next generation personalized medicines · 2021. 5. 21. · allison o’neill –dana farber cancer...
TRANSCRIPT
May 19, 2021
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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Brooklyn ImmunoTherapeutics
3
We are a clinical-stage biopharmaceutical company developing treatments for patients suffering from cancer and rare diseases
IRX-2, our lead program, is a human cell-derived cytokine therapy in Phase 2b development in head and neck cancer and is also being studied in other solid tumors both as a monotherapy and in combination with other anti-cancer therapies.
We have an exclusive license for an mRNA Gene Editing/Cell Therapy platform allowing for the development of a set of next products.
*Updated on 19 May 2021
Brooklyn ImmunoTherapeutics (BTX) - Overview
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• Strong and efficient leadership team with
60+ years of drug development expertise
• GMP Manufacturing Facility with
capabilities on both sides of the company
Cytokine TherapiesLicense with Factor: mRNA Gene Editing/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 a variety of 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/indication gene editing/cell therapy platform
*Updated on 19 May 2021
IRX-2 - Overview
• 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
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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
*Updated on 19 May 2021
mRNA Gene Editing - Overview
Factor/Novellus has an extensively patented process to
develop gene editing compounds using mRNA which are
more efficient, non immunogenic, and non mutagenic –
making this a first in class gene editing technology. License
includes opportunity for us to use mRNA gene editing
technology to develop treatments for:
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License Overview
• Solid tumor indications
• Liquid tumor indications (refractory AML under
consideration as lead candidate)
• Sickle cell anemia
• Other inherited disorders
Projected Timeline
Initiate Pre-Clinical Development Program 1H 2021
Plan to be at IND by 2024
First patient dosed in Phase 1 on 1st indication(s) in 2025
Refractory AML and sickle cell are front runners. Development plans in place by 2Q 2021.Other indications identified
BTX is Led by a Strong, Experienced Management Team
Established clinical operations professional with extensive experience in the immuno-oncology space
• Bristol Myers Squibb, Director Global Clinical Operations and Strategy
• Bristol Myers Squibb, Clinical Operations Regional Manager for Romania, Czech Republic, Hungary, and Turkey
• Bristol Myers Squibb Clinical Operations Lead for Elotuzumab
• Bristol Myers Squibb Clinical Operations Integration Manager for Medarex acquisition
LynnSadowski MasonExecutive Vice-President, Clinical Operations
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Extensive experience in domestic and international product development across diverse biotech and pharmaceutical companies
• Veloxis Pharmaceuticals, SVP Global Regulatory Affairs and Chief Compliance Officer
• Retrophin, VP Regulatory Affairs
• Pfizer, Senior Director & Therapeutic Area Head, CV• Precision Pharma Services, Sr. VP Regulatory Affairs and
Quality Systems
Ron GuidoChief Development Officer
Howard Federoff, MD, PhDChief Executive Officer and President
Proven leader in small biotech with extensive experience in drug development and gene editing/cell therapy.
• 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 MedGenesis Therapeutix 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.
*Updated on 19 May 2021
• CEO of Brooklyn ImmunoTherapeutics
• Former CEO of UCI Health, vice chancellor for health affairs and dean of the UCI School of Medicine
• Former Executive Vice President of Health Sciences and Executive Dean at Georgetown University.
• Cofounder MedGenesisTherapeutix and Brain Neurotherapy Bio
• Former 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.
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
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.
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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
*Updated on 19 May 2021
BTX’s Cutting Edge Scientific Advisory Board
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IRX-2 SAB
Steven Schnittman – Independent consultant, former Vice President, Global Clinical Research Bristol Myers Squibb
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
*Updated on 19 May 2021
IRX-2 Human Derived IL-2 Product 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
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Results supported further clinical development in multiple indications
T T Cell NK CellDendritic Cell
IRX-2 is Differentiated from other IL-2 FormulationsUnlike recombinant IL-2 drugs and drug candidates, IRX-2 is derived from human blood cells (huIL-2 ).
This difference may confer several 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
Comparative Binding Affinity rIL-2 (recombinant) v 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)
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Data demonstrate that natural huIL-2 exhibits distinct functional properties compared to recombinant rIL-2
Biologic Activity of IRX-2 in Clinical Trials
1: Page et al. A phase Ib study of pre-operative, locoregional IRX-2 cytokine immunotherapy to prime immune responses in patients with early stage breast cancer. Clin Cancer Res December 2019 2: Berinstein et al., OncoImmunology, February 2018; Barnes and Amir, British Journal of Cancer, July 2017; Nguyen et al. Head and Neck, July 2016.3: 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
Results from early-stage breast cancer clinical trial 1 Results from Phase 2a head and neck cancer clinical trial 2
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Demonstrated Biologic Activity in 3 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
Results from Phase 2b head and neck cancer clinical trial 3
Control IRX-2
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
Robust Additive Preclinical Efficacy Demonstrated with
IRX-2 in Combination with Checkpoint Inhibitor
141. 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
15
• 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
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Monotherapy studies
Combination studies
PD1 + ChemoPartnered with large pharma
* Investigator Sponsored Trial (IST)
IRX-2 is Protected by a Strong IP Portfolio
• Manufacturing process covered by patents worldwide
• New IP related to combination of IRX-2 with checkpoint inhibitors
• Own or license 90+ issued patents and 21 pending patent applications covering a variety of subject matter
• Patent protection until 2037
17
• IRX-2 is a complex biologic, manufactured in a particular way to meet consistent specifications
• Trade secrets relating to manufacturing process: IRX-2 will be very difficult to duplicate
Patent Protection
Data Exclusivity
• IRX-2 is a biologic – 12 years data exclusivity in US and 10 years data exclusivity in Europe
• Orphan drug status for Head and Neck cancer granted in US
• Investigating potential opportunities to add exclusivity
Trade Secret Protection
Future Exploration of Orphan/Rare Disease
• Potential orphan exclusivity
• Potential for new patents, term extension
18
Over 20 production runs of IRX-2 have been conducted, yielding
consistent and releasable 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
Little or no outsourcing of cell manufacturing, increases speed and
reduces cost
Established Biologics Manufacturing Capability
mRNA Gene Editing/Cell Therapy - Exclusive License Option
19
Exclusive Option signed December 2020 with Factor Bio and Novellus (Cambridge, MA) to enter into a definitive agreement by 4/30/21. $500k break up fee/$4M upfront due 2Q 2021.
