Sangamo BioSciences Announces First Presentation Of Data From ZFP Therapeutic Program For Treatment Of Sickle Cell Disease And

Sangamo BioSciences Announces First Presentation Of Data From ZFP Therapeutic
Program For Treatment Of Sickle Cell Disease And Beta-Thalassemia At American
                        Society Of Hematology Meeting

Novel Genome-Editing Approach Offers a Potential Cure for Both Diseases

PR Newswire

RICHMOND, Calif., Dec. 9, 2013

RICHMOND, Calif., Dec. 9, 2013 /PRNewswire/ -- Sangamo BioSciences, Inc.
(Nasdaq: SGMO) announced the presentation of preclinical data from its ZFP
Therapeutic program for the treatment and potential cure of both sickle cell
disease (SCD) and beta-thalassemia. The data demonstrate that Sangamo's
approach, using its proprietary and highly specific zinc finger nuclease (ZFN)
gene-editing technology, enables permanent increase in the expression of fetal
gamma-globin in adult red blood cells (RBCs). This increase restores the
normal balance of globin proteins that together form the oxygen-carrying
hemoglobin of RBCs. In addition, the pre-clinical studies demonstrate that
this can be accomplished at clinical-scale reproducibly achieving high levels
(up to 80 percent) of gene editing in hematopoietic stem cells (HSCs).


The study was carried out in collaboration with scientists in the laboratory
of George Stamatoyannopoulos, M.D., Dr.Sci., Professor of Medicine and Genome
Sciences at the University of Washington. The data were presented at the 55^th
Annual Meeting of the American Society of Hematology (ASH), which is being
held in New Orleans.

"These preclinical data demonstrate that Sangamo's precise ZFN genome editing
technology enables a unique approach that can be used to treat, and
potentially cure, both sickle cell disease and beta-thalassemia," said Mark
Walters, M.D., Director of Blood and Marrow Transplantation at Children's
Hospital & Research Center Oakland, and a leader of one of the clinical teams
that will be conducting the first Phase 1 clinical trial of this ZFP
Therapeutic in transfusion-dependent beta thalassemia patients. "The
modification process is extremely efficient and scalable. We look forward to
conducting a clinical study that employs Sangamo's technology in a patient's
own stem cells to potentially provide a safer approach than current therapies,
and eliminate the need for life-long medications and red blood cell
transfusions that are currently the standard of care for these disorders."

SCD and beta-thalassemia are genetic diseases of the blood caused by mutations
in the beta-globin gene. In SCD, the gene defect in beta-globin results in an
abnormal hemoglobin which causes the RBCs to develop a sickle, or crescent,
shape. These abnormal RBCs are stiff and sticky and can block blood flow in
the small blood vessels of the limbs and organs resulting in pain, organ
damage and an increased risk of infection. The gene defect responsible for
beta-thalassemia leads to impaired production of hemoglobin, the
iron-containing protein in red blood cells (RBCs) that carry oxygen from the
lungs to the tissues, and results in a failure to make healthy RBCs.
Individuals with thalassemia are therefore dependent on blood transfusions for

During development, a fetal form of hemoglobin is made using a beta-like
globin called gamma- or fetal-globin. In infancy, this fetal form of
hemoglobin fully protects beta-thalassemia and SCD patients from developing
disease symptoms. Later in childhood however, production of fetal hemoglobin
ceases and is replaced by synthesis of adult-type beta-globin chains that are
defective in beta-thalassemia and SCD patients and symptoms of disease appear.
It is well-known that the persistence of fetal hemoglobin beyond the newborn
stage lessens the severity of both of these hemoglobin disorders in the adult.
The goal of Sangamo's therapy is to enable production of normal RBCs in SCD
and to eliminate, or greatly reduce, the need for chronic blood transfusions
in beta-thalassemia. 

Sangamo has used its proprietary ZFN genome-editing technology to precisely
knock out key regulators of the transcriptional switch from fetal to adult
beta-globin expression, such as BCL11A, enabling the permanent production of
therapeutic fetal hemoglobin. The increased fetal gamma globin restores the
normal balance of the alpha- and beta-like globin proteins that together form
the oxygen-carrying hemoglobin of RBCs and the production of normal levels of
hemoglobin and RBCs. Comparable efficacy is observed in cells from healthy
volunteers and cells from SCD and beta-thalassemia patients.

