Form 8-K

0001193125-11-064749.txt : 20110314 0001193125-11-064749.hdr.sgml : 20110314 20110314061440 ACCESSION NUMBER: 0001193125-11-064749 CONFORMED SUBMISSION TYPE: 8-K PUBLIC DOCUMENT COUNT: 44 CONFORMED PERIOD OF REPORT: 20110311 ITEM INFORMATION: Entry into a Material Definitive Agreement ITEM INFORMATION: Regulation FD Disclosure ITEM INFORMATION: Financial Statements and Exhibits FILED AS OF DATE: 20110314 DATE AS OF CHANGE: 20110314 FILER: COMPANY DATA: COMPANY CONFORMED NAME: CELL THERAPEUTICS INC CENTRAL INDEX KEY: 0000891293 STANDARD INDUSTRIAL CLASSIFICATION: PHARMACEUTICAL PREPARATIONS [2834] IRS NUMBER: 911533912 STATE OF INCORPORATION: WA FISCAL YEAR END: 1231 FILING VALUES: FORM TYPE: 8-K SEC ACT: 1934 Act SEC FILE NUMBER: 001-12465 FILM NUMBER: 11683815 BUSINESS ADDRESS: STREET 1: 501 ELLIOTT AVE W STREET 2: STE 400 CITY: SEATTLE STATE: WA ZIP: 98119 BUSINESS PHONE: 2062827100 MAIL ADDRESS: STREET 1: 501 ELLIOTT AVE W STREET 2: STE 400 CITY: SEATTLE STATE: WA ZIP: 98119 8-K 1 d8k.htm FORM 8-K Form 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): March 14, 2011 (March 11, 2011)

CELL THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

Washington

001-12465

91-1533912

(State or other jurisdiction of

incorporation or organization)

(Commission

File Number)

(I.R.S. Employer

Identification Number)

501 Elliott Avenue West, Suite 400

Seattle, Washington 98119

(Address of principal executive offices)

Registrant’s telephone number, including area code: (206) 282-7100

Not applicable

(Former name or former address, if changed since last report).

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 (see General Instruction A.2. below):

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

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

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

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

Item 1.01.

Entry into a Material Definitive Agreement.

On March 11, 2011, Cell Therapeutics, Inc., a Washington corporation (the “Company”), entered into a Co-Development and License Agreement (the “Agreement”) with Chroma Therapeutics Ltd. (“Chroma”). Pursuant to the Agreement, the Company has acquired an exclusive license to certain technology and intellectual property controlled by Chroma to develop and commercialize the drug candidate tosedostat in North, Central and South America (collectively, the “Licensed Territory”). Tosedostat is an oral treatment for patients with blood cancers, including refractory or relapsed Acute Myeloid Leukemia (“AML”).

Pursuant to the terms of the Agreement, the Company paid Chroma an upfront fee of $5.0 million upon execution of the Agreement and will make a milestone payment of $5.0 million upon the initiation of the first pivotal trial for AML, which is expected to commence in the fourth quarter of 2011. The Agreement also includes additional development- and sales-based milestone payments related to AML and certain other indications, up to a maximum amount of $209.0 million payable by the Company to Chroma if all development and sales milestones are achieved. The Company will also pay Chroma royalties on net sales of tosedostat in any country within the Licensed Territory, commencing on the first commercial sale of tosodestat in any country in the Licensed Territory and continuing with respect to that country until the later of (a) the expiration date of the last patent claim covering tosedostat in that country, (b) the expiration of all regulatory exclusivity periods for tosedostat in that country or (c) ten years after the first commercial sale in that country.

The Company will oversee and be responsible for performing the development operations and commercialization activities in the Licensed Territory and Chroma will oversee and be responsible for performing the development operations and commercialization activities worldwide except for the Licensed Territory (the “ROW Territory”). Development costs may not exceed $50.0 million for the first three years of the Agreement unless agreed by the parties and the Company will be responsible for 75% of all development costs, while Chroma will be responsible for 25% of all development costs, subject to certain exceptions. Chroma will be solely responsible for the manufacturing of tosodestat for development purposes in the Licensed Territory and the ROW Territory in accordance with the terms of the supply agreement to be entered into by the parties. The Company will be solely responsible, by itself or through one or more third party contract manufacturers, for the manufacture of tosodestat for commercialization purposes in the Licensed Territory.

