Latozinemab

LONDON – The Jefferies Global Healthcare Conference may have found its groove. While last year’s long queues may be gone, the buzz is still palpable as thousands arrive in London to what observers describe as a key confab to plant seeds that could mature into deals in the coming months. This year, the conference ran for four days instead of three. There are more venues to meet outside the Waldorf Hilton, like a nearby pub with large Jefferies signage draped by the entrance. There are free umbrellas on hand (essential when rushing between buildings during unpredictable weather) and ginger and apple shots by the door (as temperatures hit single digits this week — that’s Celsius, not Fahrenheit). An earlier draft of the program shows that former FDA official George Tidmarsh was scheduled to make an appearance, but that has disappeared in the latest version since he left his post as CDER director earlier this month. But there was still plenty to attend: GSK announced its LTZ Therapeutics deal on the same day it hit the stage. During its session, Pfizer’s CFO indicated what’s likely to be its next move now that it has won the bidding war for Metsera. Endpoints News attended sessions featuring Alkermes (which is in the middle of its own bidding contest) and WuXi XDC. Endpoints also met with execs from cancer biotech Light Chain Bioscience and dementia drugmaker Vesper Bio. Here are the highlights: On Wednesday morning, Alkermes increased its bid for Avadel in its ongoing bidding war for Lundbeck. During Alkermes’ slot at Jefferies later that day, CEO Richard Pops was asked how the strategic value for Avadel has changed over the past several weeks. Pops said that the initial deal announcement on Oct. 22 was made before Alkermes knew about its mid-stage data in narcolepsy type 2 for its drug candidate called alixorexton. That trial, when it reported three weeks later, yielded underwhelming results . Still, Pops said Alkermes had “a tremendous amount of confidence” that alixorexton would enter the market based on its results in narcolepsy type 1 , which it reported earlier in the year. Pops said that it ultimately wants Avadel because its narcolepsy drug Lumryz is already on the market. That would allow Alkermes to tap into its existing network of clinicians and payers even before it could potentially launch alixorexton. There’s also the commercial value of Lumryz itself and the potential of drug combinations, he added. But Takeda, which has a drug with a similar mechanism to alixorexton, is likely to reach the market sooner . “We’ll see where Takeda prices the first product … but there are plenty of orphan diseases that are being well-reimbursed for on-label use at very high prices if they have a very profound impact on people’s lives,” Pops said. Light Chain executives made their case to Endpoints as to why targeting CD47 is still a promising approach in oncology. The CD47 space has seen many high-profile flops in recent years, with Gilead effectively ending development of magrolimab in 2024, and ALX Oncology’s lead asset evorpacept flunking a Phase 2 study earlier this year. CD47 is a surface protein expressed by healthy cells that gives off a “don’t eat me” signal. It’s also overexpressed by some cancers to help evade the immune system. “With a monospecific approach, you will hit CD47 on tumors but also everywhere else,” Light Chain CEO Nicolas Fischer said. “This has posed major challenges that led to the termination of previous programs — mainly toxicity, but also a huge ‘sink effect’ where you have to put enough antibody to be able to bind all the CD47 in the body.” By contrast, Fischer said Light Chain’s bispecific antibody approach features one arm that targets a tumor-associated antigen with high affinity and a second arm that blocks CD47. The CD47-targeting arm has a weaker affinity: In practice, it can only block the protein in the setting of a cancer cell, he added. One of Light Chain’s lead candidates is a mesothelin x CD47 bispecific called NI-1801, which is being developed for platinum-resistant ovarian cancer. The biotech presented early data from the candidate alone and in combination with Merck’s Keytruda at the European Society for Medical Oncology’s annual congress in October. Like Light Chain, Vesper Bio was also keen to defend its approach in light of a recent high-profile failure for a rival candidate backed by big pharma. Its CEO, Jacob Falck Hansen, met Endpoints at a flexible office space down the road from the Waldorf Hilton. Vesper is developing a medicine called VES001 for a genetic form of frontotemporal dementia. The drug is designed to restore levels of a neuron-protecting protein, progranulin, which is naturally lacking in these patients. Some onlookers have been skeptical of this approach after GSK and Alector’s candidate latozinemab significantly increased levels of progranulin in the blood but failed to improve disease progression in a Phase 3 study. But Hansen argued that nuances in exactly how these two candidates go about restoring progranulin could make all the difference to disease progression. Latozinemab was an antibody designed to degrade a receptor called sortilin that’s found on the surface of neurons. Progranulin binds to the sortilin receptor, which then transports it to the lysosomes for degradation. But sortilin also serves as the binding site for many other proteins and lipids besides progranulin, including APOE4, APOE3 and TrkB, Hansen explained. “If you want to interfere with sortilin, it’s important to do it in a targeted manner given the many important roles that sortilin has,” Hansen said. That’s where VES001 could prove itself. Instead of directly degrading the sortilin receptor, Vesper’s small-molecule drug is designed to inhibit progranulin binding to the sortilin receptor selectively. The China-headquartered ADC manufacturer will consider building in the US, if pharmaceutical companies continue to focus their manufacturing to the country, CEO Jimmy Li said during a presentation on Wednesday. After spinning out of its parent company WuXi Biologics in 2023, WuXi XDC currently operates from WuXi and Shanghai in China. It is also in the process of constructing a building in Singapore, which is expected to be operational by the end of the year. WuXi XDC does not yet have a Western footprint, but Li noted that the company’s Singapore site will be advantageous as the country currently has a very low US tariff rate. Editor’s note: A quote from Alkermes CEO Richard Pops was clarified to note that he said “on-label” rather that “unlabeled.”

