Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on
changing the possible for patients through engineered cells, today
announced that Science Translational Medicine has published a paper
titled “Human hypoimmune primary pancreatic islets avoid rejection
and autoimmunity and alleviate diabetes in allogeneic humanized
mice.” The paper details data from a series of ten in vivo
experiments demonstrating the insulin-normalization activity,
persistence, immune evasion, and lack of immunogenicity of human
hypoimmune-modified islet cells, which cluster into effective
endocrine organoids termed “pseudo islets.”
“The replacement of defective or missing cells has been the goal
for many diseases; however, immune rejection results in either
systemic immunosuppression or therapeutic failure. Sana’s
proprietary hypoimmune platform was developed to solve this
problem,” said Steve Harr, Sana’s President and CEO. “The Science
Translational Medicine paper details data demonstrating that
hypoimmune pseudo islets developed with our hypoimmune technology
survived and were able to reverse diabetes without any
immunosuppression in humanized mice. Eliminating the need for
insulin administration and reversing diabetes with normalization of
blood glucose levels, and doing this without immunosuppression,
would be a transformational advance for patients. Insights from
this research along with an expected investigator-sponsored trial
this year will inform the development plan for our SC451 product
candidate in type 1 diabetes as we move forward with our goal of
submitting an IND in 2024.”
HIP Pancreatic Islet Cells Survive, Persist, and Escape
Allogeneic RejectionSana generated human hypoimmune (HIP)
pseudo islets (p-islets) and wild-type (wt) p-islets that were
similar in size, cell type composition, and in vitro insulin
secretion. The survival of the p-islets and their cell composition
was assessed in immunocompetent, diabetic allogeneic humanized
NSG-SGM3 mice. HIP or wt p-islet clusters were injected into the
hindlimb muscle and were recovered on the same day or 7 or 28 days
later. Wt p-islets could only be recovered on the same day and were
fully rejected and dissolved at later time points. By contrast, the
total cell count and cell composition of HIP islets did not change
over time.
In another experiment, analyses were conducted a month following
exposure to HIP and wt p-islets. There were no traces of wt p-islet
grafts found in any animals after one month. Recovered splenocytes
and serum from the wt p-islet treated animals showed markedly
activated T cells (analyzed by ELISPOT) and donor-specific
antibodies (analyzed by flow cytometry) against the grafts in the
wt p-islet group, demonstrating a strong adaptive allogeneic immune
response. By contrast, HIP p-islets showed the same morphology as
before transplantation and contained alpha, beta, and delta cells.
No immune cell infiltrate was observed in or around the HIP p-islet
cells. Additionally, no adaptive allogeneic immune response was
observed in humanized mice that received HIP p-islets and diabetes
in these mice was alleviated. Confirmatory killing assays showed
killing of wt p-islets and no killing of HIP p-islets.
HIP Islet Cells Control Insulin Similarly to Unedited
Wild-Type Islet Cells in Immunodeficient MiceThe ability
to control diabetes was assessed in immunodeficient NSG mice to
remove the variable of immune rejection of allogeneic cells,
enabling the comparison of wt and HIP p-islets. Diabetes was
induced using streptozotocin (STZ) and all mice had fasting glucose
concentrations >400 mg/dl on the day of p-islet graft
transplantation. Wt and HIP p-islets both achieved glycemic control
within approximately 2 weeks and generated similar c-peptide
concentrations one months after transplantation. These functional
data confirmed that HIP p-islet cells maintained endocrine function
comparable to wt p-islets and showed unimpaired resilience toward
the transplantation procedure.