The Agreement may be terminated by the Company at its convenience upon 120 days’ written notice to Chroma. The Agreement may also be terminated by either party following a material breach by the other party subject to notice and cure periods.

The effectiveness of the Agreement is subject to regulatory clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended. In the event the transaction does not receive regulatory clearance, the $5.0 million upfront fee will be refunded to the Company.

On March 14, 2011, the Company issued a press release entitled “Cell Therapeutics Acquires Exclusive Marketing and Co-Development Rights in the Americas to Chroma Therapeutics’ Tosedostat, a First in Class Tumor Selective Oral Therapy for Treatment of Blood-Related and Other Cancers,” a copy of which is attached hereto as Exhibit 99.1 and is incorporated herein by reference.

Item 7.01.

Regulation FD Disclosure.

The information provided pursuant to this Item 7.01 shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”), or otherwise subject to the liabilities of that section, and shall not be deemed to be incorporated by reference into any filing or other document filed by the Company pursuant to the Exchange Act or the Securities Act of 1933, as amended, whether made before or after the date hereof and regardless of any general incorporation language in such filings or documents, except to the extent expressly set forth by specific reference in such a filing or document. The information furnished pursuant to this Item 7.01 shall instead be deemed “furnished.”

On March 14, 2011, members of the management team of the Company will host a presentation for investors and analysts in Milan, Italy at 8:30 a.m. Eastern time/1:30 p.m. Central European time/5:30 a.m. Pacific time regarding the Agreement and tosedostat. A copy of the Company’s slides for this presentation is furnished and not filed as Exhibit 99.2 hereto.

Also on March 14, 2011, members of the management team of the Company will host presentations for the media in Milan, Italy regarding the Agreement and tosedostat. A copy of the Company’s slides for these meetings is furnished and not filed as Exhibit 99.3 hereto.

Item 9.01.

Financial Statements and Exhibits.

(d)

Exhibits


Exhibit No.		Description

99.1		Press Release, dated March 14, 2011, entitled “Cell Therapeutics Acquires Exclusive Marketing and Co-Development Rights in the Americas to Chroma Therapeutics’ Tosedostat, a First in Class Tumor Selective Oral Therapy for Treatment of Blood-Related and Other Cancers.”

99.2		Cell Therapeutics, Inc. Presentation Slides (for Investors and Analysts).

99.3		Cell Therapeutics, Inc. Presentation Slides (for Media).

SIGNATURE

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.


	CELL THERAPEUTICS, INC.

Date: March 14, 2011	By:	/S/ JAMES A. BIANCO, M.D.
		James A. Bianco, M.D.
		Chief Executive Officer

EXHIBIT INDEX


Exhibit No.		Description

99.1		Press Release, dated March 14, 2011, entitled “Cell Therapeutics Acquires Exclusive Marketing and Co-Development Rights in the Americas to Chroma Therapeutics’ Tosedostat, a First in Class Tumor Selective Oral Therapy for Treatment of Blood-Related and Other Cancers.”

99.2		Cell Therapeutics, Inc. Presentation Slides (for Investors and Analysts).

99.3		Cell Therapeutics, Inc. Presentation Slides (for Media).

EX-99.1 2 dex991.htm PRESS RELEASE Press Release

Exhibit 99.1


		www.CellTherapeutics.com

Cell Therapeutics Acquires Exclusive Marketing and Co-Development Rights in the Americas to Chroma Therapeutics’ Tosedostat, a First in Class Tumor Selective Oral Therapy for Treatment of Blood Related and Other Cancers

