next generation personalized medicines

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SNN Network Summer Virtual Event August 18, 2021 Next Generation Personalized Medicines A platform company in cell, gene-editing & cytokine therapies

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Page 1: Next Generation Personalized Medicines

SNN Network Summer Virtual Event

August 18, 2021

Next Generation

Personalized

MedicinesA platform company in cell,

gene-editing & cytokine therapies

Page 2: Next Generation Personalized Medicines

Disclaimer

This presentation is intended to provide summary information about the business of Brooklyn ImmunoTherapeutics LLC (“BTX” or the “Company”). The information in this presentation is in no

respects complete, comprehensive, or exhaustive, and reference is made to the proxy statement/prospectus/consent solicitation statement of NTN Buzztime, Inc.dated February 8, 2021, which has

been filed by NTN with the U.S. Securities and Exchange Commission.

This presentation is not an offer to sell securities nor should it be deemed to imply an offer of securities.

This presentation, among other matters, contains forward-looking statements based on estimates and assumptions. Forward-looking statements include information concerning possible or assumed

future results of operations of the Company, and possible future financing, partnering, strategic, sale or other transaction(s) and other information relating to the Company. Forward-looking

statements include statements containing the words "believes," "plans," "hopes," "expects," "anticipates," "intends," "estimates" or other similar words or expressions. Except for the historical

information contained herein, the matters discussed are forward-looking statements. Forward-looking statements involve significant known and unknown risks and uncertainties and other factors

which may cause the actual results, performance or achievements of the Company to differ materially from any actual future results, performance or achievements expressed or implied by those

projected in the forward-looking statements for any reason. These statements involve risks and uncertainties as to which the Company can provide no assurances. No assurance can be given that

the Company will succeed in consummating any commercial relationship or transaction or the terms and conditions upon which any such relationship or transaction may be consummated. Further,

a number of factors including (i) the impact of the ongoing COVID-19 pandemic on the timeline for the Company’s clinical trials and on the Company’s business activities generally, (ii) the Company’s

ability to complete its clinical trials on a timely basis and within the budgets for such trials, (iii) whether the clinical trials undertaken or will undertake in the future will be successful, (iv) whether the

Company’s API manufacturing operations can maintain compliance with current Good Manufacturing Practices, (v) the scope of the Company’s intellectual property protections and the outcome of

any future challenges or opposition to the Company’s intellectual property, (vi) whether the Company’s future efforts to acquire or in-license complementary programs will prove successful, (vii)

whether the Company’s efforts to pursue partnerships to advance and accelerate clinical programs will prove successful, (viii) whether the Company’s merger with NTN will be completed, (ix)

whether the Company will be able to successfully list the common stock of the combined company on the NYSE American following the merger, and (x) the other factors described in the “Risk

Factors” section of the Registration Statement, could adversely affect the Company. Further, market and industry statistics contained in this presentation are based on information available to us.

While we believe that information to be accurate, it was not prepared for purposes of a securities offering or economic analysis.

All forward looking statements speak only as of the date hereof and except as required by law, the Company assumes no obligation to update these forward-looking statements even if new

information becomes available.

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Page 3: Next Generation Personalized Medicines

Brooklyn ImmunoTherapeutics

A platform company in cell, gene-editing and cytokine therapies

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Clinical stage Cytokine therapy Nucleic acid delivery

Cell reprogramming Gene editing

Page 4: Next Generation Personalized Medicines

Brooklyn ImmunoTherapeutics (BTX) - Overview

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• Strong and efficient leadership team with

>50 years in drug development/healthcare

• GMP Manufacturing Facility with

capabilities on both sides of the company

Cytokine TherapiesmRNA-based Gene Editing

and Cell Therapies

IRX-2: • Ongoing Phase 2b study in

Neoadjuvant Head and Neck Cancer

• Additional Investigator Sponsored Studies in various tumor types (including combinations with Checkpoint Inhibitors)

