8-K

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): June 3, 2007

Tapestry Pharmaceuticals, Inc.
(Exact name of registrant as specified in its charter)

Delaware	0-24320	84-1187753
(State of incorporation)	(Commission File Number)	(IRS Employer Identification No.)

4840 Pearl East Circle, Suite 300W
Boulder, Colorado 80301
(Address of principal executive offices and zip code)

(303) 516-8500
(Registrant’s telephone number, including area code)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

o     Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

o     Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

o     Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

o     Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 7.01.  Regulation FD Disclosure.

The Company presented data from two Phase I clinical trials of TPI 287 at the 43rd Annual Meeting of the American Society of Clinical Oncology on June 3, 2007.  TPI 287 is a proprietary next-generation taxane being studied for the treatment of various forms of cancer.  A copy of the poster presentation of such data for each trial is filed as Exhibits 99.1 and 99.2 hereto.  These presentations were also the subject of a press release issued by the Company on June 3, 2007.  The fact that these presentations are being furnished should not be deemed an admission as to the materiality of any information contained in the presentations.

Item 9.01 Financial Statements and Exhibits.

(d)           Exhibits

The following exhibits are filed with this Current Report on Form 8-K:

Exhibit No.	Description
99.1	Tapestry Pharmaceuticals, Inc. presentation of data from one of two Phase I clinical trials of TPI 287 at the 43rd Annual Meeting of the American Society of Clinical Oncology on June 3, 2007.
99.2	Tapestry Pharmaceuticals, Inc. presentation of data from the other Phase I clinical trial of TPI 287 at the 43rd Annual Meeting of the American Society of Clinical Oncology on June 3, 2007.

The information in this Form 8-K and the Exhibits attached hereto shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, except as shall be expressly set forth by specific reference in such filing.

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SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

Date: June 4, 2007	TAPESTRY PHARMACEUTICALS, INC.
	By:	/s/ Kai Larson
	Name:	Kai Larson
	Title:	Vice President, General Counsel

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INDEX TO EXHIBITS

Exhibit No.	Description
99.1	Tapestry Pharmaceuticals, Inc. presentation of data from one of two Phase I clinical trials of TPI 287 at the 43rd Annual Meeting of the American Society of Clinical Oncology on June 3, 2007.
99.2	Tapestry Pharmaceuticals, Inc. presentation of data from the other Phase I clinical trial of TPI 287 at the 43rd Annual Meeting of the American Society of Clinical Oncology on June 3, 2007.

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EX-99.1

Exhibit 99.1

A PHASE 1 STUDY OF TPI 287; A THIRD GENERATION TAXANE ADMINSTERED WEEKLY IN PATIENTS WITH ADVANCED CANCER

Jimmy Hwang MD*, John Marshall MD*, Tauseef Ahmed MD†, Hoo G. Chun MD†, Michele Basche MD‡, Allen Cohn MD‡, Michael Kurman MD**, Gilles Tapolsky PhD**, Sandra Silberman MD PhD+, Ernest Allen**

*              Georgetown University Medical Center, Washington, DC

†              New York Medical College, Valhalla, NY

‡              Rocky Mountain Cancer Centers, Denver, CO

**           Tapestry Pharmaceuticals, Boulder, CO

+                      Tapestry Pharmaceuticals, Roseland, NJ

1

INTRODUCTION

Taxanes have become key components of the chemotherapeutic armamentarium for a variety of cancers including tumors of the breast, lung, prostate, ovary, stomach, and head and neck.

Unfortunately, resistance to the antineoplastic effects of taxanes often develops, limiting their efficacy.  Two putative mechanisms for resistance have been proposed:

·Taxanes are substrates for the efflux protein encoded by the mdr1 gene

·Alteration of the tubulin structure (genetic or epigenetic changes) may interfere with the mechanism of action of taxanes, rendering them unable to produce microtubule stabilization

2

Tapestry Pharmaceuticals, Inc. has developed a novel taxane analog, TPI 287, which is a semi-synthetic compound manufactured from yew starting material.  TPI 287 synthesis involves modifications of the taxane side chain, rendering the molecule more lipophilic.  In addition, modifications of the baccatin ring structure were designed to enhance the affinity of ß-tubulin binding, and to circumvent multi-drug resistance.

