Mustang Presentation JulyCorporate(Presentation June%2016 1 This presentation contains...
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Corporate Presentation June 2016 1
Transcript of Mustang Presentation JulyCorporate(Presentation June%2016 1 This presentation contains...
Corporate PresentationJune 2016
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This presentation contains forward-looking statements within the meaning of the PrivateSecurities Litigation Reform Act of 1995. These statements are often, but not always, madethrough the use of words or phrases such as “anticipates”, expects”, plans”, believes”,“intends”, and similar words or phrases. Such statements involve risks and uncertaintiesthat could cause Mustang Bio’s actual results to differ materially from the anticipated resultsand expectations expressed in these forward-looking statements. These statements areonly predictions based on current information and expectations and involve a number ofrisks and uncertainties. Actual events or results may differ materially from those projected inany such statements due to various factors, including the risks and uncertainties inherent inclinical trials, drug development, and commercialization. You are cautioned not to placeundue reliance on these forward-looking statements, which speak only as of the datehereof. All forward-looking statements are qualified in their entirety by this cautionarystatement and Checkpoint Therapeutics undertakes no obligation to update thesestatements, except as required by law.
Forward Looking Safe Harbor Statement
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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
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Mission Statement
To provide long-‐term clinical remissionsfor patients with aggressive forms ofcancer by leveraging best-‐in-‐class sciencefrom COH to create novel CAR-‐T therapies
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Publicly-‐Traded CAR-‐T Companies
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Company Name (Ticker) Market Cap
Juno Therapeutics (JUNO) ~$4.0B
Kite Pharma (KITE) ~$2.5B
Cellectis (CLLS) ~$0.9B
Ziopharm (ZIOP) ~$0.7B
What is a CAR-‐T?
Transmembrane
CAR
Chimeric Antigen Receptor-‐T cell
The CAR recognizes targets on the surface of the malignant cell to direct and activate T-‐cells to destroy the tumor
Single-‐chain variable fragment (scFv)
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Co-‐stimulation domain (4-‐1BB or CD28)
CD3ζ
Antibody fragment that identifies and targets tumors (e.g. CD19, CD20)
Function:
Links co-‐stimulation/CD3 to the antibody fragment (can effect efficacy)
Strengthens patient derived T cell signaling and persistence, enhances potency
Activates the cytotoxic patient derived T Cell to which CAR is attached
How is a CAR-‐T made?
CAR-‐T
T-‐Cells extracted
T-‐Cells EngineeredAdministered back to patient
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Total time From Blood Draw to Infusion: ~2-‐4 weeks
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 (Blasticplasmacytoid dendritic cell neoplasm)• Phase 1 on-‐going
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MB-‐101 – IL13Rα2 an ideal Target for CAR-‐T
Jonnalagadda et al. Mol Therapy;; 2015 Wang et al. Immunotherapy;; 2011 Brown et al. Manuscript in preparation
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MB-‐101 CAR T Is More Potent than 1st generation IL13-‐targeted CAR-‐T
D7 D13 D16 D20 D27
1.0M
0.3M
0.1M
MockTcm
tumoronly
1.0M
0.3M
0.1M
1stgen IL13Ra2
CAR-T
2ndgen IL13Ra2
CAR-T
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Phase I Clinical Trial with MB-‐101 is ongoing
Patient Population Planned Enrollment StudyObjectivesRel/Ref GBM-‐Arm 1: ResectableArm 2: Non-‐resectable
12/arm Assess the feasibility, safety and determine MTD
Resection Arm -‐ ICT Treatment Summary
NotesPatient # Tx Arm / IL13Ra2 Manuf TreatmentDose Dose IHC CAR T cells
UPN097 Resection / Dose 1 110 64% CAR
