Products

BTK Inhibitors

Impetis has developed BTK inhibitors which are designed for selectivity and reversibility, making them highly differentiated from the competition in terms of their safety and sustained action over a long duration of treatment. Impetis’ BTK inhibitors are differentiated in the following ways:

Reversible and non-covalent inhibition

  • No risk of inhibition of other cysteine-containing kinases and other enzymes by covalent modification
  • No potential for drug resistance due to mutation of Cys-481 residue of BTK that forms covalent bonding with irreversible inhibitors
  • No potential for covalent protein conjugate adducts formation leading to immunogenicity or loss of selectivity

Intrinsic selectivity, with no/minimal inhibition of other kinases that may have potential safety risks

  • TEC-sparing: Decreased platelet dysfunction/bleeding risk
  • JAK-3-sparing: Decreased risk for profound immunosuppression
  • EGFR-sparing: Decreased potential for diarrhea/GI toxicity
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Small oral bid dose leading to full target coverage over 24 hrs, thus reducing the risk of Richter’s transformation or other mutations/clones, without compromising the safety and side-effect profile

Key assets in Impetis’ BTK Inhibitor platform include the following

PNQ-849: A reversible BTK inhibitor for Inflammation and Auto-immune Indications

Robust efficacy in standard models of Autoimmune disease
  • Robust efficacy at both BID and QD dosing in 2 RA models: Collagen Induced Arthritis (CIA) in mice and Adjuvant Induced Arthritis (AIA) in rats
Clean preclinical safety profile
  • Excellent selectivity over other BTK and diverse non-BTK family kinases vs. irreversible inhibitors and other drugs
  • Selectivity vs. diverse 100 kinase and 121 DrugMatrix targets and hERG
  • Non-mutagenic in mini-Ames test
  • Well tolerated with dose-related TK profile in 28-day safety study in rat with a NOEL of 180 mg/kg/day
IP Status
  • Composition of Matter Patent covering PNQ-849 and PNQ-617 has been granted in US (US9,233,983)
IND ready profile, with clear development path
  • Process optimization completed
  • All IND directed safety studies have been completed

PNQ-154: an early stage reversible BTK inhibitor positioned for “Ibrutinib Resistant” Cancers

Robust efficacy in standard models
  • Robust efficacy at both BID and QD dosing in 2 RA models: Collagen Induced Arthritis (CIA) in mice and Adjuvant Induced Arthritis (AIA) in rats
  • Diffuse large B-cell lymphoma (DLBCL) Xenograft model
Clean preclinical safety
  • Excellent selectivity over other BTK and diverse non-BTK family kinases vs. irreversible inhibitors and other drugs
  • Selectivity vs. diverse 100 kinase and 121 DrugMatrix targets and hERG
  • 14 day repeat oral dose toxicity in rats completed
Clear IP
  • Patent granted- field in April 2013 under PCT and was published (WO2013157022) in October 2013
IND ready in under a year
  • Process optimization and final form selection ongoing
  • Material generation for IND-enabling studies initiated