AL002 / Alector, AbbVie - LARVOL DELTA

EFFICACY AND SAFETY RESULTS OF INVOKE-2: A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED STUDY EVALUATING AL002 IN EARLY ALZHEIMER'S DISEASE (ADPD 2025) - "Conclusions Results of INVOKE-2 provide the first report of efficacy and safety data for a TREM2 agonistic antibody assessed against a placebo control in patients with early AD. These findings inform the overall benefit-risk profile of this therapeutic approach."

Clinical • P2 data • Alzheimer's Disease • Amyloidosis • CNS Disorders • Cognitive Disorders • Dementia

A Long-term Extension Study to Evaluate Safety, Tolerability, and Efficacy of AL002 in Alzheimer's Disease (clinicaltrials.gov) - P2 | N=198 | Terminated | Sponsor: Alector Inc. | Trial completion date: Dec 2025 ➔ Jan 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2025 ➔ Jan 2025; Parent study failed to meet the primary endpoint and there were no treatment effects that favored AL002 on secondary clinical and functional endpoints.

Trial completion date • Trial primary completion date • Trial termination • Alzheimer's Disease • CNS Disorders

Developing Topics. (PubMed, Alzheimers Dement) - "Taken together, the baseline characteristics data for the INVOKE-2 study represent a study population that enables testing of the effects of a TREM2 agonist in early AD."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Aβ42 • CHI3L1 • CSF1R • GFAP • IL1RN • NEFL • p-tau181 • SPP1

Developing Topics. (PubMed, Alzheimers Dement) - "The prototype VR-PrecivityAD blood-test was highly predictive of amyloid positivity, confirmed by VR-PET or CSF, among INVOKE-2 screening subjects. Use of a lower VR-APS threshold was associated with fewer false negatives without a meaningful increase in false positives when compared to the standard CL-PrecivityAD threshold in the INVOKE-2 screening population."

Biomarker • Clinical • Journal • Alzheimer's Disease • Amyloidosis • CNS Disorders • Dementia • APOE • Aβ42

Alector Announces Results from AL002 INVOKE-2 Phase 2 Trial in Individuals with Early Alzheimer’s Disease and Provides Business Update (GlobeNewswire) - P2 | N=381 | INVOKE-2 (NCT04592874) | Sponsor: Alector Inc. | "Treatment with AL002 resulted in sustained target engagement and pharmacodynamic responses indicative of microglial activation. However, AL002 failed to meet the primary endpoint of slowing of Alzheimer’s clinical progression as measured by the Clinical Dementia Rating Sum of Boxes (CDR-SB), and there were no treatment effects that favored AL002 on secondary clinical and functional endpoints. Similarly, there were no significant effects on Alzheimer’s fluid biomarkers favoring AL002, and amyloid PET imaging demonstrated no treatment-related reduction of brain amyloid levels...Based upon the results, Alector is stopping the long-term extension study...Topline data from the pivotal INFRONT-3 Phase 3 clinical trial of latozinemab in frontotemporal dementia with a progranulin gene mutation is expected in late 2025 or early 2026."

P2 data • P3 data • Trial termination • Alzheimer's Disease • CNS Disorders

Alector Secures Flexible Credit Facility for Up to $50 Million From Hercules Capital (GlobeNewswire) - "Alector, Inc...today announced that the Company has entered into a debt financing agreement with Hercules Capital, Inc...for up to $50 million...'We anticipate transformational data from both the AL002 INVOKE-2 Phase 2 trial and the latozinemab INFRONT-3 pivotal Phase 3 trial within our runway. This credit facility provides additional funding to advance our preclinical pipeline including our proprietary, versatile Alector Brain Carrier blood-brain barrier platform and programs.' Under the terms of the agreement, Alector drew an initial $10 million at closing. An additional $15 million is available at the Company’s request through June 30, 2026, with an additional $25 million available upon lender approval."

Financing • Alzheimer's Disease • CNS Disorders • Dementia

Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease. (PubMed, Alzheimers Res Ther) - P1 | "These findings support the continued clinical development of AL002 for AD and other neurodegenerative diseases in which TREM2 activation may be beneficial. AL002 is currently being tested in a phase 2, randomized, double-blind, placebo-controlled study in early AD."

