EX-99.1 2 a06-11841_3ex99d1.htm EX-99







































 

Searchable text section of graphics shown above

 


 

Forward-Looking Statements

 

Statements in this presentation that are not historical facts are “forward-looking statements” that involve risks and uncertainties. Forward-looking statements can be identified by the use of words such as “may,” “will,” “should,” “anticipates,” “expects” or comparable terminology or by discussions of future events. Such forward looking statements include statements relating to the clinical development program for TPI 287, the anticipated activity of TPI 287 in taxanes resistant tumors, the safety and efficacy of TPI 287, the time tables for future development of TPI 287, and the company’s ability to continue to fund its development programs, either through existing resources or through new funding sources. Such statements involve known and unknown risks, uncertainties and other factors that may cause our actualresults, performance or achievements to be materially different from the results, performance or achievements expressed or implied by such forward-looking statements. Such risks, uncertainties and other factors include risks that clinical trials for TPI 287 will be delayed due to institutional approvals, patient recruitment, formulation and manufacturing difficulties or other factors; and that human clinical trials may show that TPI 287 is unsafe and/or ineffective in treating cancer in human patients. General implementation risks associated with development of any of our products include the risk that we will be blocked or limited in the development or marketing because of the intellectual property rights of third parties; that we are limited in our ability to obtain, maintain and enforce our own intellectual property rights; that development of our product candidates is delayed or terminated because the costs of further development exceed the value of such candidates; and that the Company’s resources are insufficient to continue development and the Company will be unable to raise sufficient additional capital to continue operations and development. Additional risks, uncertainties and other information is contained in the Company’s reports filed from time to time with the Securities and Exchange Commission. Particular attention should be paid to information in such SEC reports under the captions “Risk Factors” and “Special Note Regarding Forward-Looking Statements.” The Company disclaims any intention or obligation to update publicly or revise any forward-looking statements contained in this presentation or any other disclosure, whether as a result of new or additional information, future events or otherwise.

 

[LOGO]

 

1


 

Investment Proposition

 

•                              Proprietary 3rd Generation Taxane

•                              Large Commercial Opportunity

•                              Experienced Oncology Drug Development Team

•                              Knowledgeable Investor Base

•                              Strong Cash Position

•                              Low Stock Price; Low Technology Value

•                              Modest Burn Rate

•                              Large Upside Potential

 

2


 

Experienced Management Team

 

•                              Leonard Shaykin, Chairman and CEO

•                        Biotechnology entrepreneur, Venture capital, Private equity

•                              Martin Batt, COO

•                        Operations expertise in multiple industries including biotechnology, aerospace, computer software

•                              Gordon Link, CFO

•                        CPA plus over 15 years of biotechnology operations

•                              Michael Kurman, MD, CMO

•                        Senior clinical research positions at Janssen Research Foundation, U.S. Biosciences Inc., and Quintiles Transnational Corp.’s Oncology Therapeutics Division.

•                              David Emerson, VP of Cancer Biology

•                        16 years in biopharmaceuticals; OSI, Gilead and GSK

•                              James McChesney, CSO

•                        Natural Products Chemistry specialist and former Director of Research Institute of Pharmaceutical Sciences and former Chairman of the Department of Pharmacognosy at the University of Mississippi

•                              Gilles Tapolsky, VP of Product Development

•                        16 years in biopharmaceuticals; FeRx, ViroTex, Rhone Poulenc Rorer and Flamel Technologies

 

3


 

New Investor Base

 

•                              Special Situations Funds

•                              Tang Capital Partners

•                              Baker Brothers Investments

•                              BioTechnology Value Fund

•                              Fort Mason Partners

•                              Heights Capital Management

•                              Xmark Funds

•                              Merlin BioMed

•                              Versant Capital Management

 

4


 

Tapestry Financial Overview

 

As of 5/09/2006

 

•                        Price: $3.60

•                        52 Week High/Low: $2.10 - $7.00

•                        Market Value: $58.4M

 

Quarter Ended 3/29/2006

 

•                        Cash and Short Term Investments: $34.6M*

•                        Net Operating Loss: $4.4

•                        Number of Shares Outstanding:  16,235,433*

 

