James A. Bianco, M.D. President and CEO C E L L T H E R A P E U T I C S, I N C. (N A S D A Q : C T I C)

Transcription

1 James A. Bianco, M.D. President and CEO C E L L T H E R A P E U T I C S, I N C. (N A S D A Q : C T I C)

2 Forward Looking Statement This presentation contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 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. The forward-looking statements contained in this presentation include statements about future financial and operating results, and risks and uncertainties that could affect CTI s product and products under development. 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 XYOTAX to prove safe and effective for treatment of non-small cell lung and ovarian cancers, the potential failure of pixantrone to prove safe and effective for treatment of non-hodgkin s lymphoma, 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 SEC, 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. CTI is under no obligation to (and expressly disclaims any such obligation to) update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.

3 CTI Company Highlights Singular focus: build a profitable cancer company $405 million WW commercial & development partnership with Novartis for XYOTAX,, pixantrone Successful product development track record - TRISENOX FDA/EMEA approved, sold to Cephalon - XYOTAX- Phase III interim results Q2/3-07, - Pixantrone- Phase III interim results Q1/ CT advancing to phase II/III Novel advanced preclinical pipeline - Bisplatinum agents (pre-ind), anti-tubulin tubulin agents Significant clinical, regulatory, & financial milestones next months

4 Novartis CTI Collaboration Worldwide license to XYOTAX - $15M in common stock - $270M in potential registration and sales milestones $50M for NSCL registration (US/EU) Option to pixantrone - $7.5M option fee* - $104M in potential registration and sales milestones* - Definitive agreement TBN Significant royalties on WW sales Once Novartis commences XYOTAX development - Reimburses for 50% of expenses* - Assumes 80% all WW costs for label expansion studies - Controls commercialization of product & 100% commercial expenses - CTI to field 35 sales/ma people in US at Novartis expense up to $9M *from date of execution of license agreement

5 Phase III Cancer Products Licensing Deals Licensee Licensor Region Up Front Equity Development Milestones Sales Milestones Royalty Total millions CTI NVRT WW - $15.0 $150.0 $120.0 Y $294.0* Genmab Serono WW $20.0 $ $170.0 Y $240.0 Exelixis Helsin WW $4.0 - $ Y $25.0 CancerVax Serono WW $25.0 $12.0 $103.0 $150.0 Y $290.0 Medarex BMY WW $25.0 $25.0 $ Y $255.0 Supergen MGI WW $15.0 $40.0 $ % $100.0 Sonus Schering WW $20.0 $15.0 $132.0 $ % $202.0 Pierre Fabre BMY WW $ $ $210.0 *includes $9M commercial expense, does not include $111.5M for pixantrone option

6 CTI Oncology Strategy Improve tolerability and/or efficacy of the most frequently used cornerstone chemotherapy drugs Cl H 3 N + 2+ NH H 2 N + NH Pt 3 R 3 NH H 3 N Pt 2 Cl Taxanes Anthracyclines Camptothecins Platinum Agents XYOTAX Pixantrone CT-2106 Bis-platinum

7 XYOTAX minute infusion Paclitaxel 3 to 24 hour infusion

8 XYOTAX Paclitaxel poliglumex A subunit of the macromolecular complex Paclitaxel Macromolecular poly L glutamate complex of XYOTAX backbone TM Singer et al. In: Adv Exp Med Biol. 2003; 519:81-99

9 XYOTAX Intracellular Uptake, Metabolism and Release of Chemotherapy Estrogen enhanced

10 for lung cancer

11 XYOTAX Phase III studies for first-line NSCLC PS2 TRIAL STELLAR 3 1 st Line NSC Lung PS2 Design Superiority Open-label Randomized Comparator dose (mg/m 2 ) Paclitaxel carbo AUC 6 Q3 weeks XYOTAX dose (mg/m 2 ) carbo AUC 6 Q3 wks Primary Endpoint Survival # of pts 400 STELLAR 4 1 st Line NSC Lung PS 2 Superiority Open-label Randomized Gemcitabine 1000 d1, 8, 15 or Navelbine 20 d1, 8, Q3 wks Survival 476

12 Survival Estimates by Gender STELLAR 3 and 4 XYOTAX Women Comparator Women XYOTAX Men Comparator Men N=97 N=101 N=293 N=290 Median Survival 285 days 233 days 220 days 207 days 1 year survival 40% 25% 30% 33% p=0.013

13 XYOTAX Potential for estrogen enhanced effectiveness Role of estrogen in lung cancer - Normal lung cells and NSCLC cells express estrogen receptors (ERβ) - Pre-menopausal status associated with worse survival Role of estrogen in XYOTAX metabolism - Significant increase in how much XYOTAX goes to lung tissue compared to standard paclitaxel - Increased metabolism of XYOTAX and release of free paclitaxel Potentially broadly applicable to ERβ+ + cancers - Lung, colorectal, prostate, breast, uterus, ovary

