Full Press Release Details
mRNA Engineered Cell & Genetic Medicines November 2021 A platform company in cell, gene-editing
& cytokine therapies
Disclaimer This presentation is intended to provide summary information about the business of Brooklyn
ImmunoTherapeutics, Inc. ("BTX"). The information in this presentation is in no respects complete, comprehensive or exhaustive, and it should be read in conjunction with BTX's public filings with the Securities and Exchange Commission,
including information set forth in those filings under "Risk Factors" and similar headings. Forward-Looking Statements. Certain statements presented below on pages 4, 8-11, 13, 16-17, 19, 21-22, 24-28 and 30 are forward-looking statements for
purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are any statements that are not statements of historical fact and may be identified by terminology such as "expect,"
"plan," "potential," "project" or "will" or other similar words. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results
may vary significantly from BTX's expectations based on a number of risks and uncertainties, including but not limited to the following: (i) the evolution of BTX's business model into a platform company focused on cellular, gene editing and
cytokine programs; (ii) BTX's ability to successfully, cost effectively and efficiently develop its technology and products; (iii) BTX's ability to successfully commence clinical trials of any products on a timely basis or at all; (iv) BTX's
ability to successfully fund and manage the growth of its development activities; (v) BTX's ability to obtain regulatory approvals of its products for commercialization; and (vi) uncertainties related to the impact of the COVID-19 pandemic on
the business and financial condition of BTX, including on the timing and cost of its clinical trials. BTX cannot guarantee any future results, levels of activity, performance or achievements. The industry in which BTX operates is subject to a
high degree of uncertainty and risk due to variety of factors, including those described in BTX's public filings with the Securities and Exchange Commission, including its Current Report on Form 8-K filed with the Securities and Exchange
Commission on May 11, 2021 and any subsequently filed Quarterly Reports on Form 10-Q for a more complete discussion of these factors and other risks, particularly under the heading "Risk Factors." BTX expressly disclaims any obligation to
update forward-looking statements after the date of this presentation. 2
Howard FederoffMD, PhDChief Executive Officer and President Kevin D'AmourPhDChief Scientific
Officer Ron Guido, MS Pharm. Med.Chief Development Officer Roger SidhuMDChief Medical Officer Jay SialMBAChief Administrative Officer Sandra GurrolaVP of Finance BTX is Led by a Strong, Experienced Management Team 3 Lynn Sadowski-
Mason, MS EVP of Clinical Operations
BTX Transforms into Regenerative Medicine Company with Platform Technology Reverse merger Exclusive
license to mRNA and LNP patents Secured $55M in Capital* Acquired Novellus Therapeutics Recruited new Exec team Nasdaq listing(from NYSE American) 2021 * Runway into 2023 4
Leveraging In-licensed Patent Portfolio to Advance Medicine BTX has an exclusive license from Factor
Bioscience to a portfolio of granted patents around mRNA-based cell engineering that will provide a competitive advantageMajor platform components: mRNA Cell Reprogramming (25 patents, extensive cellular data)mRNA Gene Editing (15 patents,
extensive cellular data)NoveSlice Gene-Editing Protein (15 patents, extensive cellular data)ToRNAdo mRNA Delivery (4 patents, extensive cell and animal data) NoveSlice and ToRNAdo are trademarks of Factor Bioscience Limited. 5
mRNA therapeutics Non-viralgenetic medicines Footnote: doesn't represent ex vivo gene editing
space In Vivo gene editing iPSC-derivedtherapies BTX has a Broad Technology Landscape 6
Brooklyn's Licensed mRNA-Based and LNP Technologies Cell reprogramming Gene editing mRNA and LNP are
toolsto make engineered cell medicine Nucleic acid delivery mRNA and LNP are the drugas in vivo gene-editing medicine 7
The Foundational mRNA Cell Reprogramming Platform Typical Results Highest efficiency generation of
iPSC: 5 factors, rapid protein expressionLow toxicity, high percentage transfectedCustom reprogramming mediaSafe: no chance of genome integrationCan combine reprogramming with gene editing to streamline autologous therapies in genetic
diseaseExtensive in-licensed patent protection 8
Unique mRNA-Based Delivery of a Novel Gene Editing Platform Gene Knockout Gene Repair Safe-harbor