• 3 independent human studies showing increases in numbers and types of immune cells after treatment with IRX-2

Exclusive license for a broad mRNA technology platform:• mRNA cell reprogramming

(cell therapy)• mRNA-based gene editing• Proprietary gene editing

protein• Proprietary lipid delivery

system

Broad portfolio including a Phase 2b cytokine asset, potential for additional cytokine compounds, and an exclusive license for a multi product gene editing and cell therapy platform

Page 5: Next Generation Personalized Medicines

BTX is Led by a Strong, Experienced Management Team

5

Howard FederoffMD, PhD

Chief Executive Officer and President

Kevin D’AmourPhD

Chief Scientific Officer

Ron GuidoMS, MS Pharm. Med.

Chief Development Officer

Lynn Sadowski MasonMS

EVP, Clinical Operations

• Sention Inc.• Therapeutic

Management

Jay SialMBA

Chief Administrative Officer

Page 6: Next Generation Personalized Medicines

BTX’s Experienced Board of Directors

• Senior advisor to the CEO of Dana-Farber Cancer Institute

• Strategic Business Development & Corporate Ventures, Verily (Google Life Sciences)

• Formerly VP, Global Mergers & Acquisitions and Business Development, Roche

• Formerly Venture Partner, Colt Ventures

• Led over $5bn in deals and investments across multiple therapeutic areas & life science sectors, co-founded biotech companies in immunotherapy & microbiome space

• Board Member, MassBio(trade association)

Luba Greenwood

• Founder & Co-Head Managing Partner of ARA Partners, a PE firm managing $2.5bn in assets

• Had led over 50 investments and sits on the board of ten companies

• Prior to ARA Partners, founded and led Intervale Capital, a PE firm

• Generated gross realized returns of 3.1x capital & 45% IRR

• Director of the Conservation Fund

Charles CheringtonChairperson

• CEO of UCI Health, vice chancellor for health affairs and dean of the UCI School of Medicine

• Executive vice president of Health Sciences and executive dean at Georgetown University.

• Cofounder MedGenesisTherapeutix and Brain Neurotherapy Bio

• CEO of Aspen Neuroscience

• Chair of the NIH Recombinant DNA Advisory Committee, the NHILBI Gene Therapy Resource and the Board of the Association of the Academic Health Centers.

Howard Federoff, M.D., Ph.D.

• Chairman of Oak Bay Biosciences

• Chairman and Chief Executive Officer of MedGenesis Therapeutics Inc.

• Previous Chief Scientific Officer of PRA International and Chief Executive Officer of CroMedica International.

• Graduate from the University of the Pacific (Bachelors degree in Chemistry/Biology) and Ph.D. in Neuropsychology from the University of Victoria

Erich Mohr, Ph.D.

6

Dennis Langer, M.D., J.D.

• Director of the Whitehead Institute for Biomedical Research, Myriad Genetics, Inc, and several private companies

• Former CEO of Neose Technologies, Inc

• Former President of Dr Reddy’s North American business

• Former SVP of Research and Development at GlaxoSmithKine plc

• Graduate of Columbia University and earned his M.D. at Georgetown University School of Medicine and his J.D. at Harvard Law School

Page 7: Next Generation Personalized Medicines

BTX’s Cutting Edge Scientific Advisory Board

7

IRX-2 SAB

Steven Schnittman – Independent consultant, former VP, Global Clinical Research BMS

Allison O’Neill – Dana Farber Cancer Institute

Gregory Wolf, MD – University of Michigan

mRNA Gene Editing/Cell Therapy SAB

Michael Andreef, MD, PhD – MD Anderson

Matthew During, MD, PhD – MeiraGTx

Christopher Rohde, PhD – Factor Bioscience

Page 8: Next Generation Personalized Medicines

BTX Most Advanced Asset: IRX-2 Human-Derived Cytokines

• Phase 2 Company Sponsored Study in 1 IST

Indication targeted to begin in 2022

• Phase 3 Study in Neoadjuvant Head and Neck

Cancer targeted to begin in 2023

8

Renal Cell Cancer

Liver Cancer

Head and Neck Cancer

Gastrointestinal Cancer

Currently in Phase 2b for Neoadjuvant Head and Neck Cancer Final data readout expected in 1H2022

