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, which cause these diseases.
An important class of genetic mutation is a premature termination codon (PTC). PTC mutations 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 a PTC. In cancer, 10% of all tumours have a PTC in P53 and PTC mutations in other important genes increase the numbers of cancers driven by this class of mutation.
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 overcome 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.
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 products to optimise for a 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.
BETs are a family of proteins characterized by two bromo-domain subunits (BD1 and BD2) plus an extra-terminal domain (EXT). BET proteins are believed to play a key role in the regulation of inflammatory and oncogenic genes involved in several diseases.
Tay’s ‘soft’ drug capabilities led to the discovery of candidate drugs that target BET bromodomains. Our candidate drug (TAY-B1; VYN201) is highly effective in pre-clinical models when applied topically to skin, lung or by local injections, but is rapidly degraded when it enters the blood stream, thereby avoiding the issues seen with orally administered BD1/2 inhibitors.
In addition, Tay has developed compounds that are highly selective for bromodomain 2 (BD2) of the BET proteins to avoid the toxicities seen with unselective inhibitors. We have delivered candidate drug (TAY-B2; VYN202) suitable for oral administration, and with utility in the commercially attractive markets for anti-inflammatory and anti-fibrotic medicines.
Developing ‘Soft’ Drugs
Drugs delivered orally are commercially attractive however other routes of administration open up local delivery with the ability to deliver a drug directly to the site of a disease. Such routes include intraperitoneal, intravenous, inhaled and dermal. 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.