•

Phase III Pivotal Trial in Acute Myeloid Leukemia Expected to Start in Q4 2011

•

Provides Potential Portfolio and Commercial Synergies with Pixantrone

•

Conference Call and Webcast to be Held on Monday, March 14, 2011 at 8:30 AM Eastern time/1:30 PM Central European time/5:30 AM Pacific time

March 14, 2011 Seattle and Oxford, UK—Cell Therapeutics, Inc. (“CTI”) (NASDAQ and MTA: CTIC) and Chroma Therapeutics Ltd. (“Chroma”) announced today that the companies have entered into a co-development and license agreement providing CTI with exclusive marketing and co-development rights to Chroma’s drug candidate tosedostat in North, Central and South America. Tosedostat is an oral, aminopeptidase inhibitor that has demonstrated significant anti-tumor responses in blood related cancers and solid tumors in phase I-II clinical trials. CTI, in collaboration with Chroma, expects to commence a phase III clinical study in the United States and Europe in elderly patients with relapsed or refractory acute myeloid leukemia (“AML”) for potential approval by the U.S. Food and Drug Administration (“FDA”) and the European Medicines Agency (“EMA”). The FDA and the EMA have granted tosedostat orphan drug status for AML.

Pursuant to the terms of the agreement, CTI will make an upfront payment of $5 million and a milestone payment of $5 million when the AML pivotal trial is initiated, which is expected to occur in the fourth quarter of 2011. The agreement also includes customary development-based milestone payments related to AML, myelodysplastic syndrome (“MDS”) and certain other indications, as well as royalties on net sales in CTI’s territories. CTI will oversee development operations and commercialization activities in its territories and Chroma will oversee development operations and commercialization activities in the rest of the world.

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Subject to a funding cap of $50 million for the first three years, CTI will be responsible for 75% of development costs and Chroma will be responsible for 25% of development costs.

“Tosedostat, similar to drugs like bortezomib and lenalidomide, represents a departure from conventional cytotoxic chemotherapy toward more tumor selective targeted therapy that interferes with cellular pathways necessary for tumor survival,” commented James A. Bianco, M.D., CEO of CTI. “In initial clinical studies, tosedostat was well-tolerated, given orally once a day and produced encouraging response rates in difficult to treat patients with acute leukemia and a variety of blood related cancers. We are excited to add tosedostat to our late-stage product pipeline alongside pixantrone as we continue with our strategy of building a pipeline of novel drugs for treating blood-related cancers.”

Chroma is an Oxford, UK based private company led by a management team with extensive public biotechnology and large pharmaceutical company experience, including former executives of Celltech, British Biotech, AstraZeneca and Roche, and backed by leading specialist investors. Chroma is focused on harnessing chromatin biology and its novel cell accumulation (ESM) technology to develop new targeted therapies for cancer and inflammatory disorders.

“We believe that this is a collaboration that should enable the rapid progression of tosedostat toward seeking regulatory approval, given CTI’s development and commercialization capabilities and experience in the blood-related cancer space,” said Ian Nicholson, CEO of Chroma. “In working with clinicians in developing tosedostat we have clearly identified significant unmet medical needs where tosedostat could provide an important therapeutic advance for patients if approved.”

AML is a hematologic cancer that is an aggressive, fast-growing cancer that starts inside the bone marrow with the production of abnormal blood cells. The American Cancer Society estimates that 12,330 new cases of AML will be diagnosed and approximately 8,950 deaths from AML will occur in the U.S. in 2010. AML is generally a disease affecting older people with the average patient age at onset of approximately 67 years. There remain a substantial proportion of elderly patients who do not receive intensive chemotherapy due to their inability to tolerate such regimens, and other risk factors. Therefore, there is a significant unmet medical need in developing a well-tolerated and effective treatment for these patients.

Tosedostat is an orally dosed aminopeptidase inhibitor which blocks the M¹/17 family of aminopeptidases. Disrupting aminopeptidases deprives sensitive tumor cells of amino acids by blocking protein recycling resulting in tumor cell death. Tosedostat has been studied in Chroma’s phase I-II clinical trials both as a single agent and in combination with other chemotherapeutic agents. Such studies have demonstrated significant anti-tumor responses

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Page 3 of 5

without the typical side effects of conventional, non-targeted cytotoxic therapies. Initial target indications include AML, MDS and multiple myeloma.

