Introduction  Soft Tissue Sarcoma (STS) are a group of highly chemotherapy resistant tumors  Doxorubicin is the only APPROVED 1 st line chemotherapy.

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Presentation transcript:

Introduction  Soft Tissue Sarcoma (STS) are a group of highly chemotherapy resistant tumors  Doxorubicin is the only APPROVED 1 st line chemotherapy for advanced STS  Aldoxorubicin can be safely administered to cancer patients at 3 ½ to 4-fold higher doses than doxorubicin. –Aldoxorubicin cumulative doses can reach 10-fold higher than doxorubicin cumulative doses without evident cardiotoxicity.  We designed a trial to demonstrate whether up to 6 doses of aldoxorubicin was more effective than up to 6 doses of doxorubicin as 1 st line chemotherapy for advanced STS. 0 CytRx Confidential. Do not copy or distribute.

Trial Design 1 Phase 1b 1.Evaluate safety & MTD in late stage cancer patients that failed prior chemotherapy 2. Determine dose for future clinical trials Phase 1b/2 Expansion 1. Selected dose is 3.5x the standard dose of doxorubicin 2. Trial expanded to evaluate preliminary efficacy Dose aldoxorubicin Dose (doxorubicin equivalents) Fold Increase over doxorubicin # of Patients (Enrollment completed) Cohort 1230mg/m 2 165mg/m 2 2.2x5 Cohort 2*350mg/m 2 260mg/m 2 3.5x 18 Cohort 3450mg/m 2 325mg/m 2 4.3x2 Doxorubicin 60-75mg/m 2 Tumor Response -Measured by CT/ MRI scans every other month - RECIST 1.1 Efficacy Endpoint *12 additional patients added. CytRx Confidential. Do not copy or distribute.

Efficacy Results 2 Best ResponseNo. of 13 Evaluable* (%) Complete Response0 (0) Partial Response5 (38) Stable Disease6 (46) Progressive Disease2 (15) PFS (median; range)11 months [ ] OS (median, range)17 months (4-35+) * 13 patients treated at 350 mg/m 2 aldoxorubicin with Soft Tissue Sarcomas CytRx Confidential. Do not copy or distribute.

Prolonged Lack of Progression Without Further Treatment  Two patients had 8 cycles of aldoxorubicin followed by no progression of disease for 23 and 15 months despite no further treatment for their STS.  Patients had received prior treatment regimens, including doxorubicin, ifosfamide, gemcitabine and docetaxel.  Tumor Types: liposarcoma; leiomyosarcoma 3

Waterfall Plot – Best Response of the 13 Evaluable STS Patients Treated at 350 mg/m 2 4 Change From Baseline in Sum of Diameter Tumor Measurement (%) CytRx Confidential. Do not copy or distribute.

Aldoxorubicin Pharmacokinetics  Elimination half-life: Long, ~20 hours  Clearance from bloodstream: Slow  Volume of Distribution: Low, primarily in blood  Free doxorubicin: less than 2% of total doxorubicin  Free doxorubicinol (major metabolite): less than 0.1% of total doxorubicin  Doxorubicin in urine: less than 2% of total doxorubicin  Doxorubicinol in urine: not found 5 CytRx Confidential. Do not copy or distribute.

Phase 2b 1st-line STS Study  A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Preliminary Efficacy and Safety of INNO-206 (Doxorubicin-EMCH) Compared to Doxorubicin in Subjects with Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma  INNO-206-P2-STS-01 6 CytRx Confidential. Do not copy or distribute.

Study Objectives  Primary Objective –To determine the preliminary efficacy of administration of aldoxorubicin compared to doxorubicin in subjects with metastatic, locally advanced, or unresectable soft tissue sarcoma as measured by progression-free survival, progression-free survival at 4 and 6 months, tumor response, and overall survival.  Secondary Objective –To evaluate the safety of aldoxorubicin compared to doxorubicin in this population as assessed by the frequency and severity of AEs, abnormal findings on physical examination, laboratory tests, vital signs, MUGA/cardiac ultrasound evaluations, ECG results, and weight. 7 CytRx Confidential. Do not copy or distribute.

8 Study Design Randomized Trial Design Arm 1 Treatment: aldoxorubicin Dose: 350 mg/m 2* Cycle: once every 3 weeks, up to 6 cycles Number of patients: 70 Arm 2 Treatment: doxorubicin Dose: 75 mg/m 2 Cycle: once every 3 weeks, up to 6 cycles Number of patients: 35 Primary Endpoint 1.Progression-free survival Secondary Endpoints 1.Tumor response 2.Overall survival 3.Safety *350 mg/m 2 of aldoxorubicin contains 260mg/m 2 of doxorubicin equivalents. This is 3.5x the standard dose of doxorubicin. Patient Population 105 patients with advanced soft tissue sarcomas that are ineligible for surgery. 31 clinical sites will be in the US, Hungary, Romania, Russia, Ukraine, India and Australia Phase 2b Principal Investigator is Dr. Sant Chawla CytRx Confidential. Do not copy or distribute.

Key Eligibility Criteria 9  Histologically or cytologically confirmed, locally advanced, unresectable, and/or metastatic soft tissue sarcoma of intermediate or high grade  Age between years (US only), and (ROW), male or female  Adjuvant or neoadjuvant chemotherapy (including doxorubicin) allowed if no tumor recurrence for at least 12 months since the last measurement, beginning or end of last chemotherapy  Prior exposure to <3 cycles or <225 mg/m 2 of either doxorubicin HCl or Doxil ® cumulative dose  ECOG performance status 0-2  Life expectancy >12 weeks CytRx Confidential. Do not copy or distribute.

