Alector Announces Completion of Enrollment in the INVOKE-2 Phase 2 Clinical Trial of AL002, a TREM2 Monoclonal Antibody, in Individuals With Early Alzheimer’s Disease

SOUTH SAN FRANCISCO, Calif., Sept. 07, 2023 (GLOBE NEWSWIRE) -- Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, today announced that it has completed enrollment in INVOKE-2, the Phase 2 clinical trial of AL002. INVOKE-2 is evaluating the safety and efficacy of AL002 in slowing disease progression in individuals with early Alzheimer’s disease (AD). Data from the trial are expected in the fourth quarter of 2024. AL002 is a novel investigational humanized monoclonal antibody (mAb) that binds to triggering receptor expressed on myeloid cells 2 (TREM2). AL002 is the most advanced TREM2 activating product candidate in clinical trials and is being developed in collaboration with AbbVie.

“The successful completion of enrollment in the INVOKE-2 Phase 2 trial marks a significant milestone in the ongoing development of AL002, bringing us one step closer to potentially introducing this prospective new class of therapeutics to individuals impacted by Alzheimer's disease,” said Arnon Rosenthal, Ph.D., Chief Executive Officer of Alector. “We are also encouraged to see that nearly all eligible participants are rolling over into the long-term extension of the INVOKE-2 trial, which will enable us to better understand the long-term effects of this potential therapeutic. Notably, results from a Phase 1 clinical trial of AL002 in healthy volunteers demonstrated both dose dependent target engagement and activation of microglia. We look forward to an INVOKE-2 data readout in the fourth quarter of 2024, which will inform a potential pivotal Phase 3 clinical development program for AL002 that enables registration.”

INVOKE-2 is a randomized, double-blind, placebo-controlled, dose-ranging, multi-center Phase 2 clinical trial being conducted at multiple sites across 11 countries. Participants with early AD are randomized to receive AL002 or placebo administered intravenously every four weeks. The trial utilizes a common close design with up to 96 weeks of randomized treatment, and all participants remain on their assigned regimen until the last participant completes 48 weeks of treatment. This design provides the opportunity to capture more observations for the primary analysis. The primary endpoint is disease progression as measured by the Clinical Dementia Rating Sum of Boxes (CDR^®-SB). The CDR-SB, which is used to assess (score) the severity of AD, is a validated instrument that assesses both cognitive and functional domains and is the accepted efficacy endpoint for FDA. The trial also employs other multiple clinical and functional outcome assessments. Additionally, the trial includes cerebrospinal fluid (CSF) and plasma biomarkers assessing microglial activation and Alzheimer’s pathophysiology, as well as brain magnetic resonance imaging (MRI) and amyloid beta and tau positron emission tomography (PET) imaging.

Additional information about INVOKE-2 (NCT04592874) may be found at ClinicalTrials.gov.

At the 2023 Alzheimer’s Association International Conference (AAIC) in July, Alector presented an update on INVOKE-2. The presentation highlighted previously reported treatment-emergent MRI findings observed in INVOKE-2 that resemble amyloid-related imaging abnormalities (ARIA). It is unknown whether the biological mechanism(s) causing these MRI changes are the same as that associated with the ARIA that has been described with anti-amyloid beta antibodies.

It is hypothesized that AL002 may provide potential benefit alone or in combination with anti-amyloid beta antibodies by potentially harnessing the broader beneficial effects of microglia. Microglia activation may not only enhance the clearance of misfolded proteins that accumulate and form amyloid plaques but may also perform other supportive microglia functions, including maintenance of neuronal and synaptic health, and warrants further investigation.

About AL002
AL002 is an investigational humanized monoclonal antibody that targets triggering receptor expressed on myeloid cells 2 (TREM2), an important genetic risk factor for sporadic Alzheimer’s disease. TREM2 is a transmembrane receptor expressed on a subset of innate immune cells and selectively on microglia, which constitute the brain’s immune system. Reduction of TREM2 functionality may lead to Alzheimer's disease and other forms of dementia. AL002 counteracts this decreased functionality by activating TREM2 signaling to improve cell survival and proliferation as well as microglia activity. The clinical benefits of this activity are unknown and are the focus of the AL002 clinical trials.

Collaboration with AbbVie
In October 2017, Alector entered into a global strategic collaboration with AbbVie (NYSE: ABBV), to co-develop and commercialize therapeutics to treat Alzheimer’s disease and other neurodegenerative diseases. Under the terms of the agreement, Alector granted AbbVie an exclusive option to global development and commercialization for the AL002 TREM2 program. If AbbVie exercises its option for the program, Alector would be eligible for additional option exercise and milestone payments totaling up to $487.5M. Both companies will share the development costs and will split global profits equally after marketing approval.

About Alzheimer’s Disease
Alzheimer’s disease is a degenerative brain disease and the most common form of dementia. It is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability of patients to care for themselves. In most people with Alzheimer’s disease, symptoms first appear in their mid-60s. The Alzheimer’s Association estimates that as of 2023, there are 6.7 million Americans aged 65 and older living with Alzheimer’s disease, and projects that number will rise to nearly 14 million by 2060.¹

About Alector
Alector is a clinical-stage biotechnology company pioneering immuno-neurology, a novel therapeutic approach for the treatment of neurodegenerative diseases. Immuno-neurology targets immune dysfunction as a root cause of multiple pathologies that are drivers of degenerative brain disorders. Alector has discovered and is developing a broad portfolio of innate immune system programs, designed to functionally repair genetic mutations that cause dysfunction of the brain’s immune system and enable rejuvenated immune cells to counteract emerging brain pathologies. Alector’s immuno-neurology product candidates are supported by biomarkers and target genetically defined patient populations in frontotemporal dementia and Alzheimer’s disease. Alector is headquartered in South San Francisco, California. For additional 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 product candidates, planned and ongoing preclinical studies and clinical trials, expected milestones, including the timing of data from our INVOKE-2 trial, 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 Quarterly Report on Form 10-Q filed on August 3, 2023, 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

1AB (media)
Dan Budwick
973-271-6085 
dan@1abmedia.com

Argot Partners (investors)
Laura Perry
Argot Partners
212-600-1902
alector@argotpartners.com

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¹ 2023 Alzheimer’s Disease Facts and Figures