Sangamo BioSciences Announces Target Date For First IND For Sangamo's In Vivo ZFN Genome-Editing Platform For Monogenic Diseases

RICHMOND, Calif., Sept. 10, 2014 /PRNewswire/ -- Sangamo BioSciences, Inc. SGMO announced plans to submit an Investigational New Drug (IND) application for the treatment of hemophilia B in the second quarter of 2015.  This program, partnered with Shire, is the first therapeutic application of Sangamo's zinc finger nuclease (ZFN)-mediated In Vivo Protein Replacement Platform (IVPRP). Sangamo is developing the IVPRP as a generally applicable strategy to provide a one-time, permanent genetic cure for monogenic diseases that are currently managed by protein replacement therapy, which involves costly repeat infusions over the lifetime of the patient. 

"Shire has been impressed by the rapid progress of the novel hemophilia B program developed by Sangamo," said Albert Seymour, Ph.D., Senior Vice President and Head of Global Research and Nonclinical Development at Shire.  "The Shire team continues to work very closely with Sangamo to submit the IND package to support this program."

"Sangamo's research and development team has succeeded in rapidly advancing the hemophilia B program through small and large animal proof of concept experiments, as well as pioneering manufacturing and regulatory pathways," said Edward Lanphier, Sangamo's president and CEO.  "I am very pleased with the progress that we and the new Shire team have made as we prepare to file an IND application for this first IVPRP program. Our experience with hemophilia B informs and supports our follow-on programs that leverage our IVPRP strategy, including our Shire-partnered program for the treatment of  hemophilia A and Sangamo's proprietary programs in lysosomal storage disorders (LSDs).  With the success of these programs, going forward, it is our goal to develop and file two to four new INDs per year for the foreseeable future."

"With the recent acceptance of an IND for mRNA delivery of ZFNs in Sangamo's SB-728-T program, upcoming initiation of Phase 1 clinical testing of our hematopoietic stem-cell program for HIV (SB-728-HSC), and the unanimous approval of our Phase 1 ZFN Bcl11a program yesterday, at the NIH Recombinant Advisory Committee (RAC) meeting, keeping us on track to file an IND application for our beta-thalassemia program by the end of the year, we are realizing our goal of developing a new class of  human therapeutics that have the potential to provide genetic cures for a range of monogenic diseases and unmet medical needs," added Mr. Lanphier.

"We are successfully forging a path to the clinic for Sangamo's ZFN-based IVPRP," said Geoff Nichol, M.B., Ch.B., Sangamo's executive vice president of research and development.  "We have gained valuable expertise in clinical scale AAV manufacturing and the regulatory requirements for IND submissions of the hemophilia B and other IVPRP programs.  We are pleased to move forward with an IND package for our hemophilia B program which supports Shire's IND requirements and, building on preclinical proof-of-concept data in our hemophilia A program, will implement a similar strategy as we bring that program to IND.  The proprietary LSD programs that Sangamo is developing based on this platform are also progressing well and on schedule.  Together, these assets are moving us rapidly towards the establishment of a ZFN-mediated platform for permanently treating protein and enzyme deficiency diseases and our long-term goal of initiating two to four new clinical programs per year."

Sangamo is targeting an IND application filing for hemophilia A by year end 2015 and anticipates providing updated guidance of the IND timeline for this program by the end of the first quarter of 2015.  The two hemophilia programs are the first in a platform of IVPRP assets that use intravenous AAV-delivered ZFNs to target the albumin locus and drive permanent expression of therapeutic proteins for a wide range of deficiency diseases, including the hemophilias, LSDs and other metabolic diseases.

Background on Hemophilia A and B and Sangamo's IVPRP Approach
Patients with hemophilia have a genetic mutation in the gene that encodes a blood-clotting factor (factor VIII in the case of hemophilia A, and factor IX in the case of hemophilia B), and, as a result, cannot make sufficient active factor VIII or IX protein to ensure efficient blood clotting. Sangamo's IVPRP is designed to provide a one-time, potentially curative treatment for patients with monogenic diseases, such as hemophilia and LSDs, who currently require repeated infusions of protein replacement therapies throughout their lives.  The IVPRP approach enables the patient's liver to permanently produce therapeutic levels of a corrective protein product such as factor VIII or IX to treat hemophilia, or replacement enzymes to treat LSDs.

The IVPRP approach makes use of the albumin gene locus, a highly expressing and liver-specific genomic "safe-harbor site", that can be edited with zinc finger nucleases (ZFNs) to accept and express any therapeutic gene. With such a large capacity for protein production (approximately 15g/day of albumin), which is in excess of the body's requirements, targeting and co-opting only a very small percentage of the albumin gene's capacity is sufficient to produce the needed replacement protein at therapeutically relevant levels with no significant effect on albumin production.

Pending acceptance of the IND application, a single intravenous infusion will be used to deliver adeno-associated viral (AAV) vectors encoding the ZFNs and a copy of a replacement gene used to correct the genetic defect. The zinc finger nucleases drive targeted, permanent insertion of a normal factor IX gene at the albumin locus in the liver cells of patients with hemophilia B.  This results in ongoing production of factor IX protein by the gene-edited liver cells under the control of the highly active albumin promoter. 

About Sangamo
Sangamo BioSciences, Inc. is focused on Engineering Genetic Cures™ for monogenic and infectious diseases by deploying its novel DNA-binding protein technology platform in therapeutic gene regulation and genome editing. The Company has ongoing Phase 2 clinical trials to evaluate the safety and efficacy of a novel ZFP Therapeutic^® for the treatment of HIV/AIDS (SB-728-T) and NGF-AAV for Alzheimer's disease (CERE-110). Sangamo's other therapeutic programs are focused on monogenic and rare diseases.  The company has formed a strategic collaboration with Shire International GmbH to develop therapeutics for hemophilia, Huntington's disease and other monogenic diseases, and with Biogen Idec for hemoglobinopathies, such as sickle cell disease and beta-thalassemia. It has also 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 www.sangamo.com.

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, references relating to research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo's ZFP technology platform for the treatment of hemophilia B and other monogenic diseases, the timing of submissions of INDs for the treatment of hemophilia B, hemophilia A and lysosomal storage diseases, and the timing of submissions of INDs for other partnered programs and Sangamo proprietary programs. 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 public filings with the Securities and Exchange Commission, including the risk factors described in its Annual Report on Form 10-K and its most recent Quarterly Report on Form 10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.

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SOURCE Sangamo BioSciences, Inc.