Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on
creating and delivering engineered cells as medicines, presented
data showing survival of transplanted allogeneic, hypoimmune cells
of several different types in a variety of locations in non-human
primates (NHPs). The transplanted cells were induced pluripotent
stem cell (iPSC)-derived cardiomyocytes, retinal pigment epithelium
(RPE) cells, and islet cells, which were engineered to include
Sana’s hypoimmune gene modifications that enable immune evasion.
Data were presented by Sonja Schrepfer, M.D., Ph.D., Head of
Hypoimmune Platform at Sana, during sessions at the International
Society for Stem Cell Research (ISSCR) 2022 Annual Meeting taking
place from Wednesday, June 15 through Sunday, June 19 in San
Francisco.
“These data, demonstrating that three types of
transplanted cells are able to survive and function in NHPs without
immunosuppression, highlight the transformative potential of Sana’s
hypoimmune platform across a number of different cell types that
can address a variety of diseases,” said Steve Harr, Sana’s
President and Chief Executive Officer. “As an example, the use of
allogeneic islet transplant has had limited success in treating
type 1 diabetes due to morbidities from the necessary
immunosuppression. In contrast, our data indicate that we
successfully engineered HIP human pancreatic islet cells to evade
immune recognition, and these cells persisted and normalized
glucose levels in in vivo models. We are applying the hypoimmune
platform to a number of programs in our pipeline, including SC291,
our CD19 targeted allogeneic CAR T therapy for blood cancers, with
a goal of an IND this year, and SC451, our islet cell program with
a goal of an IND for the treatment of type 1 diabetes in 2023.”
Transplanting cells or tissues from a donor to a
different recipient currently requires intense immunosuppression to
prevent rejection of the transplant. Sana’s HIP platform goal is to
eliminate the need for immunosuppression by cloaking cells from
immune recognition. The platform includes disruption of the major
histocompatibility (MHC) class I and MHC class II expression to
hide cells from the adaptive immune system, which includes antibody
and T cell responses. These changes alone make cells susceptible to
innate immune cell killing, in particular by natural killer (NK)
cells. However, Sana’s HIP platform additionally provides for
evasion from innate cell killing, including via the overexpression
of CD47, a molecule that protects HIP-modified cells from innate
cell killing involving either NK cells or macrophages. HIP-modified
pluripotent stem cells can serve as the starting material for the
differentiation of specialized cell types to serve as cell-based
therapeutics. Sana’s goal is to use these HIP-modified cells to
replace damaged or missing cells in the body in a number of
different diseases, including, among others, cancer, type 1
diabetes, and cardiac disease.
Survival of HIP-modified islet cells for
type 1 diabetes
Primary NHP pancreatic islet cells In this study,
allogeneic primary pancreatic islet cells were HIP edited and
transplanted intramuscularly into a healthy NHP without
immunosuppression (n=1) as proof-of-concept. Islet cell survival
was followed by in vivo bioluminescence imaging. The imaging showed
that transplanted cells survived for the duration of the study
(three months at data lock) with no evidence of a systemic immune
response, including no T cell activation, antibody production, or
NK cell activity as seen previously with other HIP edited cell
types in NHPs (iPSC, cardiomyocytes, and RPE). Allogeneic
unmodified primary pancreatic islet cells disappeared rapidly
within 2 weeks.
Autoimmune miceType 1 diabetes is a disease in
which the patient’s immune system attacks and kills their
pancreatic beta cells. Therefore, allogeneic transplanted cells in
type 1 diabetes need to overcome both allogeneic and autoimmune
rejection. Autoimmune diabetes arises spontaneously in non-obese
diabetic (NOD) mice, and the pathophysiology of this disease shares
many similarities with human type 1 diabetes. Since its development
in 1980, this model has represented the gold standard of
spontaneous disease models, allowing for investigation of
autoimmune diabetes disease progression and susceptibility traits,
as well as to test a wide array of potential treatments and
therapies.
In this study, syngeneic or allogeneic mouse islet
cells were transplanted intramuscularly without immunosuppression
into diabetic autoimmune mice (n=15), split into three cohorts. The
first cohort received unmodified syngeneic islet cells, the second
cohort received unmodified allogeneic islet cells, and the third
cohort received allogeneic HIP islet cells. The unmodified cells
disappeared rapidly in the allogeneic setting (within 10 days) as
well as in the syngeneic setting (within two weeks) due to
autoimmune recognition. Neither cohort had a decrease in glucose
levels. The HIP islet cells survived in all five diabetic mice for
the duration of the study (one month at data lock), and glucose
levels dropped, demonstrating therapeutic function of the HIP islet
cells.
