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SARC021 A Randomized Phase 3, Multicenter, Open- Label Study Comparing TH-302 in Combination with Doxorubicin vs. Doxorubicin Alone in Subjects with Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma Principal Investigator: William Tap, MD Memorial Sloan-Kettering Cancer Center

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TH-302 Combination Therapy in Soft Tissue Sarcoma Phase 3 Study Design Collaborative Trial Threshold Pharmaceuticals Sarcoma Alliance for Research through Collaboration (SARC) Independent Data Monitoring Committee (IDMC) In place to monitor the safety and efficacy

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SARC021 Eligible Patients (N=620) 15 Years of Age Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma Stratification/Randomization TH-302 + Doxorubicin 21 Day Cycle Day 1 = TH-302 (300 mg/m 2 ) and Doxorubicin (75 mg/m 2 ) Day 8 = Th-302 (300 mg/m 2 ) and Day 8 or Day 9 = G-CSF Doxorubicin 21 Day Cycle Day 1 = Doxorubicin (75 mg/m 2 ) Response evaluations end of cycles 2, 4 and 6 until progression or discontinuation Note: Patient continues monotherapy TH-302 maintenance after cycle 6 without doxorubicin and G-CSF until discontinuation Response evaluations end of cycles 2, 4 and 6 until progression or discontinuation Note: Patient is discontinued after cycle 6 Survival Follow-up

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Timelines 517 patients randomized as of mid-October Accrual goal of 620 expected to be reached around the end of 2013 Interim OS analysis projected in first half of 2014 Final OS analysis projected in first half of 2015 Timelines primarily dependent on survival rates

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Data management efforts increased due to rapid accrual Monitoring frequency increased to source document verify data Central pathology review Scanning specimen and pathology reports Following up with sites to request missing samples Request samples sufficient to confirm subtype diagnosis and histological grade Ongoing Activities

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SARC021 Austria Allemeines Kranenhaus Wein T. Brodowicz LKH Univ Klinikum Graz- H. Samonigg Univ Innsbruck W. Eisterer Belgium Universitaire Ziekenhuizen Leuven Gasthuisberg P. Schffski Canada Cancer Care Manitoba P. Wong Cross Cancer Inst. K. Mulder Juravinski Cancer Center R. Tozer McGill University T. Alcindor Tom Baker Cancer Center J. Henning Denmark University Hosp Herlev, Copenhagen A. Krarup-Hansen France Centre Antoine Lacassagne A. Thyss Centre GF Leclerc, Dijon N. Isambert Centre Leon Berard I.Ray-Coquard Centre Oscar Lambret, Lille N. Penel CHU Strasbourg J. Kurtz Hopital lda La Timone, Marseille S. Salas ICO Ren Gauducheau, Nantes E. Bompas Institut Bergoni, Bordeaux B. Bui-Nguyen Institut Claudius Regand C. Chevreau Germany Helios Klinikum Bad Saarow & Berlin-Buch P. Reichardt Krankenhaus Nordwest GmbH- S. Al-batran Mannheim University Medical Center, Mannheim P. Hhenberger Medizinische Hochschule Hannover V. Gruenwald Uniklinik Mnchen-Grohadern, Mnchen M. Schlemmer Universittsklinikum Essen S. Bauer Wilhelm's University, Muenster T. Kessler Hungary llami Egszsggyi Kzpont, Budapest Z. Ppai Jsz-Nagykun-Szolnok Megyei Hetnyi Gza, Szolnok T. Csszi Israel Sharette Institute of Oncology, Hadassah-Hebrew, Jerusalem D. Katz Italy Azienda Ospedaliera Garibaldi, Catania H. Soto Parra Centro di Riferimento Oncologico, Aviano A. Buonadonna Ospedale Gradenigo, Torino M. Aglietta Oncologia Medica, Palermo G. Badalamenti Sanitario Gradenigo S.C. di Oncologia, Torino A. Comandone Poland Centrum Onkologii Instytut M. Skodowskiej-Curie, Warsaw P. Rutkowski Centrum Onkologii Instytut M. Skodowskiej-Curie, Krakow I. Cedrych Wojewodzkie Centrum Onkologii w Gdansku J. Pikiel Russia FGU Moscow Research Institute of Oncology V.Teplyakov Regional Oncology Center GOOSE, UI Frunze G. Mukhamedshina Russian Cancer Research Center named after N N Blokhin, Moscow M. Aliyev Spain Hospital Sant Joan de Deu de Barcelona J. Mora Graupera Hospital Saint Pau, Barcelona A. Lpez Pousa Hospital Universitario Ramn y Cajal, Madrid J.A. Lpez Martn Institut Catal d'Oncologia L'Hospitalet, Barcelona X. Garca del Muro Universidad Complutense Madrid Facultad de Medicina M. A. Vaz Salgado Universidad de La Laguna- Hospital Universitario de Canarias J. Cruz Jurado

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SARC021 United States Carolinas Hematology Onc (NC) M. Livingston Case Western/University Hospital (OH) H. Koon Cleveland Clinic (OH) T. Budd Columbia University (NY) K. Kalinsky Dana Farber (MA) D. DAdamo Duke University (NC) R. Riedel Emory University (GA) W. Read Florida Cancer Research Consortium (FL) F. Recio Fox Chase Cancer Center (PA) S. Movva Indiana University (IN) D. Rushing Johns Hopkins/Sidney Kimmel (MD) C. Meyer Kootenai Cancer Center (ID) B. Samuels Massachusetts General - D. DAdamo MD Anderson Orlando G. Pennock Mayo Clinic (AZ) K. Curtis Mayo Clinic (FL) S. Attia Mayo Clinic (MN) S. Okuno Medical College of Wisconsin (WI) J. Charlson Medical University of South Carolina (SC) A. Kraft Memorial Sloan-Kettering Cancer Center (NY) W. Tap Moffitt Cancer Center & Research Institute (FL) D. Reed Montefiore (NY) S. Packer Northwestern University (IL) M. Agulnik Ohio State University (OH) A. Bhinder Oncology Specialists (IL) P. Kaiser Oregon Health and Science University (OR) C. Ryan Pennsylvania Oncology Hematology Assoc (PA) A. Staddon* Roswell Park Cancer Institute (NY) N. Khushalani* RUSH (IL) M. Batus Sarcoma Oncology Center (CA) S. Chawla* Stanford Comprehensive Cancer Center (CA) K. Ganjoo* University of Arizona (AZ) L. Cranmer* University of California, Los Angeles (CA) N. Federman* University of Iowa (IA) M. Milhem* University of Michigan (MI) S. Schuetze* University of Pittsburgh (PA) H. Tawbi* University of Southern California (CA) J. Hu University of Washington/Fred Hutchinson (WA) R. Jones Vanderbilt University Medical Center (TN) V. Keedy Vermont Cancer Center (VT) C. Verschraegen VCU Massey Cancer Center (VA) A. Poklepovic Wake Forest University (NC) P. Savage Washington Cancer Inst. (WA) D. Priebat Washington University School of Medicine (MO) B. Van Tine*