3

Figure 1:               TPI 287 and Paclitaxel Structures

4

Preclinical evaluation of TPI 287 in vitro demonstrated significant anti-tumor activity in both MDR- and MDR+ cell lines.  TPI 287 was active in tumor xenograft models in mice (breast cancers MCF-7 and MCF-7AR, colon cancers HCT-15 and HCT-116, and prostate cancer PC3).  Toxicology and safety studies were performed in rodents and dogs.  The LD10 value for multiple-dose TPI 287 was found to be 4 mg/kg/day IV (71 mg/m2/day) in dogs, the most sensitive species.  Allometric scaling of 1/10 of the dog LD10 determined an initial human starting dose of 7 mg/m2.

5

Study Objectives

Primary Objective:

To determine the Maximum Tolerated Dose (MTD) of TPI 287 administered once weekly for three weeks followed by one week of no treatment, in order to determine a safe, well tolerated dose.

Secondary Objectives:

To determine the safety of TPI 287

To determine the pharmacokinetic profile of TPI 287

This is a multi-center, dose-escalation, sequential cohort Phase I study in patients with recurrent or refractory solid tumors or Non-Hodgkin’s lymphoma.  Patients were either no longer candidates for standard therapy, had no standard therapy available, or chose not to pursue standard therapy.

6

TPI 287 was administered intravenously over 60 minutes, starting with a dose of 7 mg/m2 in the first cohort.  Up to four patients could be enrolled at each dose level and dose escalation was permitted after at least three patients had received the first cycle of therapy.  Escalation to the next dose occurred if no dose-limiting toxicity (DLT) was observed in any patient in that first cycle.  If one patient experienced a DLT, up to three additional patients were enrolled at this dose, with a minimum of six patients treated to determine the MTD.  If two or more patients in a cohort experienced a DLT, dose escalation was stopped.  Dose refinement was then initiated, which was a way to define the MTD more accurately, by enrolling three patients at a dose approximately half way between the dose level where two or more patients experienced a DLT at the preceding dose.  If no patient or one patient experienced a DLT at this intermediate dose, the cohort was expanded by an additional three patients, and if none or one patient in the expanded cohort experienced a DLT, this intermediate dose was considered to be the MTD.  However, if more than one patient in the expanded cohort experienced a DLT, the

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algorithm was repeated, i.e. three more patients were enrolled at an intermediate, lower dose.  Once the MTD is defined, additional patients will be treated at that dose, to bring the total number treated at the MTD to nine.

DLT was defined as a Grade 4 hematological toxicity lasting seven days, febrile neutropenia, Grade 3 or 4 thrombocytopenia with bleeding, Grade 3 or 4 elevation of transaminases lasting seven days, Grade 3 neuropathy or any other Grade 3 or Grade 4 drug-related non-hematologic toxicity other than inadequately treated nausea or vomiting.

After at least three patients in each cohort had been enrolled, the investigators, medical monitor and the sponsor reviewed the safety data in order to decide whether to recommend further dose escalation.  Escalation or de-escalation at smaller dosage increments than stipulated in the protocol, and enrollment of additional patients was recommended in some instances, as outlined above.

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Patients whose tumors did not progress, or who did not discontinue TPI 287 for other medical or administrative reasons, were treated with a maximum of six cycles of therapy (approximately six months) on this protocol, and were eligible to participate in a separate extension study in order to continue to receive study drug.

