cytrx (cytr) corporate presentation - jefferies · large market potential targeting most common...
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CytRx Safe Harbor Statement
THIS PRESENTATION CONTAINS FORWARD-LOOKING STATEMENTS THAT INVOLVE CERTAIN RISKS AND UNCERTAINTIES ASSOCIATED WITH A DEVELOPMENT-STAGE COMPANY. ACTUAL RESULTS COULD DIFFER MATERIALLY FROM THOSE PROJECTED IN THE FORWARD-LOOKING STATEMENTS AS A RESULT OF THE RISK FACTORS DISCUSSED IN CYTRX REPORTS ON FILE WITH THE U.S. SECURITIES AND EXCHANGE COMMISSION INCLUDING, BUT NOT LIMITED TO, THE REPORT ON FORM 10-K FOR THE YEAR ENDED DECEMBER 31, 2013, AND FORM 10-Q FOR THE QUARTER ENDED MARCH 31,2014.
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Corporate Snapshot
Proprietary world-class albumin-binding technology with demonstrated clinical efficacy
Pivotal Phase 3 trial with SPA is underway
Drug discovery operations established in Freiburg, Germany
Phase 2b results announced: Aldoxorubicin shows significantly improved
efficacy over doxorubicin in 1st-line soft tissue sarcoma
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Why Albumin-Binding Conjugates?
Large market potential targeting most common cancers
Accumulation and selective release of drug conjugates bound to albumin in solid tumors allows delivery of 3-5x higher drug doses and increased antitumor efficacy (preclinical and clinical results)
Potential to improve both Quality of Life and Overall Survival Benefit (Aldoxorubicin)
Unique Platform Technology
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CytRx R&D Lab in Freiburg
Creation of a continuous pipeline
Design of new albumin-binding drug conjugates
Optimization of their stability and cleavage
properties
Formulation of the finished product
Co-ordination of all biological investigations
and rapidly moving the drug conjugates from
bench to the clinic
drug
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Aldoxorubicin Clinical Development Program
Aldoxorubicin (delivery-enhanced doxorubicin) Preclinical Phase 1 Phase 2 Phase 3
2nd-line Soft Tissue Sarcoma (STS)
1st- Line Soft Tissue Sarcoma
Glioblastoma Multiforme (GBM)
Kaposi’s Sarcoma
Small Cell Lung Cancer
Pharmacokinetic Study
Combo with gemcitabine
Combo with ifosfamide
Phase 2 on-going
Phase 2b on-going
Phase 3 on-going
Phase 1 completed
Top-line Data announced
Phase 2 on-going
Phase 2b to start Q3 2014
Ph 1 in planning
Ph 1 in planning
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Aldoxorubicin
First and only single agent to substantially surpass doxorubicin in STS
80-100% superiority over doxorubicin in progression-free survival in 1st-line STS
Orphan drug status for STS granted in the USA and EU
Broad potential to treat solid and hematological tumors
Worldwide exclusive license from KTB Tumorforschungs GmbH in Freiburg, Germany
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Mechanism of Aldoxorubicin
Drug / linker conjugate is infused into the patient Tumor cells
Albumin transports drug to the tumor
Linker dissolves in the acidic (low pH) environment, releasing the drug payload
Linker rapidly binds conjugate to albumin
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Dox Linker
Dox Linker Albumin
Aldoxorubicin allows for 3.5x the standard dose of doxorubicin at each cycle
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Aldoxorubicin First-line STS Phase 2b Trial Design
Screened N=140
2:1 Randomization N=123
Aldoxorubicin 350mg/m2
(260mg/m2 dox equiv.) Every 3wk up to 6 cycles
N=83
Doxorubicin 75mg/m2
Every 3wk up to 6 cycles N=40
3 subjects randomized but not
dosed
14 screen failures
CT Scans every 6 weeks
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Patient Characteristics