Conference Call Information

On Monday, March 14, 2011, at 8:30 a.m. Eastern time/1:30 p.m. Central European time/5:30 a.m. Pacific time, members of CTI’s and Chroma’s management teams will host a conference call to discuss the co-development and licensing agreement.

Conference Call Numbers

Monday, March 14, 2011 8:30 a.m. Eastern/1:30 p.m. Central European/5:30 a.m. Pacific Time

1-877-941-0843 (US Participants – Toll-Free)

1-480-629-9643 (US Participants)

800-149-038 (Italy Participants – Toll-Free)

39-06-45-210-8364 (Italy Participants)

0800 358 0857 (UK Participants – Toll-Free)

44-20-8515-2302 (UK Participants)

Call-back numbers for post-listening available at 11:30 a.m. Eastern Time:

1-800-406-7325 (US Participants)

1-303-590-3030 (International)

Passcode: 4423141#

Live audio webcast at www.celltherapeutics.com will be archived for post-call listening approximately two hours after call ends.

About Cell Therapeutics, Inc.

Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit www.CellTherapeutics.com.

About Chroma Therapeutics

Chroma Therapeutics, based in Oxford (UK), is a drug discovery and development company focused in the fields of oncology and inflammatory disorders. Chroma is building a broad pipeline of first- or best-in-class treatments utilizing its expertise in chromatin biology and its

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Page 4 of 5

novel intracellular accumulation technologies, which include the ability to selectively target drugs’ tomacrophages. Chroma is backed by a number of leading specialist investors, including Abingworth, Essex Woodlands, Gilde, Phase4 and The Wellcome Trust. More information about Chroma can be found at www.chromatherapeutics.com.

This press release includes forward-looking statements that involve a number of risks and uncertainties the outcome of which could materially and/or adversely affect actual future results and the market price of the Company’s securities. Specifically, the risks and uncertainties that could affect the development and commercialization of tosestodat include risks associated with preclinical, clinical and sales and marketing developments in the biopharmaceutical industry in general and in particular, including, without limitation, the potential failure of tosedostat to prove safe and effective (including complete and overall response rates) for the treatment of blood related and other cancers as determined by the FDA and/or the EMA, that the FDA may not accept the proposed clinical trial design of tosedostat and/or may request additional clinical trials, that clinical trials may not demonstrate the safety and effectiveness of tosedostat, that the Company cannot predict or guarantee the pace or geography of enrollment of clinical trials of tosedostat, including whether or not the majority of the patients will be enrolled in the U.S., that the phase III pivotal trial for tosedostat for AML may not start during the fourth quarter of 2011, that the Company cannot predict or guarantee the outcome or results of clinical trials of tosedostat, that the Company cannot predict or guarantee whether the co-development and license agreement will strengthen the Company’s business, financial condition, operating results and prospects or the trading price of the Company’s securities, that the Company cannot predict or guarantee whether milestones will be achieved pursuant to the Agreement, the Company’s ability to continue to raise capital as needed to fund its operations and make milestone payments, as applicable, determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing and selling the Company’s products under development and co-development, and other economic, business, competitive, and/or regulatory factors affecting the Company’s business generally, including those set forth in the Company’s filings with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for its most recent fiscal year and its most recent Quarterly Report on Form 10-Q, especially in the “Factors Affecting Our Operating Results” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections, and its Current Reports on Form 8-K. Except as may be required by law, the Company does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.