14 XYOTAX Strong evidence for estrogen enhanced effectiveness STELLAR 3+4 composite analysis (n=198 women) - Significant improvement in overall survival (log rank p=0.03) 40% survival vs. 25% at 1 year (p=0.01) Highly significant correlation with age and estrogen status - Age <55 or normal estrogen levels (n=113 women) - Median survival 309 days XYOTAX vs. 181 days controls (HR 0.56, log rank p=0.008) - 43% survival XYOTAX vs. 19% control at 1 year (p=0.003) Benefit prospectively confirmed in phase II trial - 35 women (no control comparator arm) - Median survival normal estrogen: 216 days vs. low estrogen: 126 days - Survival (last contact) women with normal estrogen: 75% alive vs.. 41% of women with low estrogen

15 XYOTAX Clinical benefit in men and women* Reduction in severe side effects - Anemia (p=0.008) - Neutropenia (p=0.009) - Infection (p=0.003) 1 - Pneumonia (p=0.017) 1 Minimal to no hair loss Short minute infusion without need for pre-meds Significant cost savings (less EPO, G-CSF, G antibiotics) *STELLAR 4 (XYOTAX vs. gem/vin) 1 XYOTAX vs. vinorelbine

16 PIONEER (PGT305) Gender specific trial of XYOTAX vs. paclitaxel PGT305 multi-national, randomized trial - 80 sites North America/80 sites ex-na Entry criteria: (identical to STELLAR 4) Treatment arms: - XYOTAX 175mg/m 2 ; no routine pre-meds - paclitaxel 175mg/m 2 ; 3 hrs, routine pre-meds Sample size: 600 patients Primary endpoint: - Overall survival and overall survival by estrogen level Statistical Plan - Planned interim analysis Q2/3 07

17 XYOTAX Marketing Approval Strategy United States: : FDA agreement on interim analysis of PIONEER with STELLAR results providing supportive - Q2/ interim and potential NDA filing - Fast track status could provide priority (6 month) review - Potential approval late 2007, early 2008 European Union: EMEA agreement on switching from superiority to non-inferiority in STELLAR 4 trial - No new trials required, clinical benefit argument from STELLAR trialst - Q2/ MAA filing, - Supplement MAA with superiority (PIONEER) data when available unless PIONEER data positive and available for simultaneous filing on superiority

18 XYOTAX Front Line Maintenance Therapy in Ovarian Cancer Background for study: Maintenance paclitaxel (n=200pts) - Significant increase in PFS (21 vs. 28 months ) p< Study closed: underpowered for overall survival - Maintenance paclitaxel required dose reductions due to toxicity Phase III Trial FDA approved Special Protocol Assessment Conducted by prestigious Gyn Oncology Group (GOG) Maintenance XYOTAX at 135mg/m 2 vs. no maintenance - Endpoints: superior PFS (accelerated review); OS (full approval) - Paclitaxel comparator arm for side effect comparison and QOL benefits efits Interim data target: late 2008

19 XYOTAX In combination with radiation therapy Phase I in esophageal and gastric cancer patients Regimen: weekly XYOTAX plus 50.4 Gy radiation Endpoints: Safety, MTD, Response Rate Sample size: 21 patients treated, 12 patients with loco- regional disease evaluated Results: - 4/12 (33%) CR and 7/12 (58%) PR - 91% OOR - No severe (grade 3-4) 3 mucositis, esophagitis at MTD - MTD: 70 mg/m2/week for six weeks Potent radiation-sensitizing activity demonstrated (American Journal of Clinical Oncology, August, 2006)

20 Pixantrone

21 Anthracyclines Established cornerstone potentially curative therapy - Breast cancer / acute leukemia / lymphoma However all anthracyclines cause cumulative, irreversible damage to heart muscle Patients limited to life time maximum dose 550mg/m 2 Prevents use as repeat therapy* Prevents use in combination with targeted therapies # Dose m/mg % Herceptin 7% % Herceptin + paclitaxel 11% % Herceptin + anthracycline 28% 0% 5% 10% 15% 20% 25% 30% Incidence of Congestive Heart Failure 0% 5% 10% 15% 20% 25% 30% Incidence of Congestive Heart Failure * Swain et al. # Herceptin package insert

22 Pixantrone Improved efficacy and safety Alter chemical groups responsible for free-radical radical production and cardiac toxicity O O O HO N H 2 OH OH O O H O OH OH OH OH O O HN H N H N N H 2 HCl OH OH N O O HN HN NH 2 2 NH 2 COOH COOH Doxorubicin Mitoxantrone Pixantrone Target market - Replace current marketed agents as potentially safer, more effective treatment in NHL, leukemia, and breast cancer

23 Pixantrone Summary of phase I/II clinical experience High CR rates in relapsed aggressive NHL - CR rate 40-50% in combination regimens in > 2 nd line - CR rate 15-20% with single agent in 4 th line Well tolerated - Low incidence of nausea/vomiting - Low incidence of hair loss - No requirement for surgical placement of central catheter - Low incidence of cardiac events (<2%) Robust pivotal development program

