Corporate Presentation July 2020 Forward Looking Safe Harbor - - PowerPoint PPT Presentation

Corporate Presentation

July 2020

Forward Looking Safe Harbor Statement

This presentation may contain “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. 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 Mustang Bio undertakes no obligation to update these statements, except as required by law.

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Mustang Bio:

Building a Fully Integrated Gene & Cell Therapy Company

▪ Mustang (NASDAQ:MBIO) is a publicly-traded biotechnology company focused

• n developing next-generation medicine in areas of high patient need

▪ Transformational ex vivo lentiviral gene therapy for XSCID licensed from St. Jude

– Promising results in 2 ongoing clinical trials led by St. Jude & NIH

▪ 6 CAR-T programs from City of Hope & Fred Hutchinson Cancer Research Center, all potentially first in class

– All in Phase 1 trials, with first Mustang IND program to start enrolling 2Q2020 – Targets include: CD20, PSCA, IL13Rα2, CD123, CS1, and HER2

▪ Phase 1 oncolytic virus from Nationwide to enhance CAR-T activity in glioblastoma ▪ Targeting 2 additional Mustang IND approvals in 2020 ▪ 27,000 square foot cell processing & translational research facility on UMass Medical School campus with capacity to launch at commercial scale ▪ Team with extensive gene & cell therapy industry experience

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Leadership Team with Extensive Gene, Cell & Rare Disease Therapy Experience

4 James Edinger, PhD VP, Preclinical Sciences Debra Manning, SPHR VP, Human Resources Knut Niss, PhD Chief Technology Officer Brian Achenbach, MBA SVP, Finance & Corporate Controller Manuel Litchman, MD President & Chief Executive Officer Greg Furrow, MS, FRQA VP, Quality Lynn E. Bayless, MS Head, Regulatory Affairs Regan Flynn, SHRM-CP Executive Assistant / HR Generalist John Bernard, MD Senior Medical Director Scott Smith, MBA Senior Director, Alliance & Program Mgmt

▪ Technology licensed from City of Hope (COH), Fred Hutch Cancer Research Center (FHCRC), Nationwide Children’s Hospital, & St. Jude Children’s Research Hospital; research based on pioneering work by:

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R&D Collaborators: World Class Team of Scientific Experts

• Dr. Stephen Forman

City of Hope

• Dr. Christine Brown

City of Hope

• Dr. Brian Till

FHCRC

• Dr. Kevin Cassady

Nationwide

• Dr. Brian Sorrentino

SJCRH (1958-2018)

Therapeutic Modality Target (Partner) 2020 2021 2022 2023 Ex-vivo Gene Therapy IL2RG

(St. Jude)

CAR-T Therapy Hematologic Malignancies

CD123

(COH)

CD20

(FHCRC)

CS1

(COH)

Solid Tumors

IL13Rα2

(COH)

C134 OV

(Nationwide)

PSCA

(COH)

HER2

(COH)

Mustang files new IND COH files new IND Topline data available

• St. Jude = St. Jude Children’s Research Hospital

GBM = Glioblastoma multiforme COH = City of Hope National Medical Center Nationwide = Nationwide Children’s Hospital FHCRC = Fred Hutchinson Cancer Research Center UAB = University of Alabama at Birmingham * Partially or totally supported by grants

Robust Pipeline of Gene & Cell Therapies Addressing Rare Conditions

Pivotal Phase 1/2 Blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Mustang IND) [acute myelogenous leukemia (AML) & high-risk myelodysplastic syndrome (hrMDS) may be added at higher dose levels] Phase 1 Non-Hodgkin lymphoma (NHL) at FHCRC Pivotal Ph 1/2 NHL & chronic lymphocytic leukemia (Mustang IND) Phase 1/2 GBM: CAR-T + oncolytic virus (OV) (Mustang IND) Phase 1 Prostate cancer at COH* Phase 1/2 Prostate & pancreatic cancer (Mustang IND) Phase 1 GBM at UAB* Phase 1 GBM: CAR-T + nivolumab ± pretreatment with nivolumab and ipilimumab at COH* Phase 1 GBM: CAR-T for leptomeningeal disease at COH Phase 1/2 GBM: CAR-T + OV at COH Ph 1 Multiple myeloma (MM) at COH Pivotal Phase 1/2 Multiple myeloma (Mustang IND) Phase 1 GBM & metastatic HER2+ cancer to brain at COH* Phase 1/2 Metastatic HER2+ cancer to brain (Mustang IND)

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Pivotal Phase 2 X-SCID newly diagnosed (Mustang IND) Pivotal Phase 2 X-SCID previously transplanted (Mustang IND)

Ph 1

Ph 1 Ph 1

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▪ Facility was built & fully operational prior to enrolling first patient on Mustang IND trial ▪ Universal platform process developed for autologous CAR-Ts; 1st patient’s cells expected 2Q2020 ▪ Deep expertise of our people leveraged to also process XSCID patients’ cells starting 3Q2020

Cell Processing: A Core Competency & Competitive Advantage

Leukapheresis Enrichment Activation Transduction Wash Expansion Harvest Fill Cryopreservation Shipment Shipment Thawing Infusion

Day 0 Day -1 Day 2 Day 3 Day 7

CoA

Day 15+ Day 19+

8 day sterility

20 40 60 80 100 120 A B C D E F MBIO

Direct raw material cost (excl. LV)

