Heptares GPCR drug discovery

About Heptares

Heptares Therapeutics Ltd. (Heptares) is a British biotechnology company that conducts innovative pharmaceutical discovery and development targeting G protein-coupled receptors (GPCRs). It was established in 2007 based upon research findings from the UK's MRC Laboratory of Molecular Biology and the National Institute of Medical Research.
Heptares is a pioneer of structure-based drug discovery (SBDD) based on GPCRs, and has technology and know-how to elucidate their structure and independently explore small molecules, peptides and antibodies targeting GPCRs. While they may have clinical or biological validation, GPCRs have been difficult to drug due to the technical challenges associated with accurately solving their structures. For GPCRs, Heptares' platform technology opens up entirely new possibilities in drug discovery, generating first-in-class and best-in-class molecules.

Origin of the company's name: Heptares is a Greek word meaning seven. The company is so named because GPCRs, which are central to Heptares' business, penetrate the cell membrane seven times.

Heptares' strengths

1) Proprietary GPCR-stabilizing technology underpins unique and powerful Structure-Based Drug Discovery platform

Heptares' StaR® (Stabilised Receptor) platform technology stabilises GPCR structures based on their original three-dimensional conformations. Applying FBDD (Fragment-Based Drug Discovery) and SBDD (Structure-Based Drug Discovery) to these StaR proteins, enables Heptares to design very selective, high-affinity drug candidates. Heptares has already succeeded in elucidating world-first X-ray crystal structures of more than ten receptors, and has also succeeded in obtaining many structures for these receptors complexed to drug leads, a vital step in a viable SBDD process. Many members of the GPCR family have latterly been comparatively difficult to drug with other technologies. With Heptares 'technology, GPCRs can be used as StaR® proteins and drugs can be produced that have not existed previously.

This method is not limited to small molecule compounds but can be applied for discovery and development of peptide drug candidates. Moreover StaR® proteins can be used as antigens, so it is also possible to obtain antibodies against GPCRs which, to date, has been difficult.

There are other companies conducting GPCR-targeted drug discovery and their drug discovery techniques are diverse. However, since the receptor is unstable in detergent they require highly stabilising large ligands to stabilise and solve the receptor's structure, precluding routine SBDD. On the other hand, StaR® is the only technology in the world that can remove the GPCR structure from the cell membrane whilst retaining its conformational integrity and enabling co-structure determination with multiple small-molecule drug leads of relatively low affinity. Also, StaR® technology can be widely applied to other important membrane protein targets such as ion channels and transporters.

2) Continuing revenue from a number of platform technology alliances

Heptares has already partnered with a number of big pharmaceutical and biotechnology companies, applying the StaR® platform to partner targets to discover new small molecules and antibodies; these deals have generated over $30 million net cash to date and Heptares is eligible to receive downstream payments/milestones that could total over $1 billion and royalties under these agreements.

3) Promising pipeline

The primary focus of Heptares' business is to utilise its unique platform technology to conduct drug discovery and build its own pipeline. All the pipeline products have the potential to become first-in-class or best-in-class drugs. Going forward Heptares will develop this pipeline internally to establish the efficacy and safety of its compounds through clinical trials. Programmes will be selectively licensed or partnered during clinical development or in selective cases potentially taken to market.

View Heptares' pipeline in more detail.

What are GPCRs?

GPCRs are receptors with seven-transmembrane structures. Genetic analysis has elucidated the presence of around 800 types in vivo. Around half of these are olfactory receptors, and approximately 370 reportedly have physiologically diverse functions as receptors for hormones and other biological materials, and for neurotransmitters. However, thermodynamically the molecular structure is unstable and cannot maintain its integrity when taken out of the cell membrane, so its use as a molecular target for drug development was limited.

In addition, although 40% of marketed medicines target around 60 GPCRs, these were not found by precise drug design.
Through Heptares' drug discovery technology, it is possible to create best-in-class drugs that target medically useful known GPCR targets, and first-in-class and best-in-class drug candidates targeting unknown GPCRs.

Click here for details about Heptares.