Additional Investigator Sponsored Trials (ISTs) in:

Future Planned Studies:

Strong IP and Patent Position

Cervical/Vulvar Interstitial Neoplasia

Triple Negative Breast Cancer

Early Stage Breast Cancer

BTX expects it has cash runway through 2023

Page 9: Next Generation Personalized Medicines

IRX-2 Human Derived IL-2 Stimulates a Broad Immune Response

IRX-2 initiates a broad set of effects across multiple immune cells

NK

Natural Killer (NK Cells) are highly cytotoxic immune effectors that can kill cancer cells without prior sensitization

Cancer-specific T cells kill cancer cells by recognizing

expressed neoantigen targets

Dendritic cells present antigens to T cells leading to T cell division and

enhancement of cell killing activity

Enhances generation andT cell stimulatory capacity of

dendritic cells

Promotes cancer-specific T cell expansion and killing

capacity

Augments capacity to kill tumors formerly insensitive to NK

mediated destruction

Function

IRX-2 Impact

9

Results supported further clinical development in multiple indications

T T Cell NK CellDendritic Cell

Page 10: Next Generation Personalized Medicines

IRX-2 is Differentiated from other IL-2 Formulations

Unlike recombinant IL-2 drugs, IRX-2 is derived from human blood cells (huIL-2 ) may confer distinct advantages

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IRX-2 huIL-2 Recombinant IL-2 Pegylated IL-2 Engineered IL-2

Well-tolerated ToxicityToxicity reduced as compared

to native IL-2Toxicity data limited –

preclinical animal studies

Multiple cytokines Single cytokine Single cytokine Engineered cytokine

Natural conformation leading to greater

functionality

Abnormal folding impacting functionality

Pegylation hides active site, impairing functionality

Preclinical data only: impact of modification and selective

pegylation unknown

Physiologic dosing High dosesDoses exceeding physiologic levels

Dosing not established

Page 11: Next Generation Personalized Medicines

Comparative Binding Affinity rIL-2 (recombinant) vs huIL-2 (human)

• huIL-2 is functionally distinct from rIL-2, as

related to its ability to affect the proliferation of

resting lymphocytes

• Data has shown that huIL-2 has significantly

higher bioactivity than rIL-2 suggesting

effectiveness at lower doses and less frequent

administration than rIL-2

• This may potentially mitigate some of the

known off-target, and toxicity issuesHigh binding affinity of moIL-2* (huIL-2) , rIL-2 for the intermediate and high affinity cell types.

M.C. Denis, B.T. Huber / Molecular Immunology 40 (2003) 279–286

60

50

40

30

20

YT-1

100 1000 10,000

rIL-2

huIL-2

% I

nh

ibit

ion

IL-2 (IU/ml)

60

50

40

30

20

Kit-225

100 1000 10,000

rIL-2

huIL-2

% I

nh

ibit

ion

IL-2 (IU/ml)

11

Data demonstrate that natural huIL-2 exhibits distinct functional properties compared to recombinant rIL-2

Page 12: Next Generation Personalized Medicines

Biologic Activity of IRX-2 in Clinical Trials

1: Berinstein et al., OncoImmunology, February 2018; Barnes and Amir, British Journal of Cancer, July 2017; Nguyen et al. Head and Neck, July 2016.2: Wolf et al., Oral Oncology, July 2020 Tumor Infiltrating Lymphocytes after neoadjuvant IRX-2 immunotherapy in oral squamous cell carcinoma: interim findings from the INSPIRE trial