LEADING COMPANIES AND ACADEMIC INSTITUTES

% Company A

CD123 CS1

Direct Labor (h) for 10 processes

10 20 30 40 50 60 70 80 90 1 2 3 4 5 6 7

FTE Sum Process Day

Mustang Milestones over Next 12 Months

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Therapy Type Asset (Target) Event Type Expected Event Timing

CAR-T MB-106 (CD20) Data Potential first data at ASH from FHCRC trial in NHL Q4 IND Filing Tech transfer from FHCRC and prepare for Mustang IND filing for NHL and CLL Q1’21 MB-105 (PSCA) Data Potential first data from COH trial in prostate cancer Q1’21 MB-102 (CD123) Trial Start Treat first patient in Mustang IND multicenter trial for BPDCN, AML, & hrMDS Q3 Data Potential follow-up data from COH trial in AML & BPDCN Q4 MB-104 (CS1) Data Potential first data from COH trial in multiple myeloma Q4 IND Filing Tech transfer from COH and prepare for Mustang IND filing for multiple myeloma Q2’21 MB-101 (IL13Rα2) IND Filing Support COH IND filing for combination trial with MB-108 oncolytic virus for GBM Q4 Oncolytic Virus MB-108 Data Potential first data from UAB trial for GBM as monotherapy Q1’21 Gene Therapy MB-107, MB-207 Trial Start Begin patient accrual to newly diagnosed XSCID patients trial Q3 IND Filing File Mustang IND for multicenter trial in previously transplanted XSCID patients Q3

X-Linked Severe Combined Immunodeficiency (XSCID): Profound deficiency

• f T, B & NK Cell Immunity Due to Mutations in the IL2RG Gene1

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β chain Common  chain

IL-2, 4, 7, 9, 15

• r 21 X

Mutated c

XSCID

Interleukin receptor

• 1. Fischer A et al. Nat Rev Dis Primers. 2015 (Oct 29);1:15061.

▪ IL2RG codes for common gamma chain (c) – critical for normal development, maturation and function of immune cells ▪ Early diagnosis & treatment possible in areas with newborn screening (NBS) or in patients with family history ▪ In the absence of NBS, most patients (almost all males) are diagnosed at 3 – 6 months when maternal immunity wanes

– Recurrent bacterial, viral and fungal infections: Oral/diaper candidiasis, severe bacterial infections, opportunistic organisms such as Pneumocystis – Diarrhea, protein-losing enteropathy, failure to thrive

▪ Death by age 1 if untreated ▪ Standard of care is immune reconstitution via allogeneic hematopoietic stem cell transplant (HSCT)

XSCID Is the Most Common Form of Combined Immunodeficiency1

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▪ US estimated annual incidence of ~1:225,000 live births ▪ ~20 new cases per year ▪ Rest of world annual incidence is similar to US ~1:225,000 live births ▪ ~55 new cases per year in high/mid-income ex-US markets

Newly-diagnosed infants “Reservoir” (patients with XSCID who have been previously treated with allogeneic HSCT and who

therefore might be eligible for gene therapy now or in the future)

▪ US ≈ 400 patients ▪ High/mid-income ex-US markets ≈ 650 patients

1. Third-party analysis based on NBS data, medical literature, registry data & KOL interviews. Addressable ex-US markets include Canada & mid to high income countries in Europe, Asia, Latin America & Middle East. 2. https://primaryimmune.org/idf-advocacy-center/idf-scid-newborn-screening-campaign. 3. http://www.scid.net/the-scid-homepage/newborn-screening-where-it-began. 4. Meehan C et al. Rev Paul Pediatr. 2018;36:388-397.

▪ Newborn screening for SCID is available in all 50 states, D.C., & Puerto Rico2,3 ▪ Very few countries outside the US have nationwide newborn screening for SCID4

Collaboration with St. Jude Around XSCID Gene Therapy Leverages the Talent of Our Team As Well As the Capacity of Our Cell Processing Facility

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▪ Ex vivo lentiviral transduction of patients’ own hematopoietic stem cells with a normal copy of the mutated gene ▪ Process is analogous to the manufacturing process for our CAR-Ts ▪ Vector encodes normal ɣc receptor chain

– Strong preclinical efficacy & safety: no activation of LMO2 oncogene1 – Produced from a proprietary stable lentivirus producer cell line at St. Jude Vector Facility2 – We licensed this cell line from CSL Behring 3Q2019

1.

• S. Zhou et al. Blood. 2010;116:900-908.

2. RE Throm et al. Blood. 2009;113:5104-10.

• 1. Bone marrow

harvest or apheresis

• 2. Lentiviral vector

transduction Cryopreservation

• 4. Low-dose busulfan
• 5. Cell infusion
• 3. -160o C

MB-107

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Clinical Course of XSCID Patients Treated with HSCT

• 1. Hacein-Bey-Abina S. NEJM. 2014;371:1407-1417.
• 2. Heimall J. Expert Rev Clin Immunol. 2017;13:1029–1040.
• 3. Pai S-Y. NEJM. 2014;371:434-446.
• 4. Haddad E. Blood. 2018;132:1737-1749.
• 5. Amatuni GS. Pediatrics. 2019;143(2): doi: 10.1542/peds.2018-2300.