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Demographics

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Cohort 6	Cohort 7
	7 mg/m2	14 mg/m2	28 mg/m2	56 mg/m2	85 mg/m2	127.5 mg/m2	185 mg/m2	Total
	N = 4	N = 4	N = 4	N = 4	N = 4	N = 5	N = 5	N = 30
Age (years)	51.8	51.8	58.3	61.3	66.5	64.2	66.8	60.4
Mean	52.5	54.0	58.5	60.0	67.0	60.0	71.0	60.5
Median	37, 65	24, 75	47, 69	54, 71	53, 79	49, 86	42, 82	24, 86
Min, Max
Sex
Male	3	1	3	2	4	2	2	17
Female	1	3	1	2	0	3	3	13
Race
Asian	0	0	0	0	1	0	0	1
Black	1	0	0	0	1	1	1	4
Caucasian	3	3	4	4	2	4	4	24
Hispanic	0	1	0	0	0	0	0	1

An additional group (Cohort 8) of patients treated with 150mg/m2 is currently being enrolled

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Thirty patients have been enrolled, 17 males and 13 females, ranging in age from 24 to 86.  The majority (24) were Caucasian, four patients were Black, one was Asian, and one Hispanic.

The patients’ tumor types were as follows:

Colon (7), Prostate (3), Pancreatic (3), Lung (3), Ovarian (2), Breast (1), Hepatocellular (1), Kidney (1), Osteosarcoma (1), Cervical (2), Endometrial (1), Basal cell (1), Melanoma (1), Brain (1), Gastric (1), Squamous of buccal mucosa (1).

Twenty-nine (93%) patients had metastatic disease at the time of enrollment.  Prior cancer therapy included surgery (23 patients, 77%), radiotherapy (18 patients, 60%) chemotherapy (29 patients, 97%), and hormonal, immunological, biological or other therapy (14 patients, 47%).  One patient was enrolled but was then found to be ineligible, and is not included in this analysis (i.e. 29/30 patients are included in the analysis).

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Safety

Most Frequent Treatment-Emergent Adverse Events (Any Grade) Occurring in ≥ 15% of Patients

Adverse Event Preferred Term	Total N = 29
Any Adverse Event	28 (97%)
Fatigue	15 (52%)
Constipation	10 (34%)
Dyspnea	9 (31%)
Nausea	9 (31%)
Abdominal Pain	7 (24%)
Vomiting	8 (24%)
Urinary Tract Infection	7 (24%)
Cough	7 (24%)
Pyrexia	6 (21%)

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Back Pain	6 (21%)
Anorexia	6 (21%)
Anemia	5 (17%)
Diarrhea	5 (17%)
Neuropathy	5 (17%)
Chest Pain	5 (17%)

13

Safety

Treatment-Emergent Grade 3 or 4 Adverse Events occurring in ≥ 5% of All Patients

	Cohort 1 - 3		Cohort 4		Cohort 5		Cohort 6		Cohort 7
	7 (N = 4), 14  (N = 4)  28 (N =4)  mg/m2 N = 12		56 mg/m2  N = 4		85 mg/m2  N = 4		127.5 mg/m2  N = 5		185 mg/m2  N = 5		Total N = 29
Grade	3	4	3	4	3	4	3	4	3	4	3	4
Dyspnea	3  (25%)	0	2  (50%)	0	0	0	0	0	0	0	5  (17%)	0
Neuropathy*	1  (8%)	0	0	0	0	0	1  (20%)	0	1 (20%)	0	3  (10%)	0
Chest pain	2  (17%)	0	0	0	0	0	0	0	0	0	2  (7%)	0
Pneumonia	0	0	0	0	1  (25%)	0	1  (25%)	0	0	0	2  (7%)	0
INR increased	0	0	1  (25%)	0	0	0	1  (20%)	0	0	0	2  (7%)	0
Hypoxia	1  (8%)	0	0	0	0	0	1  (20%)	0	0	0	2  (7%)	0
Fatigue	0	0	0	0	1  (25%)	0	0	0	0	1  (25%)	1  (3%)	1  (3%)

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Liver Function Test Elevated† 1  (8%) 0 0 0 0 0 0 0 0 0 0 1  (3%)

Dose-limiting Toxicity, 2/3 patients had baseline Grade 1 neuropathy

† alkaline phosphatase elevated

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Safety
Summary of Safety

·In this ongoing study, the maximum dose of TPI 287, administered weekly was 185 mg/m2.  Treatment with 150 mg/m2 is currently ongoing.

