Annexon, Inc. (Nasdaq: ANNX), a clinical-stage biopharmaceutical
company developing medicines that stop destructive immune activity
in complement-mediated autoimmune, neurodegenerative and ophthalmic
disorders, today announced interim data from its ongoing,
open-label Phase 2 clinical trial of ANX005 in patients with
Huntington’s disease (HD) who completed the 24-week treatment
period. Annexon is developing ANX005, its lead monoclonal antibody
candidate, for the treatment of a range of complement-mediated
disorders, including HD.
HD is a fatal, progressive movement disorder involving the
activation of the classical complement pathway. C1q, the initiator
of the classical pathway, is recognized as a major driver of a
destructive immune response that leads to synapse loss and
neurodegeneration. ANX005 is designed to disrupt the disease
course, stopping the start of damaging complement activation by
blocking C1q and the entire classical complement pathway.
Interim data from the ongoing Phase 2 trial show that treatment
with ANX005 has been generally well-tolerated, with full target
engagement of C1q in both serum and cerebrospinal fluid (CSF)
observed in evaluable patients through the dosing period. Evaluable
patients maintained clinical function, as measured by changes in
mean Composite Unified Huntington's Disease Rating Scale (cUHDRS),
relative to baseline after six months of treatment, and improvement
in cUHDRS was observed in more than half of all evaluable patients
and in 75% of evaluable patients who showed excess complement
activity at baseline. NfL levels observed after six months of
treatment remained generally consistent and were comparable to NfL
levels described in published natural history data for HD patients.
Overall, these interim findings appear to build on the scientific
hypothesis of Annexon scientific founder, the late Ben Barres, who
believed that blocking C1q protects synaptic loss and can lead to
rapid functional impact on clinical outcomes in neurodegenerative
diseases.
“People with HD face a devastating condition, with no cure or
approved disease-modifying treatments available,” said Edward Wild,
FRCP, Ph.D., consultant neurologist, NHNN Queen Square and
associate director, UCL Huntington’s Disease Centre. “I believe the
interim data from this open-label trial of ANX005 are encouraging,
showing complete CSF target engagement and that ANX005 has been
generally well-tolerated, with no concern regarding the NfL levels
seen in this early readout. The apparent stabilization of cUHDRS
observed relative to normal disease progression, together with the
potential improvement seen in patients with elevated baseline C4a,
supports the hypothesis that protecting synapses via C1q inhibition
could produce meaningful functional benefit in HD, and justifies
the continued development of ANX005 for this indication.”
ANX005 Interim Safety and Target Engagement
Data
ANX005 has been generally well-tolerated in the study (n=28). As
of the data cutoff date of October 17, 2021, the most common
adverse events (AEs) reported were first dose-associated
infusion-related reactions, including transient skin rash,
consistent with the experience observed in the company’s Phase 1b
trial of ANX005 in patients with Guillain-Barré Syndrome (GBS). In
the HD trial, five patients discontinued ANX005 treatment, three of
whom discontinued due to a drug-related AE. Two patients
experienced a drug-related serious adverse event, including one
event of systemic lupus erythematosus (mucocutaneous), whose
symptoms resolved post-study drug discontinuation, and one event of
idiopathic pneumonitis, which stabilized post-study drug
discontinuation. Of note, no cases of serious infection were
identified, and no deaths were reported.
Interim data show that treatment with ANX005 has led to full
target engagement of C1q in both serum and CSF through the dosing
period in patients who were evaluable as of the cutoff date of
October 17, 2021 (n=13).
ANX005 Interim Efficacy and Biomarker Data
Patients evaluable as of the cutoff date of December 14, 2021
(n=23) experienced improvements in clinical measures, assessed by
cUHDRS, a clinical rating scale with four domains measuring the
progression of HD consisting of motor, cognitive and functional
capacity. Overall, patients maintained clinical function relative
to baseline in cUHDRS after six months of treatment. Published
natural history data show that HD patients typically experienced a
decline of approximately 1 point over one year1, or 0.5 points over
six months. Additionally, as of the cutoff date, 56% of patients
showed improvement from baseline in cUHDRS and several subdomains
of cUHDRS over six months of treatment. Moreover, in a sub-analysis
of patients assessed according to baseline complement activity
(C4a), 75% of patients with excess baseline complement activity
demonstrated a statistical improvement in cUHDRS over six months of
treatment versus 36% with low baseline complement activity,
consistent with the scientific hypothesis of rapid response to
anti-C1q therapy via enhanced synapse function. Elevated C4a is an
objective measurement of excess complement activity in CSF that has
been found to correlate with disease progression and multiple
clinical endpoints in HD.2 These findings suggest that patients
with excess complement activity may be more likely to respond to
anti-C1q therapy in future clinical trials and may inform future
trial designs.
NfL, a protein component of the neuronal cytoskeleton, has been
shown to increase in the CSF with disease severity in HD patients.
Interim data assessing NfL from patients evaluable as of the cutoff
date of October 17, 2021 (n=16) who completed 24 weeks of treatment
showed that mean plasma and CSF NfL levels remained generally
consistent and were comparable to NfL levels described in published
natural history data for HD patients.3 Published data suggest that
in slowly progressive neurodegenerative diseases like HD, synapse
loss is associated with progressive functional decline, preceding
the loss of neurons4 and NfL changes. As such, changes in NfL may
require treatment durations longer than six months and Annexon will
continue to assess NfL levels in patients over the three-month
follow-up period.
