Curve’s Microcycle^® platform addresses pressing needs in small molecule drug discovery

A powerful platform

Advances in our knowledge of disease biology has created a better understanding of the targets and pathways that play a key role in disease initiation and progression. However, many of these targets and pathways cannot be readily addressed using current drug discovery methods and there remains an urgent need for newer, more sophisticated drug discovery approaches.

Curve’s gene-encoded Microcycle platform enables the enrichment of diverse libraries on the basis of their biological function inside a mammalian cell which facilitates the discovery of biologically active molecules that can address challenging and complex targets.

Current gene-encoded drug discovery approaches fall short of Pharma’s needs

Existing macrocyclic peptide display and DNA encoded libraries can only identify hits based on their strength of binding (affinity) to a purified and immobilised target in biochemical buffer. Rarely do these binders have biological function and the large peptides that are identified with these technologies cannot be readily optimised to make orally active small molecule drugs making them poorly suited to intracellular disease targets.

Microcycles: the big leap forward

Curve’s Microcycle platform allows targets to be screened in all of their native conformations in the cytoplasm of a mammalian cell. The small size of Microcycles^® eliminates the affinity bias of larger cyclic peptides and facilitates engagement with allosteric and cryptic sites on targets.

Microcycle hits are generally cell penetrant, allowing rapid biological validation and structural biology studies.

The small size and structural rigidity of Microcycles enables lead hopping to non-peptide small molecules for lead optimisation.

An evolving platform

Curve’s droplet microfluidic system is the next generation of the Microcycle platform that comprises high efficiency functional screening of a Microcycle library within a single femtolitre liquid droplet. This technology is protected by international patents and patent applications.

This microfluidics platform is being further developed to allow co-encapsulation of mammalian cells with a Microcycle^® library within these droplets, enabling the discovery of functional hits against membrane proteins in their native conformation. The system is being further developed to screen for functional hits against non-protein targets such as RNA.

A platform built on strong foundations

IP protected

Curve’s proprietary platform is built on pioneering research by the Tavassoli lab and described in more than 30 peer-reviewed publications covering a wide range of protein-protein interactions over a 15-year period. The central components of the Microcycle screening platform are protected through international patents and patent applications and exclusively licensed to Curve.

Promising evolution

Curve’s platform has multiple applications beyond our in-house pipeline and there are clear opportunities for collaborative research and development with partners that have a depth of knowledge in target biology and expertise in drug development.

Pipeline

First in-class therapeutics

Curve is deploying its proprietary platform to build a pipeline of first-in-class small molecule drugs, initially against high-priority cancer targets, with the potential to transform the treatment of multiple solid and haematological tumours.

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Vision

Our vision is to transform the lives of patients by addressing complex and challenging disease targets that are intractable to conventional discovery methods.