Source: ASGCT presentation by MJ Cowan, May 2018.

MSD MORD MMRD URD – UCB URD

Years

MSD Matched sibling donor MORD Matched other related donor MMRD Mismatched related donor URD Unrelated donor – peripheral blood/bone marrow URD – UCB Unrelated donor – umbilical cord blood

Probability of Survival Donor Type

Only approved treatment option is allogeneic hematopoietic stem cell transplant

▪ With severe infections at time of HSCT, mortality is ~50%1 ▪ Only 15% of patients have a matched sibling donor (MSD) ▪ Absent MSD, survival is lower & complications are higher; Quality of life is poor due to late morbidities2

– 20% experience acute graft-vs-host disease; 15% chronic – T-cell immunity decreases over time in at least 20%, leading to infections & diarrhea – 20% require 2nd HSCT due to poor T-cell reconstitution3 – Only 1/3 have sufficient B-cell reconstitution at 2 - 5 years4 – Up to 70% require lifelong intravenous immunoglobulin4,5

MB-107: Impressive Results in Newborns Reported in April 2019 NEJM

Follow-up data reported at ASH, December 2019

• Multicenter trial demonstrates first successful use of a lentiviral vector following targeted low-

exposure busulfan as a primary treatment for newly diagnosed infants with X-SCID

• All patients experienced broad immune reconstitution with excellent safety profile

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Source: Mamcarz E et al. N Engl J Med. 2019;380:1525-1534.

MB-107: Patient Characteristics

Source: Mamcarz E et al. ASH 2019.

Pt No. Age (mos) Maternal Engraftment (cells/mm3) Medical Problems CD34+ Cell Dose (x106/kg) VCN of Graft (VCN/cell)

1 6 3916 Neutropenia, CMV, Coronavirus 4.46 0.16 2 3 Rhinovirus 8.67 1.13 3 4 Rhinovirus 9.26 0.80 4 14 Disseminated BCG, Legionella, Rhinovirus 6.93 0.35 5 3 None 6.02 0.44 6 11 Disseminated BCG 4.60 0.17 7 2 6 Neutropenia 15.10 1.10 8 3 <1 Aphthous ulcers 6.52 0.36 9 4 Adenovirus colitis, oral Candidiasis 18.95 0.45 10 7 23 Rhinovirus 11.01 1.09 11 6 227 BCG injection site changes 10.05 0.57

As of July 1, 2019, 11 patients with typical XSCID mutations were treated with gene therapy. Transduced autologous bone marrow CD34+ cells (median cell dose 8.7x106/kg) were successfully generated for all patients with a median vector copy number (VCN) of 0.45 VCN/cell.

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MB-107: Clinical Outcome Continues to Be Promising

Median follow-up = 23.6 months

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Pt No. Age (mos) CD34+ Cell Dose (x106/kg) VCN of Graft (VCN/cell) Follow-up (mos) Current Status

1 6 4.46 0.16 33.9 Coronavirus & CMV resolved post boost; recent detection of CMV, now resolved; developed autoimmune cytopenia, now resolved 2 3 8.67 1.13 32.1 Off IVIG, Immunized 3 4 9.26 0.80 29.1 Off IVIG, Immunized 4 14 6.93 0.35 26.1 Disseminated BCG & Legionella resolved; no response to immunizations 5 3 6.02 0.44 24.7 Off IVIG, Immunized 6 11 4.60 0.17 23.6 Disseminated BCG resolved; off IVIG; responded to polio vaccine 7 2 15.10 1.10 20.1 Outpatient 8 3 6.52 0.36 16.0 Outpatient; ulcers resolved 9 4 18.95 0.45 10.4 Outpatient; adenovirus & candidiasis resolved 10 7 11.01 1.09 6.5 Outpatient; off IVIG 11 6 10.05 0.57 1.5 Outpatient; BCG site quiescent

Source: Mamcarz E et al. ASH 2019.

All patients remain outpatient, and those with a follow-up of >3 months recovered from pre-existing infections and are off protective isolation & protective antimicrobials. Five patients are off IVIG, of whom 3 responded to vaccines.

MB-107: Robust Functional Immune Reconstitution

Peripheral blood immune-cell subsets assessed by flow cytometry

• 9 patients, with 3 months’ follow-up, achieved normal for age T-cell & NK-cell numbers within 3-4 months post

gene therapy

• Patient #1 received boost @ 12 months; normalized T-cell numbers within 3 months following boost
• Phytohemagglutinin (PHA) stimulation assays demonstrated normal T-cell function
• In all evaluable patients, IgM production normalized by 6-12 months

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Source: Mamcarz E et al. ASH 2019.

Patient #1 Patient #1

MB-107: Sustained Multi-Lineage Vector Marking Over Time

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Source: Mamcarz E et al. ASH 2019.

