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P H A R M A C E U T I C A L S , I N C . www.Pro-Pharmaceuticals.com
Amex: PRW A D V A N C I N G D R U G S T H R O U G H G L Y C O S
C I E N C E® Exhibit 99.1 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Forward Looking Statements Any statements in this presentation about future expectations, plans and prospects for the Company, including statements containing the words "believes," "anticipates," "plans," "expects," and
similar expressions, constitute forward looking statements, which are
subject to the safe harbor for such statements in the Private Securities
Litigation Reform Act of 1995. Future events could cause actual results to
differ materially from those indicated by such statements. Reference is made
to the factors discussed in the Management Discussion and
Analysis" and "Risk Factors" sections of the Company's most
recent quarterly or annual report filed with the Securities and Exchange
Commission. The forward-looking statements herein represent the Company's views as of the date of this presentation and should not be relied upon to represent the Company's views as of a subsequent date. While the Company anticipates that subsequent events may cause the Company's views to change, the Company disclaims any obligation to update such forward-looking statements. 2 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Mission Develop novel carbohydrate-based therapeutic compounds 3 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Advancing Drugs Through Glycoscience ® Drug design based on carbohydrate chemistry In-house scientific expertise in carbohydrate chemistry and manufacturing Strong patent portfolio covering critical carbohydrate chemistry technologies and products Research and Development by strategic collaboration and outsourcing 4 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Carbohydrates as Therapeutics A novel class - now being explored for therapeutic potential Structurally heterogeneous - linear and branched, small and large molecules Diverse biological forms - as glycoproteins, glycolipids, sugars, and complex carbohydrates in plants, animals, fungi, and bacteria Diverse biological roles - structure, energy, signaling, adhesion, protection Natural biological sources Interact with lectins - carbohydrate-specific proteins involved in cell-cell and cell-matrix interactions 5 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Applications Oncology Liver Microbial Inflammatory Cardiovascular Autoimmune Viral infections 6 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W First Application: Oncology DAVANAT ® The first chemotherapeutic complex carbohydrate drug 7 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Proprietary polysaccharide galactomannan (GM) polymer consisting of galactose units attached to a mannan backbone Derived from seeds of the plant Cyamopsis tetragonoloba (Guar Gum) Binds to galectin molecules Changes the efficacy, toxicity, pharmacokinetic and distribution properties of chemotherapeutic drugs DAVANAT ® 8 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Targeting Lectins on Cancer Cells Lectins are cell surface proteins that bind certain carbohydrates Galectins are a type of lectin that specifically bind galactose molecules Galectins have been shown to affect cell development, differentiation, apoptosis and tumor metastasis 9 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Pre-clinical Studies Selected 5-FU to investigate modulation of chemotherapeutic effects Screened galactomannans for ability to reduce 5-FU toxicity in mice Selected a galactomannan from Guar Gum for its potential therapeutic utility Investigated DAVANAT ® modulation of effects of other chemotherapeutics (irinotecan, doxorubicin, 5-FU, leucovorin, and Avastin ® ) 10 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W GROUP MORTALITY WEIGHT GAIN/ SIGNS LOSS, 2 WKS OF TOXICITY 5-FU (alone) 80% -1.9g Very Severe DAVANAT/5-FU 0 -.6g Mild Pre-clinical Studies Decreasing Toxicity - 3X Lethal Dose 50 11 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W CONTROL Pre-clinical Studies Increasing Efficacy: Effect of DAVANAT ® /5-FU on Tumor Size SRI Inc. Experiments 5-FU (alone) DAVANAT ® /5-FU TUMOR SIZE (110 MG) AT START OF STUDY 1400 mg 1200 mg 1000 mg 800 mg 600 mg 400 mg 200 mg 0 12 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W Response of HT-29, Human Colon Tumor
