The challenge
Protein misfolding diseases present three compounding challenges to conventional drug discovery:
- Moving targets. The relevant proteins are intrinsically disordered, conformationally dynamic, or structurally polymorphic. They lack the stable binding pockets that small-molecule discovery relies on, and they populate ensembles of transient states that vary across patients, disease stages, and tissue environments.
- Inaccessible locations. Many key targets sit inside cells or behind the blood-brain barrier, where large biologics have limited access.
- Pathology happens in living cells. Destabilisation of native states, nucleation, fibril growth, propagation, and cytotoxicity all unfold in crowded cellular environments, not in isolation.
Traditional modalities address only parts of this challenge:
- Small molecules are compact and diffusible but often lack the surface complexity needed to engage shallow, discontinuous, or dynamic conformational epitopes.
- Antibodies are highly selective but generally too large to reach intracellular targets and have limited CNS access.
- Linear peptides can bridge some of this gap but are frequently limited by poor stability and rapid degradation.
In parallel, most discovery technologies follow a binding-first logic: identify molecules that bind purified targets, then test whether those molecules rescue misfolding. The two are not equivalent. A molecule can bind with high affinity while still failing to stabilize the native state, inhibit aggregation, or reduce toxicity. For protein misfolding diseases, where efficacy depends on reshaping a dynamic conformational landscape, optimizing for binding can become a decisive limitation.
Despite decades of effort and over $100B in global investment, clinical impact has been minimal.
Drug discovery for protein misfolding diseases is a functional problem — not a binding problem.
Solution
ResQ Biotech is closing this gap with two complementary innovations:
- A next-generation therapeutic modality designed specifically to engage disease-relevant protein conformations
- A discovery platform that optimizes candidate drugs directly for biological relevance and clinical translatability in living cells
Together, these enable ResQ Biotech to drug pathogenic protein conformations that have remained out of reach.
CycloFOLDER™
A next-generation therapeutic modality for protein misfolding diseases
CycloFOLDER™ therapeutics are ultra-compact, conformationally constrained macrocyclic peptides engineered to modulate misfolded and aggregated proteins with high specificity and drug-like properties.
CycloFOLDER™ compounds:
- Engage challenging and previously undruggable protein targets, including intrinsically disordered proteins and polymorphic aggregates.
- Bridge the advantages of small molecules and biologics, combining specificity and safety with stability, permeability, and synthetic tunability.
- Occupy a unique and unexplored region of chemical space optimized for conformation-dependent protein interactions.
- Are chemically synthesized and readily optimized for stability, selectivity, and pharmacological performance.
CycloFINDER™
Living-cell drug discovery
CycloFINDER™ is ResQ Biotech's proprietary living-cell discovery engine. It biosynthesizes and functionally screens ultra-large libraries of candidate CycloFOLDERs directly in living cells, enabling the identification of molecules that rescue pathogenic protein conformations.
Unlike conventional discovery approaches that rely on static protein structures or isolated binding assays, CycloFINDER™ selects molecules based on functional rescue of protein misfolding and aggregation, prioritizing biological relevance and translational potential.
Key advantages include:
- Selects molecules by functional rescue in living cells, rather than by binding in vitro or in silico.
- Accesses cryptic sites and ensembles of transient protein conformations.
- Identifies hits in weeks rather than months or years.
- Discovers therapeutics effective against both globular and intrinsically disordered proteins.
- Applies broadly across diverse protein misfolding diseases.
AI-guided design
AI augments the platform across hit prioritization, pharmacological optimization, and structure–function learning — accelerating the path from functional hits to clinical candidates without displacing the platform's core principle: selection by functional rescue, not by predicted binding.