• In addition, vector insertion site analysis demonstrated polyclonality on all evaluated lineages

MB-107: Conclusions from Newborn Trial & Future Directions

• Clinical

– LV vector & targeted low-dose exposure busulfan gene therapy is well tolerated & results in the development of a functional immune system – No evidence of malignant transformation was observed with longer median follow-up of ~2 years – This approach may present a promising alternative to current therapies, which rely in part on high-dose chemotherapy followed by allogeneic HSCT – Study is ongoing at St. Jude, UCSF, & Seattle Children’s to determine long-term safety & sustained efficacy

• Regulatory

– MB-107 IND filed for expanded multicenter trial under Mustang IND; trial on hold pending CMC clearance by FDA

• St. Jude will remain Phase 1/2 trial sponsor until FDA approves Mustang’s IND
• In the meantime, Mustang is lining up additional US sites & laying CMC & ClinOps foundation for expansion to Europe in 2021

– Regenerative Medicine Advanced Therapy (RMAT) Designation – granted 3Q2019

• Will facilitate Mustang’s IND regulatory interactions for MB-107 (gene therapy product for newly diagnosed XSCID patients)
• Plan to request a separate RMAT designation for MB-207 (product for previously transplanted XSCID patients)

– ATMP Designation granted 2Q2020 – Requests for Rare Pediatric Disease & Orphan Drug designations submitted 2Q2020

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MB-207: Equally Encouraging Results in Previously Transplanted Patients

Transduction enhancers (LentiBOOST™ + 16,16-dimethyl Prostaglandin E2) added in 2019

19 Source: De Ravin SS et al. ASH 2019.

Acquisition of patients’ cells

• G-CSF & Plerixafor mobilization
• Apheresis CD34+ HSC collection
• CD34 selection / Cryopreservation

*Busulfan conditioning

• 3 mg/kg/day x 2 days
• Targeting on 2nd day to achieve total

AUC 9000 (μM/L)*(min) = ~32,200 (ng/ml)*(hr)

Thaw & culture CD34+ HSC 44 hr Pre- Stim 1st Vector Day -3 Day -1 Day -2 Day 0 Infusion of Transduced Cells (Fresh Product) Busulfan* Thaw & culture CD34+ HSC 20 hr Pre- Stim 1st Vector 2nd Vector Day -3 Day -1 Day -2 Day 0 Infusion of Transduced Cells (Fresh Product) Busulfan*

Original Transduction (OT) Regimen

• 2012-2016
• Patients 1 – 8

Transduction Enhancers (TE) Regimen

• 2019
• Patients 9 – 13;

patient 8 retreated

MB-207: Patient Characteristics

Pt No. Age (yrs) CD34+ (106/kg) VCN Cells Infused Date Infused PB Myeloid VCN @ 3 mos 1 23 18 0.27 Oct 2012 0.07 2 22 16 0.17 Jun 2013 0.06 3 7 20 0.31 Mar2015 0.07 4 16 22 0.57 Jul 2015 0.23 5 10 25 0.36 Jul 2015 0.29 6 23 22 0.41 Feb 2016 0.33 7 3 32 0.30 Sep 2016 0.04 8 12 36 0.27 Oct 2016 0.05

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Pt No. Age (yrs) CD34+ (106/kg) VCN Cells Infused Date Infused PB Myeloid VCN @ 3 mos 9 19 5 3.19 Feb 2019 1.72 10 13 9 4.70 Mar 2019 3.59 11 25 25 14.28 Mar 2019 6.44 12 34 28 3.07 Apr 2019 6.42 13 24 17 4.22 Jul 2019 0.23 8 15 10 4.78 Jun 2019 2.54

Original transduction (OT) regimen (2012-2016) Transduction Enhancers (TE) regimen (2019)

Source: De Ravin SS et al. ASH 2019.

*Patient 8 received a boost of cells manufactured using the ET regimen

MB-207: Results in First 8 Previously Transplanted Patients Treated with OT Regimen Confirm & Extend Positive 2016 Findings

• Safety profile maintained

– No indication of possible pre-cancerous cell proliferation – No vector insertional leukemogenesis to date – 1 patient died from pre-existing lung damage >2 years post-therapy; highlights importance of early intervention

• Substantial clinical improvement

– 6/7 cured chronic norovirus – 5/6 resolved protein losing enteropathy – 4/8 experienced protective response to immunizations & ceased IgG supplements

• Impressive biomarker improvement

– 7/8 increased host T cells chimerism from 0-2% to 28-93% – 7/8 normal T cell proliferation response – 6/8 increasing or normal CD20+ CD27+ IgG+ memory B cells – 7/8 normal levels of IgM

21 Source: De Ravin SS et al. ASH 2019.

MB-207: Stable Gene Marking in First 2 OT Patients

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Gene marking in sorted cell lineages as vector copy number per genome after treatment in Pt 1 (to 36 months) and Pt 2 (to 24 months)

Source: SS De Ravin et al. Sci Transl Med. 2016; 8(335):335ra57.

MB-207: Despite Excellent Results in First 8 Patients Treated with OT Regimen, NIH Noted Room for Improvement

• One of the 8 patients – like newborn patient #1 – failed to achieve any of the lab or clinical landmarks
• Pace to achieve lab & clinical landmarks was slow (2-3 years in most patients)
• Slow increase in peripheral blood NK cells; only patient #1 achieved normal range (at year 7)
• Vector amount used per patient was high, particularly for adults

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Transduction Enhancers (TEs) Were Included in Cell Processing in Next 6 Patients to Address These Challenges

• Increase pace of immune reconstitution & achievement of clinical benefit
• Enhance pace of NK cell generation, where higher VCN may be required
• Reduce amount of vector required (8-12 fold less vector used)

Source: De Ravin SS et al. ASH 2019.