·Overall, 28/29 patients experienced at least one adverse event, which were typically grade 1 and 2 in severity, with the most frequently cited being fatigue (52% of patients), constipation (34% of patients), dyspnea (31% of patients) and nausea (31% of patients).  There was a trend toward more patients experiencing fatigue with higher dose (80% of patients at 185 mg/m2).  The most frequent adverse events considered probably or definitely related to TPI 287 were anemia, nausea, diarrhea and neuropathy.

·In the 29 patients analyzed, overall, 17 (57%) patients experienced at least one adverse event of Grade 3 severity and 3 (10%) patients experienced at least one adverse event which was Grade 4.  The most frequent grade 3 or 4 adverse events experienced by ≥ 5% of patients were dyspnea, neuropathy, chest pain, pneumonia, increased INR, hypoxia and fatigue.  Three patients receiving 14 mg/m2, 127.5 mg/m2 and 185 mg/m2 respectively had Grade 3 neuropathy which proved to be the dose-limiting toxicity in this study. Two of these patients had baseline neuropathy of Grade 1 due to prior therapy and co-morbid conditions.  One patient receiving 7 mg/m2 had Grade 3 elevated alkaline phosphatase. There were no Grade 3 or 4 myelosuppressive events.

·Twelve patients experienced serious adverse events (SAE), resulting in cessation of treatment in three patients and interruption of treatment in four patients.  In two patients the SAEs were considered probably related (anemia) or definitely related (hypersensitivity reaction with dyspnea, dizziness/back pain/ flushing) to TPI 287 treatment.

16

Pharmacokinetics of TPI 287

Blood samples for the measurement of pharmacokinetic parameters for TPI 287 were taken from 31 patients before the first dose, and 1-2 minutes, 5, 15 and 30 minutes, and 1, 2, 3, 4, 5 , 6 and 24 hours after the end of the infusion.  The levels of TPI 287 in plasma were measured using a validated LC-MS method.  PK parameters were determined using Win Nonlin software applying non-compartmental analysis and 2-compartment modeling.

17

Non-compartmental PK Analysis

	Dose (mg/m2)
	7		14		28		56		84		127.5		185
Number of Patients	4		4		3		4		4		6		6
Cmax (ng/mL)	542.5		159.6		235.2		896		2234.4		2575.5		7825.5
Mean (SD)	(483.7	)	(77.1	)	(137.2	)	(208.9	)	(1083.6	)	(947.3	)	(2701	)
AUClast (ng*h/mL)	329		196		369.6		1876		5905.2		4347.7		11174
Mean (SD)	(363	)	(99.4	)	(86.8	)	(1075.2	)	(3855.6	)	(3060	)	(2109	)
CL (L/hr/m2)	—		29.1		49.6		28.6		16.6		30.2		15.8
Mean (SD)			(19.2	)	(5.0	)	(13.2	)	(9.3	)	(11.9	)	(2.7	)
T1/2 (h)	—		8.5		6.1		7.2		8.9		8.5		8.0
Mean (SD)			(4.1	)	(1.6	)	(2.3	)	(2.1	)	(1.3	)	(0.7	)

The AUC and Cmax were generally dose-proportional, the half-life of TPI 287 in blood was approximately 8 hours and clearance at 185 mg/m2 was 15.8 L/hr/m2.

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Efficacy

One 62-year-old female patient with pancreatic cancer had stable disease for four cycles of TPI 287 administered at 185 mg/m2.

Another 59-year-old male patient with non-small cell lung cancer had a 57% reduction in one lesion as assessed by RECIST (Figure 2) after treatment with TPI 287 at 85 mg/m2; however this patient discontinued treatment due to progression of an unrelated condition.

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Figure 2: Pre- and Post- Treatment CT Scans in Patient with Non-Small Cell Lung Cancer

20

Conclusions

·In this ongoing Phase 1 study, the maximum tolerated dose of TPI 287 to date, administered as an IV infusion over 60 minutes weekly for three weeks followed by one week rest, is still being explored.

·Dose-limiting toxicity of Grade 3 neuropathy was seen at 185 mg/m2 in three patients, two of whom had baseline neuropathy of Grade 1.

·No clinically significant myelosuppression was seen.

·Pharmacokinetics show dose-proportionality and TPI 287 had a half life of approximately 8 hours.

