Filed by Cell Therapeutics, Inc. Pursuant to Rule 425 under the Securities Act of 1933 And deemed filed pursuant Rule 14a-12 Of the Securities Exchange Act of 1934 Subject Company: Cell Therapeutics, Inc. Commission File No.: 001-12465 |
CTI-Novuspharma Merger
June 17, 2003
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CAUTIONARY STATEMENT REGARDING FORWARD LOOKING STATEMENTS
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WHERE YOU CAN FIND ADDITIONAL INFORMATION:
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Strategic Rationale
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Greater revenue growth potential | |||||
TRISENOX® gaining hematology market share | MARKETED | ||||
XYOTAX™ in pivotal trials for lung cancer | LAUNCH 2005 | ||||
Pixantrone in pivotal trials for NHL | LAUNCH 2006 | ||||
Targeting profitability in 2005 | |||||
Strong combined balance sheet | |||||
$230 million proforma end Q1, 2003 | |||||
Significant cost savings | |||||
$18-$20 million annual operating synergies | |||||
Strengthened oncology drug development expertise | |||||
Global access to patients, physicians and capital markets | |||||
Overview of CTI
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TRISENOX®: approved in US and EU for APL | ||||
100%CAGR expected through 2004 | ||||
Potential to capture significant share of hematologic malignancy market (MDS, MM) | ||||
$150 million US sales potential | ||||
XYOTAX™: safer, potentially more effective paclitaxel in pivotal trials for non-small cell lung and ovarian cancers | ||||
CT-2106 (PG-CPT): safer, potentially more effective camptothecin in phase I | ||||
Balance sheet: ~$111 million cash as of 3/31/03 | ||||
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Research coverage | ||||
CIBC World Markets, Lehman Bros., Piper Jaffray, Wells Fargo, Punk Ziegel, Delafield Hambrecht | ||||
Overview of
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Pixantrone potential “best in class” safer, more effective anthracycline in pivotal trials for NHL | ||||
Strong balance sheet: ~$120 million cash as of 3/31/03 | ||||
Former oncology drug development arm of Boehringer Mannheim, part of Hoffman La Roche | ||||
Expertise in pre-development, pharmacology, CMC, Phase I-II | ||||
Research coverage: Lehman Bros., SG Cowen, Banca IMI, Caboto | ||||
Timing
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Unanimous approval of both Boards | ||||
Subject to Novuspharma and CTI shareholder approval | ||||
Subject to approval of CTI’s application to list its shares on the Nuovo Mercato | ||||
Merger expected to close Q4 | ||||
Integration plan & team established | ||||
$18-20 million full year of cost savings expected in 2004 | ||||
Year end combined cash position forecasted at $160M | ||||
Specifics of Agreement
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CTI to issue 16 million shares of CTIC to Novuspharma shareholders | ||||
Fixed exchange ratio 2.45 | ||||
Transaction value ~$235 million | ||||
Dual listing on NASDAQ and Nuovo Mercato | ||||
Novuspharma to have two seats on board with a third independent director to be nominated prior to closing | ||||
Silvano Spinelli, CEO of Novuspharma to join CTI’s management team in following roles | ||||
EVP, Development at CTI | ||||
Managing Director, CTI’s European subsidiary in Bresso | ||||
Company Profiles
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CTI | Novuspharma | |||||||
Therapeutic focus | Cancer | Cancer | ||||||
Key Products | ||||||||
Marketed | TRISENOX® | -- | ||||||
Phase III | XYOTAX™ | Pixantrone | ||||||
Phase I/II | CT-2106 (polyglutamate camptothecin) | MT-201, BBR3576 | ||||||
Core competencies | Sales & Marketing, Phase II/III, Target discovery & validation | Preclinical (in vivo, PK/PD), CMC (analytical), Phase I-II | ||||||
Head count | 288 | 85 | ||||||
Facilities | 170,000 sq ft (Seattle) | 75,000 sq ft (Milan) | ||||||
Balance sheet 3/31/03 | $111 million | $120 million* | ||||||
*Converted to US dollars; exchange rate 1.18 | ||||||||
Merged Company
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Therapeutic focus | Cancer | |||||
Key Products | ||||||
Marketed | TRISENOX® | |||||
Phase III | XYOTAX™, Pixantrone | |||||
Phase I/II | CT-2106, MT-201, BBR3576 | |||||
