On November 6, 2024 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported third quarter 2024 financial results and recent portfolio and business updates (Press release, Alector, NOV 6, 2024, View Source [SID1234647797]). As of September 30, 2024, Alector’s cash, cash equivalents, and investments totaled $457.2 million.

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"We continue to make meaningful progress advancing our innovative pipeline of product candidates and remain on track to report data in 2024 from the INVOKE-2 Phase 2 trial of AL002, the most advanced TREM2 candidate in clinical development for early Alzheimer’s disease," said Arnon Rosenthal, Ph.D., Chief Executive Officer of Alector. "We believe that increased TREM2 signaling via AL002 may recruit disease-fighting microglia to broadly counteract the progression of Alzheimer’s disease. INVOKE-2 is designed to provide meaningful insights into AL002’s potential benefits across a combination of clinical and functional endpoints, as well as imaging and fluid biomarkers. We also believe that the broad mechanism of AL002 may have the potential to deliver potent and durable therapeutic benefits, both as a standalone therapy and in combination with anti-amyloid beta antibodies."

Dr. Rosenthal continued, "For our progranulin franchise, we recently reported the patient baseline characteristics for our INFRONT-3 Phase 3 clinical trial of latozinemab in frontotemporal dementia with a progranulin gene mutation, suggesting a representative study population in this indication. We are approaching a top-line data readout for INFRONT-3 in late 2025/early 2026. Additionally, PROGRESS-AD, the Phase 2 trial of AL101/GSK4527226 in early Alzheimer’s disease, has reached more than one-third of its target enrollment. It is an exciting time at Alector, and we are well positioned to advance our proprietary pipeline of novel immuno-neurology drugs."

Sara Kenkare-Mitra, Ph.D., President and Head of Research and Development at Alector, added, "We are actively advancing our Alector Brain Carrier, ABC, a proprietary versatile blood-brain barrier technology, and we are strategically leveraging this platform across our portfolio. We believe our ABC technology may advance treatment of neurodegenerative diseases by potentially enabling improved delivery of our therapeutics to the brain."

Recent Clinical Updates

Immuno-Neurology Portfolio
TREM2 Program (AL002) Being Developed in Collaboration with AbbVie

The results of the INVOKE-2 Phase 2 clinical trial of AL002 are expected in 2024. INVOKE-2, a randomized, double-blind, placebo-controlled, dose-ranging study, is designed to assess the efficacy and safety of AL002 in slowing disease progression in individuals with early Alzheimer’s disease (AD). AL002 is a novel investigational humanized monoclonal antibody (mAb) that is designed to bind to TREM2 to increase TREM2 signaling and, thereby, is hypothesized to improve the functionality of microglia. It is the most advanced TREM2 agonist product candidate in clinical development worldwide.
98% of eligible participants who completed the planned treatment period of INVOKE-2 have elected to participate in the long-term extension (LTE) study.
In October 2024, Alector published a manuscript titled "Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer’s disease" in Alzheimer’s Research & Therapy. The publication outlines preclinical and INVOKE-1 Phase 1 study results, demonstrating that AL002 engaged TREM2, and induced pharmacodynamic biomarker changes associated with microglial proliferation, survival, and phagocytic activity in a dose-dependent manner.
AbbVie has an exclusive option to globally develop and commercialize AL002. Alector will deliver a data package resulting from the INVOKE-2 study to AbbVie for their evaluation. AbbVie’s exercise of its option would prompt a $250 million payment to Alector.
Progranulin Programs (latozinemab (AL001) and AL101/GSK4527226) Being Developed in Collaboration with GSK

The pivotal, randomized, double-blind, placebo-controlled INFRONT-3 Phase 3 clinical trial of latozinemab targeting frontotemporal dementia with a progranulin gene mutation (FTD-GRN) is ongoing and on track, with enrollment completed in October 2023 and a treatment duration of 96 weeks. Latozinemab is a novel investigational human mAb that aims to increase progranulin (PGRN) levels by inhibiting sortilin and is the most advanced PGRN-elevating candidate in development for the treatment of FTD-GRN.
In September 2024, Alector presented a poster highlighting the patient baseline characteristics for INFRONT-3 at the 14th International Conference on Frontotemporal Dementias (ISFTD 2024). Notably, the baseline characteristics of symptomatic INFRONT-3 participants, including age, Clinical Dementia Rating scale plus National Alzheimer’s Disease Coordinating Center Frontotemporal Lobar Degeneration Sum of Boxes (CDR plus NACC FTLD-SB) score and neurofilament light chain (NfL) levels, were representative of the broader FTD-GRN registry population, based on available registry data. Additionally, Alector shared findings from the FTD Caregiver Survey and FTD Insights Survey, highlighting the challenges faced by caregivers of individuals living with FTD.
PROGRESS-AD, a global, randomized, double-blind, placebo-controlled Phase 2 clinical study evaluating AL101/GSK4527226 in early AD has reached more than one-third of its target enrollment of 282 participants, with dosing initiated in February 2024. AL101 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.
Early Research Pipeline

Alector continues to advance its Alector Brain Carrier (ABC), a proprietary, versatile blood-brain barrier technology platform, which is being applied selectively to the company’s next-generation product candidates and research pipeline. The technology platform enables customization of affinity, valency, and format to optimize effector function and half-life in preclinical models. Alector is applying its ABC technology, combined with its expertise in immuno-neurology, to work on novel targets and develop first or best-in-class therapeutics.
Third Quarter 2024 Financial Results

Revenue. Collaboration revenue for the quarter ended September 30, 2024, was $15.3 million, compared to $9.1 million for the same period in 2023. The increase was mainly due to an increase in revenue recognized for the AL002 program.

R&D Expenses. Total research and development expenses for the quarter ended September 30, 2024, were $48.0 million, compared to $46.3 million for the quarter ended September 30, 2023. The increase was mainly driven by the increase in research and development expenses for the AL101 programs resulting from the initiation of the PROGRESS-AD Phase 2 clinical trial in 2024.

G&A Expenses. Total general and administrative expenses for the quarter ended September 30, 2024, were $15.8 million, compared to $13.4 million for the quarter ended September 30, 2023. The increase was mainly due to the impairment of the right-of-use asset and the leasehold improvements as the Company transitioned operations from its laboratory and office space in Newark to its South San Francisco headquarters.

Net Loss. For the quarter ended September 30, 2024, Alector reported a net loss of $42.2 million, or $0.43 per share, compared to a net loss of $44.5 million, or $0.53 per share, for the same period in 2023.

Cash Position. Cash, cash equivalents, and investments were $457.2 million as of September 30, 2024. Management expects that this will be sufficient to fund current operations through 2026.

2024 Guidance. The Company continues to anticipate collaboration revenue to be between $60 million and $70 million, total research and development expenses to be between $210 million and $220 million, and total general and administrative expenses to be between $60 million and $70 million.