Stoking protein production
We believe Stoke’s proprietary TANGO technology platform can be used to treat a broad spectrum of genetic diseases in which the patient has one healthy copy of a gene and one mutated copy that fails to produce a protein essential to health. These diseases, in which loss of approximately 50% of normal protein expression causes disease, are called autosomal dominant haploinsufficiencies.
Using our proprietary TANGO platform, we aim to increase protein production from the remaining healthy copy of a gene and to restore the protein to near normal levels, thereby slowing or stopping disease progression.
This novel approach will allow us to pursue disease-modifying treatments for severe genetic diseases. We are initially prioritizing the development of potential medicines to treat genetic epilepsies, such as Dravet syndrome. We are also advancing several other early programs focused on multiple targets, including haploinsufficiencient diseases of the central nervous system (CNS), eye, kidney and liver. Additional non-epilepsy indications for which our technology may be applicable include autosomal dominant optic atrophy and more common genetic diseases such as autosomal dominant polycystic kidney disease or tuberous sclerosis.
We believe we have the science, the strategy and the team to tackle this tremendous unmet need.
How TANGO works
We are developing TANGO as potentially the first precision medicine platform for treating a category of severe genetic diseases known as autosomal dominant haploinsufficiencies. In a haploinsufficient patient, mutations in one copy of a gene severely reduce normal protein expression, causing disease. TANGO is designed to address this protein deficiency by precisely upregulating target protein expression.
- We are targeting genetic diseases in which the patient has one functional copy of the gene (shown in orange) and one mutated copy (in red). As a result, the patient is producing only half as much protein as is needed to maintain health.
- These genes are transcribed into pre-messenger RNA, or pre-mRNA.
- Most pre-mRNA are processed to generate productive mRNA and become a template for protein production. Some pre-mRNA, however, are processed to generate non-productive mRNA. It’s normal to have both types of mRNA in the cell.
- The non-productive mRNAs are degraded and do not generate protein. Only the productive mRNA from the functional copy of the gene produces any of the needed protein.
This is where the Stoke therapy comes in.
We synthesize small fragments of modified RNA, known as antisense oligonucleotides (ASOs), that are designed to bind to specific stretches of pre-mRNA. Preclinical studies have shown that application of our ASO therapy reduces the synthesis of non-productive mRNA and increases the synthesis of productive mRNA. The increased levels of productive mRNA from the functional copy of the gene result in increased protein production, thereby restoring the target protein to near normal levels.
The TANGO advantage
We believe the TANGO platform will allow us to address the underlying genetic cause of diseases such as Dravet syndrome, a severe and progressive genetic epilepsy, with therapies that are highly precise, durable and controllable.
Our proprietary bioinformatics
We have identified approximately 2,900 genetic diseases which we believe to be amenable to TANGO. We use next generation whole transcriptome RNA sequencing and a proprietary bioinformatics analysis to identify the most promising genes quickly.
In addition to exclusively licensing foundational TANGO patents from Cold Spring Harbor Laboratory and the University of Southampton, we have also filed patents around our top drug targets, providing us with an intellectual property estate that includes both TANGO technology and genetic targets.