Despite a high unmet need, the treatment of many genetic diseases and cancers has been limited due to a lack of drugs targeting the underlying genetic mutations that cause these diseases.
Tay Therapeutics has developed Tay-Enable™, a platform for the discovery and development of a new class of medicine that can cause the body to readthrough premature termination codon (PTC) mutations, and produce full-length, functional proteins. By restoring functional proteins, our drugs seek to address the root cause of these diseases.
A new tumour selective and pluripotent approach to the treatment of cancer
As people age the body acquires new mutations, which leads to the development of cancers. Many cancers are affected by 100s or 1000s of mutations, which healthy tissues lack. Around 5% of all mutations create PTCs. A further 5% are insertion or deletion events that also lead to a PTC.
Inducing readthrough of PTCs has the potential to disrupt tumour growth in multiple ways, especially in tumours with a high mutational burden, which are often aggressive and difficult to treat. Importantly healthy tissues lack these mutations.
Three critical processes are to be targeted:
- Restoration of tumour suppressor genes possessing PTCs will reinstate critical processes that guard against cancer formation. Around 30% of cases have PTCs in a tumour suppressor.
- Tumours with a high mutational burden may have hundreds of PTCs. Inducing the expression of multiple mutated proteins should increase cell stress, resulting in tumour cell death.
- INDEL (frameshift) mutations generate potent tumour-specific neoantigens. Readthrough drugs can enhance neoantigen production to induce or enhance immune clearing of tumours.
One drug to treat many indications
PTCs are causative in around 10% of all genetic disease cases and are often more common in the most severe forms of a disease. For instance, in recessive dystrophic epidermolysis bullosa (RDEB) around 30-50% of cases are due to PTCs.
TayEnableTM restores function in cell models of cystic fibrosis and Duchenne’s muscular dystrophy, which suggests it maybe a promising new approach to the treatment of many genetic diseases.
Key features of the TAY-Enable™ technologies
- Diseases modifying: Treat the underlying genetic mutation, not just the symptoms.
- Broad applicability: A single drug that can treat multiple indications. As we treat a class of mutation, not just the specific disease, one drug can be applied to many patient populations.
- Tailored products: Our platform capability can be applied to multiple delivery products, which allows optimisation for patients’ needs, e.g. topical (epidermolysis bullosa), inhaled (cystic fibrosis), oral (cancers, many indications).
How does the Tay-Enable™ platform work?
Healthy genes are converted into proteins by the ribosome, which converts an mRNA code into protein sequences and production finishes at a stop codon
When a gene has a premature stop mutation the ribosome ends protein production early leading to truncated, non-functional proteins.
Our Tay-Enable™ drugs help the ribosome to progress past premature stop codons. This allows production of full length, functional proteins.
Developing ‘Soft’ Drugs
Drugs delivered orally are commercially attractive, however, other routes of administration open up the ability to transport a drug directly to the site of a disease. Such routes include intraperitoneal, intravenous, inhaled and topical. Core to Tay’s capabilities is the ability to develop drug candidates for multiple routes of administration including the ability to develop compounds that possess physiochemical, pharmacokinetic and metabolic characteristics suitable not just for oral but for other such routes. Such capability maximises the number of drug candidates that can be developed from a project and the potential return to Tay.