16 days Cycles 1, 2: 2M, 10MPD; Off-‐study due to rapid tumor progression
UPN109 Resection / Dose 1 80 64% CAR
18 days
Cycles 1, 2, 3 (ICT): 2M, 10M, 10MCycles 4, 5, 6 (ICT): 10M, 10M, 10M Cycles 1, 2, 3 (ICV): 2M, 10M, 10M Cycles 4, 5 (ICV): 10M, 10M
CR; Treatment ongoing (7 months)
Cycles 6-‐9 (ICV): 10M
UPN117 Resection / Dose 1 200+ 60% CAR
15days Cycles 1, 2, 3: 2M, 10M, 10MPD; Off-‐study due to rapid tumor progression
UPN122 Resection / Dose 1 150+ 95% CAR
14 daysCycles 1, 2, 3: 2M, 10M, 10MCycles 4, 5, 6: 10M, 10M, 10M SD* (6 cycles)
UPN125 200+ SD* (6 cycles)Resection / Dose 2
73.5% CAR15 days
Cycles 1, 2, 3: 10M, 50M, 50MCycles 4, 5, 6: 50M, 50M, 50M
UPN131 Resection / Dose 2 130+ 81.3% CAR
14 days Cycles 1, 2: 10M, 50M*, 50M SD* (3 cycles)
Dose Schedule 1: Well-‐tolerated in all patients treatedNo grade 3 or higher toxicities No CRS or NeurotoxicityGrade < 2 fevers, headaches, myalgia, chills
* Preliminary data, currently under QA review
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CR = Complete Response
PR = Partial Response
PD= Progressive Disease
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Progression of New Tumors Distant from CAR T cell Infusion Site
First dose of “systemic” therapy
ICV Delivery of IL13BBζ T cells Mediates Regression multifocal GBM
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Regression of Spine Metastases Regression of distant Cranial Metastases
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
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GBM a Significant Unmet Medical Need
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Competitive therapies in development for GBMDrug Name Company Description Targets Clinical Stage
CART-‐EGFRvIII Novartis Anti-‐EGFRvIIICART
EGFR Phase I Pilot
EGFRvIII Kite Pharma Anti-‐EGFRvIIICART
EGFR Preclinical
UCART-‐EGFRvIII Cellectis Anti-‐EGFRVIII “universal CAR” through expression on allogeneic T-‐cells
EGFR Discovery
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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 PlasmacytoidDendritic 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 BloodJonnalagadda et al. 2014 Mol Ther
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MB-‐102 (CD123) – Antitumor Activity Against Human Acute Myeloid Leukemia
ARDIROS et al BLOOD, 31 OCTOBER 2013 x VOLUME 122, NUMBER 18
CD123 CARs
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Phase I Clinical Trial with MB-‐102 is Open and Recruiting Patients
Patient Population Planned Enrollment StudyObjectives
Rel/Ref AML 18Assess the feasibility, safety and determine MTD of Single Infusion
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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%
*Information taken from Datamonitor Healthcare*
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Competitive Landscape for CD123 Targeted Therapies
Drug Name Company Drug Description Targets ClinicalCART-‐CD33 CD123
Theravectys(China) CAR
CD33 IL3RA Phase I/II
CSL-‐360/362 CSL Mab IL3RA Phase I
GD006 MacroGenicsBi-‐specific antibody to CD123 and CD3
CD3 IL3RA Phase I
SL-‐401 Stemline IL3 fusion toxin EEF2, IL3RA Phase I/II
UCART123 Cellectis allogeneic T-‐cell CAR IL3RA Phase I planned
*Data taken from Bioseeker Group*
ØBPDCN is a rare but aggressive blood cancerØ Annual US incidence: <60 (similar or larger number in EU)Ø No standard of careØ Median OS 9 - 12 months
ØUniformly very high CD123 expression
ØProof of Principle:Ø IL-3 target fusion proteinØ In a pilot trial, 7/9 BPDCN responded: 5 CR, 2 PR Median duration of response: 5 months (1-24)
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Ultra-‐Orphan Opportunity: BPDCN
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
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Key Milestones for Mustang in 2016
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
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Key Take Home Messages
Corporate PresentationJune 2016
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