*  Adjusted to reflect the financing completed on April 6, 2006

 

5


 

2006 Milestones

 

•

 

Begin TPI 287 Phase I Q7Dx3 Trial

 

Done

•

 

Begin TPI 287 Phase I Q21D Trial

 

Done

•

 

Finance Company to Efficacy Milestone

 

Done

•

 

Determine MTD in both Phase I Trials

 

3Q06

•

 

Begin 1st Phase II Trial in Prostate Cancer

 

4Q06

•

 

Begin 1st Phase II Trial in NSCLC

 

4Q06

•

 

Select Optimized Oral Formulation

 

2H06

•

 

Initiate Oral GLP Tox Studies

 

2H06

 

6


 

TPI 287

A Third Generation Taxane
with Activity in
Multi-Drug Resistant Tumors

 

7


 

TPI 287: A Third Generation Taxane

 

•                              Pre-clinical data shows that TPI 287 has more activity than paclitaxel or docetaxel in a variety of taxane-resistant human tumor cell lines

 

•                              TPI 287 has the potential to:

•                       circumvent expression of the drug efflux transporter, MDR-1 protein, seen in breast, lung and prostate cancers

•                       be active in tumor types currently not responsive to paclitaxel, (i.e., colon cancer)

•                       be active in tumor cells that express mutant tubulin

 

8


 

TPI 287 Pre-clinical Biology Studies

 

[GRAPHIC]

 

9


 

TPI 287 Tumor Cell Cytotoxicity Studies

 

 

 

 

 

 

 

 

 

Cytotoxicity Index

 

 

 

 

TPI 287 IC50

 

Comparator IC50

 

(IC50 Comparator ÷

Tumor Cell Line

 

Origin

 

(µM)

 

(µM)

 

IC50 TPI 287)

 

 

 

 

 

 

 

 

 

MCF-7/NCI-ADR (mdr1+)

 

Breast

 

0.0100

 

PTX: 2.0

 

200

MCF-7 (mdr1-)

 

Breast

 

0.0006

 

PTX: 0.0003

 

0.5

 

 

 

 

 

 

 

 

 

HCT-15 (mdr1+++, mrp+)

 

Colon

 

0.0095

 

SN-38: 0.05

 

5.3

HCT-116 (mdr1+)

 

Colon

 

0.0035

 

SN-38: 0.0045

 

1.3

 

 

 

 

 

 

 

 

 

H69 (mrp-, myc+)

 

Lung

 

0.0046

 

Docetaxel: 0.0072

 

1.6

 

 

 

 

 

 

 

 

 

MIA PaCa-2 (bcl-2 inducible)

 

Pancreas

 

0.0763

 

GEM: 0.124

 

1.6

 

 

 

 

 

 

 

 

 

HepG2 (mdr1+, mrp+)

 

Hepatocellular

 

0.1000

 

Oxaliplatin: 5.5

 

55

 

 

 

 

 

 

 

 

 

DU-145 (mdr1+)

 

Prostate

 

0.0050

 

Cisplatin: 1.4

 

280

 

 

 

 

 

 

 

 

 

MESSA/Dx5 (mdr1+)

 

Uterine

 

0.0100

 

Doxorubicin: 0.8

 

80

MESSA (mdr1-)

 

Uterine

 

0.0053

 

Doxorubicin: 0.2

 

38

 

 

 

 

 

 

 

 

 

SK-N-FI (mdr1+)

 

Neuroblastoma

 

0.0034

 

Vincristine: 13.4

 

3900

SK-N-AS (mdr1-, TGF-1+)

 

Neuroblastoma

 

0.0049

 

Vincristine: 17.7

 

3600

 

TPI 287 is more potent in killing tumor cells than the comparator agents in those tumor cells expressing high levels of multi-drug resistance (mdr1+) protein.

 

10


 

Effect of TPI 287 on Human Breast MCF-7 (mdr1-) Tumor Model

SRI International

 

[CHART]

 

TPI 287 is as active as paclitaxel in this non-mdr1-human breast tumor xenograft model.