Core competencies | Fully integrated capabilities from target discovery through commercialization | |||||
Head count | ~320 | |||||
Facilities | 250,000 sq ft (Seattle-Milan) | |||||
Balance sheet (3/31/03) | ~$230 million* | |||||
*Converted to US dollars; exchange rate 1.18 | ||||||
Operating Synergies
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Center of excellence – Milan | ||||
Medicinal chemistry, lead optimization | ||||
Preclinical models, toxicology-ADME, analytical development, pharmacology | ||||
Clinical trials material production | ||||
PK/PD testing in Phase I | ||||
EU pharmacovigilance, QA/QC | ||||
European clinical development | ||||
Operating Synergies
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Corporate Headquarters – Seattle | |||||
Target discovery/validation | |||||
Clinical Development | |||||
Phase I-III | |||||
Drug Regulatory Affairs | |||||
Drug Safety & Surveillance | |||||
Sales & Marketing | |||||
Portfolio Synergies
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Key Products | Hematology | Solid Tumors | ||||||
TRISENOX® | Leukemia, CML MDS, | |||||||
Pixantrone | Aggressive NHL | Breast cancer | ||||||
XYOTAX™ |
| NSC Lung cancer | ||||||
CT-2106 |
| Colorectal cancer | ||||||
Pixantrone
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Long lasting complete/partial responses in heavily treated NHL patients as single agent | ||||
Synergistic with combination therapy (Rituxan®) | ||||
Cardiac toxicity profile superior to existing agents | ||||
Convenience of eliminating central line | ||||
Reduces need for expensive anti-emetics | ||||
Initial market entry into area of high unmet need | ||||
Pixantrone
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Extensive experience in >170 patients | |||||
7 phase I, II trials | |||||
Highly active in combination regimens for relapsed/refractory NHL replacing doxorubicin | |||||
CHOP n=17 | |||||
13 patients evaluable; 6CRs/1PR | |||||
ESHAP n=21 | |||||
19 pts evaluable; 7CRs/4PRs | |||||
Highly active in relapsed/refractory indolent NHL | |||||
FND-R n=9 | |||||
6 patients evaluable; 5CRs/1PR | |||||
Pixantrone
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Patient | NHL | Status | Prior Rx | Resistant | Respnse | Duration | ||||||||||
M-80 | DLC | 1st Rel | Dx380 | Yes | uPR(650) | NA | ||||||||||
F-79 | DLC | 2nd Rel | Dx400 | Yes | CR(1530) | 17 | ||||||||||
F-65 | DLC | 2nd Rel | Dx400 | Yes | CR(1530) | 4 | ||||||||||
M-65 | DLC | 3rd Rel | Dx250 | No | uPR(1190) | NA | ||||||||||
M-72 | DLC | 3rd Rel | Dx400 | No | PR(1530) | 6.5 | ||||||||||
M-66 | tFoll | 5th Rel | Dx240/ | No | PR(1360) | 17+ | ||||||||||
F-65 | Mant | 2nd Rel | Dx300 | Yes | CR(1060) | 12.5 | ||||||||||
M-65 | DLC | 2nd Rel | Dx300 | No | uPR(1020) | NA | ||||||||||
Pixantrone
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Patient | NHL | Status | Prior Rx | Resistant | Response | Duration | ||||||||||
F-72 | DLC | 4th Rel | Dx300 | Yes | PR(1020) | 5 | ||||||||||
F-41 | Mcy | 3rd Rel | Dx300 | No | CR(1241) | 7 | ||||||||||
F-60 | DLC | 3rd Rel | Dx400 | Yes | PR(1020) | NA | ||||||||||
M-78 | Mant | 2nd Rel | None | Yes | uPR(1020) | NA | ||||||||||
F-55 | DLC | 1st Rel | Dx300 | No | CR(1326) | 12 | ||||||||||
M-66 | DLC | 2nd Rel | Dx | Yes | uPR(425) | 1 | ||||||||||
Pixantrone
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High response rates in relapsed/resistant aggressive NHL | ||||
ORR= >30% (7CRs/5PRs + 5uPR’s) | ||||
Durable responses: TTP >8 months for responders | ||||
Well tolerated | ||||
Grade 4 neutropenia 13/33 (40%) | ||||
Grade 4 anemia/thrombocytopenia 0-1/33 (<3%) | ||||
28/33 (85%) had maximum prior anthracycline exposure | ||||
14/33 (42%) received >1,000-1500mg/m2 Pixantrone | ||||
Encouraging low incidence of cardiac events despite prior anthracycline exposure | ||||
Pixantrone
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New strategy for registration in U.S. | ||||
Pivotal trial in 3rd line aggressive NHL | ||||
Compelling phase II clinical data | ||||
High unmet need—qualifies for fast track | ||||
No approved agents—non-randomized single open label trial ~120 pts | ||||
Enrollment completion late 2004 | ||||
NDA target Q4 2005 | ||||
Potential launch 2006 | ||||
Phase III in relapsed indolent NHL ± rituximab to provide market penetration support | ||||
Pixantrone
