Corporate Overview. July 2016 NASDAQ: CYTR

Transcription

1 Corporate Overview July 2016 NASDAQ: CYTR

2 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, 2015, AND FORM 10-Q FOR THE QUARTER ENDED MARCH 31,

3 CytRx Investment Highlights Proprietary Drug Generation Platform: LADR TM (Linker-Activated Drug Release) Technology Concentrates drug release at the tumor, minimizing systemic exposure and allowing for higher doses and additional cycles Improves efficacy and side-effect profiles of known chemotherapy drugs Late-stage, technology-validating lead drug candidate Aldoxorubicin pivotal Ph 3 (SPA) on-going in 2 nd -line soft tissue sarcoma (STS) Phase 3 PFS data expected in July 2016 Potential for first FDA approval in 2017 Wholly-owned by CytRx Attractive Market Opportunity Potential to be a key therapy for treating STS Orphan drug designations in US & EU Indication expansion where doxorubicin is ineffective like SCLC, GBM Pipeline Potential Substantial in-house chemistry expertise to create new drug conjugates DK049 selected for clinical development IND filing planned for

4 LADR: Linker Activated Drug Release Targeting Ability Localization of drug at tumor using albumin, antibodies, etc. Cleavable Linker Chemistries for controlled release of drug either extra- or intra-cellularly Drug Payload Anti-cancer drugs, high potency cytotoxic agents Albumin transports drug to the tumor and is taken up by the tumor Linker covalently binds within minutes to serum albumin Tumor cells cells Linker dissolves in the acidic environment, releasing the drug payload Cancer Drug Shortcomings LADR TM Technology Potential Advantages Limited therapeutic index Prolonged drug exposure Off-target toxic effects Allows drug to accumulate in the tumor Linker structure prevents release in healthy cells Lack of efficacy Ability to delivery standard and high potency drug payloads Drug Resistance LADR TM conjugates can evade traditional drug resistance mechanism 3

5 Aldoxorubicin: A First-in-Class, Targeted Anthracycline Using LADR TM Technology Phase 3 pivotal trial in STS is fully enrolled Top-line data expected in July 2016 Superior efficacy to doxorubicin in comparative trial Ability to administer 3.5x more doxorubicin equivalents at each cycle Can treat beyond doxorubicin s black box dose limit No clinically significant cardiotoxicity to date Patients have received up to 12x more cumulative anthracycline with aldoxorubicin than possible with doxorubicin Over 550 patients treated with aldoxorubicin to date Orphan drug status granted USA: STS, small cell lung cancer, GBM, pancreatic & ovarian cancers Europe: STS 4

6 CytRx Pipeline Aldoxorubicin 2 nd -Line Soft Tissue Sarcoma 2 nd -Line Small Cell Lung Cancer Glioblastoma Multiforme Kaposi s Sarcoma Combo with gemcitabine Combo with ifosfamide Preclinical Phase 1 Phase 2 Phase 3 Phase 3 Pivotal Trial Top-line data in July 2016 Phase 2b on-going Phase 2 on-going Enrollment Complete Phase 2 Enrollment Complete Ph 1b on-going Ph 1b on-going DK049 IND planned for

7 Soft Tissue Sarcoma (STS) Cancer of the soft, connective tissue Affects muscle, fat, blood vessels, nerves, tendons and the lining of joints (synovial tissues) More than 50 different sub-types Growing, underserved target market Approximately 40,000 new cases in the U.S. and Europe annually More than 13,000 deaths annually Significant unmet medical need Doxorubicin is the standard of care All patients progress on existing therapies 10% Head and Neck 15% GI Tract 15% Retroperitoneum/ Intra-abdominal 60% Arms or Legs 6

8 Why Soft Tissue Sarcomas? It is a model tumor to establish proof of concept (POC) Single-agent doxorubicin is approved as 1 st -line therapy for STS 1 st -line STS provided setting for head-to-head Phase 2b trial comparing aldoxorubicin to doxorubicin Superior efficacy to doxorubicin in comparative trial Why 2 nd -line STS for the Phase 3 Pivotal Trial? Significant unmet medical need: no standard of care for patients PFS is acceptable primary endpoint Clinical data to support aldoxorubicin activity in 2 nd -line STS patients 1 st -line STS had competing trials 7