Survival of HIP-modified cardiomyocytes
(iPSC-derived)In this study, allogeneic iPSC-derived
cardiomyocytes were transplanted without immunosuppression into the
hearts of healthy NHPs split into two cohorts. The first cohort
received unmodified allogeneic iPSC-derived cardiomyocytes (WT;
n=2), while the second cohort received allogeneic HIP iPSC-derived
cardiomyocytes (HIP; n=4). The unmodified cells were almost
eliminated in all NHPs, with significant T cell activation in
addition to antibody production and binding. The HIP cardiomyocytes
survived in all four monkeys for the duration of the study (up to
two months at data lock), and there was no evidence of a systemic
immune response, including no T cell activation, antibody
production, or NK cell activity. After two months, injection sites
were recovered, and local immune cells were analyzed for their
donor-specific cell recognition and killing. While local immune
cells kill unmodified cardiomyocytes, HIP cardiomyocytes were not
recognized by these immune cells.
Survival of HIP-modified retinal pigmental
epithelial (RPE) cells (iPSC-derived)In this study,
allogeneic iPSC-derived RPEs were transplanted into the eye of
healthy NHPs without immunosuppression split into two cohorts. The
first cohort received unmodified allogeneic iPSC-derived RPE (WT;
n=3), while the second cohort received allogeneic HIP iPSC-derived
RPE (HIP; n=3). The unmodified cells were almost completely
eliminated in all NHPs within three weeks, with significant T cell
activation, antibody production and local microglial activation,
demonstrating in this context that the eye is not an
“immunoprivileged” site.
The HIP RPE survived in all three monkeys for the
duration of the study (three weeks at data lock), and there was no
evidence of a systemic immune response, including no T cell
activation, antibody production, microglial or NK cell activity.
Two weeks after the initial dose, the NHPs were re-injected with
the same cell type into the second eye, so that the NHPs received a
total of two doses. Unmodified WT RPEs again evoked a rapid
systemic immune response in all NHPs, with activation of T cells
and antibody production, and cells almost completely eliminate
within one week. HIP RPE cells continued to survive even after
re-injection without stimulation of adaptive or innate immune
responses. These data suggest the potential to re-administer HIP
RPE cells.
Sana intends to submit the data behind its
presentations for publication in a peer-reviewed journal.
About Hypoimmune PlatformSana’s
hypoimmune platform is designed to create cells ex vivo that can
“hide” from the patient’s immune system to enable the transplant of
allogeneic cells without the need for immunosuppression. We are
applying the hypoimmune technology to both pluripotent stem cells,
which can then be differentiated into multiple cell types, and to
donor-derived allogeneic T cells, with the goal of making potent
and persistent CAR T cells at scale. Preclinical data demonstrates
across a variety of cell types that these transplanted allogeneic
cells are able to evade both the innate and adaptive arms of the
immune system while retaining their activity. Our most advanced
programs utilizing this platform include an allogeneic CAR T
program targeting CD19+ cancers and stem-cell derived beta islet
cells for patients with type 1 diabetes.
About Sana BiotechnologySana
Biotechnology, Inc. is focused on creating and delivering
engineered cells as medicines for patients. We share a vision of
repairing and controlling genes, replacing missing or damaged
cells, and making our therapies broadly available to patients. We
are a passionate group of people working together to create an
enduring company that changes how the world treats disease. Sana
has operations in Seattle, Cambridge, South San Francisco, and
Rochester. For more information about Sana Biotechnology, please
visit https://sana.com/.
Cautionary Note Regarding Forward-Looking
StatementsThis press release contains forward-looking
statements about Sana Biotechnology, Inc. (the “Company,” “we,”
“us,” or “our”) within the meaning of the federal securities laws,
including those related to the company’s vision, progress, and
business plans; expectations for its development programs, product
candidates and technology platforms, including its pre-clinical,
clinical and regulatory development plans and timing expectations;
the potential ability to make allogeneic, hypoimmune cells,
including iPSC-derived cardiomyocytes, RPE cells, and islet cells,
that survive and evade the immune system without immunosuppression
and the potential persistence and efficacy of such hypoimmune
cells; and the Company’s expectations with respect to the
submission and publication of data. All statements other than
statements of historical facts contained in this press release,
including, among others, statements regarding the Company’s
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Investor Relations &
Media:Nicole
KeithInvestor.relations@sana.commedia@sana.com
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