Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology
company pioneering immuno-neurology, 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®). The conference is being
held online and in Philadelphia, Pennsylvania from July 28 – August
1, 2024.
INVOKE-2 is the first global Phase 2 trial exploring a novel
TREM2 agonist, AL002, in early AD. AL002 is an investigational
humanized monoclonal antibody (mAb) that binds to triggering
receptor expressed on myeloid cells 2 (TREM2), and it is the most
advanced TREM2 agonist product candidate in clinical trials. The
candidate is being developed in collaboration with AbbVie.
"The baseline characteristics of the patients in INVOKE-2 are
important for assessing the quality of our double-blind,
placebo-controlled Phase 2 clinical trial evaluating the safety and
efficacy of AL002, the most advanced TREM2-activating candidate in
clinical development for early Alzheimer’s disease,” said Gary
Romano, M.D., Ph.D., Chief Medical Officer of Alector. “We are
pleased that the baseline clinical assessments confirm that the
INVOKE-2 trial enrolled the intended population of participants
with early Alzheimer’s disease, allowing us to test Alector’s
hypothesis that treatment with this first-in-class TREM2 agonist
may slow disease progression.”
Baseline characteristics are important in Phase 2 trials because
they ensure the reliability and interpretability of trial results,
help manage patient safety, and facilitate appropriate statistical
analyses. 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.
Treatment-emergent brain MRI changes resembling amyloid-related
imaging abnormalities (ARIA) have been observed in the trial. These
changes were of greater incidence and severity in homozygous APOE
e4 carriers, and the company chose to discontinue homozygous APOE
e4 carriers early in the trial. Of the 381 enrolled participants,
59% were heterozygous APOE e4 carriers. Amyloid positivity was
confirmed in all participants prior to enrollment by analysis of
cerebrospinal fluid or amyloid PET (Positron Emission Tomography).
For those participants (n=244) with amyloid PET assessed at
baseline, the mean standard deviation (SD) in centiloids was 100.1
(38.9).
Additional details will be presented during the poster
presentation, “Baseline Characteristics for INVOKE-2: A Phase 2
Randomized, Double-Blind, Placebo-Controlled Study Evaluating AL002
in Early Alzheimer’s Disease” (#95594) on Sunday, July 28, 2024,
from 8:00 a.m. – 4:15 p.m. ET at AAIC®.
A Phase 1 study of AL002 demonstrated dose-dependent target
engagement and dose-dependent effects on microglial signaling
biomarkers, and the treatment was well-tolerated in healthy
volunteers at multiple doses.
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. Thus far, nearly
all eligible participants have rolled over into the LTE study,
which will facilitate better understanding of the long-term effects
of AL002.
About INVOKE-2INVOKE-2 (Clinicaltrials.gov
identifier NCT04592874) is a double-blind, placebo-controlled,
dose-ranging, multi-center, randomized clinical trial in patients
with early AD. 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, with data collected for
up to 96 weeks. Patients are randomized to three dose regimens,
15mg/kg IV/q4w, 40mg/kg IV/q4w, 60mg/kg IV/q4w, or placebo.
About AL002AL002 is an investigational
humanized monoclonal antibody that targets triggering receptor
expressed on myeloid cells 2 (TREM2), a key microglial membrane
receptor that senses pathological changes in the brain. Studies
have identified 40 TREM2 mutations related to Alzheimer’s disease
(AD), with heterozygous mutations increasing AD risk by as much as
threefold.1 Reduced TREM2 function may contribute to AD and other
neurodegenerative diseases. Conversely, higher levels of TREM2, as
measured by cerebrospinal fluid (CSF) levels of soluble TREM2
(sTREM2) are associated with lower amyloid and tau accumulation as
well as attenuated cognitive and clinical decline.2,3
AL002 is designed to increase TREM2 signaling and enhance
microglia proliferation, survival, and function. Binding of AL002
to the TREM2 receptor aims to trigger microglial signaling
pathways, bolstering the effectiveness of microglia in protecting
the brain against insults, including age-related neurodegeneration
in AD. The clinical potential of AL002 is currently under
investigation in clinical trials focused on evaluating its impact
on AD.
Collaboration with AbbVieIn 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 payments totaling up to $475M,
which includes the $250M option exercise fee and future milestones.
Alector and AbbVie will share development costs and profits after
marketing approval, though Alector may opt out of development cost
sharing and instead receive royalties.
About AlectorAlector 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 seek to treat
indications, including Alzheimer’s disease and genetically defined
frontotemporal dementia patient populations. Alector is
headquartered in South San Francisco, California. For more
information, visit www.alector.com.
Forward-Looking StatementsThis 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, planned and ongoing preclinical studies and clinical
trials, anticipated timing and detail or release of data for
INVOKE-2, expected milestones, expectations of our collaborations,
and expectations of our interactions with regulatory authorities.
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 May 8, 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.
REFERENCES1. Mutations TREM2 | Alzforum.
(n.d.). Retrieved November 29, 2023, from
https://www.alzforum.org/mutations/trem2.
2. Ewers M, et al.; Alzheimer’s Disease Neuroimaging Initiative.
Increased soluble TREM2 in cerebrospinal fluid is associated with
reduced cognitive and clinical decline in Alzheimer's disease. Sci
Transl Med. 2019 Aug 28;11(507):eaav6221.
3. Pereira, J.B., et al. Microglial activation protects against
accumulation of tau aggregates in nondemented individuals with
underlying Alzheimer’s disease pathology. Nat Aging 2, 1138–1144
(2022).
Alector Contacts:
AlectorKatie Hogan202-549-0557katie.hogan@alector.com
1AB (media)Dan Budwick973-271-6085 dan@1abmedia.com
Argot Partners (investors)Laura
Perry212.600.1902alector@argotpartners.com
AbbVie (NYSE:ABBV)
Historical Stock Chart
Von Jul 2024 bis Aug 2024
AbbVie (NYSE:ABBV)
Historical Stock Chart
Von Aug 2023 bis Aug 2024