Sangamo Therapeutics Announces Data From Novel Proprietary Neurotropic AAV Capsid Demonstrating Industry-leading Blood-brain Barrier Penetration and Brain Transduction in NHPs
13 Março 2024 - 9:01AM
Business Wire
- Novel AAV capsid engineered by Sangamo showed robust
penetration of blood-brain barrier (BBB) and widespread transgene
expression throughout brain in non-human primates (NHPs) following
intravenous administration.
- Demonstrated industry-leading brain tropism and enrichment in
NHPs, resulting in 700-fold higher transgene expression than
benchmark capsid AAV9.
- Capsid-enabled delivery of zinc finger payloads targeting prion
disease and tauopathies resulted in robust and widespread
repression of target genes.
- STAC-BBB capsid could potentially unlock multiple neurology
epigenetic regulation programs paused by Sangamo pending
identification of suitable capsid and could be advanced either
internally or with a collaborator.
- Sangamo expects to file up to three neurology Investigational
New Drug (IND) submissions and/or Clinical Trial Applications (CTA)
by end of 2025.
- Sangamo to discuss results in conference call scheduled for
Wednesday, March 13 at 4:30pm Eastern Time.
Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine
company, today announced preclinical data from its proprietary
adeno-associated virus (AAV) capsid variant, STAC-BBB, that
demonstrated robust penetration of the blood-brain barrier (BBB)
and strong transgene expression throughout the central nervous
system (CNS) of NHPs when administered intravenously at
clinically-relevant doses, outperforming results obtained by
Sangamo for other known neurotropic capsid variants evaluated in
the study. Importantly, potent repression of target genes was
observed in brain cells expressing the zinc finger cargo,
indicating that STAC-BBB could enable development of genomic
medicines to potentially treat a wide range of neurological
diseases.
“The advancement of neurological medicines has long been limited
by the inability to achieve widespread CNS delivery, an essential
attribute for an effective treatment for devastating neurological
disorders. We are extremely encouraged that STAC-BBB, a potentially
game-changing capsid variant engineered using our SIFTER capsid
platform, demonstrated results that outperformed other known
neurotropic capsid variants, achieving widespread brain delivery
and transgene expression, desired de-targeting of liver and other
peripheral tissues and a favorable safety profile,” said Sandy
Macrae, Chief Executive Officer of Sangamo. “Furthermore, these
data demonstrated that delivery of our zinc finger epigenetic
regulators using STAC-BBB could result in a meaningful repression
of disease-relevant target genes throughout the brain, which we
believe may result in profound improvements in disease pathology
and progression. These data further support our transformation into
a neurology-focused genomic medicine company focused on combining
potent epigenetic regulation capabilities with innovative capsid
delivery technology to develop best-in-class neurology
medicines.”
Sangamo intends to use the novel STAC-BBB capsid in its wholly
owned prion disease and tauopathy programs. In addition, STAC-BBB
could potentially unlock multiple neurology epigenetic regulation
programs that were paused by Sangamo pending the identification of
a suitable capsid, including programs previously in development
under Sangamo’s former collaboration agreements with Biogen and
Novartis. Sangamo is exploring avenues to resume development of
these programs internally, subject to receipt of adequate funding,
or with new potential collaborators.
Summary of STAC-BBB Preclinical Data
In NHP studies when administered intravenously at clinically
relevant doses, STAC-BBB demonstrated its potential to be a leading
neurotropic capsid.
Highlights include:
- Broad brain coverage. Robust penetration of the BBB and
widespread transgene expression throughout the brain, including key
regions integral to human neurological diseases such as Alzheimer’s
disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis (ALS),
Huntington’s disease and prion disease.
- Industry-leading brain tropism. Exhibited 700-fold
higher transgene expression in neurons compared to the benchmark
capsid AAV9 and outperformed all other known published neurotropic
capsid variants evaluated in the study.
- Widespread neuronal transduction across all animals.
STAC-BBB mediated robust expression of zinc finger cargo in
neurons, the key cell type to target for treatment of neurological
diseases. Moreover, results were dose-dependent and consistent
across all NHPs in the study.
- Potent and widespread repression of target genes.
Capsid-enabled delivery of zinc finger payloads resulted in the
repression of prion and tau genes across key brain regions,
demonstrating the potential for modification of disease progression
in prion disease and various tauopathies. Visualization of gene
expression in individual brain cells by RNAscope revealed highly
potent repression of tau in neurons expressing the zinc finger
cargo across multiple brain regions.
- Desired de-targeting of the liver and other peripheral
organs. Capsid biodistribution was shown to be enriched in the
CNS and de-targeted from the liver, dorsal root ganglia (DRG) and
other peripheral organs. This biodistribution profile demonstrated
by STAC-BBB is optimal for an AAV-based treatment of neurological
diseases.
- Favorable safety profile. STAC-BBB was well tolerated in
NHPs, with no notable treatment related pathological findings in
brain, spinal cord or peripheral tissues.
- Manufacturable using standard processes and at scale. We
believe STAC-BBB is manufacturable at commercial scale using
standard cell culture and purification processes, is soluble using
known excipients, and can be characterized using available
analytics.