Clinical • Journal • P1 data • Preclinical • Alzheimer's Disease • CNS Disorders • TREM2

A Long-term Extension Study to Evaluate Safety, Tolerability, and Efficacy of AL002 in Alzheimer's Disease (clinicaltrials.gov) - P2 | N=188 | Active, not recruiting | Sponsor: Alector Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders

INVOKE-2: A Phase 2 Study to Evaluate Efficacy and Safety of AL002 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=381 | Completed | Sponsor: Alector Inc. | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders

Alector Presents Baseline Characteristics for INVOKE-2 Phase 2 Clinical Trial of AL002 at the Alzheimer’s Association International Conference 2024 (AAIC) (GlobeNewswire) - "Alector, Inc...today announced the presentation of a poster on baseline characteristics for the global INVOKE-2 Phase 2 clinical trial evaluating the safety and efficacy of AL002 in slowing disease progression in individuals with early Alzheimer’s disease (AD) at the Alzheimer's Association International Conference 2024 (AAIC)...A total of 381 participants were randomized in INVOKE-2. The median age of participants was 71 years (range: 51-85 years), with 78% of participants 65 years of age or older. Overall, 50% of participants were female and 94% were Caucasian. The clinical diagnosis at enrollment was mild cognitive impairment due to AD for 67% of participants and mild dementia due to AD for 33% of participants...Results of the INVOKE-2 trial are expected in the fourth quarter of 2024, and the long-term extension (LTE) study is ongoing for those who completed the planned treatment period."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders

Alector to Present Data on Pipeline Focus Areas at the Alzheimer’s Association International Conference (AAIC) 2024 (GlobeNewswire) - "Alector, Inc...today announced presentations related to the Company’s TREM2 and progranulin programs at the upcoming Alzheimer's Association International Conference 2024 (AAIC) being held online and in Philadelphia, Pennsylvania from July 28 – August 1, 2024. Poster presentations will be available for on-demand viewing beginning on July 28 at 8:00 a.m. ET."

Clinical • P2 data • Preclinical • Alzheimer's Disease • CNS Disorders

Baseline characteristics for INVOKE-2: a phase 2 randomized, double-blind, placebo-controlled study evaluating AL002 in early Alzheimer’s disease (AAIC 2024) - "Taken together, the baseline characteristics data for the INVOKE-2 study represent a study population that enables testing of the effects of a TREM2 agonist in early AD."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Aβ42 • CHI3L1 • CSF1R • GFAP • IL1RN • NEFL • p-tau181 • SPP1

Use of a blood-based amyloid test for screening in INVOKE-2: a phase 2 randomized, double-blind, placebo-controlled study evaluating AL002 in early Alzheimer’s disease (AAIC 2024) - "The prototype VR-PrecivityAD blood-test was highly predictive of amyloid positivity, confirmed by VR-PET or CSF, among INVOKE-2 screening subjects. Use of a lower VR-APS threshold was associated with fewer false negatives without a meaningful increase in false positives when compared to the standard CL-PrecivityAD threshold in the INVOKE-2 screening population."

Clinical • P2 data • Alzheimer's Disease • Amyloidosis • CNS Disorders • Dementia • APOE • Aβ42

Alector Reports First Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Alector and GSK plan to present a poster on the design of the AL101 Phase 2 trial at the Alzheimer's Association International Conference 2024 (AAIC) in Philadelphia from July 28 to August 1, 2024....The INVOKE-2 Phase 2 clinical trial of AL002 is fully enrolled, and data from the trial are anticipated in the fourth quarter of 2024."

Clinical protocol • Enrollment closed • P2 data • Alzheimer's Disease • CNS Disorders

Trem2 Agonist Reprograms Foamy Macrophages to Promote Atherosclerotic Plaque Stability. (PubMed, Arterioscler Thromb Vasc Biol) - "In vitro studies validated that Trem2 agonism with AL002a promoted foamy macrophage oxidized low-density lipoprotein uptake, survival, and cholesterol efflux. Trem2 agonism expands atherosclerotic plaque macrophages by promoting cell survival and proliferation but improves features of plaque stability by rewiring foamy macrophage function to enhance cholesterol efflux and collagen deposition."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Inflammation

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 (GlobeNewswire) - "Alector, Inc...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."

