Therapeutic Applications

Our mission is to develop highly differentiated human therapeutics to treat unmet medical needs and we are building a pipeline of ZFP Therapeutics® to do just that. Our strategy is to develop programs to points of significant value inflection and look for an appropriate pharmaceutical or biotechnology company partner to help us advance programs through late stage clinical trials and commercialization.  In 2012 we established a therapeutic partnership with Shire AG to develop ZFP Therapeutics for hemophilia, Huntington's disease and other monogenic diseases.

We have  ongoing Phase 2 clinical trials and two Phase 1 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.

In addition, our clinical collaborators at City of Hope (COH) have initiated a Phase 1 clinical trial to evaluate a ZFN-based therapeutic for the treatment of glioblastoma multiforme, a type of brain cancer. We have other preclinical development programs of ZFP Therapeutics in hemophilia B, Parkinson’s disease, neuropathic pain, and neuroregenerative programs in spinal cord injury, traumatic brain injury and stroke.

We also have research stage programs in monogenic diseases, genetic conditions that result from a defect in a single gene, including hemophilia and other hemoglobinopathies, and certain immunodeficiencies.

We believe that 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 approaches enabling the development of therapies for a broad range of unmet medical needs.

For example, ZFP Therapeutics can:

  • Potentially be used to treat a broad range of diseases. ZFP Therapeutics act at the DNA level to regulate gene expression or modify genes. We can generate ZFPs to recognize virtually any gene target allowing direct modulation of the gene and enabling a potentially broad applicability.
  • 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 or therapeutic 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 targets have a clear role in disease processes but cannot be bound or modulated for therapeutic purposes by small molecules. Alternative therapeutic approaches may be required to modulate the biological activity of these so-called “non-druggable” targets. 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 ZFP technology.
  • Provide novel activities 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 act with high specificity and we have published such data. In addition, there are generally only two targets per cell (as a rule there are two copies of each gene per cell) in for a ZFP Therapeutic which means ZFP TFs and ZFNs 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 only brief cellular expression of ZFNs.