PGRN

--76-week trial is evaluating the safety and efficacy of a progranulin-elevating candidate in slowing disease progression-- --Enrollment completed ahead of schedule-- SOUTH SAN FRANCISCO, Calif., April 17, 2025 (GLOBE NEWSWIRE) -- Alector, Inc. (Nasdaq: ALEC), a late-stage clinical biotechnology company focused on developing therapies to counteract the devastating progression of neurodegeneration, today announced the completion of enrollment in PROGRESS-AD, a 76-week Phase 2 clinical trial evaluating the safety and efficacy of AL101/GSK4527226 in slowing disease progression in individuals with early Alzheimer’s disease (AD). Alector and GSK are co-developing AL101, an investigational human monoclonal antibody designed to block and downregulate the sortilin receptor to elevate progranulin (PGRN) levels in the brain. Modest reductions in PGRN levels due to GRN gene mutations have been shown to be associated with an increased risk of developing AD.1, 2, 3 Conversely, elevated PGRN levels have been shown to be protective in animal models of AD.4 “In partnership with GSK, we are pleased to announce the completion of enrollment ahead of schedule in the PROGRESS-AD Phase 2 clinical trial of AL101, marking an important milestone in our pursuit of developing first-in-class therapies for Alzheimer’s disease,” said Arnon Rosenthal, Ph.D., Chief Executive Officer of Alector. “This achievement brings us one step closer to assessing the potential of AL101 in slowing disease progression and to furthering our understanding of AL101’s effects on individuals living with this devastating condition. We remain committed to advancing our progranulin-elevating candidate and evaluating its impact in the ongoing trial.” PROGRESS-AD is a randomized, double-blind, placebo-controlled Phase 2 clinical trial of AL101, which GSK is conducting at multiple sites globally. Two dose levels of AL101 are being evaluated in the trial, with participants randomized to receive either AL101 or placebo intravenously. The primary endpoint of the study is disease progression as measured by the Clinical Dementia Rating Sum of Boxes (CDR®-SB). The CDR-SB is a validated instrument that tracks the progression of cognitive impairments in various categories. The trial also measures other clinical and functional outcome assessments. Additional information about PROGRESS-AD (NCT06079190) may be found at ClinicalTrials.gov. 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 are co-developing AL101 for the potential treatment of early Alzheimer’s disease (AD), and it may also be evaluated for other indications, including Parkinson’s disease (PD). Given PGRN's genetic association with neurodegeneration, elevating PGRN levels may provide a potential therapeutic approach that offers broad neuroprotection in both AD and PD. Collaboration with GSK In July 2021, Alector entered into a collaboration and license agreement with GSK (LSE/NYSE: GSK) to collaborate on the global development and commercialization of progranulin-elevating monoclonal antibodies, including latozinemab and AL101/GSK4527226. Under the terms of the GSK agreement, Alector received $700 million in upfront payments. In addition, Alector may be eligible to receive up to an additional $1.5 billion in clinical development, regulatory, and commercial launch-related milestone payments. In the United States, the companies will equally share profits and losses from commercialization of latozinemab and AL101. Outside of the United States, Alector will be eligible for double-digit tiered royalties. About Alector Alector is a late-stage clinical 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 genetically validated programs that aim to remove toxic proteins, replace deficient proteins, and restore immune and nerve cell function. Supported by biomarkers, Alector’s product candidates seek to treat a range of indications, such as frontotemporal dementia, 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 selectively applied to its next-generation product candidates 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, blood-brain barrier technology platform, research and preclinical pipeline, planned and ongoing preclinical studies and clinical trials, anticipated timing of PROGRESS-AD, expected milestones, expectations of our collaboration with GSK, expectations of our interactions with regulatory authorities, 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 Report on Form 10-K filed for 2024, 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. REFERENCES Alector Contacts: Alector Katie Hogan 202-549-0557 katie.hogan@alector.com 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.

