BIO Investor Forum- Presentation Slides

EX-99.1 2 dex991.htm BIO INVESTOR FORUM- PRESENTATION SLIDES BIO Investor Forum- Presentation Slides

P R O 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

P R O P H A R M A C E U T I C A L S , I N C.

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.

P R O P H A R M A C E U T I C A L S , I N C.

Amex: P R W

Mission

Develop novel

carbohydrate-based

therapeutic compounds

P R O P H A R M A C E U T I C A L S , I N C.

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

P R O P H A R M A C E U T I C A L S , I N C.

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

P R O P H A R M A C E U T I C A L S , I N C.

Amex: P R W

Applications

•Oncology

•Liver

•Microbial

•Inflammatory

•Cardiovascular

•Autoimmune

•Viral infections

P R O P H A R M A C E U T I C A L S , I N C.

Amex: P R W

First Application: Oncology

DAVANAT

The first chemotherapeutic

complex carbohydrate drug

P R O P H A R M A C E U T I C A L S , I N C.

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

P R O P H A R M A C E U T I C A L S , I N C.

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

P R O P H A R M A C E U T I C A L S , I N C.

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

)

P R 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 ®

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GROUP

MORTALITY

WEIGHT GAIN/

SIGNS

LOSS, 2 WKS

OF TOXICITY

5-FU (alone)

80%

-1.9g

Very Severe

DAVANAT/5-FU

-.6g

Mild

Pre-clinical Studies

Decreasing Toxicity -

3X Lethal Dose 50

P R 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 ®

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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

P R 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 ®

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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;)

P R 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 ®

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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

Time post implanatation (Days)

Control

IR40/DAV6

IR40/DAV30

IR40/DAV120

P R 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 ®

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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)

P R 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 ®

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DAVANAT

polymer exists as a “3D”

structure

in solution with lectin targeting units

protruding from the mannan backbone

Technology Platform: CARBOSOME™

P R 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 ®

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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

P R 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 ®

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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

What is the Clinical

Trial Program?

P R 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 ®

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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

)

; 5-FU

constant at 500 mg/m

;

dose for 4 consecutive

days, observe for 24 days

Patients:

40; 3-10 per cohort

Completed:

March 2005

P R 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

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Phase l Tumor Type Distribution

P R 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 ®

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Stable Disease

Progressive Disease

Non-Measurable Disease

Cycles Completed

Dose, cycle 2

/m2

1+2

1001

1002

2001

Hepatocellular

2002

Hepatocellular

3001

3002

3004

3003

5001

2004

3005

4001

4002

Colorectal

3006

Prostate

2005

Colorectal

5003

Colorectal (appendix)

5004

4003

2007

Spindle Cell

5005

Pancreatic

2008

Colorectal

2009

Colorectal

5006

Billiary

2010

Colorectal (cecal)

2014

Breast

2016

Hepatic

2018

Cholangiocarcinoma

5008

Pancreatic

280 mg

150 mg

Patient

Number

Tumor Type

Outcome, end

of cycle 2

(RECIST)

C Y C L E S

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

P R O P H A R M A C E U T I C A L S , I N C.

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

P R 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

P R 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

P R 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

P R O P H A R M A C E U T I C A L S , I N C.

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

P R O P H A R M A C E U T I C A L S , I N C.

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

P R O P H A R M A C E U T I C A L S , I N C.

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

P R O P H A R M A C E U T I C A L S , I N C.

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

P R O P H A R M A C E U T I C A L S , I N C.

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.

Company

Management

P R O P H A R M A C E U T I C A L S , I N C.

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

P R O P H A R M A C E U T I C A L S , I N C.

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

James Gourzis, M.D., Ph.D., Brian Hamilton, M.D., Ph.D., Medical

Safety

Monitors (Consultants)

P R O P H A R M A C E U T I C A L S , I N C.

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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.

President & CEO, Argus International

Chief Veterinary Medical Officer, Office of

P R O P H A R M A C E U T I C A L S , I N C.

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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 Vincent’s 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

P R 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