Selected lead candidates AL137 for the company’s Alector Brain Carrier (ABC)-enabled anti-amyloid beta antibody in Alzheimer's disease, and AL050 for its ABC-enabled GCase enzyme replacement therapy in Parkinson’s disease; both advancing toward IND-enabling studies Advancing ABC-enabled Tau, Alpha Synuclein and NLRP3 siRNA programs targeting peripheral delivery of novel therapies for neurodegenerative disorders Independent interim analysis for the PROGRESS-AD Phase 2 clinical trial of nivisnebart (AL101) in early Alzheimer’s disease planned for 1H 2026 $291.1 million in cash, cash equivalents, and investments provides runway through 2027 SOUTH SAN FRANCISCO, Calif., Nov. 06, 2025 (GLOBE NEWSWIRE) -- Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company focused on developing therapies to counteract the devastating progression of neurodegeneration, today reported third quarter 2025 financial results and recent portfolio and business updates. As of September 30, 2025, Alector’s cash, cash equivalents, and investments totaled $291.1 million. “We are well-resourced to advance our portfolio of innovative drug candidates for the treatment of neurodegenerative diseases, with a sharpened focus on our differentiated Alector Brain Carrier (ABC) platform,” said Arnon Rosenthal, Ph.D., Chief Executive Officer of Alector. “ABC represents an important driver of innovation, with the versatility to deliver antibodies, enzymes and nucleic acid to the brain. Our ABC-enabled programs have demonstrated robust brain penetration through peripheral dosing, favorable safety, and good pharmacokinetics. We are advancing AL137, our ABC-enabled anti-amyloid beta antibody, AL050, our ABC-enabled GCase enzyme replacement therapy, and ADP064, our ABC-enabled Tau siRNA, toward IND-enabling studies, with IND submissions targeted in 2026 and 2027.” Dr. Rosenthal continued, “Additionally, together with GSK, we continue to advance the Phase 2 PROGRESS-AD trial for nivisnebart (AL101), an investigational monoclonal antibody being studied for the treatment of Alzheimer’s disease. We remain on track for an independent interim analysis planned for the first half of 2026.” Recent Program Updates Alector Brain Carrier: Preclinical and Research Pipeline A key pillar of Alector’s focus is its proprietary blood-brain barrier (BBB) technology platform, Alector Brain Carrier (ABC). Built on the core design principles of versatility, tunability, and differentiated binding to a distinct region of the transferrin receptor (TfR), ABC is intended to support the targeted delivery of therapeutics to the brain and to optimize safety and efficacy. The platform’s tunable TfR binding affinities allow adjustment of binding strength and drug configuration to align with the needs of diverse therapeutic cargos, including antibodies, enzymes, and siRNA, aiming to achieve efficient transport across the BBB with the goal of balancing brain uptake and safety. AL137 Alector has selected lead candidate AL137 for its ABC-enabled anti-amyloid beta (Aβ) antibody in Alzheimer’s disease (AD) and is advancing it toward investigational new drug (IND)-enabling studies. The company is targeting an IND filing for AL137 in 2026. AL137 is engineered for optimal brain uptake, potency, safety, and convenience. This candidate features a high-affinity, humanized antibody that selectively binds PyroGlu3, a validated epitope on the toxic form of Aβ found in plaques, a fully active effector function that enables maximal recruitment of myeloid cells to remove plaques, and Alector’s proprietary ABC with tuned affinity and binding epitope designed to facilitate brain penetration and plaque removal while minimizing hematologic adverse effects. In preclinical studies to date, AL137 has demonstrated robust brain penetration at low doses, supporting the potential for low dose, subcutaneous administration. AL050 Alector has selected lead candidate AL050 for its ABC-enabled glucocerebrosidase (GCase) enzyme replacement therapy (ERT) in Parkinson’s disease (PD) and is advancing the candidate toward IND-enabling studies. The company is targeting submission of an IND application for AL050 in 2027. AL050 is an ABC-enabled GCase ERT engineered to address the key challenges of enzyme replacement for the brain. It features an engineered GCase with improved activity and stability, a silenced effector function to maximize safety, and Alector’s tunable ABC with a TfR epitope and affinity designed to enhance delivery across the BBB. In preclinical studies to date, AL050 increased GCase activity in both rodents and NHPs and reduced toxic substrate accumulation in a rodent GBA disease model with no apparent hematologic findings, supporting its potential as a therapy for Parkinson’s disease and Lewy body dementia associated with GBA loss-of-function mutations. ABC siRNA Platform The company also continues to advance its ABC-enabled