Characteristics Aldoxorubicin Doxorubicin
N 83 40
Age, median (range) 54.0 (21-77) 54.0 (23-77)
Male / Female, n (%) 38 (46) / 45 (54) 18 (45) / 22 (55)
Race, n (%)
Caucasian 61 (74) 32 (80)
Black or African American 1 (1) 1 (2.5)
Asian 16 (19) 6 (15)
Other 5 (6) 1 (2.5)
ECOG, n (%)
0-1 80 (96.4) 37 (92.5)
2 3 (3.6) 3 (7.5)
Completed Cycles, median (range) 6 (1-6) 4 (1-6)
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Phase 2b Trial 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
All Subjects
Intent-to-treat P Value
Scans Read by Investigator
Aldoxorubicin 8.4 months P=0.0004
Doxorubicin 4.7 months
Improvement over dox 3.7 mos. (79%)
Hazard ratio 0.419 (0.25-0.69) P=0.0007
Scans Read by Central Lab
Aldoxorubicin 5.7 months P=0.014
Doxorubicin 2.8 months
Improvement over dox 2.9 mos. (104%)
Hazard ratio 0.584 (0.37-0.93) P=0.024
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Kaplan-Meier Analysis of Progression-Free Survival Investigator Assessment
3.7 month improvement
HR: 0.419, p=0.0007
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Kaplan-Meier Analysis of Progression-Free Survival Central Radiology Lab Review
2.9 month improvement
HR: 0.584, p=0.024
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PFS at 6 Months Results
All Subjects
Intent-to-Treat P Value
Scans Read by Investigator
Aldoxorubicin 68.1% P=0.002
Doxorubicin 36.6%
Improvement over dox 86.1%
Scans Read by Central Lab
Aldoxorubicin 45.7% P=0.02
Doxorubicin 22.9%
Improvement over dox 99.6%
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Overall Response Rate Results
Aldoxorubicin Doxorubicin
Scans Read by Investigator
Complete Response 2.4% 0%
Partial Response 19.3% 5.0%
Overall Response Rate 21.7% 5.0%
Scans Read by Central Lab
Complete Response 0% 0%
Partial Response 23.8% 0%
Overall Response Rate 23.8% 0%
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Waterfall Plot - Investigator
Aldoxorubicin
64.5% had tumor shrinkage
Doxorubicin
41.2% had tumor shrinkage
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Waterfall Plot – Blinded Central Lab
Aldoxorubicin
60.8% had tumor shrinkage
Doxorubicin
39.4% had tumor shrinkage
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Comparison to Current STS Treatments
CytRx Phase 2b
Investigator assessed
EORTC Phase 3
Dox vs. dox+ ifosfamide
Aldox Dox Dox+ ifos Dox
N 83 40 215 217
Age 54 (21-77) 54 (23-77) 48 (18-60) 47 (18-63)
PFS (months) 8.4 4.7 7.4 4.6
P value 0.0007 0.003
ORR 21.7% 5.0% 26.5% 13.6%
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Phase 2b: Safety Data
Adverse events were consistent with known doxorubicin toxicities
Grade 3 or 4 neutropenia, mucositis and nausea/vomiting are higher in aldoxorubicin-treated subjects but are not treatment limiting
Aldoxorubicin treated subjects received more than 5 times the cumulative amount of doxorubicin in this study than the doxorubicin subjects without any evidence of clinically relevant decreased left ventricular ejection fraction (LVEF), and in more instances an increase in LVEF, either by MUGA or echocardiogram.
~6% of doxorubicin patients had clinically significant cardiotoxicity
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Ph 3 Trial in 2nd-Line STS
Randomized, Comparative Trial Design with SPA −Special Protocol Assessment (SPA) granted by FDA −SPA allows for dosing until disease progression −Trial underway; actively enrolling now at numerous sites
Patient Population −400 STS patients that have progressed following treatment
with chemotherapy −Up to 5 prior cycles or 375mg/m2 of doxorubicin or liposomal
doxorubicin equivalents allowed
Endpoints −Primary: Progression Free Survival −Secondary: Overall survival, response rates, safety, etc.
