ST-400
ex vivo Gene-Edited Cell Therapy for Beta
Thalassemia
We are conducting the Phase 1/2 THALES study, an open-label, single arm clinical trial to evaluate the safety and efficacy
of
ST-400
in up to six subjects with beta thalassemia.
ST-400
is an
ex vivo
gene-edited beta thalassemia cell therapy developed in partnership with Sanofi, that
involves gene editing of a patients own hematopoietic stem progenitor cells using
non-viral
delivery of ZFN technology.
In April 2019, we announced early preliminary data from the first patient treated with
ST-400
in the
THALES study. This patient has the most severe form of transfusion-dependent beta thalassemia (
b
0
/
b
0
) and for the two years prior to treatment in the study, received packed red blood cell, or PRBC, transfusions every other week.
During the
ST-400
infusion, the patient experienced a serious adverse event, a transient allergic
reaction considered related to the cryoprotectant present in the product. Thereafter, the post-transplant clinical course was routine.
The patient demonstrated neutrophil and platelet recovery, within two and four weeks of infusion, respectively, indicating that
ST-400
successfully reconstituted hematopoiesis following conditioning. Indels (small insertions or deletions generated at the targeted DNA sequence) have been detected in circulating white blood cells, indicating
successful editing of the
BCL11A
gene and disruption of the
BCL11A
erythroid specific enhancer, which is intended to upregulate endogenous fetal hemoglobin production in red blood cells.
At seven weeks post
ST-400
infusion, total hemoglobin levels remained stable (~9 g/dL), and levels of
fetal hemoglobin have continued to rise from approximately 1% of total hemoglobin at the time of infusion to 31% as of the most recent measurement.
The patient received several PRBC transfusions for approximately two weeks after the
ST-400
infusion.
During the subsequent five weeks, the most recent data available, no further PRBC transfusions have been required.
We caution that these
data regarding
ST-400
are very early, represent only the first patient dosed, and will require confirmation in additional patients as well as longer
follow-up
to draw
any clinical conclusion. In addition, these very early data should not be viewed as an indication, belief or guarantee that future dosed patients in the THALES study will achieve similar results or that the early results from the first patient dosed
will be maintained. For more information about the risks of early clinical data, including the risk that the very early data from the first patient dosed in the THALES study to date may not be maintained or replicated in that patient or in any other
dosed patients, see the risk factor entitled
Success in preclinical studies or early clinical trials may not be indicative of results obtained in later trials. Likewise, preliminary data from clinical trials should be considered carefully
and with caution since the final data may be materially different from the preliminary data, particularly as more patient data become available
found in Part I, Item 1A of our Annual Report on Form
10-K
for the year ended December 31, 2018, filed with the SEC on March 1, 2019.
Enrollment in the THALES study is ongoing. We expect to present longer-term
ST-400
data in the fourth
quarter of 2019, including results from additional patients. Until that time, we are not planning to report additional clinical data from the program.
In vivo Genome Editing Programs
In April 2019, we provided an update on our
in vivo
genome editing programs: the ongoing Phase 1/2 clinical trials evaluating
SB-913
(mucopolysaccharidosis type II, or MPS II),
SB-318
(MPS I), and
SB-FIX
(hemophilia B).
We announced that data will continue to accumulate throughout 2019, including in the recently treated expansion cohort patients in the
CHAMPIONS study
(SB-913),
and further updates on all three studies are expected later this year. We expect that no additional patients will be treated at this time with first-generation ZFNs given that
clinical benefit has not been demonstrated in analyses conducted to date in ongoing clinical trials and the expected near-term clinical development of second-generation ZFNs.
We are planning a new clinical trial to evaluate second-generation ZFNs for
SB-913
to treat MPS II.
In vitro
preclinical data presented last year showed three potential advantages of second-generation ZFNs for use in the clinic: (1) improvements in efficiency and potency due to structural modifications to the ZFN architecture and
expression vector; (2) the ability to function equally well in the patients with a single nucleotide polymorphism, or SNP, in the target locus in the albumin gene (~20% of the population); and (3) improvements in specificity. The clinical
trial of
SB-913
using second-generation ZFNs is planned to begin in the second half of 2019. We expect to use data from this study to make a Phase III decision for the
SB-913
program in 2020 and to define the next steps for the
SB-318
and
SB-FIX
programs.