 

11


 

Effect of TPI 287 on Human Breast MCF-7/NCI-AR (mdr1+) Tumor Model

SRI International

 

[CHART]

 

However, TPI 287 is more active than paclitaxel in this multi-drug resistant breast tumor xenograft model.

 

12


 

Effect of TPI-287 on Human Prostate PC-3 (mdr+) Tumor Model

Institute for Drug Development

 

[CHART]

 

TPI 287 is more efficacious at all doses in this human prostate tumor model than docetaxel which is an approved treatment for prostate cancer.

 

13


 

Effect of TPI 287 on Human Lung MV522 (chemoresistant) Tumor Model

Institute for Drug Development

 

[CHART]

 

TPI 287 is efficacious in this chemo resistant human lung tumor model, while docetaxel and doxorubicin are inactive

 

14


 

Effect of TPI-287 on Human Colon HCT-116 (mdr1+) Tumor Model

Institute for Drug Development

 

[CHART]

 

Low doses of TPI 287 are efficacious in this human colon cancer xenograft model (irinotecan shown as reference).

 

15


 

Cell Cytotoxicity of TPI 287 and paclitaxel in MDR+/- Cells

 

Tumor Cell
Line

 

MDR Expression

 

TPI 287 IC50
[nM]

 

Paclitaxel IC50 [nM]

 

Paclitaxel ÷ TPI 287

MESSA

 

MDR -

 

2.9

 

3.5

 

1.2

 

 

 

 

 

 

 

 

 

MESSA/Dox

 

MDR +

 

44.8

 

4,538.0

 

101.3

 

 

 

 

 

 

 

 

 

KB*

 

MDR -

 

9.4

 

7.13

 

0.8

 

 

 

 

 

 

 

 

 

KBV*

 

MDR +

 

552.0

 

>10,000.0

 

18.1

 

TPI 287 has activity equal to paclitaxel in MDR- tumor cells and is 18 to 100 fold more potent in the MDR+ tumor cell lines.

 

16


 

TPI 287 vs. Paclitaxel in KBV (MDR+)

 

NX-105, NX-105, TPI-287 vs paclitaxel in KBV

 

NX-105, NX-105, TPI-287 vs paclitaxel in KBV

 

 

 

[CHART]

 

[CHART]

 

NX-105, NX-105, TPI-287 vs paclitaxel in KBV

 

 

 

Day:

 

 

 

% Tumor Volume

 

1

 

2

 

6

 

9

 

13

 

16

 

20

 

%TGI

 

Control, D5W 200 ul (Q2Dx4)

 

100.00

 

143.05

 

394.05

 

732.96

 

1,321.19

 

1,376.46

 

1,469.28

 

0

 

paclitaxel, 24 mg/kg (Q2Dx4)

 

100.00

 

123.06

 

363.78

 

789.51

 

764.04

 

629.57

 

817.83

 

43

 

TPI-287 6 mg/kg (Q2Dx4)

 

100.00

 

130.73

 

369.71

 

679.05

 

848.49

 

607.68

 

624.61

 

40

 

TPI-287 8 mg/kg (Q2Dx4)

 

100.00

 

123.10

 

243.99

 

441.06

 

404.62

 

439.65

 

442.87

 

72

 

TPI-287 10 mg/kg (Q2Dx4)

 

100.00

 

122.69

 

295.22

 

548.61

 

545.26

 

245.90

 

243.72

 

85

 

 

 

 

Day:

 

% Body Weight

 

1

 

2

 

6

 

9

 

13

 

16

 

20

 

Control, D5W 200 ul (Q2Dx4)

 

100.00

 

100.07

 

105.08

 

108.04

 

111.73

 

112.29

 

121.03

 

paclitaxel, 24 mg/kg (Q2Dx4)

 

100.00

 

100.80

 

99.51

 

92.91

 

92.95

 

104.73

 

107.68

 

TPI-287 6 mg/kg (Q2Dx4)

 

100.00

 

100.33

 

103.63

 

104.77

 

97.92

 

95.72

 

99.51

 

TPI-287 8 mg/kg (Q2Dx4)

 

100.00

 

100.23

 

103.19

 