Subject Disposition 10 Screened N=140 Screened N=140 2:1 Randomization N=123 Aldoxorubicin 350mg/m 2 Every 3wk up to 6 cycles N=83 Aldoxorubicin 350mg/m 2 Every 3wk up to 6 cycles N=83 Doxorubicin 75mg/m 2 Every 3wk up to 6 cycles N=40 Doxorubicin 75mg/m 2 Every 3wk up to 6 cycles N=40 3 subjects randomized but not dosed 14 screen failures CT Scans every 6 weeks CytRx Confidential. Do not copy or distribute.

Patient Characteristics 11 Characteristics AldoxorubicinDoxorubicin N8340 Age, median (range)52.5 (22-76)56.1 (26-78) Male / Female, n (%)38 (46) / 45 (54)18 (45) / 22 (55) Race, n (%) Caucasian61 (74)32 (80) Black or African American1 (1)1 (2.5) Asian16 (19)6 (15) Other5 (6)1 (2.5) ECOG, n (%) (96.4)37 (92.5) 23 (3.6)3 (7.5) Completed Cycles, median (range)6 (1-6)4 (1-6) CytRx Confidential. Do not copy or distribute.

Disease Characteristics 12 Histopathology (as determined by investigator) Aldoxorubicin N = 81 Doxorubicin N = 38 Leiomyosarcoma, n (%)24 (30)11 (29) Liposarcoma, n (%)14 (17)5 (13) Fibrosarcoma, n (%)11 (14)4 (11) Synovial sarcoma, n (%)6 (7)4 (11) Others, n (%)26 (32)14 (36) CytRx Confidential. Do not copy or distribute.

Geographic Distribution 13 Country% of Total Enrolled USA30 Hungary20 Australia12 Russia12 India11 Ukraine8 Romania7 31 sites in 7 countries CytRx Confidential. Do not copy or distribute.

Efficacy Endpoints  Primary Endpoint: Progression-Free Survival  Secondary Endpoints −Progression-free survival at 6 months −Overall Response Rate (Complete and Partial) −Overall Survival – still on-going; expect 2H14 CT Scans every six weeks  Endpoints assessed using RECIST 1.1 criteria −Locally by investigator −Independent radiography review at central lab blinded to subjects’ treatments 14 CytRx Confidential. Do not copy or distribute.

PFS Results (top line) 15 All Subjects Intent-to-treat P Value Scans Read by Investigator Aldoxorubicin8.4 months P= Doxorubicin4.7 months Improvement over dox3.7 mos. (77%) Hazard ratio0.370 ( )P= Scans Read by Central Lab Aldoxorubicin5.7 months P=0.018 Doxorubicin2.8 months Improvement over dox2.9 mos. (104%) Hazard ratio0.586 ( )P=0.034 CytRx Confidential. Do not copy or distribute.

K-M Curve – Investigator Assessment 16 CytRx Confidential. Do not copy or distribute.

K-M Curve – Central Lab Assessment 17 CytRx Confidential. Do not copy or distribute.

PFS at 6 Months Results (top line) 18 All Subjects Intent-to-Treat P Value Scans Read by Investigator Aldoxorubicin67.1% P=0.008 Doxorubicin36.1% Improvement over dox85.9% Scans Read by Central Lab Aldoxorubicin46.8% P=0.038 Doxorubicin23.7% Improvement over dox97.5% CytRx Confidential. Do not copy or distribute.

Overall Response Rate (top line) 19 AldoxorubicinDoxorubicin Scans Read by Investigator Complete Response2.7%0% Partial Response21.3%5.3% Overall Response Rate24.0%5.3% Scans Read by Central Lab Complete Response0% Partial Response23.0%0% Overall Response Rate23.0%0% CytRx Confidential. Do not copy or distribute.

Comparison to Current STS Treatments CytRx Phase 2b Investigator assessed CytRx Phase 2b Central Lab EORTC Phase 3 Dox vs. dox+ ifosfamide EORTC Dox vs. liposomal dox AldoxDoxAldoxDoxDox+ ifosDoxDoxilDox N PFS P value NS ORR24.0%5.3%23.0%0%26.5%13.6%10%9% 20 CytRx Confidential. Do not copy or distribute.

Grade 3/4 TEAEs (2013 CTOS) 21 CytRx Confidential. Do not copy or distribute.

Treatment Related SAEs (2013 CTOS) 22 CytRx Confidential. Do not copy or distribute.

Cardiac Evaluation (2013 CTOS) 23 CytRx Confidential. Do not copy or distribute.

Conclusions  Aldoxorubicin demonstrates significantly greater efficacy than doxorubicin as 1 st line chemotherapy for advanced STS.  Aldoxorubicin also induces prolonged tumor shrinkage in STS patients who have received prior doxorubicin chemotherpy.  Major side effect, neutropenia, is treatable with G-CSF.  No clinically significant cardiotoxicity has been observed in over 140 patients at up to 10x the cumulative dose of standard doxorubicin  Many adult and pediatric cancers could be amenable to aldoxorubicin chemotherapy –Long-term therapy is possible.  Aldoxorubicin represents the FIRST EXAMPLE of a pipeline of albumin-binding chemotherapies. 24 CytRx Confidential. Do not copy or distribute.