Compound Profile - Anti-Inflammatory - Arthritis Compound

Compound	QR- 440 QR-440(c) Anti-Inflammatory - Arthritis
Patent Number(s)	6,827,945
Possible Regulatory Category	Dietary Supplement
Area Under Investigation	Anti-Inflammatory Disease Modification
Indications Under Investigation	For the reduction of pain and symptoms associated with Rheumatoid Arthritis, Osteoarthritis and other inflammatory diseases
Description	A blend of standardized botanical extracts derived of GRAS (Generally Regarded as Safe) commercial spice and food plant materials. Pre-clinical in-vitro experiments indicate that  QR-440  possesses anti-inflammatory properties. Based on early findings, the formulation is being considered as a treatment for human and/or canine rheumatoid arthritis.  Canine RA afflicts an estimated 70 to 80 percent of dogs of certain breeds, particularly larger breeds.
Proposed Administration	Oral Tablets/ Capsules.  Medical Animal Feed.
Development Phase	QR-440 human indication Pre-Clinical in-vitro QR-440 (c) canine indication – Investigational New Animal Drug   Number 11-460
Research Path	Ingredient & formulation refinements, Analytical development, Stability evaluations, Preliminary toxicity profiling (cellular and/or animal), Efficacy and or dose response in rodent model.

QR-440

1.    Inhibits migration of granulocytes – shown in animal model

2.    Reduces C Reactive Protein – shown in animal model

3.    Inhibits IFNy and TNFa at 24 and 48 hours at low doses.

4.  Inhibits delayed type hypersensitivity.

With a subsequent inhibition in IFNy and TNFa, the compound could be classified as a DMARD as well as an NSAID.  The compound may reduce inflammation and its subsequent symptoms as well as mediate in the cartilage destruction endemic of disease pathology.   Dosing studies will demonstrate levels required for anti-inflammatory and Disease Modification results.

Marketing   

Rheumatoid Arthritis market.  2003-2008 forecast compound annual growth rate is 24.4%, driven by technological advances, increased competition and significant unmet need.

Significant unmet need exists for a safe anti-inflammatory product to offset the number of patients discontinuing their use of COX 2 inhibitors. 

If Treatment endpoints for this botanical anti-rheumatic compound meet current treatment results for COX-2, NSAIDS and DMARDS with a superior safety profile then achieving 25% market share of rheumatoid arthritis market is a potential.

Estimated Peak Sales of QR440 could range between $500 million to $2.5 billion yearly for the US market assuming efficacy and safety endpoints meet gold standards in phase 3 trials.  This would translate to between roughly 5-25% of the projected $10 billion US Rheumatoid Arthritis Market.

Treatment Cost

Current crop of DMARD’s have significant side effect profiles as they are immuno-suppressants.   Methotrexate is dosed 3x weekly and costs per patient are approximately $1500.00 per year

TNF inhibiting drugs are being sold at a premium.  A 25 mg syringe kit of Enbrel is $750. Dosage is 50 mg per week. Drug costs per patient can reach $75,000.

Celebrex a COX 2 inhibitor sells at $2.79 per pill at retail makes treatment with this COX 2 inhibitor cost between $2000-$3000 per patient.

Research History 

2005
Pre-clinical research showed that QR-440 can inhibit inflammatory cell recruitment and delayed type hypersensitivity (DTH). The study suggested that the mechanism of action affecting cell recruitment and DTH is the inhibition of a broad range of cytokines including IL-2, IL-5 and IL-12. In particular, these studies demonstrated that low doses of the compound inhibits IFN-y and TNF-a at 24 and 48 hours.

Animal studies conducted on QR-440 found that the compound significantly reduced delayed type hypersensitivity (DTH), the cellular response that initiates immune-mediated inflammation. A second study tested the compound’s effect on granulocyte migration by introducing an anaerobic bacterial growth medium into mice to induce the mobilization of the granulocytes. QR-440 significantly inhibited the recruitment of granulocytes into the site of inflammation. The studies demonstrated QR-440s effects on both sterile and immune-mediated inflammation at small doses.