MB-207: TE Regimen Resulted in Accelerated Increase in NK Cell VCN & in Peripheral Blood NK Cells in 1st 3 Months

24 Source: De Ravin SS et al. ASH 2019 (from abstract).

OT ET OT ET

MB-207: TE Regimen Resulted in Accelerated Clearance of Chronic Norovirus Infection

OT Regimen

• 6/7 patients with norovirus cleared infection
• Patients required 1 – 3 years post therapy to cure infection
• Patient 8 did not clear the infection

TE Regimen

• Patients 9 & 10 cured chronic norovirus infection by 6 months post therapy
• Patients 11, 12 & re-treated 8 with norovirus infection are symptom free @ 3 – 6 months

25 Source: De Ravin SS et al. ASH 2019.

MB-207: Summary of Regimen With TEs & Future Plans

• Several advantages for regimen with TEs observed with limited follow-up

– Accelerated clearance of norovirus & GI symptoms – Accelerated production of NK cells – Uniformly higher transduction product VCN – Accelerated increase in vector marking – Accelerated spike in IgM – Requires 1/8 to 1/12 amount of vector used in first 8 patients

• Safety profile of regimen has been similar to safety profile in patients treated with OT regimen
• Mustang currently considering possibility of incorporating less aggressive TE regimen in MB-207 pivotal trial
• Pre-IND meeting planned for 3Q2020, with subsequent IND filing expected shortly thereafter
• Requests for Rare Pediatric Disease & Orphan Drug designations submitted 2Q2020
• Mustang expects to submit request for ATMP designation 3Q2020; RMAT in 2021

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MB-106: CAR T Therapy for B-cell NHL & CLL1,2

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▪ CD20 is a commercially validated target,3 and CD20 CAR Ts have been active in small pilot trials 4,5 ▪ Mustang in-licensed FHCRC’s CD20 CAR-T program in 2017 just prior to the start of the first-in-human trial

1. Lee SY et al. J Immunother. 2018;41:19-31. 2. NHL = Non-Hodgkin lymphoma; CLL = Chronic lymphocytic leukemia 3. https://www.genengnews.com/the-lists/the-top-15-best-selling-drugs-of- 2017/77901068?page=2 4. Till BG et al. Blood. 2012;119:3940-3950. 5. Zhang W-y et al. Signal Transduction and Targeted Therapy. (2016) 1, 16002; doi:10.1038/sigtrans.2016.2

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Source: Brian Till, Fred Hutchinson Cancer Research Center, unpublished data.

Spacer (IgG2 hinge linker) Co-stimulatory domains (CD28 and 4-1BB) Signaling domain (CD3ζ) Fully human CD20 scFv

ζ ζ

CD19t

NSG mice were injected i.v. with Raji-ffLuc tumor cells, followed 2 days later by i.v. injection of central memory T cells transduced with MB-106, an anti-CD19 CAR-T, or an empty vector.

Tumor burden over time as assessed by bioluminescence imaging Kaplan‐Meier plot of overall survival

In vivo antitumor effect of MB-106 compared with CD19 CAR

MB-106: Little Competition in CD20-Targeted Cell Therapy Space

• One clinical-stage pharma/biotech CD20 CAR-T in the US: Precision BioSciences off-the-shelf PBCAR20A

(1st patient dosed April 2020)

– 2 academic CD19/CD20 dual CAR-Ts – Several clinical-stage CD20 CAR-Ts in China

• 1 preclinical CD20 gamma-delta CAR-T (Adicet Bio, ADI-001)
• Major investigational competition for target is in bispecific antibody space (Regeneron, Genmab, Roche)
• FHCRC initiated a single-center investigator IND trial with MB-106 in B-cell NHL 4Q20171

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• 1. https://clinicaltrials.gov/ct2/show/NCT03277729

MB-106: Background to Cohort 4

▪ Due to safety concerns, protocol started with cyclophosphamide alone as lymphodepleting (LD) chemotherapy ▪ Little activity in first 3 cohorts

• Cohort 1 (no fludarabine): 3.3 x 105 CAR-T cells/kg
• Cohort 2 (no fludarabine): 1 x 106 CAR-T cells/kg
• Cohort 3 (cyclophosphamide + fludarabine): 3.3 x 105 CAR-T cells/kg

▪ In collaboration with Mustang CMC team, FHCRC optimized cell processing

▪ In vivo experiments at FHCRC demonstrated superiority of the new process, resulting in decision to amend the IND & implement the process starting with Cohort 4 ▪ First patient then enrolled in Cohort 4

• Due to enhanced in vivo potency of CAR-T cells relative to prior cohorts, dose was reduced to starting level:

3.3 x 105 CAR-T cells/kg

• Complete LD chemotherapy regimen administered: Cyclophosphamide + fludarabine

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MB-106: CR Achieved at Day 28 in FL Patient

1st patient dosed after Mustang-led optimization of cell processing

• Disease was refractory to initial therapy & 2 salvage regimens
• Patient experienced no cytokine release syndrome (CRS) or neurotoxicity
• Good CAR-T expansion noted
• Awaiting further follow-up data; trial continues to accrue well

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MB-106: Next Steps

• CMC: Tech transfer to start 3Q2020; plan for process development to address CLL
• Anticipate pre-IND meeting 4Q2020, IND filing 1Q2021