Insertion Use of mRNA for Delivering Gene-Editing ProteinsRapid, high expression (efficiency)Transient expression (specificity)Amenable to non-viral deliveryNo risk of vector insertionMultiple in-licensed patents cover mRNA encoding CRISPR,
TALEN, ZFN, etc Chromatin Context-Sensitive Gene Editing EndonucleaseNovel nuclease (clear IP landscape)High specificity (36-40 base site)Blocked by histone modifications (specificity)Unlimited genomic sites (no PAM) 9
Novel Lipid with Effective mRNA Delivery In Vitro and In Vivo U.S. Pat. No. 10,501,404 A compound of
Formula (I) Wherein n is 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, or 15. Novel, single lipid component LNPNovel lipid, composition of matter IPLow toxicity enables repeated transfectionEfficient transfection in context of
serumTransfection of many cell types demonstrated 10
Platform Technology Deployed in Four Regenerative Medicine Pillars Allogenic Stem CellPlatform
(iMSC)ARDS Bone marrow transplant failure/poor functionSolid tumors Autologous, Gene Edited PlatformHemoglobinopathiesOpportunities in many genetic diseases Autologous iPSCPlatformParoxysmal nocturnal
hemoglobinuria Partnership opportunities In Vivo Gene EditingPlatformTransthyretin amyloidosisStargardt disease Non-syndromic hearing loss Opportunities in many genetic diseases 11
Allogeneic iMSC Therapies
Allogeneic iMSC Product Platform iPSC-derived Mesenchymal Stem Cells (iMSC)Low risk of toxicity, proven
across many clinical studiesLow immunogenicity, no need for immunosuppressive drugsLeveraging decades of work with MSC process development and manufacturingA single Drug Product can be used across multiple and varied indicationsiPSC can be gene
edited to program the iMSC with additional properties, expanding indicationsMSC therapies have had inconsistent clinical efficacy due to product heterogeneity 13
Brooklyn's iMSC Address Issues with Tissue-derived MSC Historical Issues with MSC field Tissue-derived
MSC Brooklyn's iMSC Donor to donor variability Tissue source variability Manufacturing variability Limited or inconsistent characterization Poor mechanistic understanding Capacity to precisely genetically
Extensive Characterization of iMSC to Ensure Consistency Characterization to include:Stability of
phenotypes with progressive passagesChanging responses to hypoxia and other stimuli Single cell RNA-seq Mass Cytometry Secretome Kehl et. A. (2019) Hutton et. A. (2021) Liu et. A. (2019) 15
MSCs modulate immunological responses, support hematopoiesis, and repair bone marrow stromaClinical
applications in hematopoietic stem cell transplant (HSCT)Treating engraftment failure or poor graft function Promoting HSC engraftment Working with world class KOLs in HSCT to focus on best clinical population(s) and trial designAnticipate FIH
in 4Q-2023 iMSC Application in Graft Failure/Poor Graft Function Zhou, T et al. (2021) Challenges and advances in clinical applications of mesenchymal stromal cells. J Hematol Oncol 14:24, 1-24 16
Gene-editing iPSC and thorough characterization; followed by differentiation to iMSC Multiple engineered
iMSC products to deliver agents locally and avoid systemic toxicities IL-7 & IL-15 drive expansion and engraftment Combination with CAR-T and checkpoint inhibitors Developing a Family of Gene-edited iMSC Products To Address High Unmet
Need Solid Tumors Song, N et al. (2020) Mesenchymal Stem Cell Immunomodulation: Mechanisms and Therapeutic Potential. Trends in Pharm Sci 9, 653-664 17
Autologous Cell Therapies
Autologous Cell Therapy, Efficient mRNA Gene Editing Autologous HSC-based gene therapy for many
addressable indicationsHemoglobinopathies Primary immunodeficienciesCongenital cytopeniasLeverages 30 years of clinical experience and isolation techniques for CD34+ HSC; robust engraftment and safetymRNA-based gene editing is less complex than
viral methodsFuture partnering possibilities 19 GeneEditing
Autologous iPSC Therapies
Autologous iPSC Cell Therapy Platform Licensed technology is the safest, most efficient, and fastest
method for iPSC derivation Safe: Non-integrating method using synthetic mRNA to produce reprogramming factorsEfficient: Uses LNP for repeated in vitro delivery with low toxicityEfficient: Can combine reprogramming and gene editing in single
step derivationFast: Reprogramming and iPSC colony formation within 2 weeksThe safety, reliability and speed enable autologous iPSC programsEfficiency of reprogramming permits low quantity of cells from biopsy and simultaneous correction of
gene defects Can quickly produce multiple iPSC clones per patientAbsence of genome integration facilitates screening to identify and characterize a safe clone 21
Autologous HSC from iPSC Autologous iPSC / Gene-modified autologous iPSC for: Genetic disease (e.g.
