Products

Adenosine Receptor Antagonists

Impetis has developed a platform of Adenosine receptor Antagonists which hold the promise of being best-in-class therapeutics for Cancer as well as other selected indications. Our Adenosine receptor antagonists are differentiated from others in the class on multiple aspects that confer benefits for Oncology and other Indications, such as:

  • Potency at nanomolar and sub-nanomolar ranges
  • Longer receptor residence time
  • Superior efficacy in 2 immuno-therapy resistant animal models viz. 4T1 Syngeneic model of Breast Cancer and CT 26 Syngeneic model of colon Cancer
  • Robust efficacy in models of Parkinson’s and other cognitive disease
  • Increased compound safety basis rodent toxicity studies
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Key assets in Impetis’ Adenosine Receptor Antagonists platform include the following

PNQ-370: A Potent, Selective A2A AdoR Antagonist

Potential best-in-class profile for Lung and multiple other cancers
  • Low nM potency, > 500-fold selectivity over A1 AdoR, good PD effect
  • Excellent PK, with high availability in key tissues
  • Excellent and extended target engagement in ex vivo studies
  • Superior efficacy in multiple CNS disease models
Clean preclinical safety profile, with no anticipated liabilities in the clinic
  • Non-mutagenic and clean in cardiovascular safety pharmacology screens
  • Safe and well-tolerated in 14d exploratory tox & 28d GLP tox studies at highest dose in rat
Long patent life till 2031
  • US (US 9,006,177) and EP (EP2619211) patents granted for Composition of Matter
IND enabling Studies close to completion
  • 8 Months to IND filing

PNQ-103/-1: A Potent, Selective A2B AdoR Antagonist

First-in-class profile with excellent efficacy & PK
  • Efficacy demonstrated in 2 Syngeneic models of immune resistant cancers
  • Shows excellent efficacy in mouse models
  • High oral bioavailability, low volume of distribution, low clearance and no potential for drug-drug interaction
Clean preclinical safety profile, with no anticipated liabilities in the clinic
  • No safety issues in off target activity, mini Ames and exploratory toxicology studies in rats – NOAEL has been established
  • No hERG inhibition and has no effect on CV parameters in telemetered dogs
  • Rat safety studies complete, dog ongoing
Long patent life till 2031
  • Composition of Matter Patent for PNQ-103 granted in US (US 9,284,316), EP (EP 2405917) and JP (JP 5765239)
  • Composition of Matter Patent for the pro-drug PNQ-103-1 granted in US (US 8,940,751) and JP (JP 5827998) while EP patent is allowed
IND ready profile, with clear development path
  • Large scale synthesis has been completed for IND directed studies
  • Rodent safety studies complete, studies in Dog ongoing
Potential for fast track development
  • Option for registration as orphan indication (SCD)

PNQ-201: A Potent, gut-restricted A2B AdoR Antagonist

First-in-class profile with excellent efficacy & PK for Colo-rectal indications
  • Excellent efficacy in the DSS mouse model of ulcerative colitis in both the prophylactic and the therapeutic modes and in the TNBS model of colitis in the prophylactic mode
  • Minimal systemic exposure while maximizing its exposure in the GI tract, the primary site of action
  • Adenosine A2B receptors are consistently up-regulated in colorectal carcinoma tissues and cell lines compared to normal colorectal mucosa
  • 67% Adenocarcinomas and 17% tubular carcinomas are immuno-positive for A2B
  • Efficacy and target engagement established in Colitis models to demonstrate gut A2B antagonism – robust efficacy expected in Colorectal cancer
Clean preclinical safety profile, with no anticipated liabilities in the clinic
  • No safety concerns for safety pharmacology and genetic toxicology
  • No off-target activity in over 150 target assays (MDS PanLabs Screen) and was non-mutagenic in an Ames test
  • No hERG inhibition and has no effect on CV parameters in telemetered dogs
  • No safety issues in regulatory tox studies up to 1000 mg/Kg/day in rats and 750 mg/kg/day in dogs through oral route
Long patent life till 2031
  • Composition of Matter Patent covering PNQ-201 filed, PCT for PNQ-201 filed and published (WO2010103547); US, EP and Japanese patents have been granted
IND ready profile, with clear development path
  • Large scale synthesis for carrying out 28-day IND directed safety studies have been completed
  • Robust synthetic route for large scale synthesis has been developed