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Anthracyclines | |||||
Standard of care | |||||
Front line and relapsed aggressive NHL (CHOP) | |||||
Front line for acute myeloid leukemias | |||||
Front line breast cancer, relapsed HR prostate cancer | |||||
$500+ million in annual sales | |||||
Market leaders | |||||
Doxorubicin (US) | |||||
Epirubicin (EU) | |||||
Major limitation—life time cardiac toxicity threshold | |||||
Pixantrone
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If approved in 3rd line aggressive NHL | ||||
100% would use it in 2nd & 3rd line | ||||
50% would replace doxorubicin in 1st line for aggressive especially high cardiac risk patients | ||||
>50% would use it in 2nd and 3rd line indolent | ||||
Zevalin™ and Bexxar® would be used after Pixantrone due to difficulty with nuclear medicine scheduling issues | ||||
With supportive data in clinical trials could move into breast and prostate cancers | ||||
Base case forecast $150 million peak U.S. sales | ||||
TRISENOX®
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Product approved U.S. and EU | ||||
100% CAGR forecasted through 2003 | ||||
$150+ million peak U.S. sales potential | ||||
Compelling efficacy in hematologic cancers (APL, MM, MDS) | ||||
Gaining US market share | ||||
EU penetration limited to initial label (APL) | ||||
Potential for MDS filing in 2004 allows for re-evaluation of EU commercial potential and strategy | ||||
TRISENOX®
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Myelodysplasia (120 patients) | ||||
Decreases or eliminates RBC and platelet transfusion independence | ||||
80% of responding patients became transfusion independent lasting up to 2 yrs | ||||
32% objective responses including high risk patients | ||||
Well tolerated, no dose reductions required | ||||
Projected sNDA and sMAA filing in both EU and US in 2004 | ||||
Multiple myeloma (86 patients) | ||||
High response rates in combination with vitamin C | ||||
40% objective responses | ||||
100% improvement in kidney function | ||||
Well tolerated, manageable side effects | ||||
Reported at conferences in May, 2003 | ||||
TRISENOX®
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XYOTAX™
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Novel, patented polyglutamate polymer technology links paclitaxel to a “digestible” polymer | ||||
Polymer bound paclitaxel accumulates preferentially in tumor blood vessels | ||||
Allows the chemotherapy to enter cancer cells through a different mechanism than standard paclitaxel | ||||
Selectively releases chemotherapy in tumor | ||||
A new chemical entity; not a reformulation | ||||
Patent protection through 2017 | ||||
XYOTAX™
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Premedications | |||||
Special Infusion kits | |||||
Infusion time | |||||
Hair Loss | |||||
Lung Toxicity | |||||
Neuropathy | |||||
Tolerability | |||||
Efficacy | Superior | — | — | ||
XYOTAX™
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Designated fast track by FDA | ||||
“PS2 NSC lung cancer is incurable and current treatments offer modest benefit” | ||||
“XYOTAX has the potential to demonstrate improvement over available therapy in these patients based on anti-tumor activity reported in phase I and phase II clinical trials” | ||||
FDA approved Phase III program in NSC lung cancer to demonstrate superior survival | ||||
Front line therapy in PS2 | ||||
Second line treatment | ||||
Gynecologic Oncology Group to run phase III in ovarian cancer | ||||
Front line therapy | ||||
Phase II XYOTAX™
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PS2 accounts for 25% of 170,000 patients with NSC lung cancer (most are elderly) | ||||
Current treatments are poorly tolerated (median 2 doses) | ||||
Disease progresses rapidly | ||||
Median 6 weeks | ||||
Median survival poor (2.4 – 3.9 months)* | ||||
High unmet need—potential accelerated regulatory review | ||||
Phase II XYOTAX™ clinical data supports phase III investigation | ||||
Principle investigators on Phase III program are key opinion leaders of major cooperative groups (CALGB, ECOG, SWOG) | ||||
*Single agent v. combination therapy respectively | ||||
Phase II XYOTAX™
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Efficacy (PS2) | Response Rate | Median # of Doses | Progression (months) | Survival (months) | ||||||||