9 Phase 2b STS Trial: PFS Results All Subjects Intent-to-treat P Value Scans Read by Investigator Aldoxorubicin Doxorubicin 8.3 months 4.6 months P= Improvement over dox 3.7 mos. (80%) Hazard ratio 0.44 ( ) P= Scans Read by Central Lab Aldoxorubicin Doxorubicin 5.6 months 2.7 months P= Improvement over dox 2.9 mos. (107%) Hazard ratio 0.60 ( ) P= Results published in JAMA Oncology in September

10 PFS Comparison to Recent STS Trials Single agent aldoxorubicin achieved superior PFS to combination therapies Aldox - Investigator Aldox- central lab Aldoxorubicin Max of 6 cycles Dox+Ifos 7.4 Dox+TH-302 Dox+Olaratumab PFS Dox PFS Dox+Pali Ph Trabectedin Months Last treatment Cycle 6 (21 day cycle) TH-302 and olaratumab treatment continued until disease progression; doxorubicin stopped after six cycles 9

11 Waterfall Plot - Investigator Aldoxorubicin 64.5% had tumor shrinkage Doxorubicin 41.2% had tumor shrinkage JAMA Oncology2015 Dec;1(9):

12 Waterfall Plot Blinded Central Lab Aldoxorubicin 60.8% had tumor shrinkage Doxorubicin 39.4% had tumor shrinkage JAMA Oncology2015 Dec;1(9):

13 Phase 2b: Safety Data Adverse events were consistent with known doxorubicin toxicities Certain grade 3 or 4 AEs such as neutropenia, mucositis, nausea/vomiting and leukopenia, were higher in aldoxorubicintreated subjects but were not treatment limiting Aldoxorubicin treated subjects had no evidence of clinically relevant decreased left ventricular ejection fraction (LVEF) ~9% of doxorubicin treated patients had clinically significant cardiotoxicity 12

14 2 nd -Line STS: No Standard of Care Dacarbazine Phase 3 comparators Gemcitabine & Docetaxel Ifosfamide Doxorubicin Aldoxorubicin Potential to become the standard of care for treating relapsed and/or refractory patients with soft tissue sarcoma Pazopanib Excludes liposarcoma Trabectedin Liposarcoma and Leiomyosarcoma only Eribulin Liposarcoma only 13

15 Phase 3 Pivotal Trial in 2 nd -Line STS Randomized, Comparative Trial Design with SPA Special Protocol Assessment (SPA) granted by FDA Protocol allows for dosing until disease progression Patient Population 433 STS patients that have progressed following treatment with chemotherapy Up to 5 prior cycles or 375mg/m 2 of doxorubicin or liposomal doxorubicin equivalents allowed Endpoints Primary: Progression Free Survival Secondary: Overall survival, response rates, safety, etc. 14

16 Phase 3 Trial Design: 2 nd -line STS Trial is currently on-going 79 sites located in the USA, Canada, Europe, Israel, Australia and Chile Timing Achieved 191 events in April 2016 triggering the data analysis of the primary endpoint of PFS Enrollment completed ahead of schedule in Q415 PFS data expected to be available July 2016 Projected NDA filing at end of 2016 Commercial launch in 2017 Soft tissue sarcoma patients that have relapsed or are refractory to prior chemotherapy 1:1 Randomization N=400 Aldoxorubicin 350mg/m 2 (260mg/m 2 dox equiv.) Every 3weeks until disease progression N=200 Physicians Choice: Doxorubicin Ifosfamide Dacarbazine Pazopanib Gemcitabine+ docetaxel N=200 CT Scans every 6 weeks 15