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Phase 3 Trial Design: 2nd-line STS
Soft tissue sarcoma patients that have relapsed or are refractory to prior chemotherapy
1:1 Randomization N=400
Aldoxorubicin 350mg/m2
(260mg/m2 dox equiv.) Every 3weeks until disease progression
N=200
Physicians Choice: Doxorubicin Dacarbazine Ifosfamide
Gemcitabine+docetaxel Pazopanib
N=200
CT Scans every 6 weeks
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Aldoxorubicin Efficacy in 2nd-line STS
-60
-50
-40
-30
-20
-10
0
10
20
30
40
* Indicates prior therapy with doxorubicin, epirubicin or Doxil®
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*
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Phase 1b/2: Best Response of the 13 Evaluable STS Patients Treated at 350 mg/m2
PFS = 11.3 months OS = 21.7 months ORR = 38%
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Glioblastoma Multiforme (GBM)
GBM is one of the most frequent adult primary brain tumors
Affects 12,500 new patients in the U.S. annually
Median survival is 14 months despite current standard of care treatment including surgery, radiotherapy and chemotherapy with temozolomide
5 year survival: ~4%
GBM
GBM
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Aldoxorubicin significantly improves survival in vivo
Dox: dashed green Vehicle: dashed red
Survival benefit confirmed in three animal studies
− Aldoxorubicin increased lifespan in orthotopic xenograft mouse model with intracranial implanted human GBM cells versus doxorubicin and saline
− Aldoxorubicin crosses the blood-brain barrier. Doxorubicin does not
− Demonstrated that aldoxorubicin accumulates in the brain tumor and not in healthy brain tissue
Phase 2 trial enrolling
− Evaluating aldoxorubicin as a treatment in late-stage glioblastoma multiforme following surgery, radiation and chemotherapy
− Patients to be treated until progression
Aldox treated
P<0.0001
Preclinical GBM results presented at the ESMO Meeting on September 30, 2013
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Aldoxorubicin accumulates in the tumor and not in healthy brain tissue
Doxorubicin does not enter the brain
Dox+ Aldox+
Tumor
Tumor
Healthy brain tissue
Healthy brain tissue
Aldoxorubicin enters brain and delivers
dox to tumor
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2Q15: Results from Ph 2 Kaposi’s Sarcoma trial
2H15: Complete enrollment in Ph 3 STS trial
2H15: Start Ph 1 new conjugate
4Q15: Results from Ph 1 combo trials expected
Ph 2 Kaposi’s Sarcoma trial initiated
Initiated Ph 3 clinical trial in 2nd-line soft tissue sarcoma
Oral presentation of Ph 2b STS results at ASCO Annual Meeting
2H14: Initiate Phase 2b 2nd-line SCLC trial
2H14: Preliminary Phase 2 GBM results expected
2H14: OS data expected from Phase 2b 1st-line STS trial
2014
Expected Upcoming Catalysts
2015 2016
2Q16: Ph 3 STS PFS data
4Q16: NDA filing in STS
2H16: Ph 2b 2nd-line SCLC data expected
2017: NDA approval for aldoxorubicin in STS
2017
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Financial Summary
Balance sheet (as of 3/31/14) −Cash: $112.6M −Debt: $ 0.0M
Shares Outstanding 55.8M
Options 6.7M −Average strike price: $3.20
Warrants 7.9M −Average strike price: $4.80
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Conclusion
Aldoxorubicin demonstrates superiority to doxorubicin − Achieved highly statistically significant results on all efficacy endpoints − Potential to replace doxorubicin for treating many types of cancer
Novel delivery platform with broad applicability − Improves efficacy and side-effect profiles of known chemotherapy drugs − Provides potential partnership opportunities for anti-cancer agents that are
losing patent protection
Late-stage pipeline with near-term clinical catalysts − Phase 3 with SPA as 2nd-line treatment for STS is enrolling − Phase 2 trials in glioblastoma and HIV-related Kaposi’s sarcoma are enrolling − Phase 2b 1st-line STS overall survival results expected 2H14 − Phase 2b 2nd-line SCLC trial planned start in 3Q14 − Phase 1 combination trials to start in 2H14
Risk-mitigated strategy − Creates potential blockbuster oncology therapies with known chemotherapy
payloads