Contact: Dr Brad WalshMobile: +61 413 231 296
Ground Floor, 75 Talavera Rd Macquarie Park, NSW 2113 Australia
www.glytherix.com
1 Confidential
• This presentation was prepared primarily for the general information of potential investment/commercial partners. This presentation is not an offer or invitation to subscribe for or purchase securities.
• This presentation does not purport to summarize all information that an investor should consider when making an investment decision. None of GlyTherix Ltd (GlyTherix) or their respective directors, employees or advisers warrant or represent the accuracy or completeness of the information contained in this presentation. Except for any statutory liability that cannot be excluded, GlyTherix and their respective directors, employees and advisers disclaim all responsibility and liability for any loss or damage that may be incurred by any recipient relying on the information in the presentation whether that loss or damage is caused by any fault or negligence on the part of GlyTherix or any of their directors, employees or advisers, or otherwise.
• To the extent that the presentation contains any forecasts, projections or other forward looking statements, those statements involve known and unknown risks, uncertainties and other facts that may cause actual results, performance or achievements to be materially different from those expressed or implied by those statements. There can be no guarantee that actual results, performance or achievements will be as stated.
• You represent and confirm by attending and/or by retaining this presentation, that you accept these conditions
Forward Looking Statements
2
Investment Highlights• Huge Potential Market – immuno-oncology US$51Billion market
• Strong IP position for Glypican-1 – demonstrated role in aggressiveness and spread of cancer and first-in-class antibody
• Multiple targets – Glypican-1 known to be expressed in cancers from prostate, bladder, pancreas, breast, esophageal, ovary and glioblastoma
• Strong early licensing prospects - good engagement with a number of large pharma companies
• Influential thought leadership - Clinical Advisory Panel membership by world renowned clinicians and academics
• Strong safety profile - drug already administered to 12 human patients with no drug related adverse events and no off-target binding
3
• $3M Government Grant awarded 22 June 2020
• Matched with $3M from R&D Tax Incentive loan facility
• Current capital raise of US$5M
• Funds raised will be used to:ü Manufacture clinical batch of GMP grade Miltuximab®ü Conduct Phase 1 trial with 89Zr and 177Lu radiolabeled
Miltuximab®ü Perform further pre-clinical experiments for other
cancer indications
Capital Raising
4
Recent Deals/Values in the Same Space
5
Company Price Acquirer Clinical trial stage at acquisition
Advanced Accelerator Applications 3.9 B Novartis -2018 Marketed & Phase 1/2
Endocyte 2.1 B Novartis 2018 Phase 2/3 Blue Earth Diagnostics 450 M Bracco Imaging Spa - 2019 Commercial stage products
Algeta ASA 2.9 B Bayer - 2014 Commercial stage products Sirtex Medical Ltd 1.2 B China Grand Pharma -2018 Commercial stage products
Comparable Companies
6
Company Market cap USD
Enterprise Valuation IP Portfolio Clinical trial stage
Actinium Pharma (NYSE) 97 M 88 M Targeted Radio- immunotherapy Phase 3 trial lead drug Immutep* (NASDAQ/ASX) 85 M 72 M LAG-3 checkpoint inhibitor Phase 1/2
Celsion (NASDAQ) 82 M 76 M Cytokine immunotherapy Phase 3 and Phase 1/2 OSE Immuno (Paris SE) 99 M 72 M IO in solid tumours Phase 1/2
4SC AG* (XETRA) 85 M 52 M IO in blood cancers Phase 1/2 Mustang Bio* (NASDAQ) 183 M 128 M CAR-T immunotherapy/gene therapy Phase 1
Jounce Therap.* (NASDAQ) 156 M 82 M Cancer immunotherapies Phase 2 Tyme Technol.* (NASDAQ) 197 M 171 M Solid tumours anticancer therapies Phase 1
Nordic* Nanovectors (NOR) 139 M 109 M Blood cancer radioimmunotherapies Phase 1/2 Alligator Biosciences (SWE) 72 M 56M IO for solid tumours Phase 1
Cantargia AB* (SWE) 165 M 160 M CAN04 MAb against solid tumours Phase 2 Progenics Pharma. (USA) 415 M 386 M Radioimmunotherapies/theranostics Commercial stage
Telix Pharma (ASX) 250 M 216 M Molecular targeted radiotherapy Clinical stage Autolus Therap. (NASDAQ) 684 M 441 M CAR-T in blood/solid tumours Phase 1/2 Immunomedics (NASDAQ) 7.4 B 6.9 B ADC & RIT against solid tumours Phase 3
7
Technology and Data to Date
• GPC-1 is a cancer cell-surface protein
ü Expressed in a variety of solid tumors and critically involved in cancer growth, invasion, metastasis
ü Associated with poor prognosis and resistance to standard of care treatments
ü Not expressed in normal tissue
• Miltuximab® is our antibody to GPC-1 shown to be safe in Phase Ia clinical trial
ü No drug related adverse events
ü Evidence of targeting in prostate cancer patients
• 177Lu-Miltuximab® demonstrated proof-of-concept in vivo in GPC-1 expressing prostate tumor model
ü Specific targeting and retention in tumor
ü Excellent safety profile
ü Dose-dependent inhibition of tumor growth
ü Improved animal survival
Miltuximab® Targets Novel Tumor Antigen Glypican-1 (GPC-1)
8
Glypican 1 Cell Surface Density Across Indications
9
• Glypican 1 cell surface density was determined using the QIFIKIT
• QIFIKIT has beads labelled with known numbers of monoclonal antibodies. Cells are stained with a monoclonal antibody that recognises the antigen of interest. Number of antigen molecules can be calculated based on the fluorescence intensity of the stained sample, as compared to a calibration curve of beads.