HIP Islet Cells Ameliorate Diabetes in Models of
Autoimmunity: NOD Mice as well as Humanized Autoimmune
Mice The ability of HIP islet cells to avoid autoimmunity
was assessed in two different models. The first set of experiments
were in the NOD mouse, which is the primary animal model for
studying autoimmunity in diabetes due to the similarities to the
human disease. These studies demonstrate that mouse HIP p-islets
survive while syngeneic p-islets are rejected due to autoimmune
killing. Additionally, the impact of autoimmunity was studied in a
humanized, diabetic autoimmune mouse. To generate a humanized,
autoimmune mouse, immune cells and iPSCs were generated from PBMCs
collected from a person with type 1 diabetes (T1D). Mice were
engrafted with the T1D immune cells and diabetes was induced. The
iPSCs were then either hypoimmune-modified or mock-modified,
differentiated into islet cells, and transplanted into these
immunocompetent, diabetic humanized mice to study autoimmunity in
vivo. All HIP iPSC-derived p-islets survived and glycemic control
was achieved in all recipients of HIP iPSC-derived p-islets. In
contrast, all autologous, mock-modified
iPSC-derived p-islets were fully rejected within 10 days due to
autoimmunity and showed no effect on blood glucose, even
temporarily, and animals had no detectable c-peptide after one
month.
About Sana’s 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 hypoimmune technology to both donor-derived allogeneic T
cells, with the goal of making potent and persistent CAR T cells at
scale, and pluripotent stem cells, which can then be differentiated
into multiple cell types at scale. Preclinical data from a variety
of cell types demonstrate that these transplanted allogeneic cells
can evade both the innate and adaptive arms of the immune system
while retaining their function. Our most advanced programs using
hypoimmune technology include our allogeneic CAR T program
targeting CD19+ cancers, our allogeneic CAR T program targeting
CD22+ cancers, our allogeneic CAR T program targeting BCMA+
cancers, and our stem-cell derived pancreatic islet cell program
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,
including the expected timing of IND submissions for the Company’s
product candidates and indications for which the Company is
developing its product candidates and for which such INDs will be
submitted, and expected impact of data from pre-clinical studies of
cells made using hypoimmune technology and from an
investigator-sponsored trial using hypoimmune primary human islet
cells in patients with type 1 diabetes (the “IST”), including the
potential of pre-clinical data and the IST to provide insight that
will inform development of its SC451 product candidate;
expectations regarding the IST, including the ability to initiate
the IST and expected timing, substance, and availability of data
therefrom; the potential ability of the hypoimmune platform 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, and the potential benefits associated
therewith; and the potential ability to make potent and persistent
CAR T cells at scale and of hypoimmune pluripotent stem cells to
differentiate into multiple cell types at scale. All statements
other than statements of historical facts contained in this press
release, including, among others, statements regarding the
Company’s strategy, expectations, cash runway and future financial
condition, future operations, and prospects, are forward-looking
statements. 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,” “target,”
“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. The Company has based
these forward-looking statements largely on its current
expectations, estimates, forecasts and projections about future
events and financial trends that it believes may affect its
financial condition, results of operations, business strategy and
financial needs. In light of the significant uncertainties in these
forward-looking statements, you should not rely upon
forward-looking statements as predictions of future events. These
statements are subject to risks and uncertainties that could cause
the actual results to vary materially, including, among others, the
risks inherent in drug development such as those associated with
the initiation, cost, timing, progress and results of the Company’s
current and future research and development programs, preclinical
and clinical trials, as well as the economic, market and social
disruptions due to the ongoing COVID-19 public health crisis. For a
detailed discussion of the risk factors that could affect the
Company’s actual results, please refer to the risk factors
identified in the Company’s Securities and Exchange Commission
(SEC) reports, including but not limited to its Annual Report on
Form 10-K dated March 16, 2023. Except as required by law, the
Company undertakes no obligation to update publicly any
forward-looking statements for any reason.
Investor Relations & Media:Nicole
Keithinvestor.relations@sana.commedia@sana.com
Sana Biotechnology (NASDAQ:SANA)
Historical Stock Chart
Von Jun 2024 bis Jul 2024
Sana Biotechnology (NASDAQ:SANA)
Historical Stock Chart
Von Jul 2023 bis Jul 2024