Alector Announces Publication of Preclinical and Phase 1 Data Validating Potential of AL002, a TREM2 Activating Antibody for ...
25 June 2020 - 11:00PM
Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology
company pioneering immuno-neurology, announced the publication of
preclinical and preliminary Phase 1 clinical data of AL002, a TREM2
activating antibody, in The Journal of Experimental Medicine. The
paper elucidates how a variant of AL002 reduces pathology in an
Alzheimer’s disease mouse model and induces a novel transcriptional
signature in microglia associated with proliferation, and it
includes data from the AL002 Phase 1 clinical trial that
demonstrates target engagement in healthy volunteers and AL002’s
overall safety profile. The paper, “Anti-human TREM2 antibody
induces microglia proliferation and reduces pathology in an
Alzheimer's Disease model,” was carried out in collaboration with
Marco Colonna, M.D. at Washington University in St. Louis and can
be accessed here.
“This publication is a culmination of years of research by the
Alector team and our academic collaborators,” said Robert Paul,
M.D., Ph.D., Chief Medical Officer of Alector. “Specifically, the
data show that antibody-mediated engagement of TREM2 enhances
neuroprotective microglia and restrains neurotoxic plaques and
neuronal damage in an Alzheimer’s disease mouse model. Together
with the safety and target engagement data from our Phase 1 trial
of AL002, these results provide strong support for continued
development of AL002 as a potential treatment for Alzheimer’s
disease. We look forward to the expected initiation of a Phase 2
trial of AL002 later this year.”
Highlights of the findings from the Preclinical Study:
- TREM2 is a receptor for lipids expressed in microglia. The R47H
variant of human TREM2 impairs ligand binding and increases
Alzheimer’s disease risk. In mouse models of amyloid beta
accumulation, defective TREM2 function affects microglial response
to neuronal damage, inflammation, and toxic amyloid beta plaques,
whereas TREM2 overexpression attenuates these
pathologies.
- The study examined the impact of an anti-human TREM2 agonistic
monoclonal antibody, AL002c, a variant of AL002, in a mouse model
of Alzheimer’s disease expressing either the common variant or the
R47H variant of human TREM2 to determine potential benefit from
TREM2 activation on Alzheimer’s disease.
- The study found that a single injection of AL002c expanded
unique subpopulations of metabolically active and proliferating
microglia. Prolonged treatment with AL002c tempered the microglial
inflammatory response and reduced the formation of toxic
filamentous plaques, which curtailed neurite dystrophy.
- The study further showed that AL002c treatment was beneficial
after plaque formation, suggesting that anti-TREM2 antibodies may
be helpful even if introduced at relatively late stages of
disease.
Highlights of Findings from Phase 1 Clinical Study:
- The Phase 1a clinical study was a first-in-human study in
healthy adults, designed to assess the safety (including
immunogenicity), tolerability, pharmacokinetics (PK) and
pharmacodynamics (PD) of AL002.
- In the single ascending dose portion of the Phase 1 study, 56
healthy volunteers were sequentially enrolled into 10 cohorts and
received a single intravenous dose of AL002. In addition to safety,
the study assessed the effect of AL002 on cerebrospinal fluid
biomarkers, sTREM2 and sCSF-1R.
- Preliminary data from the completed Phase 1 study of AL002
indicates that AL002 was generally well-tolerated with no
drug-related serious adverse events or dose-limiting toxicities up
to the highest dose. The data also indicated target engagement of
AL002 in the brain, as measured by the cerebrospinal fluid
biomarkers sTREM2 and sCSF-1R.
About AL002 AL002 is a monoclonal antibody that
targets a triggering receptor expressed on myeloid cells 2 (TREM2)
with the strongest genetic links after APOE4 to 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. TREM2 is thought to promote
improved cell migration to the site of injury, improved cell
survival, increased phagocytosis, and increased cell proliferation.
Loss of TREM2 function leads to Alzheimer's disease and other forms
of dementia and research suggests that boosting TREM2 levels in the
brain may prevent or reduce the severity of neurodegenerative
disorders.
About Collaboration with AbbVieIn October 2017,
Alector entered into a global strategic collaboration with AbbVie
(NYSE: ABBV), a leader in neuroscience drug development, 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
two programs, including TREM2. For each program, Alector is
responsible for the design and execution of Phase 1 and Phase 2
studies, leveraging the Company’s in-house expertise in running
clinical trials in Alzheimer’s disease. Following its exercise of
an option for a program, AbbVie will be responsible for certain
development activities and global commercialization. The terms of
the agreement included an initial upfront payment of $205M in cash
and $20M in equity and if AbbVie exercises its option for either
program (or both programs), Alector is eligible for additional
option exercise and milestone payments totaling up to $986M.
Following AbbVie’s exercise of its option, Alector and AbbVie 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 2018, there are 5.7 million Americans
suffering from Alzheimer’s disease, and projects that number will
rise to nearly 14 million by 2050.
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 is developing a broad portfolio of
programs designed to functionally repair genetic mutations that
cause dysfunction of the brain’s immune system and enable the
rejuvenated immune cells to counteract emerging brain pathologies.
The Company’s 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 StatementsThis press release
contains forward-looking statements within the meaning of the
Private Securities Litigation Reform Act of 1995. Such statements
are subject to numerous important factors, risks and uncertainties
that may cause actual events or results to differ materially from
current expectations and beliefs, including but not limited to
risks and uncertainties related to the Company’s plans for and
anticipated benefits and mechanism of the Company’s product
candidates, the timing and objectives of the Company’s clinical
studies and anticipated regulatory and development milestones,
Alector and its business as set forth in Alector’s Annual Report on
Form 10-Q filed with the Securities and Exchange Commission (the
“SEC”) on May 13, 2020, 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.
Contacts: Media 1AB Dan Budwick, 973-271-6085
dan@1abmedia.com
or
Investors: Alector, Inc. ir@alector.com
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