The properties of the blood-brain barrier serve a vital protective role, but they also keep drugs from reaching the organ. Big pharmaceutical companies have been making deals for technologies that could help them get their molecules through this protective membrane and now GSK is joining in, striking up an alliance that gives it a new way to shuttle drugs into the brain to treat neurodegeneration. The agreement announced Monday gives GSK access to a platform technology developed by ABL Bio. Specific diseases covered by the pact were not disclosed. The deal kicks off with GSK paying South Korea-based ABL £38.5 million (about $49.1 million) up front. The drug delivery approach of ABL is based on Grabody, a platform technology that develops bispecific antibodies, proteins engineered to bind to two targets. For treating brain diseases, the bispecific antibodies from Grabody contain a domain designed to bind to insulin-like growth factor 1 receptor (IGF1R), a receptor that transports proteins across the blood-brain barrier. The other binding domain is designed to go after the desired target for treating a brain disorder. Sponsored Post Changes in Nurse Staffing Answer Clinician Demands The ongoing nursing shortage facilitates high turnover rates since nurses know they won’t have difficulties finding new jobs. In order to retain and attract staff, it’s in a facility’s best interest to understand what nurses want. By Tomasz Rezik GSK and ABL aren’t disclosing the brain targets they’re pursuing. But the agreement covers multiple programs for novel targets that could be treated with various therapeutic modalities. For example, they say an ABL brain drug could be used to deliver genetic medicines to the brain, such as a small-interfering RNA drugs or antisense oligonucleotides. ABL’s most advanced brain program is a Parkinson’s disease drug candidate in development under a partnership with Sanofi. The brain target of this preclinical drug, ABL301, is alpha-synuclein. While that protein is also the target of other Parkinson’s drug candidates, ABL contends the bispecific approach of its drug could more efficiently target alpha-synuclein compared to traditional monoclonal antibodies. Under GSK’s deal, ABL will transfer to the pharma giant technology and know-how related to the Grabody-B platform. GSK will take on responsibility for preclinical and clinical development, along with manufacturing and potential commercialization. Depending on the progress of the research, ABL could receive up to £2.075 billion (about $2.6 billion) in milestone payments, plus royalties if any drugs resulting from collaboration reach the market. “Many of the most promising new therapies are antibodies, which cannot efficiently reach the brain without a shuttle to get them across the [blood-brain barrier],” Christopher Austin, senior vice president of research technologies, GSK, said in a prepared statement. “This agreement reflects our commitment to innovative platform technologies to overcome the BBB and thus open entirely new opportunities for treating these devastating diseases, an important component of our emerging pipeline.” presented by Sponsored Post What Are the Best Medical Coding Outsourcing Companies? Outsourcing your medical coding can help ensure a healthy revenue cycle. Discover the best medical coding outsourcing companies and find the right one for you. By Global Healthcare Resources GSK already has clinical-stage Alzheimer’s programs from a partnership with Alector that began 2021. Latozinemab (formerly AL001) is in Phase 3 testing; Alector has said it expects preliminary data by the end of 2025. AL101 (also known as GSK4527226) is in Phase 2. Both drugs are monoclonal antibodies intended to reduce degradation of progranulin, a protein that regulates immune activity in the brain. The targeting of a receptor to deliver a therapy across the blood-brain barrier gives GSK another way to potentially treat neurodegeneration, but it’s not alone in this approach, called receptor-mediated transcytosis. The platform technology of Aliada Therapeutics engineers antibodies to target the transferrin and CD98 receptors to transport molecules across the blood-brain barrier. Similar to ABL, Aliada said its technology can be applied to multiple types of therapeutic cargos, such as enzymes, proteins, and oligonucleotides. With the biotech’s lead program in early clinical development for Alzheimer’s disease, AbbVie last year agreed to pay $1.4 billion to acquire Aliada. ABL’s research also spans Grabody drugs in development for cancer. A partnership with I-Mab is developing PD-L1- and claudin 18.2-targeting drugs; both programs are in Phase 1 for solid tumors. The most advanced ABL program is ABL001 (also known as tovecimig), a VEGF-targeting drug in late-stage clinical development for biliary tract cancer among other cancer indications under a partnership with Compass Therapeutics.

Topline data from the pivotal INFRONT-3 Phase 3 clinical trial of latozinemab in FTD-GRN expected by Q4 2025 Anticipate completing enrollment in the PROGRESS-AD Phase 2 clinical trial of AL101/GSK4527226 in participants with early Alzheimer’s disease by mid-2025 Applying Alector Brain Carrier to advance therapeutic candidates, including those targeting amyloid beta and replacing GCase $413.4 million in cash, cash equivalents and investments provide runway through 2026 Management to host conference call and webcast today at 4:30 p.m. ET/1:30 p.m. PT SOUTH SAN FRANCISCO, Calif., Feb. 26, 2025 (GLOBE NEWSWIRE) -- Alector, Inc. (Nasdaq: ALEC), a late-stage clinical biotechnology company focused on developing therapies to counteract the devastating progression of neurodegeneration, today reported fourth quarter and full year 2024 financial results and recent portfolio and business updates. As of December 31, 2024, Alector’s cash, cash equivalents and investments totaled $413.4 million. “Alector