Importantly, by performing this genome editing in HSCs that are isolated and
returned to the same patient, a so-called autologous bone marrow transplant
(BMT), Sangamo's approach eliminates both the need for a matched donor and the
risk of acute and chronic graft-versus-host disease (GvHD). The unmet medical
need in transfusion-dependent beta-thalassemia is significant, with reduced
life expectancy due to multi-organ failure caused by iron overload,
blood-borne infections and other disease complications. A BMT of HSCs from a
"matched" related donor (allogeneic BMT) is curative for both diseases.
However, this therapy is limited due to the scarcity of matched donors and the
significant risk of GvHD after transplantation of the foreign cells.

In May 2013, Sangamo was awarded a $6.4 million Strategic Partnership Award
from the California Institute for Regenerative Medicine (CIRM) to develop this
potentially curative ZFP Therapeutic for beta-thalassemia. The four-year grant
provides matching funds for preclinical work that will support an
Investigational New Drug (IND) application and a Phase 1 clinical trial in
transfusion-dependent beta-thalassemia patients, which will be carried out at
City of Hope by a team directed by Dr. Stephen Forman, M.D., F.A.C.P.,
Director, Department of Hematology and Hematopoietic Cell Transplantation and
at Children's Hospital & Research Center Oakland.

"These data demonstrate the versatility, specificity and high level of
efficiency of Sangamo's ZFP genome-editing technology," said Edward Lanphier,
Sangamo's president and CEO. "Although our initial clinical study is planned
for beta-thalassemia, this same ZFP Therapeutic approach can be directly
applied to related hemoglobinopathies such as sickle cell disease. We look
forward to working with a team of world-renowned experts in this field,
including the team at Children's Hospital & Research Center Oakland, City of
Hope and our colleagues at CIRM, to bring this treatment through IND
application and into Phase 1 clinical testing."

The abstract for this oral presentation (#434 -"Targeted Gene Modification In
Hematopoietic Stem Cells: A Potential Treatment For Thalassemia and Sickle
Cell Anemia"), along with a second Sangamo abstract (#433 - "Using Forced
Chromatin Looping to Overcome Developmental Silencing of Embryonic and Fetal
beta-Type Globin Genes In Adult Erythroid Cells"), were two of three studies
highlighted at a press briefing organized by the American Society for

Sangamo Abstracts at ASH Pertinent to Sangamo's Programs in Hemoglobinopathies
Abstract#433-- Using Forced Chromatin Looping to Overcome Developmental
Silencing of Embryonic and Fetal Beta-Type Globin Genes in Adult Erythroid
Oral Session 112: Thalassemia and Globin Gene Regulation: Targeted Engineering
of Globin Gene Expression
Monday, December 9, 2013: 2:45 PM

Abstract#434-- Targeted Gene Modification in Hematopoietic Stem Cells: A
Potential Treatment For Thalassemia and Sickle Cell Anemia
Oral Session 112: Thalassemia and Globin Gene Regulation: Targeted Engineering
of Globin Gene Expression
Monday, December 9, 2013: 3:00 PM

Abstract#2904 --Zinc Finger Nucleases Targeting the Beta-Globin Locus Drive
Efficient Correction of the Sickle Mutation in CD34+ Cells
Session 801: Gene Therapy and Transfer: Poster II
Sunday, December 8, 2013, 6:30 PM-8:30 PM

Abstract#4213-- Autologous Hematopoietic Stem/Progenitor Cell (HSPC) Therapy
for Monogenic Blood Disorders: Scalable, cGMP-Compliant Process for Generating
Highly Efficient Genome Edited HSPC
Session 801: Gene Therapy and Transfer: Poster III
Monday, December 9, 2013, 6:00 PM-8:00 PM