XYOTAX™ | ~10% | 4 | 2.6 | ³5.4 | ||||||||
Toxicities (Grade 3 / 4) | ||||||||||||
Highest (Grade 4) | 10% | |||||||||||
Neutropenia | 4% | |||||||||||
Neuropathy/Fatigue | 7% | |||||||||||
Paclitaxel | ~10% | 2 | 1.5 | 2.4 | ||||||||
Toxicities (Grade 3 / 4)*** | ||||||||||||
Highest (Grade 4) | 53% | |||||||||||
Neutropenia | 63% | |||||||||||
Neuropathy/Fatigue | >10% | |||||||||||
*ASCO 2003 poster ** ASCO 2002 presentation, R.C. Lilenbaum *** Paclitaxel/carboplatin regimen, NEJM Vol 346, No. 2, June 10, 2002 | ||||||||||||
STELLAR 2-3-4 trials
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STELLAR 2 | STELLAR 4 | ||||||||
Second line therapy | Front line PS2 XYOTAX™ v. | ||||||||
XYOTAX™ v. docetaxel | gemcitabine or vinorelbine | ||||||||
840 patients | 370 patients | ||||||||
Target enrollment- end Q2-2004 | Target enrollment- end Q1-2004 | ||||||||
STELLAR 3 | |||||||||
Front line PS2 XYOTAX™/platinum v. paclitaxel/platinum | ENDPOINTS on all trials– Superior Survival | ||||||||
370 patients | |||||||||
Target enrollment- end Q4-2003 | |||||||||
XYOTAX™ for Ovarian Cancer
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XYOTAX™ (175mg/m2) (n=91, Salvage^) | ||||
CR/PR | ||||
SD | ||||
XYOTAX™* + cisplatin (75mg/m2) (n=12) | *175,210,225,250 mg/m2 ^ patients with 2 prior regimens Results reported at 2002 EORTC Meeting | |||
Platinum Sensitive/ Resistant | ||||
PR | ||||
SD | ||||
Phase II XYOTAX™
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XYOTAX™*** | Taxol®* | Doxil®** | Topotecan** | |||
Efficacy | 28% | 15% | 28% | 28% | ||
Response rate | ||||||
Side Effects | ||||||
Neutropenia | 2% | 65% | 12% | 77% | ||
Neuropathy | 10% | 21% | N/A | N/A | ||
Skin toxicity | 0% | 0% | 23% | 0% | ||
Hair loss | 0% | 87% | 16% | 49% | ||
Dose reduction | 1% | N/A | 57% | 78% | ||
* Taxol® package insert, 2nd line data ovarian cancer, 3hr infusion ** J Clin Oncology 2001, Randomized trial Doxil® v. Topotecan in 2nd line ovarian cancer *** Third-line treatment |
XYOTAX Phase III Ovarian Cancer
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Front Line Ovarian Cancer | ||||
XYOTAX™/platinum v. paclitaxel/platinum | ||||
Conducted by 200+ GOG centers in US | ||||
1200 patients (12 months enrollment) | ||||
Start late 2004 | ||||
Endpoint: non inferior PFS, Superior side effect profile | ||||
Why Novuspharma?
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Economically superior | ||||
$120M in cash | ||||
$18M-$20M in cost savings | ||||
Contributes additional phase III $150M+ product | ||||
Critical mass in “global” oncology drug development | ||||
Increases commercial capabilities in EU for expanded TRISENOX® label and sales potential | ||||
FDA’s XYOTAX™ fast track designation significant validating value driver | ||||
Retention of WW (excluding Asia) rights critical among the potential multi-national pharma companies | ||||
Allows the Company to re-evaluate prior interest in focusing solely on ex-US partner for XYOTAX™ and turn attention to more global strategic relationship | ||||
Portfolio Synergies
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TRISENOX® | |||||
EU sales driven by product label indications | |||||
Potential MDS label expansion makes ex-US commercial prospect attractive | |||||
Expanded label has attracted interest among several pharma companies for co-promotional relationship | |||||
Investment in EU commercial presence would maximize WW revenue potential | |||||
XYOTAX™ | |||||
Stronger EU presence to allow more efficient pivotal trial management | |||||
35-40% of phase III enrollment in the EU | |||||
Transaction allows CTI to retain WW rights and explore growing interest for potential “global” partnership | |||||
Portfolio Synergies
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Pixantrone | ||||
Strong US hematology presence will facilitate clinical and regulatory development | ||||
Same customer base as TRISENOX® provides sales and marketing efficiencies | ||||
CT-2106 | ||||
Enhances access to clinical sites in EU to expedite phase II trials | ||||
Provides cost synergies for required preclinical, manufacturing activites | ||||
Preclinical targets | ||||
HIF-1a and LPAAT promising novel targets | ||||
Remaining product programs with greatest commercial potential will be reviewed and prioritized | ||||