BRISBANE, Calif., Feb. 7, 2019 /PRNewswire/ -- Sangamo
Therapeutics, Inc. (NASDAQ: SGMO) today presented interim data from
the Phase 1/2 EMPOWERS Study evaluating the SB-318 zinc finger
nuclease (ZFN) in vivo (inside the body) genome editing
product candidate in patients with Mucopolysaccharidosis Type I
(MPS I). These data, along with interim results of the CHAMPIONS
Study evaluating SB-913 for MPS II, were presented today at the
WORLDSymposium 2019 being held in Orlando, Florida. Sangamo believes data from
these two studies provide complementary evidence supportive of a
favorable safety profile and of the activity of the ZFN in
vivo genome editing technology used in both SB-318 and SB-913.
The two WORLDSymposium presentations have been made
available on the Sangamo website.
"The results so far suggest a dose-dependent increase in
leukocyte IDUA enzyme activity," said Dr. Paul Harmatz, a professor at UCSF Benioff
Children's Hospital Oakland and a lead investigator on the study.
"Leukocytes are an easily accessible target tissue for IDUA and
therefore provide an estimate of tissue enzyme activity for
patients with MPS I. Whether these observed increases will
translate into clinical benefit from SB-318 is yet to be
determined."
MPS I, also known as Hurler syndrome, is a rare genetic
disorder caused by a deficiency of alpha-L-iduronidase (IDUA),
a lysosomal enzyme which is required to break down or recycle the
toxic buildup of glycosaminoglycans (GAGs). Without IDUA enzyme
activity, GAGs accumulate in cells throughout the body, leading to
widespread tissue and organ damage. The current standard-of-care
treatment for MPS I is enzyme replacement therapy (ERT), given as
weekly intravenous infusions. For severe MPS I patients, bone
marrow transplant is also a common treatment. SB-318 is an
investigational product candidate being evaluated to treat MPS I
using ZFNs, which are designed to insert a normal copy of the IDUA
gene into a precise location in the DNA of liver cells. The goal of
SB-318 treatment is to enable a patient's liver to produce a
continuous supply of functional IDUA enzyme.
"It is a tremendous responsibility to undertake the first in
vivo genome editing clinical trials, and we are learning
quickly about our technology and about these rare diseases," said
Dr. Edward Conner, Chief Medical
Officer of Sangamo. "While additional data will be critical in
assessing the safety profile and potential therapeutic benefit of
SB-318, these early data provide evidence of the progress that we
are making toward a potential new treatment for MPS I using in
vivo genome editing with ZFNs."
Interim EMPOWERS Study Results Presented at
WORLDSymposium
The primary objective of the EMPOWERS Study is to determine the
safety and tolerability of SB-318, and secondary objectives include
evaluation of change from baseline in IDUA activity and urine GAG
levels. Biochemical measurements of urinary GAGs, as well as plasma
and leukocyte IDUA activity, are assessed at screening and baseline
visits, and every two to four weeks during the initial phase of the
trial.
Patients with mild MPS I receiving weekly ERT were enrolled in
the study. One patient has been dosed with 1e13 vector genomes per
kilogram body weight (vg/kg) of SB-318 and two patients have been
dosed with 5e13 vg/kg of SB-318. None of the three patients
enrolled in the study have received a bone marrow transplant.
Safety data were collected and analyzed for the three patients.
Administration of SB-318 was generally well tolerated. No treatment
related serious adverse events (SAEs) have been reported. Of the
six total adverse events (AEs) reported, all were mild or moderate
and consistent with ongoing MPS I disease, and none were considered
related to SB-318 treatment.
The results suggest a dose-dependent increase in leukocyte IDUA
activity, with activity levels rising above baseline and in the
normal range (normal range is 6.0-71.4 nmol/hr/mg). Plasma IDUA
activity was unchanged from baseline in all three patients.
Baseline urine GAG measurements for the three patients in the
EMPOWERS Study were in a range considered to be at or slightly
above normal. In the limited duration data set available at the
time of the WORLDSymposium presentation, urine GAG
measurements show no meaningful change.