99.34

 

86.45

 

89.39

 

97.17

 

TPI-287 10 mg/kg (Q2Dx4)

 

100.00

 

98.89

 

101.71

 

96.57

 

80.84

 

78.78

 

82.42

 

 

Note: 85% Tumor growth inhibition

 

17


 

Efficacy Comparison in MDR+ Breast Tumor Model

 

NX-134, Taxane Comp MCF-7/AR (mdr+)

 

[CHART]

 

Treatment

 

%TGI

 

Control

 

0

 

Paclitaxel

 

0

 

Docetaxel

 

22

 

Abraxane

 

24

 

TPI 287

 

59

 

 

18


 

Efficacy Comparison in MDR+ Colon Tumor Xenograft Model

 

NX-132, Taxane Comp HCT-15 (mdr+)

 

[CHART]

 

Treatment

 

%TGI

 

LCK

Control

 

0

 

0

Paclitaxel

 

26

 

.1

Docetaxel

 

20

 

.1

Abraxane

 

30

 

.1

TPI 287

 

60

 

.4

 

19


 

Comparative Efficacy Study with MDR+ CNS Tumor Xenograft Model

 

NX-136, Taxane Comp SK-N-FI (mdr+)

 

[CHART]

 

Treatment

 

%TGI

Control

 

0

Paclitaxel

 

0

Docetaxel

 

9

Abraxane

 

27

TPI 287

 

65

 

20


 

Comparative MT Polymerization ED50s

 

Compound

 

ED50, µM

 

ED50 Compound / ED50 Paclitaxel

 

 

 

 

 

TPI 287

 

1.58 ± 0.46

 

0.53

 

 

 

 

 

Paclitaxel

 

2.97 ± 0.50

 

1.00

 

 

 

 

 

Docetaxel

 

3.18 ± 0.45

 

1.07

 

 

 

 

 

Epothilone B

 

3.31 ± 0.51

 

1.11

 

TPI 287 has a higher binding affinity to wild type tubulin than paclitaxel, docetaxel, or epothilone B.

 

21


 

TPI 287 Oral Efficacy in Mice

 

NX-102,Oral efficacy of TPI-287 in DU145

 

NX-102, Oral efficacy of TPI-287 in DU145

 

 

 

[CHART]

 

[CHART]

 

NX-102, TPI-287 vs paclitaxel in DU145

 

 

 

Day:

 

 

 

 

 

% Tumor Volume

 

1

 

6

 

9

 

11

 

14

 

17

 

22

 

25

 

%TGI

 

TD

 

Control vehicle 200ul (Q2Dx4)

 

100.00

 

228.02

 

291.96

 

300.79

 

302.77

 

334.12

 

385.13

 

380.94

 

0

 

0

 

TPI-287 (SK608-20.1) 10mg/kg (Q2Dx4)

 

100.00

 

138.11

 

192.93

 

187.86

 

186.09

 

218.47

 

268.58

 

246.55

 

40

 

0

 

TPI-287 (SK608-20.1) 12mg/kg (Q2Dx4)

 

100.00

 

145.94

 

186.27

 

168.78

 

147.42

 

198.71

 

185.37

 

221.82

 

51

 

0

 

TPI-287 (SK608-20.1) 14mg/kg (Q2Dx4)

 

100.00

 

180.53

 

181.78

 

137.42

 

115.52

 

149.34

 

267.09

 

207.88

 

64

 

3

 

 

 

 

Day:

 

% Body Weight

 

1

 

6

 

9

 

11

 

14

 

17

 

22

 

25

 

Control vehicle 200ul (Q2Dx4)

 

100.00

 

101.69

 

101.42

 

101.57

 

101.36

 

103.92

 

103.90

 

109.00

 

TPI-287 (SK608-20.1) 10mg/kg (Q2Dx4)

 

100.00

 

103.22

 

100.91

 

96.90

 

94.56

 

98.64

 

100.50

 

107.43

 

TPI-287 (SK608-20.1) 12mg/kg (Q2Dx4)

 

100.00

 

102.39

 

97.75

 

91.08

 

87.61

 

87.86

 

93.43

 

