Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology
company pioneering immuno-neurology, presented results from the
INFRONT-2 Phase 2 clinical trial of AL001 (latozinemab) in
frontotemporal dementia patients (FTD) with a C9orf72 genetic
mutation (FTD-C9orf72) at the AD/PD™ 2022 International Conference
on Alzheimer’s and Parkinson’s Diseases and related neurological
disorders taking place virtually and in person in Barcelona, Spain.
Latozinemab is a potential first-in-class monoclonal antibody
designed to elevate progranulin, a key regulator of immune activity
and lysosomal health in the brain. FTD is a rare and rapidly
progressing neurodegenerative disease that is the most common form
of dementia for people under the age of 60.
In 2021, Alector presented results showing that latozinemab
elevated progranulin levels in a cohort of symptomatic carriers of
the progranulin mutation causative of FTD (FTD-GRN) patients for
the duration of treatment, and as compared to matched controls,
showed associated changes in exploratory biomarkers and a trend
toward a delay in annual disease progression. Today’s data from the
FTD-C9orf72 cohort build upon the results observed in the Company’s
studies to date in FTD-GRN patients.
The results presented include 12-month data from up to 10
symptomatic FTD-C9orf72 patients treated with 60 mg/kg of
latozinemab every four weeks in an open-label study designed to
primarily assess the safety and tolerability of chronic dosing. The
study also includes exploratory clinical outcomes assessments and
biomarkers. Highlights from the presentation included the following
observations:
- Latozinemab was generally well tolerated when administered
monthly for a year or more, consistent with other study
cohorts.
- Latozinemab elevated progranulin in both plasma and
cerebrospinal fluid (CSF) in FTD-C9orf72 patients for the duration
of treatment.
- Clinical outcome assessments using the CDR® plus NACC FTLD-SB
scale, a standard FTD clinical rating instrument that assesses
cognitive, functional, behavioral and language impairments over
time, found that when compared to a matched control cohort from the
ALLFTD consortium, treatment with latozinemab in FTD-C9orf72
patients resulted in a trend toward a delay of approximately 54
percent in annualized disease progression.
- Mean levels of neurofilament light chain (NfL), a marker of
axonal damage, remained stable over the course of treatment in both
plasma and CSF in latozinemab-treated FTD-C9orf72 patients.
- Mean levels of glial fibrillary acidic protein (GFAP), a
biomarker of astrogliosis that is an indicator of disease and/or
injury to the central nervous system, decreased over 12 months in
both plasma and CSF in latozinemab-treated FTD-C9orf72
patients.
In published preclinical studies from the literature, using
multiple models of acute and chronic neurodegeneration, increased
progranulin levels have been shown to be protective against TDP-43
pathology. TDP-43 pathology has been shown to be associated with
the C9orf72 repeat expansion.
“Mutations in the C9orf72 gene are the most common genetic cause
of frontotemporal dementia, a devastating disease with no approved
treatments. These mutations are also an important cause of ALS,”
said Sam Jackson, M.D., interim Chief Medical Officer of Alector.
“Building upon the results we presented last year on the potential
benefit associated with using latozinemab to elevate progranulin
levels in the symptomatic FTD-GRN cohort of our INFRONT-2 Phase 2
clinical study, these data further validate Alector’s approach of
elevating progranulin levels to address a range of
neurodegenerative diseases. We are encouraged by these findings and
look forward to evaluating latozinemab in additional indications as
part of our progranulin franchise in partnership with
GlaxoSmithKline (GSK).”
Alector is actively enrolling the Phase 3 INFRONT-3 pivotal
clinical study of latozinemab in at-risk and symptomatic FTD-GRN
patients. The global randomized, double-blind, placebo-controlled
study is designed to assess the efficacy and safety of latozinemab
in inhibiting disease progression as measured through the primary
endpoint, CDR® plus NACC FTLD-SB scale. Latozinemab is being
developed in collaboration with GSK.
INFRONT-2 Phase 2 Clinical Trial ResultsThe
open-label study was designed to assess safety and tolerability of
chronic dosing of latozinemab, as well as to gather data related to
pharmacokinetics and pharmacodynamics, exploratory biomarkers of
pharmacologic activity and efficacy. INFRONT-2 included three
cohorts of patients with FTD: asymptomatic FTD-GRN mutation
carriers, symptomatic FTD-GRN patients, and symptomatic FTD-C9orf72
patients. Data presented today focused on the FTD-C9orf72 cohort
and included 12-month data for up to 10 patients with at least one
post-baseline clinical outcomes assessment, who received 60 mg/kg
of latozinemab every four weeks. As of the data cut, six
FTD-C9orf72 patients had completed 12 months of treatment and all
biomarker and clinical outcomes assessments.