·Two patients enrolled at the highest dose levels had clinical benefit as documented by disease regression (Non-small cell lung cancer) or stabilization of disease (pancreatic cancer).

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EX-99.2

Exhibit 99.2

A PHASE 1 STUDY OF TPI 287; A THIRD GENERATION TAXANE ADMINSTERED EVERY 21 DAYS IN PATIENTS WITH ADVANCED CANCER

Manuel Modiano MD*, Patricia Plezia PharmD*, Jacob Baram MD†, Raphael Catane MD†, Allen Cohn MD‡, Michele Basche MD‡

Michael Kurman MD**, Gilles Tapolsky PhD**, Sandra Silberman MD PhD+, Susan Yancik MS**

*              Arizona Clinical Research Center, Tucson, AZ USA

†              Sheba Medical Center, Tel Hashomer, Israel

‡              Rocky Mountain Cancer Centers, Denver, CO USA

**           Tapestry Pharmaceuticals, Boulder, CO USA

+              Tapestry Pharmaceuticals, Roseland, NJ USA

1

INTRODUCTION

Taxanes have become key components of the chemotherapeutic armamentarium for a variety of cancers including tumors of the breast, lung, prostate, ovary, stomach, and head and neck.

Unfortunately, resistance to the antineoplastic effects of taxanes often develops, limiting their efficacy.  Two putative mechanisms for resistance have been proposed:

·Taxanes are substrates for the efflux protein encoded by the mdr1 gene

·Alteration of the tubulin structure (genetic or epigenetic changes) may interfere with the mechanism of action of taxanes, rendering them unable to produce microtubule stabilization

Tapestry Pharmaceuticals Inc. has developed a novel taxane analog, TPI 287, which is a semi-synthetic compound manufactured from yew

2

starting material.  TPI 287 synthesis involves modifications of the taxane side chain, rendering the molecule more lipophilic.  In addition, modifications of the baccatin ring structure were designed in order to enhance the affinity of mutant ß-tubulin binding, and to circumvent multi-drug resistance.

Figure 1:               Structure of TPI 287 and Paclitaxel

3

Preclinical evaluation of TPI 287 in vitro demonstrated significant anti-tumor activity in both MDR- and MDR+ cell lines.  TPI 287 was active in tumor xenograft models in mice (breast cancers MCF-7 and MCF-7AR, colon cancers HCT-15 and HCT-116, and prostate cancer PC3).  Toxicology and safety studies were performed in rodents and dogs.  The LD10 value for multiple-dose TPI 287 was found to be 4 mg/kg/day IV (71 mg/m2/day) in dogs, the most sensitive species.  Allometric scaling of 1/10 of the dog LD10 determined an initial human starting dose of 7 mg/m2 for the first Phase 1 study (TPI 287-01) administering TPI 287 once weekly for three weeks followed by a one week rest.  The current study was started after a weekly dose of 56 mg/m2 was found to be safe and well tolerated.

4

Study Objectives

Primary Objective:

To determine the Maximum Tolerated Dose (MTD) of TPI 287 administered once every 21 days

Secondary Objectives:

To determine the safety of TPI 287

To determine the pharmacokinetic profile of TPI 287

To determine the anti-tumor activity of TPI 287

This was a multi-center, dose-escalation, sequential groups Phase I study in patients with recurrent or refractory solid tumors or non-Hodgkin’s lymphoma.  Patients had either failed prior chemotherapy, were no longer candidates for standard therapy, had no standard therapy available, or chose not to pursue standard therapy.

5

TPI 287 was administered intravenously over 60 minutes, starting with 56mg/m2, a dose chosen based on the ongoing Phase I trial described above.

An accelerated dose escalation schema was used, which enrolled one patient at each dose level: escalation to a 50% higher dose was performed if that patient had no dose limiting toxicity (DLT) after one dose and a three week follow-up period. This dose escalation was repeated until one patient experienced drug-related toxicity of ≥ grade 2 (using NCI CTCAE criteria) excluding nausea and vomiting, at which point the cohort was expanded up to four patients. Up to four patients were then enrolled in each subsequent dose cohort and toxicity evaluated after three patients had received one treatment plus three weeks follow-up.  If one of the three patients experienced a dose limiting toxicity, up to an additional three patients were enrolled at that dose level.  Once two patients had experienced a ≥ Grade 2 toxicity, the dose below was

6

considered to be the MTD and up to 6 additional patients were enrolled for a total of nine at the MTD.