MB-105: CAR-T Therapy for Prostate, Pancreatic, Gastric & Bladder Cancers1

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Target

PSCA (Prostate Stem Cell Antigen) PSCA overexpressed on numerous solid tumors2,3

Market

Estimated new cases in U.S. in 2018

• Prostate: 164K
• Pancreatic: 55K
• Gastric: 26K
• Bladder: 81K

CAR-T Competition

Bellicum: PSCA CAR-T (Ph 1, NCT02744287) Poseida: PSMA CAR-T (Ph 1, NCT04249947) Tmunity: PSMA CAR-T (Ph 1, NCT04227275) (Not recruiting) Autolus: PSMA CAR-T (to start phase 1 1H2021)

Status

Prostate cancer trial is enrolling under COH IND4

Next Steps

Possible initial data disclosure 4Q2020 Awaiting grant funding in order to initiate phase 1 trial in pancreatic cancer 1. Priceman SJ et al. Oncoimmunology. 2017 Oct 16;7(2):e1380764. 2. Saeki N et al. Clin Cancer Res. 2010;16:3533-3538. 3. Abate-Daga D. Human Gene Therapy. 2014;25:1003-1012. 4. https://clinicaltrials.gov/ct2/show/NCT03873805

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• 3 patients treated in 1st cohort @ 100M cells without lymphodepleting (LD) chemotherapy
• 1st patient in 2nd cohort – with LD chemo – experienced significant PSA decline at 28 days + substantial improvement on

scans

• Therapy well tolerated; cytokine release syndrome treated only with tocilizumab
• Trial continues to accrue well; may permit full data disclosure 1Q2021
• Mustang is targeting IND filing for 4Q2021

MB-105: PSCA CAR-T Showed Substantial Activity in 1st Patient with LD Chemo

• ~11,800 new patients diagnosed in the US annually; 7% 5-year

survival2

• IL13R⍺2 is an attractive target for CAR-T development

– overexpressed in >75% of GBM patients – Not expressed on normal brain cells

• No CAR-T programs competing for target; only CAR-Ts directed

to other targets are in phase 1 at COH (HER2, chlorotoxin)

• MB-101 is the first CAR-T to demonstrate durable remission in

the solid tumor setting

• Complex 60-patient phase 1 trial now complete, with

assistance from $12.8M funding from CIRM3

4-1BB IgG4 CD3ζ 5’ 3’ CD4 tm human IL- 13

Mutated at (E13Y) to preferentially bind IL-13R⍺2

• 1. Brown CE et al. Mol Ther. 2018;26:1-14.
• 2. Ostrom QT et al. Neuro-Oncology. 2019;21(S5):v1-v100. doi: 10.1093/neuonc/noz150.
• 3. California Institute for Regenerative Medicine

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Co-stimulatory domain (4-1BB) Signaling domain (CD3ζ) Fully human binder to human IL13Rα2 Spacer [ IgG4(∆CH2) ]

ζ ζ

MB-101: IL13Rα2 CAR-T Therapy for Glioblastoma (GBM)1

MB-101: Phase 1 Clinical Trial Completed

Study has laid foundation for combination & patient selection trials

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Optimization of Dose, Schedule, Route of Administration & T Cell Selection Over the Course of 5 Strata:

Stratum 1: Biopsy, then intratumoral injection Stratum 2: Resection, then intracavitary (ICT) injection Stratum 3: Multifocal disease, intracerebroventricular (ICV) injection Stratum 4: Dual ICT & ICV (added Q2’17) Stratum 5: Dual ICT & ICV, novel T cell selection (added Q4’17) Treatment may continue with additional

• ptional

infusions

Cycle 1 Cycle 2+

DL1 2 x 106 CAR+ 10 x 106 CAR+ DL2 10 x 106 CAR+ 50 x 106 CAR+ DL3 20 x 106 CAR+ 100 x 106 CAR+

Dosing regimen

Unique Features of the Phase 1 Trial

• 1. No lymphodepleting chemotherapy
• 2. Repeat dosing
• 3. Intracerebroventricular dosing, starting

with stratum 3

• 4. Selection for TN/MEM cells in stratum 5

MB-101: ICV CAR-T Cells Achieved Dramatic Results in a Refractory GBM Patient

Tumor noted to be “hot” (high infiltration of T cells) with significant component of leptomeningeal disease

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5 tumors followed T4 T5 T6 T7 T8 400 300 200 100 100 150 200 300 250

First ICV infusion

Maximum Lesion Area (mm2) Intracavitary Cycles 1 - 6 Intracerebroventricular (ICV) Cycles 12 - 16 ICV Cycles 7 - 11

Source: Brown et al. NEJM. 2016;375:2561-9.

T6 T7 T6 T7

Pre-Therapy Post-Therapy

▪ Complete response sustained for 7.5 months ▪ Initial tumors did not recur ▪ New lesions had ↓ IL13Rα2 expression

Days after enrollment

Day 86 Day 108 Day 289 Day 295

MB-101: Applying Learnings from Complete Responder

• Pt had by far the highest infiltration of CD3+ cells: Do “hot” tumors respond better to MB-101?