Latozinemab was well tolerated in the INFRONT-2 study.
Twenty-eight study participants from all three cohorts were
assessed for safety, with twenty-one patients treated for 12 months
or more. Within the FTD-C9orf72 cohort there were a total of seven
treatment related AEs, all of which were mild or moderate.
Treatment with latozinemab in the FTD-C9orf72 cohort resulted in
elevated levels of progranulin when measured in both the plasma and
CSF.
Table 1: Progranulin Levels from Baseline to 12 months with
Latozinemab Treatment (ng/mL) |
Plasma |
CSF1 |
Baseline(N=10) |
25 weeks (N=7) |
49 weeks(N=6) |
Baseline(N=8) |
25 weeks (N=7) |
49 weeks(N=6) |
123.6 (13.49) |
324.4 (37.41) |
315.7 (21.12) |
4.4 (0.42) |
9.3 (1.31) |
1.7 (0.90) |
- CSF: cerebrospinal fluid, mean (standard error of the
mean)
The CDR® plus NACC FTLD-SB scores in the ALLFTD matched control
cohort had a projected annual increase of 3.4 points from baseline
over one year. By comparison, the projected annual increase in the
latozinemab treated FTD-C9orf72 cohort (N=10) from baseline was
estimated at 1.6 points over one year. This suggested a trend
toward an approximately 54 percent decrease in the annualized rate
of clinical progression for patients treated with latozinemab. The
CDR® plus NACC FTLD-SB scale is the primary endpoint being used to
measure latozinemab’s efficacy in Alector’s ongoing INFRONT-3 Phase
3 clinical study.
Table 2: Clinical Outcomes Assessment as Measured by the
CDR® plus NACC
FTLD-SB |
Parameter |
Estimate |
95% CI |
Annual Change in ALLFTD matched control (n=10)1 |
3.4 |
[1.30,5.60] |
Annual Change in latozinemab-treated group (n=10)2 |
1.6 |
[-0.63,3.78] |
Difference in Annual Change (ALLFTD –
latozinemab)3 |
1.9 |
[-1.21,4.95] |
Percentage Decrease in Rate of Disease
Progression |
~54% |
n/a |
1. ALLFTD matched control – one post-baseline timepoint at ~12
months.2. Latozinemab-treated group – all available post-baseline
assessments (range from 3 to 12 months).3. Model – Random
coefficient model with repeated measurements.
In order to provide context for the clinical outcomes assessed
in the FTD-C9orf72 patients enrolled in the open-label INFRONT-2
study, a matched control cohort of FTD-C9orf72 patients from the
ALLFTD database was created using propensity score matching and
blinded clinical adjudication. ALLFTD is a comprehensive natural
history study of FTD collecting cognitive and behavior assessment
data, as well as imaging, blood and CSF biomarkers co-directed by
Dr. Brad Boeve at the Mayo Clinic in Rochester, Minnesota, and Drs.
Adam Boxer and Howard Rosen, at University of California, San
Francisco (UCSF). A total of 10 ALLFTD patients were identified
whose baseline cognitive assessment scores and characteristics,
including age, sex, NfL level at baseline and diagnosis or variant
of FTD-C9orf72, were comparable to those of the FTD-C9orf72 patient
cohort in the INFRONT-2 Phase 2 study. Propensity score matching
and clinical adjudication was performed by researchers blinded to
the one-year follow-up data from the ALLFTD matched control cohort.
Cognitive assessment was measured using the CDR® plus NACC FTLD-SB
scale, a standard FTD clinical rating instrument that assesses
cognitive, functional, behavioral and language impairments over
time.
Changes in exploratory biomarkers from baseline to 12-months
were also assessed. NfL, a marker of axonal damage, was measured in
plasma and CSF. During the 12-month period of treatment, NfL levels
in plasma and CSF remained stable in the latozinemab-treated
FTD-C9orf72 cohort.
GFAP, a biomarker of astrogliosis that is an indicator of
disease and/or injury to the central nervous system and is
associated with faster rates of brain atrophy in FTD, was also
measured. Treatment with latozinemab resulted in a decline of GFAP
in both plasma and CSF in the latozinemab-treated FTD-C9orf72
cohort.
Conference Call InformationAlector management
will host a conference call to review and discuss data presented at
AD/PD™ today at 8:30 a.m. ET. Analysts and investors are
invited to participate in the conference call by dialing (888)
705-0365 from the U.S. and Canada or (415) 817-9241 internationally
and using the conference ID 6957317. The live webcast can be
accessed on the investor page of Alector’s website at
investors.alector.com. A replay of the webcast will be available on
Alector’s website approximately two hours after the completion of
the event and will be archived for up to 30 days.
