1. 12 th Annual CTOS Meeting 2006 AP23573 Induced Long-term Stability in 2 Patients with Desmoplastic Small Round Cell Tumor (#561) Scott Schuetze, Warren Chow, Jean-Yves Blay, George Demetri and Suzanne George DSRCT is an aggressive sarcoma arising in young adults and is frequently advanced at diagnosis. AP23573 is a novel non-prodrug inhibitor of mTOR. Patients with advanced/metastatic sarcoma were enrolled in a Phase II trial of AP23573 infused on days 1-5 and 15-19 every 28 days. 4 patients with metastatic DSRCT were enrolled and the clinical course on treatment with AP23573 was reviewed.

2. 12 th Annual CTOS Meeting 2006 Results of AP23573 treatment in 4 patients with DSRCT Demographics Age (range)29 – 34 Sex (M / F)3 / 1 # prior therapies (range) 1 – 5 Median 2 EWS-WTI fusion confirmed (Y / N) 3 / 1 AP23573 Therapy Maximum # of cycles received # of patients 22 81 16+1 2 of the 4 patients with DSRCT had stable disease for more than 6 months 1 of the patients remains on treatment with stable disease for more than 16 months mTor inhibitor may benefit some patients with advanced DSRCT

3. 12 th Annual CTOS Meeting 2006 Clinical characteristics and outcomes of advanced sarcoma patients who achieved clinical benefit response (CBR) while receiving AP23573 in a phase 2 trial (#675) Background & Methods AP23573 is a novel, non-prodrug mTOR inhibitor 212 patients treated with AP23573 QDx5 every other week –Fixed dose, intravenous infusion of 12.5 mg over 30 minutes –4 histological cohorts (Bone, Leiomyosarcoma, Liposarcoma, Other STS) CBR was primary endpoint –Defined as CR, PR or SD ≥4 months by RECIST –25% CBR in a cohort was considered success Objectives Describe clinical features of patients who achieved CBR, including safety and efficacy following prolonged exposure (>4 mos) Characterize the PFS of CBR patients to assess utility of this endpoint as a surrogate for PFS

4. 12 th Annual CTOS Meeting 2006 61 / 212 advanced sarcoma patients achieved CBR, most had prolonged stable disease with some partial responses observed –CBR patients were similar to overall population in extent of disease and # of prior therapies received AP23573 was well tolerated over time, without cumulative toxicity or need for continuous dose adjustments or delays CBR designation is a useful surrogate for PFS in this population Long term follow-up for survival is ongoing, further analyses planned Disease cohort Overall trial population (N=212)CBR patients (n=61) PFS rate at 6 months Median (wks)PFS rate at 6 months Median (wks) Bone sarcoma 25%1663%34 All soft-tissue sarcoma 24%1573%39 Leiomyosarcoma 22%1667%33 Liposarcoma 30%1688%40 Other STS 23%1575%48 Overall 24%1570%36 Median PFS ~20 weeks longer for the CBR subset of trial population relative to the overall population Data available in study database as of 25Aug2006

5. 12 th Annual CTOS Meeting 2006 Phase I study of trabectidin in combination with doxorubicin in patients with soft tissue sarcoma (#612) Rationale Trabectedin (ET-743, YONDELIS®), an alkaloid compound derived from the marine ascidian Ecteinascidia turbinata, is a first-in-class antitumor agent with a complex mechanism of action1,2: –Binds to the minor groove of DNA –Inhibits gene activation via a promoter-specific mechanism and transcription-dependent nucleotide excision repair Trabectedin has demonstrated consistent single-agent activity in patients with chemotherapy-naïve and -pretreated STS in several Phase II trials3-6 Doxorubicin is considered a standard of care for the treatment of STS, and synergistic effects have been observed in vitro between doxorubicin and trabectedin against STS cells Thus, the combination of trabectedin and doxorubicin may fulfill the need for a more active regimen to treat STS

6. 12 th Annual CTOS Meeting 2006 The combination of trabectedin and doxorubicin with G-CSF support is safe and well tolerated After institution of G-CSF, there were no DLTs in Cohort 1 (doxorubicin 60 mg/m2 + trabectedin 0.9 mg/m2) or Cohort 2 (doxorubicin 60 mg/m2 + trabectedin 1.1 mg/m2) MTD of trabectedin is 1.1 mg/m2 in combination with doxorubicin 60 mg/m2, both administered every 3 weeks Preliminary data suggest activity for the trabectedin/doxorubicin combination in patients with recurrent or persistent STS, with 4 patients achieving a partial response and 32 maintaining stable disease (13 patients with stable disease  6 months) Conclusions