hemoglobinopathies)Paroxysmal nocturnal hemoglobinuria (PIG1A)Infectious disease 22
In Vivo Gene Editing Therapies
Second Pillar is a Genetic Medicine Product Platform Proprietary lipid nanoparticle for nucleic acid
deliveryNovel lipid with composition of matter IPProperties can be tuned to target different cell types and tissuesCan deliver RNA or DNA; facilitates gene correction approachesDelivery of mRNA encoding proprietary site-specific nucleaseCan
target any gene through design of protein binding domainsHigh specificity to target genomic siteAchieves high level but transient expression, enhancing safety 24
Developing In Vivo Gene-editing Products Addressing Rare Disease Indications (Orphan Designation) Direct
gene editing in the liver, brain or eye for monogenic disordersAbility to knock-out or correct the target geneInitial gene target is knock-out of TTR for Familial Transthyretin Amyloidosis (ATTR) ToRNAdo is a trademark of Factor Bioscience
Amyloidosis Caused by Transthyretin (ATTR) Caused by misfolded transthyretin (TTR), aggregating into
toxic oligomeric forms Death 5-15 years after onset of symptoms is typical Non-Familial (200,000-500,000 worldwide) Owing to tissue deposition of normal TTR amyloid Common clinical feature is peripheral neuropathyFamilial (~50,000
worldwide) Autosomal dominant Owing to mutations in TTR (>140) Mutations increase amyloidogenic property Brooklyn's Focus 26
Three sites of TTR synthesis, determine distinct clinical phenotypes Liver: cardiomyopathy, peripheral
neuropathy Choroid plexus: LeptomeningealNeuroretina: Ocular toxicity Current treatments address only
liverFull phenotypic recovery requires both hepatic and CNS/choroid plexus intervention Brooklyn initial focus on unmet need: oculo/leptomeningeal disease Clinical Features of Familial ATTR 27
Polyneuropathy Cardiomyopathy Ocular depositions Leptomeningeal depositions Subtype
Observed across subtypes (except leptomeningeal) Observed across subtypes (except leptomeningeal) Chiefly leptomeningeal subtype Restricted mutations + observed across subtypes Epidemiology
Most common, hATTR and senile (WT) disease 25% of ATTR population over age 80 Rare restricted mutations; small other subsets Rare restricted mutations; small other subsets
Approved/ R&D synthesis inhibitors siRNA, ASO, CRISPR IV/SC (hepatocytes) IV/SC (hepatocytes) BTX: in vivo gene editing IV (hepatocytes) IV (hepatocytes)
Subretinal injection (Retinal Pigment Epithelium) Intracisternal injection (Choroid Plexus) BTX can treat all known ATTR regardless of mutation BTX In Vivo Editing Addresses all ATTR Manifestations 28
BTX Cell Therapy and Gene-Editing Pipeline
Summary Indication Genetargets Delivery Discovery Preclinical IND-enabling Clinical Comments iMSC: iPSC-derived mesenchymal stem cells ARDS (all etiologies) n/a I.V. injection NoveCite
program BMT/HSCT setting n/a I.V. injection TBD n/a I.V. or local Solid tumors IL7, IL15 I.V Oncology Undisclosed I.V Autologous HSC, gene
edited Undisclosed Undisclosed I.V. Autologous iPSC-derived cell therapy TBD n/a I.V. In vivo gene editing Transthyretin Amyloidosis TTR I.V.
or CNS Stargardt Disease ABCA4 Retina 29
BTX Will Leverage Best In ClassmRNA-based Technologies to Deliver Transformative Regenerative
Medicines Exclusive license to foundational mRNA & gene editing IP Diversified product strategy for multiple clinical applications Experienced management team with deep expertise in C> Strong partnership for translational execution
and future innovation In-licensed patent portfolio offers sub-licensing opportunities 30