DLT was defined as a Grade 4 hematological toxicity lasting seven days, febrile neutropenia, Grade 3 or 4 thrombocytopenia with bleeding, Grade 3 or 4 elevation of transaminases lasting seven days, Grade 3 neuropathy or any other Grade 3 or Grade 4 drug-related non-hematologic toxicity other than inadequately treated nausea or vomiting.

TPI 287 was administered every 21 days until patients experienced disease progression or unacceptable toxicity.

Patients whose tumors did not progress, or who did not discontinue TPI 287 for other medical or administrative reasons, were treated with a maximum of six cycles of therapy on this protocol, and were eligible to participate in a separate extension study in order to continue to receive study drug.

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Demographics

	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
	56 mg/m2	84 mg/m2	126 mg/m2	185 mg/m2	160 mg/m2	Total
	N = 2	N = 1	N = 3	N = 6	N = 9	N = 21
Age (years)
Mean	56.5	60.0	58.3	60.0	58.7	58.9
Median	56.5	60.0	59	60.0	55.0	58.0
Min, Max	55, 58	60, 60	57, 59	49, 72	35,78	35, 78
Sex
Male	1	0	1	2	3	7
Female	1	1	2	4	6	14
Race
Asian	0	0	0	0	1	1
Black	0	0	0	0	0	0
Caucasian	2	1	2	3	6	14
Hispanic	0	0	1	3	2	6

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Twenty-one patients were enrolled, 7 males and 14 females, ranging in age from 35 to 78 years.  The majority (14) were Caucasian, one was Asian and six were Hispanic.

The patients’ tumor types were as follows:

Colon (6), Rectal (1), Breast (5), Pancreatic (3), Esophageal (1), Gastric (1), Papillary cystadenocarcinoma (1), Cholangiosarcoma (1), Carcinoid (1), Unknown primary (1).

All patients had metastatic disease at the time of enrollment.  Prior cancer therapy included surgery (17 patients, 81%), radiotherapy (6 patients, 29%) chemotherapy (20 patients, 95%), and hormonal, immunological, biological or other therapy (11 patients, 52%).

9

Safety

Most Frequent Treatment-Emergent Adverse Events (Any Grade) Occurring in ≥ 15% Patients

Adverse Event Preferred Term	Total N = 21
Anemia	9 (43%)
Peripheral neuropathy	9 (43%)
Diarrhea	7 (33%)
Nausea	7 (33%)
Vomiting	7 (33%)
Abdominal pain	6 (29%)
Fatigue	6 (29%)
Myalgia	6 (29%)
Neutropenia	5 (24%)
Asthenia	5 (24%)

10

Peripheral edema	4 (19%)
Pyrexia	4 (19%)
Urinary tract infection	4 (19%)
Anorexia	4 (19%)
Arthralgia	4 (19%)

11

Treatment-Emergent Grade 3 or 4 Adverse Events Occurring in ≥ 5% of All Patients

	Cohort 1 - 3		Cohort 4		Cohort 5
	56 (N = 2), 84 (N = 1) 126 (N =3)  mg/m2 N = 6		185 mg/m2 N = 6		160 mg/m2 N = 9		Total N = 21
Adverse Event	Grade 3	Grade 4	Grade 3	Grade 4	Grade 3	Grade 4	Grade 3	Grade 4
Neuropathy*†	0	0	3 (50%)	0	1 (11%)	0	4 (19%)	0
Neutropenia*	1 (17%)	0	0	2 (33%)	0	0	1 (5%)	2 (10%)
Anemia	1 (17%)	0	0	0	0	0	1 (5%)	0
Anaphylactic shock	0	0	0	0	0	1 (11%)	0	1 (5%)
Fatigue	0	0	0	0	2 (22%)	0	2 (10%)	0
Asthenia	0	0	0	0	1 (11%)	0	1 (5%)	0
Vomiting	0	0	1 (17%)	0	0	0	1 (5%)	0

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Anorexia 0 0 0 0 1 (11%) 0 1 (5%) 0

*  Dose Limiting Toxicities: Grade 3 neuropathy; Grade 4 neutropenia

† One of the four patients with Grade 3 neuropathy had Grade 1 at baseline

13

Summary of Safety

·The maximum tolerated dose of TPI 287 administered every 21 days was 160 mg/m2.