– Together with our COH colleagues, we decided that combination of the CAR-T with an oncolytic virus (OV) would be the preferred mechanism for trying to turn cold GBM tumors hot – In 1Q2019 we in-licensed a preclinical OV from Nationwide Children’s Hospital1

• 1st patient dosed 4Q2019,2 initial proof-of-concept observed
• Preclinical combination studies (OV + MB-101) to start at COH 3Q2020

– Anticipate filing IND for investigator-initiated single-center combination trial at COH 4Q2020 for R/R GBM

• Tech transfer to Mustang in 2021 if COH data are encouraging
• Patient had substantial component of leptomeningeal disease: Is this the best solid tumor “substrate” for

cell-cell interactions required for optimal activation of CAR-T cells?

– Anticipate filing IND for investigator-initiated single-center trial at COH 3Q2020 for R/R GBM with significant component of leptomeningeal disease

• With grant funding, COH has also started combination trial with checkpoint inhibitors3

36

• 1. Cassady KA et al. Mol Ther Oncolytics. June 2017, vol 5. https://doi.org/10.1016/j.omto.2017.02.001.
• 2. https://clinicaltrials.gov/ct2/show/NCT03657576
• 3. https://clinicaltrials.gov/ct2/show/NCT04003649

MB-102: CD123 CAR-T Therapy for R/R AML, BPDCN & hrMDS1,2,3

Median survival for all 3 diseases is generally ≤ 1 year7

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Target

Overexpressed in high percentage of patients4,5,6 Cellectis’ CD123 CAR-T in Ph 1 for AML Other competitors: ADCs, bispecifics

US Annual Incidence

AML: ~19,520 MDS: ~15,000 BPDCN: ~500-1,000

Status

Ph 1 at City of Hope8 Orphan Drug Designation for BPDCN & AML Mustang IND approved 3Q2019

Next Steps

Expect treatment of 1st patient in Mustang IND trial 3Q2011

▪ CD123 validated as target for BPDCN: Stemline’s IL-3 fusion toxin SL-401 approved 4Q2018 (ELZONRIS™)9, 10

• 1. Mardiros A et al. Curr Opin Hematol. 2015;22:484-488.

2. Jonnalagadda M et al. Mol Ther. 2015;23:757-768. 3. Zhang W et al. Blood. 2017;130:1917.

• 4. Also known as IL-3R⍺
• 5. Testa U et al. Biomarker Research. 2014;2:4.
• 6. Stevens BM et al. Blood. 2015;126:4104.
• 7. American Cancer Society; https://www.cancer.org/cancer/acute-

myeloid-leukemia/about/key-statistics.html

• 8. https://clinicaltrials.gov/ct2/show/NCT02159495
• 9. https://ir.stemline.com/node/10281/pdf
• 10. Pemmaraju N, et al. Blood. 2017;130:3855.
• 11. https://clinicaltrials.gov/ct2/show/NCT04109482

AML = acute myelogenous leukemia BPDCN = blastic plasmacytoid dendritic cell neoplasm hrMDS = high risk myelodysplastic syndrome

MB-102: CAR-T Targeting CD123 Expressing Tumors

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Murine anti- CD123 scFv IgG4-Fc CD28 costimulatory domain CD3ζ 3’ scFv IgG4-Fc CD28 CD3ζ T2A EGFRt 5’

Improved survival for mice treated with CD123 CAR-T cells

Sources:

• Mardiros A et al. Blood. 2013;122:3138–3148.
• Budde L et al. Blood. 2017;130:811.

MB-102: Ongoing Phase 1 Clinical Trial at COH

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Patient Population Current Dose Level Planned Enrollment Study Objectives Refractory / Relapsed AML BPDCN (arm added Q3’17) Dose level 3: 500 x 106 cells Dose level 1: 100 x 106 cells 21 21

• Feasibility & safety
• MTD of single infusion

(Flu 25 mg/m2/d x 3; Cy 300 mg/m2/d x 3)

SOC AlloSCT

≥ day 28 post T cell infusion, proceed to ablation if elected

MB-102: AACR Tumor Immunology & Immunotherapy Meeting, November 20181: COH Reported 2 MRD Negative CRs in AML, 1 CR in BPDCN

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Pt. No. Age/Sex Dx Prior Lines; Allo (donor) BM Blasts; CD123 Cytogenetics/ Molecular Lympho- depletion CAR T dose Response at Day 28

1 44/F AML/MDS 6; Y (MRD) 20%;

• ve to dim
• 7, Inv(3)

Flu/Cy 50M Donor PD 40% blasts 2 54/F AML/MPD 4; Y (MRD) 18%; Dim to mod IDH1 Flu/Cy 50M Donor Morphologic leukemic-free state (MLFS) 3 43/F AML 4; Y (MRD) 20%; Dim Normal Flu/Cy

200M

Donor

CRi (MRD-ve by flow on day 14)

4 54/F AML 7; Y (MUD) 37%; Mod t(3;7), +21 Flu/Cy

200M

Donor (DLI) SD 20% blasts 5 42/F AML/MDS 6; Y (MRD) 41% Mod

• 7, +8

Flu/Cy Decitabine

187M

Donor (DLI) SD 46% blasts 6 28/M AML 7; Y (MRD) 3% Dim Complex FLT3-TKD, N-RAS Flu/Cy

200M

Donor CR (MRD+, 0.10% day 28) 7 36/F AML 10; Y (MRD, MUD)) 0.64% Dim Complex

• 7, inv(3)