Sangamo expects to file an IND submission for its Nav1.7 program
addressing chronic neuropathic pain, which leverages an
intrathecally administered capsid, in the fourth quarter of 2024,
and a CTA submission for its prion disease program, which is
expected to leverage the STAC-BBB capsid, in the fourth quarter of
2025, each subject to additional funding. Sangamo also intends to
resume development of its tau program leveraging the STAC-BBB
capsid, with an IND submission expected as early as the fourth
quarter of 2025.
The Sangamo management team will discuss these results on a
conference call on Wednesday, March 13 at 4:30pm Eastern Time.
Participants should register for, and access, the call using
this link. While not required, it is recommended you join 10
minutes prior to the event start. Once registered, participants
will be given the option to either dial into the call with the
number and unique passcode provided or to use the dial-out option
to connect their phone instantly.
An updated corporate presentation is available in the Investors
and Media section under Presentations.
The link to access the live webcast can also be found on the
Sangamo website in the Investors and Media section under Events. A
replay will be available following the conference call, accessible
at the same link.
About Sangamo Therapeutics
Sangamo Therapeutics is a genomic medicine company dedicated to
translating ground-breaking science into medicines that transform
the lives of patients and families afflicted with serious
neurological diseases who do not have adequate or any treatment
options. Sangamo’s zinc finger epigenetic regulators are ideally
suited to potentially address devastating neurological disorders
and Sangamo’s capsid discovery platform is expanding delivery
beyond currently available intrathecal delivery capsids, including
in the central nervous system. Sangamo’s pipeline also includes
multiple partnered programs and programs with opportunities for
partnership and investment. To learn more, visit www.sangamo.com
and connect with us on LinkedIn and Twitter/X.
Forward-Looking Statements
This press release contains forward-looking statements regarding
our current expectations. These forward-looking statements include,
without limitation, statements relating to: expectations regarding
the therapeutic potential of Sangamo’s technologies, including the
delivery of zinc finger epigenetic regulators using STAC-BBB to
result in the repression of disease-relevant target genes in the
brain, to result in profound improvements in disease pathology and
progression, to modify disease progression in prion disease and
various tauopathies, to be manufacturable at commercial scale using
standard cell culture and purification processes, to be soluble
using known excipients, and to be characterized using available
analytics; Sangamo’s intentions to use STAC-BBB in two of its
epigenetic regulation product candidates under development
internally; expectations that preclinical data from STAC-BBB will
support Sangamo’s transformation into a neurology-focused genomic
medicine company; expectations regarding STAC-BBB’s potential to
unlock multiple neurology epigenetic regulation programs that have
been paused by Sangamo pending the identification of a suitable
capsid, and plans to either resume their development internally,
with receipt of additional funding, or with a new potential
collaborator; Sangamo’s plans to file INDs submissions and/or CTAs
and the expected timing of such regulatory submissions; and other
statements that are not historical fact. These statements are not
guarantees of future performance and are subject to certain risks
and uncertainties that are difficult to predict. Factors that could
cause actual results to differ include, but are not limited to,
risks and uncertainties related to the uncertain and costly
research and development process, including the risk that
preclinical results may not be indicative of results in any future
clinical trials; Sangamo’s lack of capital resources to fully
develop, obtain regulatory approval for and commercialize its
product candidates, including Sangamo’s ability to secure a
partnership or the funding required to initiate planned IND and/or
CTA submissions in a timely manner or at all; Sangamo’s need for
substantial additional funding to execute its operating plan and to
continue to operate as a going concern, including the risk that
Sangamo will be unable to obtain the funding necessary to advance
Sangamo’s Nav1.7, prion disease and tau programs and to otherwise
continue to operate as a going concern, in which case, Sangamo may
be required to cease operations entirely, liquidate all or a
portion of its assets, and/or or seek protection under applicable
bankruptcy laws; the effects of macroeconomic factors or financial
challenges, including as a result of the ongoing overseas conflict,
current or potential future bank failures, inflation and elevated
interest rates, on the global business environment, healthcare
systems and business and operations of Sangamo and our
collaborators; the research and development process; the potential
for technological developments that obviate technologies used by
Sangamo; Sangamo’s reliance on collaborators and its potential
inability to secure additional collaborations, and Sangamo’s
ability to achieve expected future operating results.
There can be no assurance that we and our current or potential
future collaborators will be able to develop commercially viable
products. Actual results may differ materially from those projected
in these forward-looking statements due to the risks and
uncertainties described above and other risks and uncertainties
that exist in the operations and business environments of Sangamo
and its collaborators. These risks and uncertainties are described
more fully in Sangamo’s Securities and Exchange Commission, or SEC,
filings and reports, including in its Annual Report on Form 10-K
for the year ended December 31, 2023, filed with the SEC, and
future filings and reports that Sangamo makes from time to time
with the SEC. Forward-looking statements contained in this
announcement are made as of this date, and Sangamo undertakes no
duty to update such information except as required under applicable
law.
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Investor Relations & Media
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