The path to the clinic

To date HotSpot has successfully uncovered and targeted regulatory hotspots across multiple protein classes, including kinases, transcription factors and E3 ligases. Pathways and diseases long abandoned by drug developers are now within our reach, especially those autoimmune, metabolic and mitochondrial diseases with well-validated targets but traditionally, limited means to affect them.

Our lead targets include

PKC-theta (protein kinase C)

Opportunity and challenge

  • Genetically-validated immunokinase in autoimmune and rare metabolic disease
  • Enhances 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 Th2 and regulatory T cell driven disease

HotSpot’s Current Progress

  • SpotFinder™ has uncovered a previously unexploited regulatory hotspot
  • HotSpot chemistry has delivered the first and only allosteric, sub-type selective, drug-like inhibitors across multiple series
  • Differentiated effects on effector and regulatory T cells
  • Robust PK/PD effects in vivo
S6K (S6 kinase)

Opportunity and challenge

  • Critical regulator of mitochondrial function, insulin sensitivity and lipid metabolism
  • Clinical proof of concept demonstrated with traditional inhibitors
  • Intrinsic features of active site limits potential for robust pharmacology and selectivity
  • Opportunity for multiple product opportunities with through tissue selective chemistry

HotSpot’s Current Progress

  • SpotFinder™ has uncovered an attractive druggable hotspot site, offering selectivity handles over related enzymes
  • First and only allosteric, drug-like inhibitors across multiple series with demonstrated in vivo pharmacology
  • <100 nM cell based activity leveraging novel, attractive chemotypes