JAK Inhibitors

Impetis JAK inhibitors are selective and safe compounds with the optimal balance of safety and efficacy. Animal studies have clearly established their superior safety profile without any compromise in efficacy for multiple autoimmune/inflammatory indications.

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Key assets in Impetis’ JAK Inhibitor platform include the following

PNQ-701: An oral, highly selective JAK 1 inhibitor with minimal inhibition of JAK2 /3, positioned for treatment of Rheumatoid Arthritis

Robust efficacy in standard models of Autoimmune disease
  • Excellent efficacy in AIA model in rat for Arthritis
  • PK properties supporting QD dosing in humans
Safety profile that can afford a wide safety window
  • Selectivity vs.100 kinase and 123 Drug Matrix targets and hERG
  • Non-mutagenic in mini-Ames test
  • Well tolerated with dose-linear TK profile in 14-day safety study in rat (no safety concerns identified)
  • Greater selectivity over JAK2 >>> GLPG0634 (211 vs 30 fold in human whole blood assay) – lower risk of anemia
  • Selective over JAK3 (~90 fold in kinase assay )- reduced risks from immunosuppression
  • Greater selectivity over a diverse panel of 100 kinases vs. GLPG0634- lower risk of general safety liabilities
  • No ADME liabilities
Clear IP position
  • PCT filed in March 2012 and published in (WO2012127506) September 2012; US patent allowed
IND ready in 6-8 months
  • 14-day non-GLP Rodent studies completed with dose linear TK profile in 14-day rat study
  • Robust synthetic route for large scale synthesis has been developed
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PNQ-401: an oral and safe inhibitor of JAK1/3, selective over JAK 2 positioned for the treatment of Psoriasis and Rheumatoid Arthritis

Robust efficacy in standard models of Autoimmune disease
  • Superior potency vs Tofacitinib in 2 RA models: Collagen Induced Arthritis (CIA) in mice and Adjuvant Induced Arthritis (AIA) in rats
  • Robust efficacy in RA models in BID as well as QD dosing suggesting QD potential in humans (vs. BID with Tofacitinib)
Clean preclinical safety profile
  • Good selectivity vs. 150 kinase and 123 DrugMatrix targets
  • 28-day GLP tox study in rats completed. Well tolerated with dose-proportional TK profile
Long patent life
  • PCT filed in March 2012 and published in (WO2012127506) September 2012; US patent allowed
IND ready profile, with clear development path
  • Process optimization completed
  • All IND directed safety studies have been completed except for studies in Dog
  • BA/FA method development and validation in support of regulatory toxicology studies completed
Improved side effect profile
  • PNQ-401 at 3 mg/kg showed trend towards normalization of total leukocyte count in the blood.
  • PNQ-401 at 3 mg/kg decreased neutrophil count in blood by ~45% (ED50 > 3 mg/kg)
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