Four biological problems, stated as problems.

Anti-infectives

The clinical problem is well documented. Gram-negative organisms combine an outer membrane that excludes most chemistry with efflux systems that remove what does get in, and the enzymatic resistance mechanisms that defeat existing classes now circulate on mobile genetic elements. In fungal disease the situation is narrower still: a small number of drug classes carry almost the entire clinical burden, and resistance in Candida and in dermatophyte species is rising against all of them.

Our interest is in compounds whose activity depends on the physical organisation of the microbial envelope rather than on the inhibition of a single enzyme. That property changes the resistance arithmetic: escape requires the organism to alter something structurally load-bearing, at a fitness cost, rather than to acquire one mutation or one plasmid.

This is the area closest to our founding research, and the one where the gap between what medicine needs and what the pipeline contains is widest.

Hair and skin biology

Skin and the hair follicle are unusually tractable systems to work in. They are accessible, they can be modelled in culture with reasonable fidelity, and the biological processes involved — oxidative stress handling, barrier function, pigment biology, the follicular growth cycle, and the resident microbial community — are increasingly well characterised at a molecular level.

What that field is short of is not understanding but chemistry. A large proportion of actives in use are variations on a small number of long-established molecules, and claims frequently outrun the evidence supporting them. We are interested in compounds with a defined mechanism and reproducible activity in relevant cell systems, developed to a standard of evidence borrowed from therapeutic work rather than from cosmetics.

Practically, this area also has the shortest experimental cycle of the four. Results arrive faster, which makes it valuable for validating methods that later apply elsewhere.

Wound repair

A chronic wound is a wound stuck in the inflammatory phase. Proteolytic activity stays elevated, growth factors are degraded as fast as they are produced, and the tissue never progresses to proliferation and remodelling. In a large share of cases, a bacterial biofilm is what holds it there — structurally protected, tolerant of antibiotics at concentrations far above the planktonic minimum, and continuously driving the inflammatory signal.

This makes infection and healing difficult to separate, and it is why we treat this area as adjacent to our anti-infective work rather than apart from it. Chemistry that can act on biofilm structure while remaining tolerable to host tissue addresses both halves of the problem at once, which is a considerably more interesting proposition than either half alone.

Cellular protection

Our longest-horizon area, with an initial interest in renal biology. The kidney is metabolically demanding, densely mitochondrial, and continuously exposed to whatever is circulating — which makes proximal tubular cells particularly vulnerable to oxidative and toxic injury. Injury in this tissue is also self-amplifying: damage drives inflammation and fibrosis, which drives further loss of function.

Despite a very large and growing patient population, there are remarkably few agents that protect cells prospectively rather than manage the consequences of injury after the fact. The scientific question we find interesting is whether compounds that stabilise cellular stress responses can shift that outcome.

We are early here, and we say so. This area is at the stage of defining the right assay questions rather than answering them.