next generation personalized medicines
TRANSCRIPT
SNN Network Summer Virtual Event
August 18, 2021
Next Generation
Personalized
MedicinesA platform company in cell,
gene-editing & cytokine therapies
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.
2
Brooklyn ImmunoTherapeutics
A platform company in cell, gene-editing and cytokine therapies
3
Clinical stage Cytokine therapy Nucleic acid delivery
Cell reprogramming Gene editing
Brooklyn ImmunoTherapeutics (BTX) - Overview
4
• 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
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
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
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
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
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
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
10
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
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
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
12
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
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
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
14
• 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%)
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
15
Monotherapy studies
Combination studies
PD1 + ChemoPartnered with large pharma
* Investigator Sponsored Trial (IST)
16
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
Platform of mRNA-based Gene Editing and Cell Therapies
Exclusive license of Factor Bioscience technology and acquisition of Novellus Therapeutics
17
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.
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
Novellus Technology: iPSC-derived MSCs
Cells can be gene-edited to provide additional properties
19
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
20
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.
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
22
SNN Network Summer Virtual Event
August 18, 2021
Next Generation
Personalized
MedicinesA platform company in cell,
gene-editing & cytokine therapies