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Mustang Presentation July Corporate Presentation June 2016 1 Forward Looking Safe Harbor Statement This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are often, but not always, made through the use of words or phrases such as “anticipates”, expects”, plans”, believes”, “intends”, and similar words or phrases. Such statements involve risks and uncertainties that could cause Mustang Bio’s actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any such statements due to various factors, including the risks and uncertainties inherent in clinical trials, drug development, and commercialization. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Checkpoint Therapeutics undertakes no obligation to update these statements, except as required by law. 2 Corporate Overview ØFounded by Fortress Biotech in 2015 ØChimeric Antigen Receptor (CAR) T Cell technology from City of Hope (COH) § Based on the research of Stephen Forman and Christine Browne, pioneers of CAR-T technology ØFirst two CAR-Ts entered the clinic in 2015 and 2016 ØResearch collaboration between Mustang and COH to identify additional CAR-T clinical candidates 3 Mission Statement To provide long-term clinical remissions for patients with aggressive forms of cancer by leveraging best-in-class science from COH to create novel CAR-T therapies 4 Publicly-Traded CAR-T Companies Company Name (Ticker) Market Cap Juno Therapeutics (JUNO) ~$4.0B Kite Pharma (KITE) ~$2.5B Cellectis (CLLS) ~$0.9B Ziopharm (ZIOP) ~$0.7B 5 What is a CAR-T? CAR Function: Antibody fragment that identifies and Single-chain targets tumors (e.g. CD19, CD20) Chimeric Antigen variable fragment Receptor-T cell (scFv) Transmembrane Links co-stimulation/CD3 to the The CAR recognizes targets antibody fragment (can effect efficacy) on the surface of the Co-stimulation Strengthens patient derived T cell malignant cell to direct and domain (4-1BB or activate T-cells to destroy CD28) signaling and persistence, enhances potency the tumor Activates the cytotoxic patient derived CD3ζ T Cell to which CAR is attached 6 How is a CAR-T made? CAR-T T-Cells extracted T-Cells Engineered Administered back to patient Total time From Blood Draw to Infusion: ~2-4 weeks 7 Lead CAR-T Programs • MB-101 • Targets IL13Rα2 • For the treatment of Malignant Glioma (GBM) tumors • Phase 1 on-going • MB-102 • Targets CD123 • For the treatment of AML and BPDCN (Blastic plasmacytoid dendritic cell neoplasm) • Phase 1 on-going 8 MB-101 – IL13Rα2 an ideal Target for CAR-T Jonnalagadda et al. Mol Therapy; 2015 Wang et al. Immunotherapy; 2011 9 Brown et al. Manuscript in preparation MB-101 CAR T Is More Potent than 1st generation IL13-targeted CAR-T D7 D13 D16 D20 D27 tumoronly MockTcm 0.1 M T 0.3 M - CAR gen IL13Ra2 IL13Ra2 gen 1.0 M st 1 0.1 M T - 0.3 M CAR gen IL13Ra2 IL13Ra2 gen 1.0 M nd 2 10 Phase I Clinical Trial with MB-101 is ongoing Patient Population Planned Enrollment Study Objectives Rel/Ref GBM- Arm 1: Resectable 12/arm Assess the feasibility, safety and Arm 2: Non-resectable determine MTD 11 Resection Arm - ICT Treatment Summary Patient # Tx Arm / IL13Ra2 Manuf Treatment Dose Notes Dose IHC CAR T cells PD; Off-study due Resection / 64% CAR UPN097 110 Cycles 1, 2: 2M, 10M Dose 1 16 days to rapid tumor CR = progression Complete Cycles 1, 2, 3 (ICT): 2M, 10M, 10M Response Cycles 4, 5, 6 (ICT): 10M, 10M, 10M CR; Treatment Resection / 64% CAR 80 Cycles 1, 2, 3 (ICV): 2M, 10M, 10M UPN109 Dose 1 18 days ongoing (7 PR = Partial Cycles 4, 5 (ICV): 10M, 10M months) Response Cycles 6-9 (ICV): 10M PD; Off-study due Resection / 60% CAR PD= 200+ Cycles 1, 2, 3: 2M, 10M, 10M UPN117 Dose 1 15days to rapid tumor Progressive progression Disease Resection / 95% CAR Cycles 1, 2, 3: 2M, 10M, 10M 150+ UPN122 Dose 1 14 days Cycles 4, 5, 6: 10M, 10M, 10M SD* (6 cycles) Resection / 73.5% CAR Cycles 1, 2, 3: 10M, 50M, 50M 200+ UPN125 Dose 2 15 days Cycles 4, 5, 6: 50M, 50M, 50M SD* (6 