siRNA platform. The platform is designed for peripheral dosing, offering the potential for more convenient administration compared with traditional intrathecal or intracerebroventricular delivery, as well as homogeneous drug distribution throughout the brain. Current programs include Alector’s lead siRNA program, ADP064-ABC, an anti-tau siRNA for AD and other tauopathies, as well as ADP062-ABC, an alpha-synuclein siRNA for PD and eventually Lewy body dementia; and ADP065-ABC, an NLRP3 siRNA, for a range of neurodegenerative diseases. Progranulin Programs (nivisnebart (AL101/GSK4527226) and latozinemab (AL001)) in Collaboration with GSK Nivisnebart (AL101/GSK4527226) The 76-week, global, randomized, double-blind, placebo-controlled PROGRESS-AD Phase 2 clinical trial of nivisnebart (AL101/GSK4527226) in early AD is ongoing, with enrollment completed in April 2025. An independent interim analysis is planned for the first half of 2026. Nivisnebart is an investigational human monoclonal antibody (mAb) designed to block and internalize the sortilin receptor to elevate the concentrations of progranulin (PGRN) in the brain. It is distinct from latozinemab, with differentiated pharmacokinetic and pharmacodynamic properties that may make it suitable for the potential treatment of more prevalent neurodegenerative diseases. Latozinemab In October 2025, Alector and GSK announced topline results from the INFRONT-3 Phase 3 clinical trial of latozinemab for the potential treatment of frontotemporal dementia due to a GRN gene mutation (FTD-GRN). The study did not demonstrate clinical benefit. Based on these results, the open-label extension portion of the INFRONT-3 trial and the continuation study for latozinemab will be discontinued. Corporate News In October 2025, the company implemented a reduction in force of approximately 47% intended to focus the company’s resources on its highest-priority programs, to ensure continued progress across its portfolio, and extend cash runway through 2027. Third Quarter 2025 Financial Results Revenue. Collaboration revenue for the quarter ended September 30, 2025, was $3.3 million, compared to $15.3 million for the same period in 2024. The decrease was mainly due to the satisfaction of the performance obligation associated with the AL002 program and the latozinemab FTD-C9orf72 Phase 2 trial in the fourth quarter of 2024. R&D Expenses. Total research and development expenses for the quarter ended September 30, 2025, were $29.4 million, compared to $48.0 million for the quarter ended September 30, 2024. The decrease was mainly due to a decrease in research and development expenses for the AL002 program as well as a decrease in personnel related costs as a result of the reductions in force. G&A Expenses. Total general and administrative expenses for the quarter ended September 30, 2025, were $11.5 million, compared to $15.8 million for the quarter ended September 30, 2024. The decrease was mainly driven by the absence of impairment charges related to the right-of-use asset and leasehold improvements recognized in the third quarter of 2024. No comparable impairment occurred in the current period. Additionally, personnel-related costs declined as a result of the reductions in force. Net Loss. For the quarter ended September 30, 2025, Alector reported a net loss of $34.7 million, or $0.34 per share, compared to a net loss of $42.2 million, or $0.43 net loss per share, for the same period in 2024. Cash Position. Cash, cash equivalents, and investments were $291.1 million as of September 30, 2025. This includes approximately $14.7 million in net proceeds raised through the company’s at-the-market (ATM) equity offering in September. In October 2025, the company raised $5.3 million in ATM equity offerings. Management anticipates that its current cash position will be sufficient to fund Alector’s operations through 2027. 2025 Guidance. The company continues to anticipate collaboration revenue to be between $13 million and $18 million, total research and development expenses to be between $130 million and $140 million, and total general and administrative expenses to be between $55 million and $65 million. About Alector Alector is a clinical-stage 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, Parkinson's disease, and frontotemporal dementia. The company is also developing Alector Brain Carrier (ABC), a proprietary blood-brain barrier platform, which is being selectively 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, workforce reduction, product candidates, research and preclinical pipeline, blood-brain barrier technology platform, planned and ongoing preclinical studies and clinical trials, anticipated timing of and detail regarding release of data for PROGRESS-AD, expected milestones, expectations of our collaborations and financial and cash guidance. 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.