###

Media Contact:

Dan Eramian

T: 206.272.4343

C: 206.854.1200

E: deramian@ctiseattle.com

www.CellTherapeutics.com/press_room

Investors Contact:

Ed Bell

T: 206.282.7100

Lindsey Jesch Logan

T: 206.272.4347

F: 206.272.4434

E: invest@ctiseattle.com

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www.CellTherapeutics.com/investors

Medical Information Contact:

T: 800.715.0944

E: info@askarm.com

Chroma Therapeutics Ltd.:

Ian Nicholson, CEO

Richard Bungay, CFO

T: +44 (0) 1235 829120

Brunswick PR

Jon Coles

Justine McIlroy

T: +44 (0)20 7404 5959

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EX-99.2 3 dex992.htm CELL THERAPEUTICS, INC. PRESENTATION SLIDES (FOR INVESTORS AND ANALYSTS) Cell Therapeutics, Inc. Presentation Slides (for Investors and Analysts)

Tosedostat

Exclusive Marketing License and Co-Development Agreement

Exhibit 99.2

Forward looking statements

This presentation contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation

Reform Act of 1995. The forward-looking statements contained in this presentation include statements about future financial and operating results,

and risks and uncertainties that could affect Cell Therapeutic Inc.’s (“CTI”) products under development. These statements are based on

management’s current expectations and beliefs and are subject to a number of factors and uncertainties that could cause actual results to differ

materially from those described in the forward-looking statements. These statements are not guarantees of future performance, involve certain

risks, uncertainties and assumptions that are difficult to predict, and are based upon assumptions as to future events that may not prove accurate.

Therefore, actual outcomes and results may differ materially from what is expressed herein. In any forward-looking statement in which CTI

expresses an expectation or belief as to future results, such expectation or belief is expressed in good faith and believed to have a reasonable

basis, but there can be no assurance that the statement or expectation or belief will result or be achieved or accomplished.

The following factors, among others, could cause actual results to differ materially from those described in the forward-looking statements: risks

associated with preclinical, clinical and sales and marketing developments in the biopharmaceutical industry in general and in particular including,

without limitation, the potential failure of Tosedostat to prove safe and effective (including complete and overall response rates) for the treatment of

blood related cancers and selected tumors as determined by the U.S. Food and Drug Administration (the “FDA”) or other regulatory agencies in

the territories where CTI has exclusive rights, that the FDA may not accept the proposed clinical trial design of Tosedostat and/or may request

additional clinical trials, that clinical trials may not demonstrate the safety and effectiveness of Tosedostat, that CTI cannot predict or guarantee

the pace or geography of enrollment of clinical trials of Tosedostat, including whether or not the majority of the patients will be enrolled in the U.S.,

that CTI cannot predict or guarantee the outcome or results of clinical trials of Tosedostat, that CTI’s cannot predict or guarantee whether the

exclusive marketing license and co-development agreement with Chroma Therapeutics Ltd (the “Agreement”) will strengthen CTI’s business,

financial condition, operating results and prospects or the trading price of CTI’s securities, that CTI cannot predict or guarantee whether

milestones will be achieved pursuant to the Agreement, CTI’s ability to continue to raise capital as needed to fund its operations, determinations

by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing

and selling CTI’s products under development; and other economic, business, competitive, and/or regulatory factors affecting CTI’s business

generally, including those set forth in CTI’s filings with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K

for its most recent fiscal year and its most recent Quarterly Report on Form 10-Q, especially in the “Factors Affecting Our Operating Results” and

“Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections, and its Current Reports on Form 8-K. Except

as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future

events, or otherwise.

Product/Deal Highlights

Tosedostat: Novel tumor-selective targeted therapy

•

Oral, once daily dosing, well tolerated

Encouraging phase I/II data

•

27% mono-therapy response rate elderly r/r AML

•

Ongoing trials provide clinical news flow through 2012

Potentially rapid registration timeline: pivotal study

estimated to start Q4-2011

Leverages CTI’s access to and expertise in blood-related

cancer market

•

Potential development cost and sales synergies with pixantrone

Exclusive rights in Americas on reasonable deal terms

Targets billion dollar market applications

Chroma Therapeutics

Public company expertise in a private company

•

Seasoned management and Board of Directors

•

Facilitates co-development interactions and synergies

Investor group

•

Abingworth, Wellcome Trust, Essex Woodlands, Nomura, GSK,

Gilde

Innovators in new targeted therapies harnessing

chromatin biology and novel cell accumulation (ESM*)

technology

Validating partnership with GlaxoSmithKline

* Esterase Sensitive Motifs

Tosedostat: Mechanism of Action

Targets members of aminopeptidase family

Induces genes characteristic of Amino Acid Deprivation response

(AADR)