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Demonstrated Biologic Activity in Multiple Independent Studies

• Studies show immune marker activation in patients treated with IRX-2 in all studies

• Correlation between marker activation and improved disease survival in Phase 2a head and neck cancer trial

Page 13: Next Generation Personalized Medicines

D a y s p o s t T u m o r C e l l I n o c u la t io n

Tu

mo

r v

olu

me

( m

m3

)

1 0 1 5 2 0 2 5 3 0 3 5 4 0 4 5

0

2 0 0

4 0 0

6 0 0

8 0 0

1 0 0 0

1 2 0 0

1 4 0 0

1 6 0 0

In je c t S C C 7 s .c .

1 x 1 06/m o u s e

a n t i - m P D L 1 0 .0 3 m g /m o u s e

P B S

I R X -2 1 0 0 I U /m l

I R X -2 1 0 0 I U /m l+ a n t i- m P D L 1 0 .0 3 m g /m o u s e

p = 0 .0 2 5 5

p < 0 .0 1

IRX-2 Additive in Combination with Checkpoint Inhibitor

Robust additive preclinical efficacy in PDX mouse model

131. IRX-2 therapy with PD-L1 blockade in immunocompetent animal model. Lu Wen, Gregory T. Wolf, Monil Shah, David B. Page, Lynn Sadowski-Mason, Mark Prince, Jeffrey Moyer, Alfred E. Chang, and Qiao LiJournal of Clinical Oncology 2019 37:15_suppl, e14149-e14149

Page 14: Next Generation Personalized Medicines

Global Phase 2B Study: INSPIRE Study Design + Safety Data

Surgery(Post treatment

sample)

Randomization

Investigational Arm (Regimen 1)

Control Arm (Regimen 2)

SOC: Chemo+/- RTAdjuvant Therapy

SurgeryRegimen minus IRX-2 biologic

SOC: Chemo+/- RT Adjuvant Therapy

Booster IRX-2 Regimen (Every 3 months for 1

year)

Biopsy(Pre-Treatment

Sample)

Approximately D35

Follow-up

Follow-up

Booster IRX-2 regimen minus IRX-2 biologic

(Every 3 months for 1 year)

Single Low Dose of Cyclophosphamide

Subcutaneous IRX-2 (10 days)

141 4

Fully enrolled

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• Completed randomization of 105 patients, 2:1 in favor of the investigational arm (March 2016 –February 2018)

• All receive standard of care surgery and postoperative adjuvant therapy, as appropriate

• Primary endpoint: Event Free Survival (EFS)

Topline readout anticipated - 1H 2022

IRX-2 Related Adverse Events >5% have included: • Nausea (10.3%)• Fatigue (5.9%)• Injection Site Pain (5.9%)• and Neck Pain (5.9%)

Page 15: Next Generation Personalized Medicines

BTX Cytokine Platform Clinical Pipeline

2019 2020 2021 2022

Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4

INSPIRE Phase 2BNeoadjuvant SCCHN

105 Pts

Neoadjuvant Breast Cancer (BR-101) *16 pts

Cervical Neoplasm/Vulvar Neoplasm(CIN/VIN) (CIN-201) *

60 pts

Basket Study - Metastatic Bladder, Renal,NSCLC, Melanoma, H+N (BAS-104) *

11 pts

Metastatic Hepatocellular Carcinoma (HCC-107) * 28 pts

Metastatic Gastric and Esophageal (GI-106) * 26 pts

Metastatic Head and Neck (MHN-102) * 15 pts

Neoadjuvant Triple Negative Breast Cancer (NeoTNBC) (BR-202) *

30 pts

Completed, biomarker endpoint

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Monotherapy studies

Combination studies

PD1 + ChemoPartnered with large pharma

* Investigator Sponsored Trial (IST)