About FTD-C9orf72C9orf72
repeat expansions are the most common genetic cause of the
neurodegenerative diseases frontotemporal dementia (FTD) and
amyotrophic lateral sclerosis (ALS). Both decreased progranulin
levels and mutations in the chromosome 9 open reading frame 72
(C9orf72) gene are associated with abnormal accumulation of the TAR
DNA-binding protein 43 (TDP-43). Excess aggregation of TDP-43 in
brain cells is thought to lead to neuronal cell death and is
associated with multiple neurodegenerative diseases.
About Frontotemporal DementiaFTD is a rare
neurodegenerative disease, but it is the most common form of
dementia for people under the age of 60. It affects an estimated
50,000 to 60,000 people in the United States and roughly 110,000 in
the European Union, with potentially higher prevalence in Asia and
Latin America. There are multiple heritable forms of FTD, including
FTD-GRN and FTD-C9orf72. Patients with FTD frequently develop
symptoms such as behavioral changes, lapses in judgment, and
diminished language skills when they are in their 40’s and 50’s
with the disease running its course in 7-10 years. There are no
FDA-approved treatment options available for any form of
frontotemporal dementia.
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 the 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,
Alzheimer’s disease, and amyloid lateral sclerosis. This scientific
approach is also the basis for the company’s immuno-oncology
programs. Alector is headquartered in South San Francisco,
California. For additional information, please visit
www.alector.com.
Cautionary Note Regarding Forward-Looking
StatementsThis press release contains forward-looking
statements as that term is defined in 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
preclinical studies, clinical trials, expected milestones,
expectations of our collaborations, and financial guidance. Such
forward-looking statements include, among other things, statements
regarding the continued clinical development of AL001; the expected
timing of reporting future data from the AL001 clinical trial; the
potential benefits of AL001 or Alector’s (the Company) other
product candidates; and statements by the Company’s chief medical
officer. Words such as “believes,” “anticipates,” “plans,”
“expects,” “intends,” “will,” “goal,” “potential” and similar
expressions are intended to identify forward-looking statements.
The forward-looking statements contained herein are based upon
Alector’s current expectations and involve assumptions that may
never materialize or may prove to be incorrect. Actual results
could differ materially from those projected in any forward-looking
statements due to numerous risks and uncertainties, including but
not limited to: the Company’s plans relating to the development and
manufacturing of its product candidates and research programs; the
ability of the Company’s clinical trials to demonstrate safety and
efficacy of its product candidates, and other positive results; the
timing and focus of the Company’s future clinical trials, and the
reporting of data from those trials; the Company’s plans relating
to commercializing its product candidates, if approved, including
the geographic areas of focus and sales strategy; the expected
potential benefits of strategic collaborations with third parties
and the Company’s ability to attract collaborators with
development, regulatory and commercialization expertise; the
Company’s estimates of the number of patients in the United States
who suffer from the diseases it is targeting and the number of
patients that will enroll in its clinical trials; the size of the
market opportunity for the Company’s product candidates in each of
the diseases it is targeting; the Company’s ability to expand its
product candidates into additional indications and patient
populations; the success of competing therapies that are or may
become available; the beneficial characteristics, safety, efficacy,
and therapeutic effects of the Company’s product candidates; the
timing or likelihood of regulatory filings and approvals, including
the Company’s expectation to seek special designations, such as
orphan drug designation, for its product candidates for various
diseases; the Company’s ability to obtain and maintain regulatory
approval of its product candidates; the Company’s plans relating to
the further development and manufacturing of its product
candidates, including additional indications that it may pursue;
existing regulations and regulatory developments in the United
States and other jurisdictions; the Company’s continued reliance on
third parties to conduct additional clinical trials of its product
candidates, and for the manufacture of its product candidates for
preclinical studies and clinical trials; and other risks.
Information regarding the foregoing and additional risks may be
found in the section entitled “Risk Factors” in Alector’s Annual
Report on Form 10-K filed with the Securities and Exchange
Commission (the “SEC”) on February 24, 2022, and Alector’s future
reports to be filed with the SEC. These forward-looking statements
are made as of the date of this press release, and Alector assumes
no obligation to update the forward-looking statements, or to
update the reasons why actual results could differ from those
projected in the forward-looking statements, except as required by
law.
1AB (media)Dan Budwick973-271-6085dan@1abmedia.com
Argot Partners (investors)Eric Kasper/Carrie McKimArgot
Partners212.600.1902alector@argotpartners.com
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