100.53

 

TPI-287 (SK608-20.1) 14mg/kg (Q2Dx4)

 

100.00

 

102.10

 

91.46

 

81.99

 

72.63

 

85.13

 

92.37

 

100.93

 

 

Note: 64% Tumor growth inhibition

 

22


 

TPI 287 Rat Oral Bioavailability

 

•                        Comparison of two experimental formulations dosed orally

•                  IV formulation (Cremophor El P/alcohol)

•                  Suspension of TPI 287 in aqueous medium

 

•                        Findings

•                  IV formulation has an oral bioavailability of about 45%

•                  Aqueous suspension has an oral bioavailability of about 35%

 

TPI 287 demonstrates significant bioavailability when compared to paclitaxel (45% vs. less than 10%).

 

Non-optimized formulation of TPI 287 shows remarkable bioavailability.

 

23


 

TPI 287 Single Dose Toxicology Studies

 

•                              Intravenous or Intraperitoneal dose tolerance and MTD

 

•                              Maximum Tolerated Dose (MTD)

•                        Mouse – 80 mg/kg or 240 mg/m2

•                        Rat – 48 mg/kg or 288 mg/m2

•                        Dog – 12.5 mg/kg or 221 mg/m2

 

The toxicology profile and the maximum tolerated dose of TPI 287 are similar to other taxanes.

 

24


 

TPI 287 Repeat Dose Toxicology Studies

 

•                              Intravenous or Intraperitoneal dose tolerance and MTD

•                              Maximum Tolerated Dose

•                        Mouse – 12 mg/kg or 36 mg/m2

•                        Rat – 14 mg/kg or 84 mg/m2

•                        Dog – 4 mg/kg or 71 mg/m2 (basis for human dosing)

 

The toxicology profile and the maximum tolerated dose of TPI 287 are similar to other taxanes.

 

25


 

TPI 287: Pre-clinical Summary

 

•                              In Vitro Studies

•                        Evidence of activity in various cell lines including: breast, colon, lung, pancreas, prostate, and others

•                              Tumor Xenograft Studies

•                        Evidence of activity in breast, colon, lung, and prostate tumors models, including those tumors with expression of mdr-1 protein

•                              Toxicity

•                        Generally well-tolerated

•                        Key findings are GI in nature

•                        MTD based on dog repeat study is 4 mg/kg or 71 mg/m2

•                              Starting human dosing programs

•                        Based on 1/10 of MTD in dog

•                        Starting dose is 7 mg/m2

 

26


 

TPI 287:

Q7D (7-day dosing) Phase I

Study

 

[GRAPHIC]

 

27


 

Q7D Trial Sites and Investigators

 

Lombardi Comprehensive Cancer Center at Georgetown University, Washington, D.C.

•                        John Marshall, M.D., Principal Investigator, Associate Professor of Oncology and Medicine at Georgetown University and Director of the Developmental Therapeutics program at the Lombardi Comprehensive Cancer Center.

 

•                              Westchester Medical Center, Valhalla, New York

•                        Tauseef Ahmed, M.D. Professor of Medicine and Chief of the Division of Oncology/Hematology at New York Medical College

 

•                              Rocky Mountain Cancer Center, Denver, Colorado

•                        Allen L. Cohn, M.D., Principal Investigator, Director Hematology/Oncology

 

28


 

Q7D Phase I Trial Objectives

 

Primary Objective:

•                        To determine the maximum tolerated dose of TPI 287

 

Secondary Objectives:

•                        To determine the safety of TPI 287

 

•                        To determine the antitumor activity of TPI 287

 

•                        To determine the pharmacokinetic profile of TPI 287

 

•                        To determine the pharmacodynamic profile of TPI 287

 

29


 

Q7D Phase I Trial Design - 1

 

•                              Open-Label

•                              Multicenter Sequential groups

•                              Dose-escalation until MTD

•                              Anticipated number of patients: up to 48

 

30


 

Q7D Phase I Trial Timelines

 

•                              IND Submission Completed :  December 2004

 

•                              First patient in Q7D Protocol:  May 2005

 

•                              Expected Q7D Phase I trial MTD:   3Q06

 