is entering a potentially transformative period for the company, as we continue to advance our clinical programs toward key milestones while also driving the development of our wholly owned, early-stage pipeline,” said Arnon Rosenthal, Ph.D., Chief Executive Officer of Alector. “We look forward to reporting topline data from the pivotal INFRONT-3 Phase 3 trial of latozinemab targeting frontotemporal dementia with a granulin gene mutation by the fourth quarter. Additionally, we expect to complete enrollment in the PROGRESS-AD Phase 2 trial of AL101/GSK4527226 in participants with early Alzheimer’s disease by mid-2025. With our broad and diverse portfolio of genetically validated drug candidates for the treatment of neurodegenerative diseases, backed by a strong financial position that will fund operations through 2026, Alector is well-positioned to advance our mission to deliver transformative therapies for patients with neurodegenerative brain disorders.” Sara Kenkare-Mitra, Ph.D., President and Head of Research and Development at Alector, added, “We are making significant progress in advancing Alector’s preclinical and research pipeline. By leveraging our expertise in neuroscience and drug discovery, and selectively applying our proprietary Alector Brain Carrier technology platform, we are able to enhance brain delivery and biodistribution of therapeutic cargo to potentially improve safety and efficacy. We are currently selecting lead candidates for two programs, ADP037-ABC, targeting amyloid beta, and ADP050-ABC, replacing GCase. We aim to advance these programs toward IND-enabling studies later this year, with plans to enter the clinic in 2026.” Recent Clinical Updates Progranulin Programs (latozinemab (AL001) and AL101/GSK4527226) Being Developed in Collaboration with GSK Latozinemab The pivotal, randomized, double-blind, placebo-controlled INFRONT-3 Phase 3 clinical trial of latozinemab targeting frontotemporal dementia with a granulin gene mutation (FTD-GRN) is ongoing. Topline data are anticipated by the fourth quarter of 2025. Latozinemab is a novel investigational human monoclonal antibody (mAb) designed to block and downregulate the sortilin receptor to elevate the level of progranulin (PGRN) in the brain. It has been granted Orphan Drug, Breakthrough Therapy and Fast Track designations, and the company believes it is the most advanced PGRN-elevating candidate in development for this condition. AL101/GSK4527226 PROGRESS-AD, a global, randomized, double-blind, placebo-controlled Phase 2 clinical trial evaluating AL101/GSK4527226 in early Alzheimer’s disease (AD) continues to enroll well, with substantial progress toward its target enrollment of 282 participants. Alector and GSK plan to complete trial enrollment by mid-2025. AL101/GSK4527226 is an investigational human mAb designed to block and downregulate the sortilin receptor to elevate the level of PGRN in the brain in a manner that is similar to investigational latozinemab but with different pharmacokinetic and pharmacodynamic properties, making it suitable for the potential treatment of more prevalent neurodegenerative diseases. Preclinical and Research Pipeline Alector is advancing a preclinical and early research pipeline focused on removing toxic proteins, replacing deficient proteins, and restoring immune and nerve cell function. Leveraging its deep expertise in drug development and proprietary technologies, including protein engineering, antibody discovery, and its Alector Brain Carrier (ABC) platform for blood-brain barrier transport, the company is progressing a curated portfolio of programs targeting genetically validated disease mechanisms. This approach has led to a suite of innovative programs with the potential to make a significant impact on neurodegeneration. ADP037-ABC is a proprietary anti-amyloid beta (Aβ) antibody paired with the company’s ABC for the treatment of AD. It is designed to remove brain Aβ plaques, with the potential to reduce the incidence and/or severity of amyloid-related imaging abnormalities (ARIA) and enable subcutaneous delivery. It targets a validated epitope, specific to brain Aβ plaques, combined with an optimized antibody constant region to enhance phagocytosis of Aβ plaques. By leveraging ABC technology, ADP037-ABC aims to clear Aβ efficiently, thereby reducing plaque accumulation and potentially slowing disease progression while minimizing ARIA. ADP050-ABC is a GCase replacement therapy paired with the company’s proprietary ABC for GBA gene mutation carriers with Parkinson’s disease (PD) and Lewy body dementia. In these patients, mutations in the GBA gene lead to deficient GCase activity. ADP050-ABC uses Alector-engineered GCase, which is proprietary and has been designed to have a longer half-life and to break down glucocerebroside, a lipid that accumulates in neurons and contributes to neurodegeneration. This mechanism aims to reduce cellular dysfunction and slow disease progression. ADP056 is a Reelin modulator designed to block tau pathology and promote synaptic function in AD. Reelin, a large, secreted protein, regulates neuronal function and tau accumulation. Gain-of-function Reelin variants protect against familial AD through a mechanism that appears to uncouple amyloid and tau pathology. ADP056 is designed to mimic these protective effects of the Reelin mutation. ADP063-ABC and ADP064-ABC are therapeutic candidates paired with the company’s proprietary ABC that target tau pathology in AD through distinct approaches. First, ADP063-ABC will focus on combining a proprietary anti-tau antibody directed to a validated tau epitope with ABC and an optimized antibody constant region. It is designed to block the spread of tau aggregates and has the potential for subcutaneous delivery. Second, ADP064-ABC will focus on using an anti-tau siRNA combined with ABC, which aims to prevent the synthesis of the tau mRNA and