AADR changes only seen in transformed (tumor) cells and not normal cells

Consequences of amino acid

deprivation in leukemic cells

Cells attempt to solve deficiency (up-regulation of amino

acid transporters –

AADR response)

Cells switch off protein synthesis (e.g. remove mTOR

drive)

Cells switch on stress-related pathways (NFKB, etc.)

Cells produce pro-apoptotic regulators, CHOP, NOXA,

etc., that lead to cell death

Studies indicate that these effects are not seen

in either normal human cells treated

with Tosedostat or in insensitive tumor cells.

Tosedostat Clinical Program

Blood-Related Cancers

Acute Myeloid Leukemia (AML) Overview

One of the most common types of leukemia in adults

U.S. Incidence >12,000/yr

Median age at diagnosis –

67 years

Poor prognostic factors include

•

Elderly (>60 yo.)

•

Elevated WBC counts (>100,000/mm

)

•

Secondary AML resulting from other primary cancers

•

History of MDS or another antecedent hematologic disorder

Response rates and survival in elderly r/r disease is grim

(10%, <3months)

Acute Myeloid Leukemia (AML) Overview

Cytarabine

(Ara-C)

and

anthracyclines

mainstay

line

•

~75% relapse within 1 year

Approximately 2/3 of elderly patients do not tolerate

intensive chemotherapy

•

70% of AML patients are >60yrs old

•

Up to 35% treatment related mortality

Significant unmet medical need in elderly AML for

•

Better tolerated agents

•

Oral, chronic dosing

•

Better efficacy

Phase I/II (002) Study

Phase I/II Study (002)

Objectives

•

Define MTD and anti-leukemic activity of oral Tosedostat

Study population

•

Elderly (>60yrs), r/r AML, MDS, MM not eligible for chemo

Phase I (3+3) designed for up to 84 days of dosing

•

60mg, 90mg, 130mg, 180mg (oral, 1xdaily)

•

MTD determined during first 28 days

Phase II determines activity in AML, high risk MDS

•

Bone marrow assessment days 28, 56, 84

•

Extended dosing >84 days permissible

Phase I/II: Patient characteristics

* Not reported for 1 patient

Phase I

(n = 16)

Phase II

(n = 43)

Median age, years (range)

68.4 (45-84)

68 (35-83)

Male/Female

13/3

28/15

Diagnosis

No. (%)

AML

13 (81.3)

40 (93)

MDS

1 (6.3)

3 (7)

2 (12.5)

0 (0)

ECOG at baseline

No. (%)

No. (%)*

8 (50.0)

16 (37.2)

6 (37.5)

18 (41.9)

2 (12.5)

8 (18.6)

Phase I/II: Patient characteristics (cont)

* Excluding the 2 patients that did not receive CHR-2797 in phase II

Phase I

(n = 16)

Phase II

(n = 43)

Median time from diagnosis

3.1 years (0.1-8.8)

7 months (0-39)

Previous treatment*

Untreated

4 (25%)

12 (29.3%)

Cytotoxic Therapy

12 (75%)

29 (70.7%)

Median # priors

2 (range 0-8)

1 (range 1-8)

Tosedostat: Treatment duration*

* Including

extended treatment

Dose

No. of patients

Median duration of

therapy, days (range)

Phase I

60 mg

140 (119-196)

90 mg

40 (13-174)

130 mg

69 (42-222)

180 mg

21 (9-77)

Phase II

130 mg

72 (1-471)

Phase I/II: Dose Limiting Toxicities

The recommended dose of 130 mg for the phase II part was determined during

phase I and was based on the following DLT’s:

DLT

Dose

No. of patients

No. of

occurrences

ALT elevation

(Grade 3)

130 mg

Thrombocytopenia

(Grade 4)

180 mg

Most common adverse events

in phase I-II: time of occurrence

Adverse Event

(Preferred Term)

Incidence

Day 1 -

Incidence

Day 28 -

End

Patients (n=57)

Fatigue

Thrombocytopenia

Edema –

peripheral

Diarrhea

Pyrexia

Cough

Dyspnea

Epistaxis

Anemia

Phase I/II: Efficacy (response rates)

Disease

Total #

patients

AML

7**

MDS

Myeloma

Phase I/II

AML

ORR (CR+PR)

27.5%

* 4 went into remission (duration 4-9 months); 1 cytogenetic response; 1 patient (0101) had a de facto CR (low volume BM tap)

** 1 PR was short

Overall Survival For AML Patients*

NR –

non responders

*Overall survival data for 2 out of the 38 AML patients is not known

**Overall survival data for 1 patient unknown

JCO 28:4333-4338

Disease

Number of

patients

Median Overall Survival

from first treatment with

Tosedostat

to death, days (range)

Phase I

All patients

AML

135 (40-420)

•

AML

334 (73-420)

•

AML

121 (40-402)

Phase II

All patients

AML

38*

126 (8-696)

•

AML

272 (73-835)

•

AML

7**

170 (31-505)

•

AML

27**

100 (8-941)

Phase I/II Study (002): Conclusions

Well-tolerated mono-therapy

•

Oral once-a-day dosing

•

Transient reduction in platelets

Encouraging phase I/II mono-therapy data

•

27% response rate in elderly r/r AML

•

All responders >60yrs, 79% with r/r disease

•

Overall survival data encouraging

Similar results in MDS warrant separate studies with

hypo-methylating agents

Tosedostat Clinical Program

Blood Related Cancers -

AML

Randomized Controlled Trials

Proposed Pivotal Study Design

Tosedostat

Ara-C

6 months

Ara-C

6 months

Relapsed/

refractory

AML

(>60yrs)

35 patients

120 mg

6 months

35 patients

240 mg

(2 months)

120 mg

(4 months)

120 mg

240/120 mg

Complete: Q1 2011

Est. start: Q4 2011

Risk/benefit

review,

Dose

selection

Line AML (HOVON)

Phase I

Assessment of optimal

induction dosing regimen

Dose-finding

Tosedostat

dauno/ara-C

Phase II

Optimum induction

regimen and

maintenance

Optimal

Tosedostat

dauno/ara-C

regimen

Tosedostat

maintenance

Standard

dauno/ara-C

regimen

consolidation

Arm A

Arm B

•

Patients with AML, RAEB or

RAEB-t, previously untreated,

age >60 yrs, fit for standard

chemo

•

N=~270

•

Study open

AML Competitive Landscape

7 candidates in Phase III mostly cytotoxics

Elderly AML life-threatening disease with poor survival

(~3 months) low tolerability to chemotherapy

•

clofarabine iv NDA and laromustine iv NDA: Rejected

•

Mylotarg®

iv approval in relapsed AML: Withdrawn

•

decitabine iv: Failed primary O.S. endpoint in front-line AML

•

lintuzumab iv: Failed primary O.S. endpoint in front-line AML

•

sapcitibine : 1

line +/-decitabine elderly AML

•

Flt-3 kinase inhibitor

Oral, well-tolerated, chronic treatments improving

survival addresses a major unmet medical need

Tosedostat highly differentiated profile addressing

unmet medical need

Tosedostat Clinical Program

Other Blood-Related Cancers

Phase I/II

Myelodysplastic Syndrome (MDS)

Disease of elderly :

•

Lower-risk patients-

Lenalidomide;

•

Higher-risk patients -

HSCT (<10%)/ De-methylating agents

•

Age (>60yrs) –

high-intensity therapies not generally offered

Unmet medical need: low-intensity therapies

with improved efficacy and toxicity profiles

Tosedostat:

‘High risk MDS’

is attractive target

Two MDS (RAEB) patients did very well in study 002

Two AML patients were ex-MDS (AHD)

Phase I/II combination with decitabine planned

Multiple Myeloma (MM)

Strong biologic and preclinical rationale

•

Tosedostat inhibits myeloma cell proliferation and induces apoptosis

cell

lines

and

primary

patient

cells,

with

minimal

effects

bone

marrow stroma (Faith Davies)

•

Tosedostat is synergistic with other anti-myeloma therapies

(dexamethasone, bortezomib) in vitro.