About SCD and Beta-Thalassemia
Mutations in the genes encoding globin, the oxygen carrying protein of red
blood cells, lead to the hemoglobinopathies, sickle cell disease (SCD) and
beta-thalassemia. The mutation giving rise to SCD causes the red blood cells
to form an abnormal sickle or crescent shape, making them fragile and less
able to deliver oxygen to tissues. They can also get stuck more easily in
small blood vessels and break into pieces that can interrupt healthy blood
flow. These problems further decrease the amount of oxygen flowing to body
tissues. Almost all patients with SCD have painful episodes (called crises),
which can last from hours to days. Current standard of care is to manage and
control symptoms, and to limit the number of crises. Treatments include blood
transfusions, iron chelation therapy and administration of hydroxyurea, pain
medications and antibiotics. The CDC currently estimates that there are 90,000
to 100,000 Americans living with SCD which occurs in approximately 1 out of
every 500 African-American births and 1 out of every 36,000 Hispanic-American

There are several forms of beta-thalassemia, but generally the disorder
results in excessive destruction of red blood cells leading to
life-threatening anemia, enlarged spleen, liver and heart, and bone
abnormalities. Cooley's anemia (beta-thalassemia major) is a severe form of
thalassemia that requires regular, often monthly, blood transfusions and
subsequent iron-chelation therapy to treat iron overload. The CDC currently
estimates that 1,000 people have Cooley's anemia in the United States, and an
unknown number carry the genetic trait and can pass it on to their children.
Thalassemia is most common among people of Mediterranean descent and is also
found among people from the Arabian Peninsula, Iran, Africa, Southeast Asia,
and Southern China.

About Sangamo
Sangamo BioSciences, Inc. is focused on research and development of novel
DNA-binding proteins for therapeutic gene regulation and genome editing. The
Company has ongoing Phase 2 and Phase1/2 clinical trials to evaluate the
safety and efficacy of a novel ZFP Therapeutic^® for the treatment of
HIV/AIDS. As part of its acquisition of Ceregene Inc., Sangamo acquired a
fully-enrolled and funded, double-blind, placebo-controlled Phase 2 trial to
evaluate NGF-AAV (CERE-110) in Alzheimer's disease. Sangamo's other
therapeutic programs are focused on monogenic diseases, including hemophilia,
Huntington's disease and hemoglobinopathies such as beta-thalassemia and
sickle cell anemia. Sangamo's core competencies enable the engineering of a
class of DNA-binding proteins known as zinc finger DNA-binding proteins
(ZFPs). Engineering of ZFPs that recognize a specific DNA sequence enables
the creation of sequence-specific ZFP Nucleases (ZFNs) for gene modification
and ZFP transcription factors (ZFP TFs) that can control gene expression and,
consequently, cell function. Sangamo has entered into a strategic
collaboration with Shire AG to develop therapeutics for hemophilia,
Huntington's disease and other monogenic diseases and has established
strategic partnerships with companies in non-therapeutic applications of its
technology including Dow AgroSciences and Sigma-Aldrich Corporation. For more
information about Sangamo, visit the company's website at

ZFP Therapeutic^® is a registered trademark of Sangamo BioSciences, Inc.

This press release may contain forward-looking statements based on Sangamo's
current expectations. These forward-looking statements include, without
limitation, the potential of ZFNs to treat human monogenic diseases, including
the treatment of beta-thalassemia, sickle cell disease and other monogenic
diseases, the timing, process and outcome of Sangamo's clinical trials for
such diseases, research and development of novel ZFP TFs and ZFNs and
therapeutic applications of Sangamo's ZFP technology platform. Actual results
may differ materially from these forward-looking statements due to a number of
factors, including uncertainties relating to the initiation and completion of
stages of our clinical trials, whether the clinical trials will validate and
support the tolerability and efficacy of ZFNs, technological challenges,
Sangamo's ability to develop commercially viable products and technological
developments by our competitors. For a more detailed discussion of these and
other risks, please see Sangamo's SEC filings, including the risk factors
described in its Annual Report on Form 10-K and its most recent Quarterly
Report on Form 10-Q. Sangamo BioSciences, Inc. assumes no obligation to update
the forward-looking information contained in this press release.

SOURCE Sangamo BioSciences, Inc.

Contact: Sangamo BioSciences, Inc., Elizabeth Wolffe, Ph.D., 510-970-6000,
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