Overcoming the limitations of current drug discovery approaches

Can you provide an overview of your company’s current drug discovery pipeline, and any recent milestones or achievements?

Our discovery platform allows us to efficiently discover hits against complex and challenging intracellular targets. From this platform, we have initiated four research programmes:

• A dual inhibitor of HIF1 and HIF2 which inhibits the protein-protein interactions between both HIF1α and HIF1β and between HIF-2α and HIF1β. This has potential in a broad range of solid tumours beyond the approved HIF-2-selective inhibitor, Belzutifan. The programme is currently in early lead optimisation.
• An inhibitor of ATIC homodimerization, which impacts the catalytic activity of the enzyme and stops de novo purine biosynthesis and impacting the growth of tumours. The programme is currently in early lead optimisation.
• An inhibitor of the RAS-RAF protein-protein interaction that does not engage with the Switch-2 pocket and engages equally with activated and non-activated RAS. The programme is currently in hit characterisation.
• Our fourth programme is directed against FOXA1 – a pioneer factor in breast cancer progression. The programme is currently in screening.

With our £40 million Series A investment, we are now ramping up activities against all of these programmes.

How does Curve Therapeutics’ innovative discovery platform, which identifies functional microcycles, set your drug discovery approach apart from industry competitors?

By screening a library against intracellular targets inside a mammalian cell and selecting hits based on their biological function, the Microcycle platform is designed to overcome the limitations of current gene-encoded, affinity-based, drug discovery approaches.

The process starts by engineering and validating a mammalian cell-based assay that can be used for screening to identify functional hits. Into each of these engineered cells is inserted a single member of a Microcycle gene library. From this gene, multiple copies of a single Microcycle are expressed inside each cell and those rare members of the library that have the desired biological function are identified, their DNA isolated and the cycle repeated – each time enriching for those Microcycles with the desired biological function.

By screening inside a cell, the Microcycle platform can address complex and challenging targets that are poorly suited to conventional drug discovery methods.

How do you prioritise which therapeutic areas or disease to focus on in your drug discovery efforts?

Our initial choice of cancer was driven by the need to focus on a therapeutic area that we, as founders, understood reasonably well and where there are many drug targets for which the biology is well understood, but have been difficult to address with drugs. However, the platform is therapeutic area agnostic, and we will be exploring that further during the Series A round.

Target selection within each therapeutic area is one of the most important activities that we undertake, and we take as much advice as we can from multiple advisers as part of the process. In essence, we are looking for targets in which the biology is well validated but there is little or no chemical matter from conventional screening approaches.

Looking back, what do you wish you knew when you first started in the drug discovery industry, and how has that now influenced your approach as CEO?

I started in drug discovery as a bench scientist at G D Searle in 1984. The biotech sector was in its infancy in the UK (I didn’t hear the term ‘biotechnology’ used until 1989) and most chemists and biologists worked, like I did, in the pharma industry. At that time, the idea of being a CEO of a drug discovery company was not something that any bench scientist would have thought reasonable or possible.

I find the question “what do you wish you knew then” a difficult one: the challenges that we face as CEOs, from fundraising to recruiting to delivering on R&D plans, has changed so much over the last 40 years and a large part of what forges you as a leader is what you learn along the way. However, if I was to highlight one particular learning, it is the criticality of time: therapeutics and discovery platforms do not exist in a vacuum – others are developing drugs against your targets and diseases of interest and scientists are working on new ways of drug discovery that will compete with yours. Disease targets, in particular, can fall out of favour extremely quickly, independently of how good your own programme is. As biotech CEOs, our responsibility is to try and find ways to expedite programmes as efficiently as possible, to stay ahead of the competition.

How do you envision the future of drug discovery and development, and how is Curve preparing to adapt to potential changes in the industry?

More and more tools and techniques are becoming available to drug researchers, from gene-encoded platforms like Curve’s, to AI based tools. All of these will play a part in future drug discovery. In terms of the drugs themselves, I see that more and more non-conventional drug modalities (beyond antibodies and ‘rule-of-five’ small molecules) will be needed to address challenging disease targets. This can already be seen in cell-based therapies, gene-based medicines, CRISPR, ADCs and targeted degradation and we are at the very start of seeing cyclic peptides and peptide-like compounds as drugs.

Our responsibility is to remain alert to these changes and, where possible, add to or adapt our platform to meet emerging needs so that we remain on the cutting edge of drug discovery.

About the author

Simon Kerry PhD MBA, CEO, Curve Therapeutics

A co-founder of Curve, Simon is a life-science entrepreneur with over 30 years’ experience in leadership roles within European biotechnology companies. He has been an Operating Partner at Advent Life Sciences, a leading trans-Atlantic venture investor, since 2017.

Prior to joining Advent, Simon was CEO of cancer drug discovery company Karus Therapeutics (Oxford, UK), leading the company from spin-out to clinic. Before Karus, Simon led the Business Development functions at Ablynx (Ghent, Belgium), Active Biotech (Lund, Sweden) and Isogenica (Cambridge, UK).

Following a first degree in Medicinal and Pharmaceutical Chemistry (1984), Simon began his career as a chemist at GD Searle (High Wycombe, UK). He completed a life-science PhD in 1989 and obtained an Executive MBA from Loughborough University Business School in 1995.