HDAC inhibitors being explored in MM

•

Potential synergy between Tosedostat and HDAC inhibitors

2 Planned phase I/II studies

•

Combination trial between Tosedostat and CHR-3996 (HDAC inhibitor)

planned in MM (Royal Marsden)

•

Combination with bortezomib

Tosedostat: Conclusion

Tosedostat

is a novel aminopeptidase inhibitor with tumor

selective anti-proliferative activity

Well-tolerated oral agent (once daily)

Demonstrated synergy in combination with currently

approved targeted therapies

•

Bortezomib, decitabine, azacytidine, HDAC inhibitors

Potentially applicable across a variety of blood related

cancers and select solid tumors

Pivotal study (AML) estimated to begin in Q4-2011

Summary Deal Terms & Structure

CTI gets exclusive development and marketing rights

in the Americas; Chroma retains ROW

Cost-sharing

•

CTI bears 75% of agreed-upon direct development expenses

•

Trials aimed at US/EU regulatory approval

Joint Governance (Development/Marketing Committees)

•

CTI lead party in America’s/Chroma lead in ROW

Development budget capped at $50mm over 3 years

•

75% CTI -

25% Chroma

Initial Payments

•

$5mm upon execution

•

$5mm upon initiation of r/r AML phase III pivotal trial

Summary Deal Terms & Structure

Success-based Milestones

•

Scaled by number of potential patients in a given indication taking

into account line of approval (1

line Vs r/r)

•

Successful clinical trial results and NDA approvals

•

Blood-related cancers -

AML, MDS, or Myeloma

•

Solid Tumor indication <10,000 pts/yr >50,000 pts/yr

•

Sales Thresholds

Standard royalty rate scaled to increasing net sales

Potential Market Opportunity

Blood-related Cancers is large US market opportunity

•

AML

~12,000 pts/yr

•

MDS

~12,000 pts/yr

•

Myeloma

~26,000 pts/yr

Estimated 2010 WW annual sales for drugs

approved/used in AML/MDS or Myeloma

•

AML/MDS (clofarabine, decitabine, azacytidine)

>$ 900 million

•

Myeloma (lenalidomide/bortezomib)

>$2.4 billion

Indication

WW 2010

sales*

Patent

expiration

MDS

$200MM

2013

MDS

$534MM

2011

Ped. ALL

$103MM

2018

Multiple

Myeloma/Mantle Cell

$1.5B

2017

Multiple

Myeloma/Deletion 5q MDS

$2.5B

2019

Market Opportunity: Current agents

VELCADE

*Information from SEC filings.

Summary

Late-stage opportunity potentially addressing unmet

medical needs in large markets

•

Potential 1

oral non-cytotoxic treatment for AML

•

Synergistic activity with “blockbuster”

products (Velcade®,

Dacogen®, Vidaza®, Revlimid®) in MDS, myeloma

•

Potential rapid registration timeline-

pivotal study to start Q4-2011

Good data visibility and news flow over next

18-24 months while phase III trial completes

Development and sales synergies with pixantrone

makes deal accretive at product launch

Partnership enhanced by Chroma’s seasoned

management and expertise

EX-99.3 4 dex993.htm CELL THERAPEUTICS, INC. PRESENTATION SLIDES (FOR MEDIA) Cell Therapeutics, Inc. Presentation Slides (for Media)

Tosedostat

Exclusive Marketing License and Co-Development Agreement

Exhibit 99.3