·The dose limiting toxicities of TPI 287 on this schedule were Grade 3 neuropathy and Grade 4 neutropenia.

·All 21 patients experienced at least one adverse event: the most frequent adverse events occurring in four or more patients (≥ 15%) were anemia, neuropathy, neutropenia, fatigue, diarrhea, nausea, vomiting, asthenia, abdominal pain and myalgia.

·Overall, seven patients (33%) experienced at least one Grade 4 adverse event and 13 patients (62%) experienced at least one Grade 3 adverse event.  Four patients had Grade 3 neuropathy,

14

although one of them had Grade 1 neuropathy at baseline.  Three patients had neutropenia (one Grade 3 and two Grade 4), and one patient had Grade 3 anemia

·Seven patients experienced serious adverse events (SAE), resulting in the death of two patients.  Only one, non-lethal, SAE of anaphylactic shock, was considered to be definitely related to TPI 287.  In the remaining five patients, SAEs resulted in cessation of treatment with TPI 287 in one patient

15

Pharmacokinetics of TPI 287

Blood samples for the measurement of pharmacokinetic parameters for TPI 287 were taken before the first dose, and 1-2 minutes, 5, 15 and 30 minutes, and 1, 2, 4, 6-8 and 24 hours after the end of the infusion.  The levels of TPI 287 in plasma were measured using a validated LC-MS method.  PK parameters were determined using Win Nonlin software applying non-compartmental analysis and 2-compartment modeling.

16

Non-compartmental PK Analysis

	Dose mg/m2
	56	84	126		160		185
Number of Patients	2	1	3		6		5
Cmax (ng/mL)	649.6	977.5	3402		3392		2997
Mean (SD)			(485	)	(1456	)	(1020	)
AUClast (ng*h/mL)	2531	3748.5	6111		9888		7067
Mean (SD)			(3024	)	(3744	)	(2923	)
CL (L/hr/m2)	18.9	15.4	22.1		15.2		24.7
Mean (SD)			(11.2	)	(7.6	)	(12.2	)
T1/2 (h)	11.8	15.4	8.5		5.9		10.6
Mean (SD)			(0.7	)	(1.3	)	(7.1	)

The AUC and Cmax were generally dose proportional.  At a dose of 185 mg/m2 the plasma half life of TPI 287 was 10.6 hours and the clearance was 24.7±12.2 L/hr/m2

17

Efficacy

One 67-year-old female patient with pancreatic cancer and multiple metastases to the liver had a partial response (51% decrease according to RECIST) after the fourth cycle of TPI 287 at 185 mg/m2 (Figure 2) which was confirmed after the sixth cycle.  The duration of response was nine cycles (189 days).

18

Figure 2: Treatment CT Scans in a Patient with Pancreatic Cancer

A 54 year-old female patient with breast cancer, treated with 160 mg/m2, had stable disease for over 8 cycles following a 4-month history of progressive disease prior to enrollment.

19

Conclusions

·The maximum tolerated dose of TPI 287, administered as an IV infusion over 60 minutes every 21 days, was 160 mg/m2.

·Dose-limiting toxicities were Grade 3 neuropathy and Grade 3 and 4 neutropenia.

·Pharmacokinetics showed dose-proportionality: at a dose of 185 mg/m2 the plasma half life of TPI 287 was 10.6 hours.

·One patient with pancreatic cancer had a sustained partial response, confirmed by a 51% decrease according to RECIST.  This response was sustained for more than 9 cycles.

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·A patient with breast cancer had prolonged (8+ cycles) stable disease after documented prior progression.

·Phase 2 studies exploring efficacy are currently ongoing.

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