17 Beyond STS: Indication Expansion Small Cell Lung Cancer ~15% of all lung cancers Poor prognosis; topotecan is the only approved 2 nd -line drug Randomized Phase 2b 132 patient trial is enrolling comparing aldoxorubicin to topotecan in 2 nd -line SCLC Glioblastoma Stage IV brain cancer Poor prognosis; doxorubicin does not cross the blood-brain barrier (BBB) Preclinical and clinical data suggest aldoxorubicin crosses the BBB and has anti-cancer activity Updated data presented at ASCO

18 ASCO Update Phase 2 Glioblastoma First demonstration of an albumin-binding therapy entering the brain and having anti-tumor activity Median OS of 8.6 months 7 patients still being followed Baseline Week 6 Phase 2 Kaposi s Sarcoma 15 patients received low dose aldoxorubicin 11 of 13 (85%) had partial responses at week 4 Very well tolerated by late stage patients Higher doxorubicin concentrations detected in KS lesions compared to nontumor tissues Phase 1b Trial of Aldoxorubicin + Gemcitabine Able to administer combo to heavily pretreated patients (range 1-15 prior regimens) 11 of 13 (85%) had partial responses or stable disease Final cohort still ongoing Baseline Cycle 2 17

19 DK049: Novel LADR TM -Enhanced Gemcitabine Derivative Advantages over gemcitabine After infusion, binds albumin for transport and accumulation at the tumor Dual releasing linker for prolonged release of the active drug at the tumor site Gemcitabine DK049 Targeted to the tumor No Yes via albumin Deactivated by cytidine deaminase >90% No hent1 transporter dependent Yes No Half-life Short Long Pre-clinical activity in multiple models including non-small cell lung, pancreatic, and ovarian cancers 13-fold greater anti-tumor activity with 85% less drug than comparator Data presented at the American Association for Cancer Research (AACR) Annual Meeting in April

20 DK049: Non-Small Cell Lung Cancer Absolute Tumor Volume [mm3] LXFE 937 xenograft model Control Vehicle Gemcitabine 4 x 240 mg/kg DK049 8 x 18 mg/kg p < 0.05 vs. gemcitabine Days after Randomization 19

21 DK049: Ovarian Cancer 2500 OVXF 899 xenograft model Absolute Tumor Volume [mm3] Starting tumor volume 200 mm 3 Control Vehicle Gemcitabine 4 x 240 mg/kg DK049 8 x 18 mg/kg p < 0.05 vs. gemcitabine Days after Randomization 20

22 Expected Upcoming Catalysts Q16: Enrollment in Phase 3 STS trial - Completed ahead of schedule in Q : NDA approval for aldoxorubicin in STS 2Q16: Present data on DK049 at the AACR Annual Meeting in April 2017: Commercial launch of aldoxorubicin for soft tissue sarcoma 2Q16: Present clinical trial updates at ASCO on GBM, Kaposi s sarcoma and gemcitabine combination with aldoxorubicin July 2016: Phase 3 STS PFS data 2017: DK049 Phase 1 results 2017: Initiate Phase 1 trial with next drug-conjugate 2H16: GBM OS data 2H16: Begin NDA filing in STS 2H16: Phase 2b 2 nd -line SCLC data expected 2H16: Initiate Phase 1 trial with DK049 2H16: Select next drug-conjugate for clinical development 21

23 Financial Summary Balance Sheet (3/31/16) Cash: $68.2M Debt: $25.0M $40M long-term loan secured 2/8/16; Initial tranche of $25M Additional $15M in long-term debt is available at CytRx s option in 2016 subject to R&D milestones Shares Outstanding 68.3M Options Average strike price: $ M Warrants Average strike price: $ M 6.4M expire on Aug 1,

24 Conclusion Aldoxorubicin demonstrated superiority to doxorubicin in a global Phase 2b trial in 1 st -line STS Top-line results from pivotal Phase 3 trial expected in July 2016 Commercial launch in STS planned for 2017 Novel LADR TM technology platform with broad applicability Next generation of LADR TM derived oncology drugs in development including DK049 - IND planned for