Our mission is to engineer genetic cures for monogenic and infectious diseases with unmet medical needs through the development of our highly differentiated pipeline of novel ZFP Therapeutics®. Our strategy is to develop programs up to points of significant value inflection and look for an appropriate partnership with a pharmaceutical or biotechnology company to help us advance programs through late-stage clinical trials and commercialization. In the longer term, our goal is to integrate manufacturing, development and commectial operations to capture the value of our proprietary ZFP Therapeutic products.
We have ongoing Phase 2 clinical trials to evaluate the first therapeutic application of our ZFN technology, SB-728-T, a ZFN-modified T-cell product for the treatment of HIV/AIDS.
We are also developing a ZFN-modified hematopoietic stem cell product, SB-728mR-HSC, for HIV/AIDS. The IND for this program is active and the Phase 1 study is expected to begin at City of Hope in 2015, partially funded by a $5.6 million CIRM Strategic Partnership Award.
In Vivo Protein Replacement Platform™ (IVPRP)
Sangamo's IVPRP is a broadly leverageable approach designed to produce a life-long therapeutic solution for diseases that are currently addressed using enzyme replacement therapy. The approach harnesses the body's powerful albumin promoter within liver cells, to transcribe and translate therapeutic levels of a relevant replacement protein.
Several of our ZFP Therapeutic preclinical programs are being developed using this approach.
Our hemophilia A & B programs are among the first therapeutic applications being developed using the IVPRP. The goal is to permanently produce human factor VIII and factor IX proteins for hemophilia A and B, respectively, at therapeutic levels. We use AAV-delivery and ZFN-mediated gene editing to insert the replacement clotting factor gene under control of the albumin promoter.
Lysosomal Storage Disorders
We are also using the IVPRP approach to develop our proprietary ZFP Therapeutic programs for lysosomal storage disorders (LSDs). Our first progams are in Hurler (MPS I) and Hunter (MPS II) syndromes, Gaucher disease and Fabry disease.
Beta-thalassemia & Sickle Cell Disease
In partnership with Biogen Inc., our ZFP technology platform is also being applied toward the development of ZFP Therapeutics to functionally cure hemoglobinopathies such as beta-thalassemia and sickle cell disease (SCD). Through ex vivo mRNA electroporation and ZFN-mediated knockout of the Bcl11a Enhancer DNA sequence in the red blood cell precursor subset of CD34+ stem cells, our ZFP Therapeutic product can simultaneously down-regulate the mutant adult hemoglobin gene and activate the functional fetal hemoglobin gene specifically in erythroid cell lineages to facilitate the switch from adult to fetal hemoglobin production in beta-thalassemia and SCD patients.
Huntington's Disease (HD)
Using the gene regulation capabilities of ZFP TFs we can selectively target and repress the mutant Huntingtin gene allele in HD patients to effectively reduce mutant Huntingtin protein production and eliminate the disease phenotype. Our Huntington's disease preclinical program is partnered with Shire International GmbH.
To learn more about our ZFP Therapeutic programs, refer to our product pipeline.
Advantages of ZFP Therapeutics®
We believe ZFP Therapeutics® provide a unique and proprietary approach to drug design and have differential competitive advantages over small-molecule drugs, protein pharmaceuticals and RNA-based therapeutic approaches, thus catalyzing the development of therapies for a broad range of unmet medical needs.
For example, ZFP Therapeutics® can:
- Target “non-druggable” targets. ZFP TFs and ZFNs act through a mechanism that is unique among biological drugs: direct regulation or modification of the disease-related target gene as opposed to the RNA or protein target encoded by that gene. Following the sequencing and publication of the human genome, and the industrialization of genomics-based drug discovery, pharmaceutical and biotechnology companies have validated many new drug targets. Many of these "non-druggable" targets have a clear role in disease processes but cannot be bound or modulated, for therapeutic purposes, by small molecules. This creates a significant clinical and commercial opportunity for the therapeutic regulation or modification of disease-associated genes using engineered ZFP TFs or ZFNs. Thus, a target which may be intractable to treatment using a small molecule or monoclonal antibody could be turned on, turned off or modified at the DNA level using Sangamo's proprietary ZFP technology.
- Provide novel mechanisms such as activation of gene expression and gene modification to address drug targets. Engineered ZFP TFs enable not just the repression of a therapeutically relevant gene but its activation, and ZFNs enable the disruption, correction or targeted addition of a gene sequence. This gives the technology a degree of flexibility not seen in other drug platforms. Activation of gene expression and direct modification of genes are not functions that can be achieved using antisense RNA, or siRNA, which act by interfering with the expression of cellular RNA, or conventional small molecules, antibodies, or other protein pharmaceuticals that primarily act to “block” or antagonize the action of a protein.
- Provide high specificity and selectivity for targets. ZFP Therapeutics® can be designed to be highly specific and we have published data to demonstrate the singular specificity of our therapeutic products. In addition, there are generally only two targets per cell (as a rule there are two copies of each gene per cell) for a ZFP Therapeutic, which means ZFP TFs and ZFNs only need to be available in the cell in very low concentrations. In contrast, drugs that act on protein and RNA need to be administered in higher concentrations, as their targets are naturally present in higher amounts in the cell. Many small molecule and RNA-based approaches either affect multiple targets demonstrating so-called “off-target effects” or are toxic at concentrations required to be therapeutically effective.
- Be used transiently to obtain a permanent therapeutic effect. Permanent gene disruption, correction or addition requires a single administration and only brief cellular expression of ZFNs.