Xenografts to
DAVANAT® in Combination with 5-FU and Leucovorin Charles River Labs (Dose: I.V., Q4D x 4, of 5-FU: 48 mg/kg; DAVANAT ® : 120mg/kg; Oral, Leucovorin 25 mg/kg;) 13 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W Response of SC ZR75-1,Human Mammary Tumor Xenografts, to dose escalation DAVANAT ® in combination with Irinotecan Southern Research Institute (Dose I.V., Q4D x 4, of IR 40 mg/kg; DAVANAT ® : 6, 30 & 120 mg/kg) 100 1000 10000 0 10 20 30 40 Time post implanatation (Days) Control IR40/DAV6 IR40/DAV30 IR40/DAV120 14 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W Response of COLO 205, Human Colon Tumor Xenografts, to DAVANAT ® Co-Administrated with AVASTIN ® and 5-FU Southern Research Institute (Dose: I.V., Q4D x 4, of 5-FU 50 mg/kg; DAVANAT ® : 120 mg/kg; AVASTIN: 20-80 mg/kg) 15 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W DAVANAT ® polymer exists as a 3D structure in solution with lectin targeting units protruding from the mannan backbone Technology Platform: CARBOSOME 16 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W Amex: P R W Product Development Pipeline: October 06 PRODUCT INDICATION DEVELOP PRE-CLINICAL PHASE 1 PHASE 2 DAVANAT ® / 5-FU/ LV Irinotecan/ Oxaliplatin DAVANAT ® / 5-FU/LV/ Bevacizumab DAVANAT ® / 5-FU PRO-GR 300 Colorectal Cancer Colorectal Cancer Colorectal Cancer Liver Disease Microbial Disease PHASE 3 DAVANAT ® / 5-FU Biliary Cancer PRO-NAC 050 17 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W Second Application: Liver Disease Research collaboration w/ Mt. Sinai School of Medicine to evaluate the anti-fibrotic effects of carbohydrate compounds Fibrosis (scarring) is the reason patients develop liver failure & may need a transplant 25 million Americans are or have been afflicted by liver/biliary disease More than 4 million Americans w/ Hepatitis C virus; many will develop severe fibrosis & liver failure 18 |
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is the Clinical Trial Program? 19 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W Phase I Clinical Trial All Solid Tumors Indication: All solid tumors. End stage patients; minimum 12 weeks to live Objectives: Primary Safety Secondary Tumor progression Design: Multi-center (4 sites), open label study. Two cycles; six cohorts. Cycle 1 DAVANAT ® alone Cycle 2- DAVANAT ® /5-FU Regimen: DAVANAT ® escalating dose level (30-280 mg/m 2 ) ; 5-FU constant at 500 mg/m 2 ; dose for 4 consecutive days, observe for 24 days Patients: 40; 3-10 per cohort Completed: March 2005 20 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W Phase l Tumor Type Distribution 21 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W SD Stable Disease PD Progressive Disease NM Non-Measurable Disease Cycles Completed Dose, cycle 2 /m2 1+2 3 4 5 6 7 1001 PD 1002 SD 2001 Hepatocellular PD 2002 Hepatocellular SD 3001 PD 3002 SD 3004 PD 3003 PD 5001 SD 2004 SD 3005 PD 4001 PD 4002 Colorectal PD 3006 Prostate NM 2005 Colorectal SD 5003 Colorectal (appendix) NM 5004 SD 4003 PD 2007 Spindle Cell PD 5005 Pancreatic SD 2008 Colorectal SD 2009 Colorectal SD 5006 Billiary SD 2010 Colorectal (cecal) SD 2014 Breast SD 2016 Hepatic PD 2018 Cholangiocarcinoma SD 5008 Pancreatic PD 280 mg 150 mg Patient Number Tumor Type Outcome, end of cycle 2 (RECIST) C Y C L E S Colorectal Colorectal 210 mg 30 mg 60 mg Colorectal 100 mg Colorectal Phase l Patient Summary Stable Disease (RECIST) in 14 of 26 patients with measurable disease 7/10 patients stabilized at the highest dose level >> 13 cycles completed 22 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Phase I Clinical Trial Summary DAVANAT ® (with and without 5-FU) was well tolerated MTD of DAVANAT ® (with and without 5-FU) not reached DAVANAT 280 mg/m² brought forward as the recommended