cycles) Resection / 81.3% CAR 130+ Cycles 1, 2: 10M, 50M*, 50M ) UPN131 Dose 2 14 days SD* (3 cycles Dose Schedule 1: Well-tolerated in all patients treated No grade 3 or higher toxicities * Preliminary data, No CRS or Neurotoxicity currently under QA review 12 Grade < 2 fevers, headaches, myalgia, chills Progression of New Tumors Distant from CAR T cell Infusion Site First dose of “systemic” therapy 13 ICV Delivery of IL13BBζ T cells Mediates Regression multifocal GBM Regression of Spine Metastases Regression of distant Cranial Metastases 14 GBM a Significant Unmet Medical Need ØGlioblastoma, aka glioblastoma multiforme (GBM) is the most common primary malignant brain tumor ØGBM is also the most aggressive form of brain tumor, and is associated with extremely poor prognosis and survival. ØMedian overall survival from diagnosis of approximately 15 months Ø5 year survival of only 5% Ø~30,000 newly diagnosed GBMs annually in the US, Japan and five major eU markets 15 Competitive therapies in development for GBM Drug Name Company Description Targets Clinical Stage CART-EGFRvIII Novartis Anti-EGFRvIII EGFR Phase I Pilot CART EGFRvIII Kite Pharma Anti-EGFRvIII EGFR Preclinical CART UCART-EGFRvIII Cellectis Anti-EGFRVIII EGFR Discovery “universal CAR” through expression on allogeneic T- cells 16 MB-102 – CAR-T Targeting CD123 Expressing Tumors • CD123 is expressed on cells of myeloid lineage and is overexpressed on AML, ALL and BPDCN (Blastic Plasmacytoid Dendritic Cell Neoplasm) • Human proof of principle with fusion toxin directed at target in BPDCN • Limited CAR-T competition (Novartis, Juno and Kite not in or near clinic) Wang et al. 2011 Blood Mardiros et al. 2013 Blood 17 Jonnalagadda et al. 2014 Mol Ther MB-102 (CD123) – Antitumor Activity Against Human Acute Myeloid Leukemia CD123 CARs ARDIROS et al BLOOD, 31 OCTOBER 2013 x VOLUME 122, NUMBER 18 18 Phase I Clinical Trial with MB-102 is Open and Recruiting Patients Patient Population Planned Enrollment Study Objectives Assess the feasibility, safety and Rel/Ref AML 18 determine MTD of Single Infusion 19 AML a Significant Unmet Medical Need • Acute Myeloid Leukemia is the most common acute leukemia in adults • Approximately 30,000 newly diagnosed cases of AML per year in the US, Japan, and five major eU markets • Overall five-year survival rate in the US was ~25% 20 *Information taken from Datamonitor Healthcare* Competitive Landscape for CD123 Targeted Therapies Drug Name Company Drug Description Targets Clinical CART-CD33 Theravectys CD33 CD123 (China) CAR IL3RA Phase I/II CSL-360/362 CSL Mab IL3RA Phase I Bi-specific antibody CD3 GD006 MacroGenics to CD123 and CD3 IL3RA Phase I EEF2, SL-401 Stemline IL3 fusion toxin IL3RA Phase I/II Phase I UCART123 Cellectis allogeneic T-cell CAR IL3RA planned 21 *Data taken from Bioseeker Group* Ultra-Orphan Opportunity: BPDCN Ø BPDCN is a rare but aggressive blood cancer Ø Annual US incidence: <60 (similar or larger number in EU) Ø No standard of care Ø Median OS 9 - 12 months Ø Uniformly very high CD123 expression Ø Proof of Principle: Ø IL-3 target fusion protein Ø In a pilot trial, 7/9 BPDCN responded: 5 CR, 2 PR Median duration of response: 5 months (1-24) 22 Key Milestones for Mustang in 2016 Ø Preliminary safety data from dosing at least 6 patients for MB-101 ØPreliminary safety data from dosing at least 6 patients for MB-102 ØAdditional CAR-Ts from the research collaboration entry into development phase 23 Key Take Home Messages ØRobust CAR-T platform technology in partnership with pioneers in CAR-T technologies from COH ØLead CAR-T with no current competition for the target (IL13Rα2) already in the clinic with data in 2016 ØSecond CAR-T in pipeline where target CD123(IL3Rα) has been validated in Ultra Orphan indication ØCAR-T collaboration with COH to generate additional CAR-Ts to build world- class robust CAR-T company 24 Corporate Presentation June 2016 25.
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