“We are quite
encouraged by the interim data generated with ANX005 in HD. We are
particularly excited to see a heightened clinical response in
patients with excess baseline complement activity, suggesting that
the classical complement pathway plays a key role in the
neurodegenerative disease process and that ANX005 has the potential
to provide meaningful benefit to HD patients,” remarked Douglas
Love, Esq., president and chief executive officer of Annexon.
“These early data in HD patients, coupled with prior
proof-of-concept data in GBS, provide a growing body of evidence
for the potential role of anti-C1q in treating complement mediated
neurodegenerative and autoimmune diseases, and we look forward to
continuing to assess the full potential of our approach in several
ongoing trials in diseases of high unmet need.”
The Phase 2 trial remains ongoing, and Annexon anticipates
reporting full data from all patients enrolled, including data from
the three-month follow-up period, in the second quarter of 2022.
Pending results from the full dataset, Annexon plans to evaluate
the opportunity for a Phase 3 trial of ANX005 in HD patients.
Conference Call Information Annexon management
will host a conference call today at 4:30 p.m. ET. To participate
in the conference call, please dial (833) 649-1187 (domestic) or
(281) 206-0036 (international) and refer to conference ID 6297344.
The webcast and accompanying slides can be accessed under the
‘Events & Presentations’ section on the Investors page
at www.annexonbio.com. A replay of the webcast will be
archived on the Annexon website for 30 days.
About the Phase 2 Trial (ANX005-HD-01)The Phase
2 multi-center, open-label trial is evaluating ANX005 administered
intravenously for a 24-week (six-month) dosing period in patients
with, or at risk for, early manifest HD. The study enrolled a total
of 28 patients in May of 2021, and 23 patients completed the
24-week treatment period. The interim data reported today include
safety data for all 28 patients enrolled, efficacy data as measured
by UHDRS in all 23 evaluable patients, pharmacokinetics (PK) and
pharmacodynamics (PD) data for the first 13 patients, and NfL for
the first 16 patients who completed the 24-week treatment period
based on cutoff dates required to obtain data for this interim
analysis.
About AnnexonAnnexon (Nasdaq: ANNX) is a
clinical-stage biopharmaceutical company developing a new class of
complement medicines for patients with classical
complement-mediated autoimmune, neurodegenerative, and ophthalmic
disorders of the body, brain and eye. The company’s pipeline is
based on its platform technology addressing a broad spectrum of
well-researched classical complement-mediated autoimmune and
neurodegenerative diseases triggered by aberrant activation of C1q,
the initiating molecule of the classical complement pathway.
Annexon is advancing a portfolio of innovative product candidates
designed to block the activity of C1q and the entire classical
complement pathway: ANX005 (intravenous administration), ANX007
(intravitreal administration), and ANX009 (subcutaneous
administration). Annexon is deploying a disciplined,
biomarker-driven strategy designed to improve the probability of
technical success of its portfolio. For more information,
visit www.annexonbio.com.
Forward Looking StatementsThis press release
contains forward-looking statements within the meaning of Section
27A of the Securities Act of 1933, as amended, and Section 21E of
the Securities Exchange Act of 1934, as amended. In some cases, you
can identify forward-looking statements by terminology such as
“aim,” “anticipate,” “assume,” “believe,” “contemplate,”
“continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,”
“intend,” “may,” “objective,” “plan,” “positioned,” “potential,”
“predict,” “seek,” “should,” “suggest,” “target,” “on track,”
“will,” “would” and other similar expressions that are predictions
of or indicate future events and future trends, or the negative of
these terms or other comparable terminology. All statements other
than statements of historical facts contained in this press release
are forward-looking statements. These forward-looking statements
include, but are not limited to, statements about: initial findings
and observations related to the interim data from the company’s
ongoing, open-label Phase 2 clinical trial of ANX005 in patients
with HD; the potential benefits from treatment with anti-C1q
therapy; timing of full data from the Phase 2 trial of ANX005 in HD
patients; plans to evaluate the opportunity for a Phase 3 trial of
ANX005 in HD patients; and continuing advancement of the company’s
innovative portfolio. Forward-looking statements are not guarantees
of future performance and are subject to risks and uncertainties
that could cause actual results and events to differ materially
from those anticipated, including, but not limited to, risks and
uncertainties related to: the company’s history of net operating
losses; the company’s ability to obtain necessary capital to fund
its clinical programs; the early stages of clinical development of
the company’s product candidates; the effects of COVID-19 or other
public health crises on the company’s clinical programs and
business operations; the company’s ability to obtain regulatory
approval of and successfully commercialize its product candidates;
any undesirable side effects or other properties of the company’s
product candidates; the company’s reliance on third-party suppliers
and manufacturers; the outcomes of any future collaboration
agreements; and the company’s ability to adequately maintain
intellectual property rights for its product candidates. These and
other risks are described in greater detail under the section
titled “Risk Factors” contained in the company’s Annual Report on
Form 10-K and Quarterly Reports on Form 10-Q and the company’s
other filings with the SEC. Any forward-looking statements that the
company makes in this press release are made pursuant to the
Private Securities Litigation Reform Act of 1995, as amended, and
speak only as of the date of this press release. Except as required
by law, the company undertakes no obligation to publicly update any
forward-looking statements, whether as a result of new information,
future events or otherwise.
Investor Contact:
Chelcie ListerTHRUST Strategic
Communicationschelcie@thrustsc.com
Media Contact:
Sheryl SeapyReal
Chemistry949-903-4750sseapy@realchemistry.com
1 Schobel 20172 Suri, et al., HSG conference 20213 Tabrizi 2019
and Rodrigues 20204 Delva, et al., Neurology, 2021; Albin, et al.,
Ann Neurol, 1991; Gomez-Tortosa, Ann Neurol, 1991
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