Introduction

Soft Tissue Sarcoma (STS) are a group of highly
chemotherapy resistant tumors

Doxorubicin is the only APPROVED 1st 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 1st line chemotherapy for advanced STS.
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Trial Design
Phase 1b
Phase 1b/2 Expansion
1. Evaluate safety & MTD in
late stage cancer patients
that failed prior chemotherapy
1. Selected dose is 3.5x the
standard dose of doxorubicin
2. Trial expanded to evaluate
preliminary efficacy
2. Determine dose for
future clinical trials
Dose
aldoxorubicin
Dose (doxorubicin
equivalents)
# of Patients
2
2.2x
5
2
3.5x
18
2
4.3x
2
165mg/m
2
260mg/m
2
325mg/m
230mg/m
Cohort 2*
350mg/m
Cohort 3
450mg/m
Doxorubicin
Tumor Response
- Measured by CT/
MRI scans every
other month
- RECIST 1.1
Fold Increase
over
doxorubicin
2
Cohort 1
Efficacy Endpoint
(Enrollment
completed)
2
60-75mg/m
*12 additional patients added.
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Efficacy Results
Best Response
No. of 13 Evaluable* (%)
Complete Response
0 (0)
Partial Response
5 (38)
Stable Disease
6 (46)
Progressive Disease
2 (15)
PFS (median; range)
11 months [4.8-21.7]
OS (median, range)
17 months (4-35+)
*13 patients treated at 350 mg/m2 aldoxorubicin with Soft Tissue Sarcomas
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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
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Waterfall Plot – Best Response of the 13
Evaluable STS Patients Treated at 350 mg/m2
40
Change From Baseline in Sum of Diameter
Tumor Measurement (%)
30
20
*
10
*
0
-10
-20
*
*
-30
-40
*
*
*
-50
-60
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* Indicates prior therapy with doxorubicin, epirubicin or Doxil®
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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
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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
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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.
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Study Design
Phase 2b Principal Investigator is Dr. Sant Chawla
Randomized Trial Design
Arm 1
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
Treatment: aldoxorubicin
Dose: 350 mg/m2*
Cycle: once every 3 weeks,
up to 6 cycles
Number of patients: 70
Arm 2
Primary Endpoint
1. Progression-free survival
Secondary Endpoints
1. Tumor response
2. Overall survival
3. Safety
Treatment: doxorubicin
Dose: 75 mg/m2
Cycle: once every 3 weeks,
up to 6 cycles
Number of patients: 35
*350 mg/m2 of aldoxorubicin contains 260mg/m2 of doxorubicin equivalents.
This is 3.5x the standard dose of doxorubicin.
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Key Eligibility Criteria
 Histologically or cytologically confirmed, locally advanced, unresectable,
and/or metastatic soft tissue sarcoma of intermediate or high grade
 Age between 15-80 years (US only), and 18-80 (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/m2 of either doxorubicin HCl or
Doxil® cumulative dose
 ECOG performance status 0-2
 Life expectancy >12 weeks
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Subject Disposition
Screened
N=140
14 screen failures
2:1 Randomization
N=123
Aldoxorubicin
350mg/m2
Every 3wk up to 6 cycles
N=83
3 subjects
randomized but not
dosed
Doxorubicin
75mg/m2
Every 3wk up to 6 cycles
N=40
CT Scans every 6 weeks
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Patient Characteristics
Characteristics
Aldoxorubicin
Doxorubicin
83
40
Age, median (range)
52.5 (22-76)
56.1 (26-78)
Male / Female, n (%)
38 (46) / 45 (54)
18 (45) / 22 (55)
61 (74)
32 (80)
1 (1)
1 (2.5)
Asian
16 (19)
6 (15)
Other
5 (6)
1 (2.5)
80 (96.4)
37 (92.5)
3 (3.6)
3 (7.5)
6 (1-6)
4 (1-6)
N
Race, n (%)
Caucasian
Black or African American
ECOG, n (%)
0-1
2
Completed Cycles, median (range)
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Disease Characteristics
Histopathology
Aldoxorubicin
N = 81
Doxorubicin
N = 38
Leiomyosarcoma, n (%)
24 (30)
11 (29)
Liposarcoma, n (%)
14 (17)
5 (13)
Fibrosarcoma, n (%)
11 (14)
4 (11)
6 (7)
4 (11)
26 (32)
14 (36)
(as determined by investigator)
Synovial sarcoma, n (%)
Others, n (%)
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Geographic Distribution
31 sites in 7 countries
Country
% of Total Enrolled
USA
30
Hungary
20
Australia
12
Russia
12
India
11
Ukraine
8
Romania
7
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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
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PFS Results (top line)
All Subjects
Intent-to-treat
P Value
Scans Read by Investigator
Aldoxorubicin
8.4 months
Doxorubicin
4.7 months
Improvement over dox
Hazard ratio
P=0.0002
3.7 mos. (77%)
0.370 (0.212-0.643)
P=0.0004
Scans Read by Central Lab
Aldoxorubicin
5.7 months
Doxorubicin
2.8 months
Improvement over dox
Hazard ratio
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P=0.018
2.9 mos. (104%)
0.586 (0.358-0.960)
P=0.034
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K-M Curve – Investigator Assessment
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K-M Curve – Central Lab Assessment
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PFS at 6 Months Results (top line)
All Subjects
Intent-to-Treat
P Value
Scans Read by Investigator
Aldoxorubicin
67.1%
Doxorubicin
36.1%
Improvement over dox
P=0.008
85.9%
Scans Read by Central Lab
Aldoxorubicin
46.8%
Doxorubicin
23.7%
Improvement over dox
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P=0.038
97.5%
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Overall Response Rate (top line)
Aldoxorubicin
Doxorubicin
2.7%
0%
Partial Response
21.3%
5.3%
Overall Response Rate
24.0%
5.3%
0%
0%
Partial Response
23.0%
0%
Overall Response Rate
23.0%
0%
Scans Read by Investigator
Complete Response
Scans Read by Central Lab
Complete Response
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Comparison to Current STS Treatments
CytRx
Phase 2b
Investigator
assessed
CytRx
Phase 2b
Central Lab
Aldox
Dox
Aldox
Dox
Dox+ ifos
Dox
Doxil
Dox
N
83
40
83
40
215
217
50
44
PFS
8.4
4.7
5.7
2.8
7.4
4.6
2.8
2.8
P value
ORR
0.0002
24.0%
5.3%
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0.018
23.0%
EORTC
Phase 3
Dox vs. dox+
ifosfamide
EORTC
Dox vs.
liposomal
dox
0.003
0%
26.5%
13.6%
NS
10%
9%
20
Grade 3/4 TEAEs (2013 CTOS)
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Treatment Related SAEs (2013 CTOS)
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Cardiac Evaluation (2013 CTOS)
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Conclusions

Aldoxorubicin demonstrates significantly greater efficacy
than doxorubicin as 1st 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.
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