Enrollment closed • P2 data • Alzheimer's Disease • CNS Disorders

INVOKE-2: A Phase 2 Study to Evaluate Efficacy and Safety of AL002 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=328 | Active, not recruiting | Sponsor: Alector Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders

INVOKE-2: A Phase 2 Study to Evaluate Efficacy and Safety of AL002 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=328 | Recruiting | Sponsor: Alector Inc. | Trial completion date: Jan 2024 ➔ Nov 2024 | Trial primary completion date: Dec 2023 ➔ Oct 2024

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

Alector Reports Second Quarter 2023 Financial Results and Provides Business Update (Yahoo Finance) - "Alector closed screening and plans to complete enrollment in the INVOKE-2 clinical trial in the third quarter of 2023, with data expected in the fourth quarter of 2024. The INVOKE-2 Phase 2 trial is designed to evaluate the efficacy and safety of AL002 in slowing disease progression in individuals with early Alzheimer’s disease (AD)."

Enrollment status • P2 data • Alzheimer's Disease • CNS Disorders

AL002c-mediated reduction in amyloid β pathology is reflected by changes in plasma Alzheimer’s disease biomarkers in 5XFAD mice (AAIC 2023) - "AL002c-associated changes in plasma Aβ42/40 and tau were consistent with a concomitant reduction in filamentous plaques and neurite dystrophy. 1 These results lend further support to the clinical utility of plasma Aβ42/40 as a marker for the reduction of neurotoxic amyloid plaques in clinical trials with AL002."

Preclinical • Alzheimer's Disease • CNS Disorders • Aβ42 • Plasma Aβ40 • Plasma T-Tau • TREM2

INVOKE-2: Phase 2 trial of a TREM2 mAb in Early AD (AAIC 2023) - "The INVOKE-2 trial is an ongoing global Phase 2 randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of AL002 in participants with early Alzheimer’s disease. This presentation will provide an update on AL002 clinical development."

P2 data • Alzheimer's Disease • CNS Disorders

A Long-term Extension Study to Evaluate Safety, Tolerability, and Efficacy of AL002 in Alzheimer's Disease (clinicaltrials.gov) - P2 | N=190 | Recruiting | Sponsor: Alector Inc.

New P2 trial • Alzheimer's Disease • CNS Disorders • Aβ42 • CHI3L1 • CSF P-tau • CSF1R • IL1RN • Plasma Aβ40 • SPP1

A Clinical Trial to evaluate AL002 in Participants with early Alzheimer's Disease Ensayo clínico para evaluar AL002 en participantes con enfermedad de Alzheimer temprana (clinicaltrialsregister.eu) - P2 | N=190 | Ongoing | Sponsor: Alector, Inc.

New P2 trial • Alzheimer's Disease • CNS Disorders • Aβ42 • CHI3L1 • CSF P-tau • CSF1R • IL1RN • Plasma Aβ40 • SPP1

A Phase 1 Study of AL002 in Healthy Volunteers (AAN 2022) - "AL002 treatment resulted in TREM2 target engagement and proof of activity in the CSF of HVs. These results have supported progressing AL002 to an ongoing Phase 2 study (INVOKE-2) to investigate its effects on cognitive decline and neurodegeneration in subjects with early AD."

Clinical • P1 data • Alzheimer's Disease • CNS Disorders • CSF1R • IL1RN • SPP1

INVOKE-2 - A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AL002 in Participants with Early Alzheimer’s Disease (AAN 2022) - P2 | "INVOKE-2 is designed to investigate the efficacy and safety of AL002, representing a novel, first-in-class neuro-immunological approach for treating AD. Enrollment is ongoing."

Clinical • P2 data • Alzheimer's Disease • Amyloidosis • CNS Disorders • Immunology