Phase II dose Pharmacokinetic conclusions Data suggest increase in 5-FU AUC 0-last and C max at highest DAVANAT ® dose (280 mg/m²) 5-FU when co-administered with DAVANAT ® is 28-137 minutes; compared with 6-22 minutes for 5-FU alone Trend to increase in 5-FU AUC 0-last and C max with repeated daily X 4 dosing Stable disease (RECIST) in 14 of 26 efficacy evaluable patients 7/10 patients stabilized at the highest DAVANAT ® dose level 23 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W Phase II (Third/Fourth Line) Colorectal Cancer Trial Indication: Colorectal cancer; Third/fourth line patients. Objectives: Complete/ partial tumor response (RECIST); stable disease. Design: Multi-center (6 sites), open label study. Evaluate at least two cycles or to disease progression. Regimen: DAVANAT ® 280 mg/m²; 5-FU 500 mg/m²; dose for 4 consecutive days, observe for 24 days. Patients: Began dosing in May 2005. Study finalized in August 2006. Results: 20 patients: 1 Partial Response (RECIST) (unconfirmed) 6 Stable Disease DAVANAT ® /5-FU 24 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W Phase II Clinical Trial Summary Evidence of anti-tumor activity was seen with DAVANAT ® /5-FU in this study. 1 patient experienced Partial Response, as assessed by the Core Laboratory, with a duration of ~2 months 6 patients had Stable Disease, as determined by the Investigator and Core Laboratory No clear effect on tumor markers or other efficacy parameters, including weight, ECOG performance status, and quality of life were seen in this study 25 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W Phase II Clinical Trial Summary (continued) DAVANAT ® /5-FU was well tolerated Most adverse events were Grade 1 or 2 in intensity and manageable Common adverse events included general gastrointestinal disorders (i.e., nausea, vomiting, diarrhea, and constipation with/without abdominal pain) and fatigue DAVANAT ® /5-FU does not appear to be associated with any systematic changes in clinical laboratory measurements Results compare very well with recent studies in similar patient populations 26 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Phase II (First Line) Colorectal Cancer Trial Indication: First line treatment of patients with metastatic, unresectable colorectal cancer. Objectives: Complete/partial tumor response (RECIST); 14 of 41 responders (34%). Progression Free Survival at 6 and 12 months. Design: Multi-center, open label study. Evaluate for at least 2 cycles or to disease progression. Regimen: DAVANAT ® , AVASTIN ® , 5-FU & Leucovorin. Dose for 3 consecutive days. Repeat cycles every 2 weeks until disease progression or unacceptable toxicity. Patients: Up to 50. Begin enrolling/ dosing patients in 2006. DAVANAT ® / AVASTIN ® / 5-FU / LV 27 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W DAVANAT ® /5-FU Phase II (First Line) Colorectal Cancer Trial Indication: First-line treatment of patients with mCRC who are unable to tolerate irinotecan or oxaliplatin Regimen: DAVANAT ® /5-FU, LV, AVASTIN ® Repeat cycles every 2 weeks to disease progression or toxicity Objectives: Complete/Partial Response (RECIST) Stable Disease; PFS at 6 and 12 months; Safety; QoL Design: Multi-center, open label study Simon Optimal 2-stage design Patients: 17 + 24 Begin enrolling/ dosing patients in 2006 28 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Phase II (First Line) Biliary Cancer Trial Indication: Biliary cancer (cholangiocarcinoma). First line therapy. Objectives: Complete/ partial tumor response (RECIST); 7 of 35 responders (20%). Design: Multi-center, open-label study. Regimen: DAVANAT ® with 5-FU. Evaluate for 2 cycles or to disease progression. Measure after 8 & 12 weeks. Patients: Up to 42. Begin enrolling/ dosing patients in 2006. DAVANAT ® / 5-FU 29 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W DAVANAT ® /5-FU Phase II (First Line) Biliary Cancer Trial Indication: First line treatment of patients with biliary tract cancer Regimen: DAVANAT ® (280 mg/m²) + 5-FU (600 mg/m²) IV daily x 4 days Repeat cycles every 28 days to disease progression or toxicity Objectives: Complete/Partial Response (RECIST) Stable Disease; PFS; Safety; QoL Design: Multi-center, open label study