24 Randomized Trial Rituxan +/- pixantrone in relapsed/refractory indolent NHL Initially designed as phase III trial (800 patients) - Indolent NHL (up to 5 prior Rx failures) - Randomized to Rituxan +/- pixantrone - Endpoints: (1 o ) TTP; (2 o ) CR rate, safety Study closed due to difficulty with enrollment - 32/800 patients randomized in 24 months Results confirm significant benefit of pixantrone on TTP and Complete Response (CR) rates

25 Pixantrone + Rituxan Significantly Prolongs Time to Disease Progression Primary endpoint of PIX302 Trial % Patients With Disease Progression 100% 75% 50% 25% P< % 1 Year 2 Years Pixantrone + Rituxan Rituxan

26 Pixantrone + Rituxan Significantly Increases Overall Response Rate Secondary endpoint of PIX302 trial 75% % Response 50% 25% P=0.02 0% Overall Response Rate Complete Response Partial Response Pixantrone + Rituxan Rituxan

27 Phase III Trial in Third-Line Relapsed Aggressive NHL Study Population - Aggressive NHL 2 prior regimens (transplants allowed) Study Design (up to 320 patients) - Randomized Phase III (Special Protocol Assessment) Treatment - Pixantrone vs. single agent of physician s s choice Primary endpoint - Complete Response (CR) or unconfirmed (ucr( ucr) Drug granted fast track by FDA

28 Phase III Trial in Third-Line Relapsed Aggressive NHL July Interim analysis - First efficacy/safety look conducted (40 patients) - CR/uCR blended rate higher than forecasted - Time to progression data encouraging - No safety concerns - Recommended un-blinded interim after patients completed therapy and follow up TTP data available Q1/ Interim analysis - CR/uCR and TTP differences by treatment arm - If significant, FDA meeting to discuss NDA filing

29 CT-2106 Polyglutamate Camptothecin

30 CT-2106 Camptothecins (Camptosar Hycamtin ) - Second most widely prescribed class of cancer drugs - Highly active class of drugs but limited by toxicity CT-2106 links 20S-camptothecin to polyglutamate CT-2106 is currently in phase II trials - In combination with 5FU/LV for second-line colorectal cancer - As a single agent for advanced metastatic ovarian cancer Phase II data to date - Anti-tumor tumor activity in FOLFOX failures in combination with 5FU/LV - Elimination of major toxicity of 5FU/LV +CPT-11 (Salz( regimen) No grade 3/4 GI toxicity (expected incidence with Salz~60%) Anti-tumor tumor activity observed in relapsed NSC lung, pancreatic, - Anti colorectal and ovarian Phase II/III studies being evaluated

31 Streamlined Operations 2005* 2006* FTEs Compensation Operating Exp 1 Corporate Exp 1 Direct Expense TOTAL ~400 $42M $13M $14M $48M $117M FTEs Compensation Operating Exp 1 Corporate Exp 1 Direct Expense TOTAL ~175 $21M $ 9M $ 6M $39M $75M Cash 6/30/06: $48.1M Registered direct 9/18/06: $40.0M* Novartis investment: $15.0M* Plan as of beginning of the year 1 Does not include interest charges, occupancy costs, and other non-cash charges *Gross proceeds prior to green shoe exercise, Stock purchase to close following HSR clearance

32 Capital Structure Market capitalization: approx. $231M Shares outstanding 9/25/06: 133.9mm* Principal Conversion Shares Coupon Maturity $53.3M $2.09/share 25.3mm 7.50% 2011 $ 7.7M $2.63/share 2.9mm 6.75% 2010 $55.1M $13.50/share 4.1mm 4.00% 2010 $27.4M $10.00/share 2.7mm 5.75% 2008 $28.5M $34.00/share 0.8mm 5.75% 2008 * Does not include 8.67M shares reserved for Novartis investment

33 Target milestones Next months Establish global partner for XYOTAX Completed 9 months ahead of target Pixantrone interim analysis: Q Encouraging CR/UCR rates and TTP supports second analysis at patients Report pixantrone and XYOTAX phase II data at clinical meetings - EORTC-AACR AACR-NCI, Chemotherapy Foundation Symposium, SGO, ASCO Report interim results on pixantrone: Q1/ Report interim PIONEER results: Q2/ File XYOTAX NDA & MAA: Q2/ File potential NDA for pixantrone: Q1-2008

34 CTI Company Highlights Singular focus: build a profitable cancer company Worldwide $405mm commercial and development partnership with Novartis for XYOTAX, pixantrone Successful product development track record - Trisenox FDA/EMEA approved, sold to Cephalon - XYOTAX- Interim PIONEER phase III results Q2/ Pixantrone- 2 nd interim analysis EXTEND phase III results Q1/ CT advancing to phase II/III - First in class bisplatinum agents advancing to IND Significant clinical, regulatory & financial milestones next months