The path to the clinic

HotSpot is uncovering important regulatory hotspots to address pathways and diseases long abandoned by drug developers. These are inflammatory, autoimmune, metabolic and mitochondrial diseases with well-validated targets but traditionally, limited means to affect them.

Our initial targets include

PKC-theta (protein kinase C)

Opportunity and challenge

  • Well validated immunokinase in autoimmune and rare disease
  • Enhance regulatory T-cells while inhibiting effector T-cell responses
  • Active-site inhibitors lack selectivity handles and/or drug-like properties
  • Opportunity for new therapies for rheumatologic and graft-versus-host disease

HotSpot unique approach

  • SpotFinder™ uncovers previously unexploited regulatory hotspot
  • HotSpot chemistry delivered first and only allosteric, sub-type selective, drug-like inhibitors across multiple series
S6K (S6 kinase)

Opportunity and challenge

  • Sought after immuno-metabolic target
  • Critical regulator of insulin sensitivity, steatosis and Th17 inflammatory response
  • Historical active-site inhibitors are non-selective, with poor drug-like properties
  • Opportunity to impact both metabolic and inflammatory pathways in
    NASH, diabetes

HotSpot unique approach

  • Attractive druggable hotspot site uncovered, offering selectivity handles over related enzymes
  • First and only allosteric, drug-like inhibitors across multiple series