontotemporal dementia, Alector was working with GSK, which fronted $700 million in 2021 to collaborate on two programs. October 22, 2025 · 2 min read · Tristan Manalac