Kindex Final2010v3

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Kindex Therapeutics Industry-debut presentation at WBBA Life Science Innovation Northwest 2010. Created graphics and digital presentation.

Kindex Therapeutics Industry-debut presentation at WBBA Life Science Innovation Northwest 2010. Created graphics and digital presentation.

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  • 1. Multi-Target Protein Kinase Modulators derived from Humulus Lupulus ‘Hops’
  • 2. Certain statements made in this presentation areforward-looking such as those, among others, relatingto the development, safety and efficacy oftherapeutic drugs and potential applications forthese products. The Company undertakes noobligation to update the forward-looking statementscontained herein or to reflect events orcircumstances occurring after the date hereof
  • 3. Company Highlights Focus on pharmacophores with history of safe use Target small molecules modulating key metabolic networks Pre-clinical and clinical evidence supporting activity and safety Initiating safety pharm/tox for IND in Type 2 Diabetes Business Model: conduct Phase 1through 2a POC clinical trials and seek a partner 4Q2009: $20M Series A investment by partner, Alticor
  • 4. Background Modified phytochemical extracts demonstrate selective protein kinase modulation 1st Generation Product : R200 (Tetrahydro-iso-acids) Mixture of 3 chemically distinct analogs Potent anti-inflammatory activity KDT500: most potent analog Large patent portfolio protecting our position
  • 5. Intellectual Property PortfolioR200 >140 patents & applications worldwide Methods of Treatment Composition Purification/Isolation Process Indications Diabetes/Metabolic Syndrome Inflammation Arthritis
  • 6. 1st Generation Product:Tetrahydro-iso- -acids Family (R200) R= Isobutyl KDT500 R= sec-butyl R= isopropyl
  • 7. R200 Safety Cell free In Vitro Animal HumanMulti-target selective Cytochrome p450 Extensive R200 Bioavailable in humans (orallymodulator Studies- IC50 (ug/ml) Toxicology studies absorbed within one hour & -indicates CYP450 in animal models persists in serum for over 8Gini Coefficient 2C9 is the route of hours)calculation metabolismdemonstrates high Does not decreasekinase specificity prostacyclin formation indicating CV safety No elevation of liver enzymes No elevation of fecal Calprotectin indicating GI safety Safe to GI system when orally consumed at therapeutic doses
  • 8. Type 2 Diabetes Market Approximately 90-95% of all diabetes cases in the U.S. are Type 2 >20 million people in the U.S. currently have Type 2 Diabetes Combined U.S. sales of glitazones alone in 2007 were > $6.6 Billion
  • 9. Unmet Needs in Diabetes Therapeutic needs: Multiple effects not achieved by single agent (e.g. anti-hyperglycemic, anti-obesity, hypertriglyceridemia) Undesired side effects/patient compliance Metformin: GI effects, lactic acidosis Secretagogues: weight gain, hypoglycemia, tid dosing Glitazones: weight gain, edema, liver safety Insulin: injectable, hypoglycemia, weight gain
  • 10. Diabetes R200 comparable to Metformin R200 Metformin db/db Mouse Type 2 Diabetes model Treatment: 100 mg/kg/ day 7 day treatmentGlucose Reduction Insulin Reductionmg/ml ng/ml
  • 11. R200 Prevents High Fat Diet Induced Obesity HF HF + R200 LF
  • 12. Diet Shift HF to HF HF + R200 to HF + R200 HF to HF + R200 HF + R200 to HF HF to HF+R200Body weight (g) HF+R200 to HF weeks pre post shift
  • 13. R200 Reduces Fat Storage in Miceon a Westernized High Fat DietHF to HF HF to HF+R200 HF+R200 to HF+R200 HF+R200 to HFLiver Weight (g) Subcutaneous fat (g) Epididymal fat(g)
  • 14. R200 Insulin Effects HF LF HF+R200 Fasting Glucose p<0.05 p<0.01 Fasting Insulin p< 0.05 Insulin Sensitivity in High Fat diet induced Obesity Mouse model
  • 15. R200 Diabetes Cell free In Vitro Animal MiscMulti-target selective Stimulates the Improves insulin/ Demonstrated QSARkinase modulator secretion of GLP-1 glucose dynamics among various R200 in intestinal L-cells in animal model of analogs; KDT 500 mostInhibits P70S6K kinase (NCI-H716) diabetes activeactivity and proteinphosphorylation in Reduces inflammation/ Dramatically reducesmonocytes and glucose stimulated weight gain in high fatmacrophages adherence of mono- diet induced obesity cytes to endothelial cells modelNon-competitive ATPbinding to kinases Improves insulin Produces weight /fatIndicates allosteric sensitivity in 3T3L1 lossmodulation adipocytes in HF obese miceIncreases activity of Increases adipocyte Reduces fatIGF1R receptor function in models of accumulationSeveral fold lipid accumulation and in HF mice adiponectin secretionIncreases activity of after inflammatoryAMPK stimulation
  • 16. R200 Competitive Advantages Multiple actions Decrease insulin sensitivity, fasting glucose, and insulin levels Large impact on weight gain (in high fat rodent study) Improves lipid values Excellent safety profile in humans Does not decrease prostacyclin formation in humans, indicating CV safety No elevation of liver enzymes in humans ingesting therapeutic doses No elevation of fecal calprotectin in humans ingesting therapeutic doses indicating GI safety Safe to GI system when orally consumed at therapeutic doses Orally Bioavailable
  • 17. Product PipelineDiscovery & Pre-clinical IND Phase 1Candidate Selection Development KDT 500 (Type 2 Diabetes) KDT 500 (Inflammation) S KDT 600 (Obesity) New CandidatesMid-shaded arrows illustrate pipeline through 1H2011
  • 18. Development Plan 2010 cGMP manufacture of KDT500 FDA pre-IND meeting Safety pharmacology and GLP toxicology 1H2011 IND submission Initiate POC (Type 2 Diabetes) in long-term canine and rodent studies 2H2011 Phase 1 SAD (in healthy subjects) Phase 1 MAD (in healthy subjects) 1H2012 Phase 2a POC (in early diabetic subjects)
  • 19. Experienced Management & Advisory TeamJeffrey Bland, Ph.D. Metagenics, Healthcomm InternationalPresident and CEO Linus Pauling InstituteMatthew Tripp, Ph.D. Metagenics, KelloggSr. V.P. R&D Phillip Morris BiotechnologyNeile Grayson, Ph.D. Sonus Pharmaceuticals, NeoRxV.P. Drug Development Mallinckrodt, NIHLincoln Bouillon, MBA MetagenicsBusiness Manager Functional Medicine Res. Center ActivX Biosciences, Merck ResearchJohn Kozarich, Ph.D. Labs, Scripps Research Institute,SAB Member Yale School of MedicineBenjamin Cravatt, Ph.D. Scripps Research InstituteSAB MemberPaul Schimmel, Ph.D Scripps Research Institute, Sirtris,Senior Advisor and Board Member Alnvlam, Repligen, Momenta, Cubist