The clinical relevance of the biochemical changes observed
following administration of SB-318 will be assessed as clinical
data and patient outcomes are analyzed following a trial of
withdrawal from ERT. ERT withdrawal is expected for these patients
later in 2019. Sangamo also expects to report analyses of liver
biopsies later this year.
Sangamo has developed second-generation, potentially more potent
ZFN constructs designed to increase editing efficiency. Preclinical
data of these second-generation ZFNs were reviewed by U.S.
regulators. The preclinical data showed three potential advantages
for use in the clinic: (1) a 5- to 30-fold improvement in
efficiency and potency due to structural changes; (2) the ability
to function equally well in the patients who have a single
nucleotide polymorphism (SNP) in the target locus in the albumin
gene (approximately 20% of the population); (3) improved
specificity. The second-generation ZFNs are already being
manufactured and are expected to be ready for use in the clinic
later this year. Additional data from Sangamo's in vivo
genome editing programs will be assessed before potential
integration plans for the second-generation ZFNs are finalized.
Conference Call
Sangamo will host a conference call today, February 7, 2019, at 12:30
p.m. Eastern Time, which will be open to the public. The
call will also be webcast live and can be accessed via a link on
the Sangamo Therapeutics website in the Investors and Media section
under Events and Presentations.
The conference call dial-in numbers are (877) 377-7553 for
domestic callers and (678) 894-3968 for international callers. The
conference ID number for the call is 4387585. For those unable to
listen in at the designated time, a conference call replay will be
available for one week following the call. The conference call
replay numbers for domestic and international callers are (855)
859-2056 and (404) 537-3406, respectively. The conference ID number
for the replay is 4387585.
About Sangamo Therapeutics
Sangamo Therapeutics, Inc. is focused on translating
ground-breaking science into genomic medicines with the potential
to transform patients' lives using the Company's platform
technologies in genome editing, gene therapy, gene regulation and
cell therapy. For more information about Sangamo, visit
www.sangamo.com.
Forward-Looking Statements
This press release contains forward-looking statements based
on Sangamo's current expectations. These forward-looking statements
include, without limitation, statements relating to the potential
therapeutic applications for SB-318 and SB-913, the potential for
SB-318 to treat MPS I, including the potential for increased
leukocyte IDUA activity to translate into clinical benefit and for
SB-318 to potentially cause the liver to produce a continuous
supply of functional IDUA enzyme, the timing and nature of
additional data from SB-318, the potential advantages of
second-generation ZFNs, the timing of the use of the
second-generation ZFNs, Sangamo's belief that the second-generation
ZFNs have the potential for greater benefit for patients, and other
statements that are not historical fact. These statements are not
guarantees of future performance and are subject to certain risks,
uncertainties and assumptions that are difficult to predict.
Factors that could cause actual results to differ include, but are
not limited to, risks and uncertainties related to early data,
including the risk that the early data from the EMPOWERS Study may
not be representative of final results after all patients are
treated in the study and all data are collected and analyzed;
Sangamo's ability to complete the EMPOWERS Study and the CHAMPIONS
Study; whether the final results from the EMPOWERS Study and
CHAMPIONS Study will validate and support interim results and the
overall safety and efficacy of SB-318 and SB-913, respectively,
including the risk that the early efficacy data from the EMPOWERS
Study and the CHAMPIONS Study may not be maintained or replicated;
whether Sangamo will be able to effectively deliver its ZFNs to
produce a beneficial therapeutic effect, including the risks that
the second-generation ZFNs may not be successfully integrated into
Sangamo's product candidates and even if successfully integrated,
the second-generation ZFNs may not have any advantages over
Sangamo's first-generation ZFNs or otherwise may not produce any
beneficial therapeutic effect; Sangamo's reliance on partners and
other third-parties to meet their clinical and manufacturing
obligations, and its ability to maintain strategic partnerships.
Further, there can be no assurance that the necessary regulatory
approvals for SB-318 or SB-913 will be obtained or that Sangamo and
its partners will be able to develop commercially viable product
candidates for the treatment of MPS I, MPS II and other diseases.
These risks and uncertainties are described more fully in Sangamo's
Quarterly Report on Form 10-Q for the quarter ended September 30, 2018 as filed with the Securities
and Exchange Commission. Forward-looking statements contained in
this press release 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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