Flu/Cy Decitabine

200M

Auto

MLFS (MRD-ve CR day 84)

1 Presented by Dr. Budde at AACR Tumor Immunology

& Immunotherapy Conference, Nov. 30, 2018. MRD = Matched related donor MUD = Matched unrelated donor MRD = Minimal residual disease

Pt. No. Age/Sex Dx Prior Lines; Allo (donor) BM Blasts; CD123 Cytogenetics/ Molecular Lympho- depletion CAR T dose Response at Day 28

8 74/M; BPDCN 1 (SL-401 x 6 => PR; No NED Normal Flu/Cy 100M; Auto

CR

9 BPDCN Flu/Cy 100M; Auto MRD+ CR

AML BPDCN

MB-102: Summary of COH Adverse Events1

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Adverse Events Grade 2 Grade 3 Grade 4 Cytokine release syndrome 1 Febrile neutropenia 3 Chills 2 Fever 4 Alanine aminotransferase increased 1 Aspartate aminotransferase increased 1

Grade 2 & above toxicities (probably or definitely attributed to CAR-T cells)

▪ Maximum neurotoxicity grade 2 (dizziness, headache, somnolence) ▪ Patient 7 achieved full bone marrow recovery on day 56 ▪ No grade 5 events or DLTs

• 1. Presented by Dr. Budde at AACR Tumor Immunology &

Immunotherapy Conference, Nov. 30, 2018.

MB-102: Next Steps for Mustang Multicenter Trial

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• Due to increased potency of cells processed by Mustang, dose reduced by 50% from highest safe dose

achieved by COH at time of IND submission; starting dose will be 100M cells

• 4 sites: COH + major enrollers to Stemline’s pivotal BPDCN trial (MDACC, DFCI, Duke)
• Anticipate treating first patient 3Q2020

MB-104: CS1 CAR-T Therapy for Multiple Myeloma1

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Target

Expressed on plasma cells & >95% MM patients Lower on NK cells & activated T cells; absent

• n other normal cells1

Cellectis’ CS1 CAR-T has also started Ph 1

US Annual Incidence

~ 30,7702 Median survival for advanced disease is 3.5 years3

Status

COH study is accruing4

Next Steps

Expect to file Mustang IND for multicenter Ph 1/2 trial 2Q2021

1. Wang X et al. Clin Cancer Res. 2018;24:106-119. 2. https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html 3. https://www.cancer.org/cancer/multiple-myeloma/detection-diagnosis-staging/survival-rates.html 4. https://clinicaltrials.gov/ct2/show/NCT03710421

CS1 CAR-T Is Superior to BCMA CAR-T in Preclinical Mouse Model of Multiple Myeloma

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Untreated Mock CS1 BCMA e4-e5 D0 D8 e5-e6 D15 D22 e6-e7 D28 D49 e7-e8 Euthanized Euthanized P<0.003

Scale Source: Xiuli Wang, City of Hope, unpublished data (used with permission).

Spacer [IgG4(∆CH2)] Co-stimulatory domain (4-1BB) Humanized CS1 binder

(selective binding to CS1 on malignant cells vs. activated T cells)

ζ ζ

EGFRt-epHIV7

Improved survival for mice treated with CS1 CAR-T cells

Signaling domain (CD3ζ)

Board of Directors

Executive Title Previous Experience

Michael S. Weiss, JD Chairman Lindsay A. Rosenwald, MD Director Manuel Litchman, MD President & Chief Executive Officer Adam J. Chill, JD Director Neil Herskowitz Director ReGen Group (ReGen Capital Investments LLC, Riverside Claims Investments LLC) Michael J. Zelefsky, MD Director

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Financial Summary

▪ As of March 31, 2020, cash, cash equivalents and restricted cash of $56.8 million (1Q20 net loss of $11.9M) ▪ $35.0M gross proceeds in June 2020 from underwritten public offering, excluding exercise of the

• ver-allotment option

▪ 2019 financing

▪ $20 million venture debt financing with Horizon Technology Finance announced April 2019

• $15 million funded at closing
• $5 million upon achieving certain milestones

▪ $31.6M gross proceeds in May 2019 from underwritten public offering, including full exercise of the

• ver-allotment option

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Mustang Target Goals in 2020: 3 Open INDs

Anticipate initiating pivotal XSCID trials & building on early indications of CAR-T activity

▪ Newly diagnosed XSCID

− Begin accrual to Mustang IND trial 3Q2020

▪ Previously treated XSCID: File Mustang IND for multicenter trial 3Q2020 ▪ Treat first patient on Mustang IND multicenter CD123 CAR-T trial (NCT04109482) 3Q2020 ▪ File COH IND for innovative combination trial in GBM (IL13Rα2 CAR-T + oncolytic virus) 4Q2020 ▪ Tech transfer & prepare for 1H2021 Mustang IND filings for CD20 & CS1 CAR-Ts ▪ Possible data disclosures from collaboration partners’ trials 4Q2020/1Q2021

− Follow-up data from FHCRC CD20 CAR-T trial, COH CD123 CAR-T trial − First data from COH PSCA trial, COH CS1 CAR-T trial, & Nationwide OV trial

▪ Continue BD&L activities

− In-licensing opportunities to expand our ex vivo gene therapy franchise for rare diseases − Partnering opportunities to access non-dilutive capital

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