Simon Optimal 2-stage design Patients: 18 + 17 Begin enrolling/dosing in 2006 30 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Phase lll (Second Line) Colorectal Cancer Trial FOLFOX+DAVANAT ® FOLFOX FOLFIRI FOLFIRI +DAVANAT ® Indication: Metastatic colorectal cancer; Second-line therapy. Objectives: Progression-free survival 6 months); Response rate, time-to-progression, and quality of life. No minimum vs control. Design: Multi-center, randomized, double blind study. Regimen: DAVANAT ® with 5-FU/ leucovorin, irinotecan or oxaliplatin. Evaluate for at least 2 cycles or to disease progression. Patients: 100 patients. Begin enrolling/ dosing patients in 2007. 31 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Founded: July 2000 Capital raised: $36M (cumulative ) Inception to Phase ll: $26M Cash: $9.7M (06/30/06) Burn rate: $2M per quarter Shares outstanding: 28M (08/07/06) Fully diluted: 37M (08/07/06) Corporate Overview 33 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Management Team David Platt, Ph.D., Chairman & Chief Executive Officer- PRW co-founder, co-developer of Glycoscience (carbohydrate) technology. Founder: Safe Science,
developed anti-angiogenesis drug. Univ. of Michigan, Weizmann
Institute, Hebrew Univ. Anatole Klyosov, Ph.D., D.Sc., Chief Scientist- Fellow, World Academy of Arts & Sciences; National Prize in Science & Technology (Russia); Former Visiting
Prof. of Biochemistry (8 years) at Harvard Medical. Moscow State
Univ. Carl Lueders, M.B.A., C.P.A., Chief Financial Officer- 20+ years in finance & strategic planning at Polaroid Maureen Foley, Chief Operating Officer- eHealthDirect, Thermo Electron Eliezer Zomer, Ph.D., Exec. V.P., Product Development & Mfg- Former Research Associate at Harvard Medical. Anthony Squeglia, M.B.A., V.P., Investor Relations- 20+ years in IR James Gourzis, M.D., Ph.D., Brian Hamilton, M.D., Ph.D., Medical Safety Monitors (Consultants) 34 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Scientific Advisory Board David Platt, Ph.D. Edgar Ben-Josef, M.D., Assoc. Prof. of Radiation Oncology,
University of Michigan Medical School Mildred Christian, Ph.D., Dale Conaway, M.S., D.V.M., Research Oversight, U.S. Dept. of Health & Human Services Henry Esber, Ph.D., Former Sr.V.P., Primedica Irwin Goldstein, Ph.D., Prof. Emeritus, Univ. of Michigan;
Guggenheim Fellow; Pasteur Institute; Hudson Award Anatole Klyosov, Ph.D., D.Sc. Zbigniew Witczak, Ph.D., Assoc. Prof., Wilkes Univ.; former Chair,
Carbohydrate Chemistry Division, ACS Eliezer Zomer, Ph.D. 35 President & CEO, Argus International Chief Veterinary Medical Officer, Office of |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C I E N C E ® Amex: P R W Medical Advisory Board Edgar Ben-Josef, M.D. Leslie R. Laufman, M.D., President of
Hematology Oncology Cons. Served as P.I. for the Columbus (OH)
Community Clinical Oncology Program and investigator for the Ohio State
University Comprehensive Cancer Center John S. Macdonald, M.D., Professor of Medicine at New York
Medical College, and Chief of Gastrointestinal Oncology Service at
Saint Vincents Comprehensive Cancer Center Bruce Silver, M.D., F.A.C.P., 20+ years of oncology practice.
Principal, Clinical Science and Development; former Senior Director, Global Product Development Services, PRA International 36 |
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O P H A R M A C E U T I C A L S , I N C. A D V A N C I N G D R U G S T H R O U G H G L Y C O S C
I E N C E ® Amex: P R W Summary and Conclusions Company strength in carbohydrate chemistry with strong patent position Pre-clinical animal data shows DAVANAT ® improves toxicity and efficacy characteristics of co- administered chemotherapeutics Phase I results show that DAVANAT ® is well-tolerated in cancer patients, with/without co-administered 5-FU Phase II colon cancer study suggests efficacy of DAVANAT ® with 5-FU in stabilizing disease Stable disease in 20/60 end-stage patients, who were refractory to chemotherapy Enrolling Phase II studies address first line therapies with DAVANAT ® in combination with other chemotherapeutics and biologics Experienced management team 37 |