31


 

TPI 287:
Q21D (21-day dosing)
Phase I Study

 

[GRAPHIC]

 

32


 

Q21D Trial Sites and Investigators

 

•                              Rocky Mountain Cancer Center, Denver, Colorado

•                        Allen L. Cohn, M.D., Principal Investigator, Director Hematology/Oncology

 

•                              Sheba Medical Center, Tel Hashomer, Israel

•                        Jacob Baram, M.D., Principal Investigator, Acting Director Inpatient Department

 

•                              Arizona Clinical Research Center, Tucson, Arizona

•                        Manuel R. Modiano, M.D., Principal Investigator, Medical Director

 

33


 

Q21D Phase I Trial Timelines

 

•                              Q21D Protocol Submission Completed :  July 2005

•                              First patient in: January 2006

•                              Expected Q21D Phase I trial MTD:   3-4Q06

 

34


 

TPI 287 Oral Program

 

[GRAPHIC]

 

35


 

Oral Program for TPI 287

 

•                              Results of oral efficacy studies in mouse xenografts and oral bioavailability studies in rats were presented at the AACR/NCI/EORTC International Conference on Molecular Targets and Cancer Therapeutics in Philadelphia in November 2005

 

•                              These studies were performed using a non optimal formulation, thus on-going formulation work towards the development of a better formulation

 

•                              IND enabling studies early 2007 in support of a new IND to initiate the clinical development of TPI 287 orally administered

 

36


 

Board of Directors

 

•                              Leonard P. Shaykin

Chairman of the Board, Chief Executive Officer

 

•                              Stephen K. Carter, M.D.

Former Senior Vice President, Worldwide Clinical Research and Development, Bristol-Myers Squibb and Deputy Director, Division of Cancer Treatment, National Cancer Institute

 

•                              George M. Gould, Esq.

Attorney, Of Counsel, Gibbons, Del Deo, Dolan, Giffinger & Vecchione; formerly Vice President and Chief Patent Counsel of Hoffman-La Roche

 

•                              Arthur Hull Hayes, Jr., M.D.

President, MediScience Associates a pharmaceutical consulting company; Former FDA Commissioner

 

•                              The Honorable Richard N. Perle

Former U.S. Assistant Secretary of Defense

 

•                              Patricia Pilia, Ph.D.

Co-founder of Company

 

•                              Robert E. Pollack, Ph.D.

Professor of Biological Sciences and Director of the Center for the Study of Science and Religion at Columbia University

 

•                              Elliot M. Maza, J.D., C.P.A.

Chief Financial Officer of Emisphere Technologies, Inc.

 

37


 

Scientific Advisory Board

 

•                              Paul A. Bunn, Jr., M.D. (Chair)

Director of the University of Colorado Cancer Center, past president of American Society of Clinical Oncology (2002-2003), and former chairman of the Oncologic Drugs Advisory Committee (ODAC) for FDA

 

•                              S. Gail Eckhardt, M.D.

Professor of Medicine and Director of the Developmental Therapeutics and GI Malignancies Programs at the University of Colorado Health Sciences Center in Denver

 

•                              Robert E. Pollack, Ph.D.

Professor of Biological Sciences and Director of the Center for the Study of Science and Religion at Columbia University

 

•                              Eric K. Rowinsky, M.D.

Former Director of the Institute for Drug Development, Cancer Therapy and Research Center and Clinical Professor of Medicine at the University of Medicine at the University of Texas Health Science Center at San Antonio

 

•                              Daniel D. Von Hoff, M.D.

Professor of Medicine, Pathology, Molecular and Cellular Biology and the Director of the Arizona Health Sciences Center’s Cancer Therapeutics Program

 

38


 

Investment Proposition

 

•                              Proprietary 3rd Generation Taxane

•                              Large Commercial Opportunity

•                              Experienced Oncology Drug Development Team

•                              Knowledgeable Investor Base

•                              Strong Cash Position

•                              Low Stock Price; Low Technology Value

•                              Modest Burn Rate

•                              Large Upside Potential

 

39


 

[LOGO]

 

Strategies for LifeTM

 

40