protein. Both approaches seek to leverage a highly brain-penetrant approach to remove toxic tau and potentially slow cognitive decline in AD. In December 2024, Alector and co-recipient University of Luxembourg were awarded a $1.7 million grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) for collaborative research on glycoprotein nonmetastatic melanoma protein B (GPNMB), a PD target. Alector plans to hold an educational webinar in the second quarter of 2025 to present additional preclinical data on the company’s anti-amyloid beta and GCase programs, as well as advancements in ABC. TREM2 Program (AL002) On April 5, 2025, Alector plans to present the results from the INVOKE-2 Phase 2 clinical trial, which evaluated the safety and efficacy of AL002, a TREM2 agonist, in individuals with early AD, during an oral presentation at the AD/PD™ 2025 International Conference on Alzheimer’s and Parkinson’s Diseases, taking place in Vienna, Austria. While the trial did not meet its primary endpoint, Alector remains committed to advancing the understanding of AD pathophysiology and the development of effective therapeutics for the disease. Fourth Quarter 2024 Financial Results Revenue. Collaboration revenue for the quarter ended December 31, 2024, was $54.2 million, compared to $15.2 million for the same period in 2023. Collaboration revenue for the year ended December 31, 2024, was $100.6 million, compared to $97.1 million for the same period in 2023. The increase in year-over-year collaborative revenue was primarily due to an increase in revenue recognized for the AL002 and latozinemab programs. Collaboration revenue under the AbbVie Agreement was fully recognized as of December 31, 2024. R&D Expenses. Total research and development expenses for the quarter ended December 31, 2024, were $46.5 million, compared to $47.7 million for the quarter ended December 31, 2023. Total research and development expenses for the year ended December 31, 2024, were $185.9 million compared to $192.1 million for the same period in 2023. The decrease in year-over-year R&D expenses was mainly due to the Company’s strategy to prioritize selected programs. G&A Expenses. Total general and administrative expenses for the quarter ended December 31, 2024, were $15.0 million compared to $14.9 million for the quarter ended December 31, 2023. Total general and administrative expenses for the year ended December 31, 2024, were $59.6 million compared to $56.7 million for the year ended December 31, 2023. The increase in year-over-year G&A expenses is primarily due to the impairment of the right-of-use asset and the leasehold improvements as the Company approved a plan to transition operations from our laboratory and offices in Newark, California to our South San Francisco Headquarters. Net Loss. For the quarter ended December 31, 2024, Alector reported a net loss of $2.1 million, or $0.02 net loss per share, compared to a net loss of $41.4 million, or $0.49 net loss per share, for the same period in 2023. For the year ended December 31, 2024, Alector reported a net loss of $119.0 million or $1.23 net loss per share, compared to a net loss of $130.4 million or $1.56 net loss per share, for the same period in 2023. Cash Position. Cash, cash equivalents, and investments were $413.4 million as of December 31, 2024. Management expects that this will be sufficient to fund current operations through 2026. 2025 Guidance. Management anticipates, for the year ending 2025, collaboration revenue to be between $5 million and $15 million, total research and development expenses to be between $175 million and $185 million, and total general and administrative expenses to be between $55 million and $65 million. Fourth Quarter and Full Year 2024 Conference Call Alector’s management team will host a conference call to discuss Alector’s results for the fourth quarter and full year 2024, as well as provide a business update. The conference call will be webcast and accessible via the investor relations section of Alector’s website at www.alector.com. To access the call, please use the following information: Date: Wednesday, February 26, 2025 Time: 4:30 p.m. ET, 1:30 p.m. PT The event will be webcast live under the investor relations section of Alector’s website at https://investors.alector.com/events-and-presentations/events and following the event a replay will be archived there for 30 days. Interested parties participating by phone will need to register using this online form. After registering for dial-in details, all phone participants will receive an auto-generated e-mail containing a link to the dial-in number along with a personal PIN number to use to access the event by phone. About Alector Alector is a late-stage clinical 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 genetically validated 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, including frontotemporal dementia, Alzheimer’s disease, Parkinson's disease, and Lewy body dementia. The company is also developing Alector Brain Carrier (ABC), a proprietary blood-brain barrier platform, which is being selectively applied to its next-generation product candidates 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, blood-brain barrier technology platform, research and preclinical pipeline, planned and ongoing preclinical studies and clinical trials, anticipated timing of and detail regarding release of data for INFRONT-3, expected milestones, expectations of our collaborations, expectations of our interactions with regulatory authorities, 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 Quarterly Report on Form 10-K filed for 2024, 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: Alector Katie Hogan 202-549-0557 katie.hogan@alector.com Argot Partners (media) David Rosen (212) 600-1494 alector@argotpartners.com Argot Partners (investors) Laura Perry 212-600-1902 alector@argotpartners.com Source: Alector, Inc.