The license includes intellectual property held by Factor Bio and Novellus for novel Gene Editing and Cell Therapy – 92 Issued Patents, over 75 pending.
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.
We believe this is a potentially disruptive technology given high efficiency and reduced cost of manufacturing
On completion of the license, BTX immediately becomes a player in Gene Editing for Cell Therapies for use in Oncology and other indications: augments BTX’s existing CMC.
Transforms BTX to a PLATFORM company with numerous products in its pipeline of next generation engineered cellular medicines.
*Updated on 19 May 2021
Factor Bioscience Patented Technologies
20 © 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
mRNA Cell Reprogramming Platform
21 © Factor Bioscience Limited
Teratoma
(proof of pluripotency)
• Regenerative Therapeutic Platform
– Highest efficiency & footprint-free
– Applications in autologous & allogeneic cell
therapies
– Combine with gene editing to eliminate off-target
effects
“The main advantages of the RNA method are speed of colony
emergence, high efficiency, a complete absence of integration,a very low aneuploidy rate and a low donor cell requirement”
– Thorsten M Schlaeger, PhD, Boston Children’s HospitalSchlaeger, et al. A comparison of non-integrating reprogramming methods. Nature Biotechnology. 2015.
The foundational mRNA Cell Reprogramming patent portfolioU.S. Patent Nos: 8,497,124; 9,127,248; 9,399,761; 9,562,218; 9,695,401; 9,879,228; 9,969,983; 10,131,882; 10,201,599; 10,443,045;
Granted patents in: CH, DE, FR, GB, IE, CN, JP, MX, HK, AU, RU;Multiple patents pending in the US and other major market countries.
Mesenchymal Stem Cells (MSCs)
AdipocytesOil Red O stain
OsteoblastsAlizarin Red S stain
ChondrocytesAlcian Blue stain
Typical Results
Neuronsβ-tubulin
Retinal Pigment Epithelial Cells
Cardiomyocytes
Multimodal Gene-Editing Platform
22 © Factor Bioscience Limited
mRNA Vectorization of Gene-Editing Proteins
(Multiple U.S. Patents)
Kopacz, M., et al. Mol Ther, Vol 28 No 4S1,2020.
Chromatin Context-Sensitive Gene-Editing Endonuclease
(Multiple U.S. Patents)
Figure 1. High-efficiency gene editing of TRAC and PD1 in human epidermal keratinocytes and human iPS cells.
Figure 2. High-efficiency gene editing of the AAVS1 genomic safe harbor locus in human iPS cells.
ToRNAdo™ Delivery System
23 © Factor Bioscience Limited
• Efficient delivery of mRNA ex vivo and in vivo to skin, brain, eye, and lung
Subretinal injection illustration adapted from Ochakovski, et al., Lipofectamine® is a registered trademark of Thermo Fisher Corporation
Rat Brain (in vivo) Lateral Ventricle(brown cells = GFP+)
Rat Retina (in vivo)(brown cells = GFP+)
Human Skin (in vivo)Ventral Forearm
(red cells = RFP+)
Very low expression, inhibited by serum
Human Epidermal Keratinocytes (ex vivo)
(green cells = GFP+)
ToRNAdo™ outperforms Lipofectamine®2000 and 3000 (“LF3000” shown above),which are inhibited by serum.
ToRNAdo™ safely and effectively delivers mRNA to human skin in vivo when administered by intradermal injection.
Kostas, F., et al. Mol Ther, Vol 28 No 4S1, 2020.
100 Patents in 14 Countries (>40 in the United States)
24 © Factor Bioscience Limited
• Global IP portfolio with patent terms extending into 2039
– Deep portfolio in 7 families, including CRISPR and TALEN coverage
2018 2019
CN JP
CN
AU
EUR
U
AU JPR
epro
gram
min
g
U.S
.
2017 2019Ther
apeu
tic
Ind
icat
ion
s
U.S
.
20172012 2013 2014 2015 2016
Priority
Filing
Gen
eEd
itin
g
2018 2019
U.S
.
Del
iver
ySy
stem
2019 2020
U.S
.
2011 2012 2013 2014 2015 2016 2017
HK
HK
MX
RU
CN
MX
AU JP RU
EB Cancer Cancer Cancer Cancer AATA
U
AU
EU RU
EB EBEB HIV
HIV
2018
HIV HIV HIV EB
CH,DE,FR, GB,IE
Priority
Granted= Patent
2020
Filing
BTX Clinical Pipeline
25
Technology
Program 2021 2022 2023 2024 2025
Cytokine Therapy
IRX2: Neoadj
H&N
IRX2: IST Lead
Indication
New Cytokine Formul.
mRNA Gene
Editing/ Cell
Therapy
Indication #1
Indication #2
Phase 2b Phase 3
Research Lead Optimization IND Enabling
Research IND Enabling IND Filed First in Human Study
Research IND Enabling IND Filed First in Human Study
Phase 1 IST
Mtg with FDA
Phase 2 Company Sponsored Study
Mtg with FDA
*Updated on 19 May 2021
May 19, 2021
Next Generation
Personalized
Medicines