Page 16: Next Generation Personalized Medicines

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Over 20 production runs of IRX-2 have been conducted, yielding

consistent clinical supply material

In-house manufacturing and process development capabilities provide

opportunity to develop additional drugs with a variety of cytokine mixtures

to expand product offerings

Leverage existing BTX staff along with new hires to establish new gene

editing, cellular reprogramming modalities and GMP manufacturing

Little or no outsourcing of manufacturing, increases speed and reduces

cost

Established Biologics Manufacturing Capability

Page 17: Next Generation Personalized Medicines

Platform of mRNA-based Gene Editing and Cell Therapies

Exclusive license of Factor Bioscience technology and acquisition of Novellus Therapeutics

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In-licensed intellectual property held by Factor Bioscience and Novellus Therapeutics for novel mRNA-based Gene Editing and Cell Therapy.

License covers over 100 issued Patents and over 75 pending Applications.

License is for exclusive use to develop gene editing and cellular therapies for Liquid Tumor Types, Solid Tumor Types, Sickle Cell Anemia and other indications.

BTX acquired Novellus Therapeutics securing technology and know-how to iPSC-derived mesenchymal stem cells (iMSC), unrestricted by field of use.

Acquisition eliminates any future license payments to Novellus. Also transfers 25% ownership of NoveCite(developing iMSCfor ARDS).

Transforms BTX to a PLATFORM company with numerous products in its pipeline of next generation engineered cellular medicines.

Page 18: Next Generation Personalized Medicines

Factor Bioscience Patented Technologies

18 © Factor Bioscience Limited

mRNA Cell Reprogramming

ToRNAdo™ DeliverySystem

• Protects from RNase• Not inhibited by serum• Delivers to primary & iPS cells• Delivers ex vivo and in vivo• Multiple granted U.S. patents

mRNA Gene Editing

• Highest efficiency• No risk of vector insertion• Delete, repair & insert• Multiple granted patents cover mRNA

encoding CRISPRs, TALENs, ZFNs, etc.

Context-Specific Gene-Editing Protein• High specificity (40-base)• Blocked by histone modifications

(prevents unwanted cutting)• Multiple granted patents, not

limited by expression vector

The foundational mRNA Reprogramming patent portfolio

• 27 granted patents (11 U.S.)

Engineered Cellular Medicines

The desired mechanism of action is engineeredin

• Allogeneic – off-the-shelf• Clonal – superior batch-to-batch consistency• Restored telomeres – enormous expansion potential

Page 19: Next Generation Personalized Medicines

Novellus Technology: iPSC-derived MSCs

Cells can be gene-edited to provide additional properties

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Page 20: Next Generation Personalized Medicines

Targeted Clinical Indications for iMSC Products

• Non gene-modified iMSC for bone

marrow stroma rejuvenation in

setting of prior BMT failure

• Gene-modified iMSC for multiple

solid tumor indications; addition of

cytokines and chemokines

• Potential for iMSC applications in

settings of autoimmunity

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Page 21: Next Generation Personalized Medicines

Development of In Vivo Gene-editing Products

• Direct gene editing in the liver, brain and eye for treatment of monogenic disorders

• Ability to knock-out or correct gene of interest

• Targets include

– TTR for familial TTR amyloidosis (ATTR)

– ABCA4 for Stargardt disease

21ToRNAdo is a trademark of Factor Bioscience Inc.

Page 22: Next Generation Personalized Medicines

BTX’s Balance Sheet Enables Future Clinical Growth

• BTX raised $51 million in second quarter 2021

• BTX projects it has cash runway to fund IRX-2 through end of Phase 2b and expansion into gene

editing and cell therapies

• BTX seeking BD relationships, partnerships, and other sources of capital to fuel new pipeline

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Page 23: Next Generation Personalized Medicines

SNN Network Summer Virtual Event

August 18, 2021

Next Generation

Personalized

MedicinesA platform company in cell,

gene-editing & cytokine therapies