Lym
phom
a
Ovar
ian
Brea
st
Mes
othe
liom
a
Glio
blas
tom
a
Panc
reat
ic
Blad
der
Pros
tate
DU
-14
5
PC
3
NC
I-H
66
0
LN
Ca
P
C3
UC
6
T2
4
Ca
pa
n-1
MIA
Pa
Ca
-2
PA
NC
-1
U-8
7
U-2
51
NC
I-H
20
52
MD
A-M
B-2
31
SK
BR
SK
-OV
-3
Ra
ji 0
3 0 0 0 0
6 0 0 0 0
9 0 0 0 0
1 2 0 0 0 0
# G
PC
1 m
ole
cu
les
pe
r c
ell
First-in-Human, First-in-World Miltuximab® Study
10
FIH Objectives Key Outcomes
Primary endpoint(Safety & tolerability)
• Primary endpoint of the study met in all patients• Single doses up to 25 mg presented no drug related adverse reactions
Secondary endpoint(Dosimetry and Targeting)
• Targeting present in more advanced metastases• Best timepoint 48 hr post-infusion and dosing at 24 mg increases blood half-life
Radioactive Dose Predictions
• Amount of 67Ga-Miltuximab® dosed well below published safety limit• Higher energy isotopes (89Zr- or 177Lu-Miltuximab®) can increase tumor dosage
Cohort/Cancer Types (2-15 mets/patient) Total Dose (mg) Dose at mg/kg
#1: 1 prostate, 2 pancreatic 1 0.01
#2: 3 prostate 4.5 0.06
#3: 2 prostate, 1 bladder 12.5 0.17
#4: 3 prostate 25 0.33P2: Foot Uptake in Bone Mets at 24h
89Zirconium-Miltuximab® Targets Prostate Tumor Xenografts In Vivo
11
a ba. Day 7 PET imaging of mouse bearing a DU-145 xenograft post intravenous injection of 89Zr-Miltuximab®-DFO
b. Biodistribution of 89Zr-Miltuximab®-DFO in BALB/c/nude mouse organs 7 days after injection of 89Zr-Miltuximab® (n=2) by ex vivo analysis of organs by gamma counter
Data are expressed as % Injected Dose (ID)/gram tissue, bars represent SD
• DU-145-RFP-Luc cells injected subcutaneously to right flank of BALB/c/nude mice. On day 25 mice received either Miltuximab®-DOTA (n=8), 3 MBq 177Lu-Miltuximab®-DOTA (n=9) or 10 MBq 177Lu-Miltuximab®-DOTA (n=9) I.V. Mice were weighed and tumor volumes measured via calipers twice weekly and mean mouse weight over time did not vary between groups
a. Mean weekly mouse tumor volume. *p<0.05; **p<0.01; ***p<0.001 by unpaired t test, treatment group compared to control, at each time point
b. Kaplan-Meier survival curve, comparison of survival curves was performed using a Mantel-Cox test
Ab Inhibits Tumor Growth and Improves Animal Survival
12
a b
Yeh et al EJNMMI 10:46, 2020
Miltuximab® Targets Glioblastoma Lines In Vitro and In Vivo
13
• A. Binding of Miltuximab® to cell lines U-251 (116,941 GPC-1 molecules) and U-87 (10,395 GPC-1 molecules)• B. Binding to and internalization of Miltuximab® has been observed for patient derived GBM 998 cells by fluorescence
microscopy in live (left) and fixed (right) cells
• C. Targeting of Miltuximab-IR800 to U-87 tumors showed specific tumor uptake and retention as compared to labelled isotype control in vivo
2ndary control Miltuximab®
A. U-2512ndary controlMiltuximab®
B.
C. U-87
Treatment of Prostate Tumor Xenografts With Enzalutamide
14
• Mouse model of enzalutamide resistance - mice first castrated, when tumors recur mice enzalutamide treated (A)
• Tumors regress but eventually regrow (enzalutamide resistance)
• Tumors harvested from mice at each stage analysed for GPC-1 mRNA expression - showed increase in response to enzalutamide resistance
Castration
Enzalutamide
ENZnadir
ENZendpoint
ENZintermediate
tum
orVo
lum
e
Seru
m P
SA
1.0 1.1 0.91.3
1.8
2.8
1.5
3.6
0.00.51.01.52.02.53.03.54.0
Sham en
dpoint
Sham in
termedia
te
castr
ation in
termed
iate
castr
ation e
ndpoint
castr
ation n
adir
ENZ interm
ediate
ENZ endpoint
ENZ nadir
Rel
ativ
e Ex
p (F
C)
Treatment groups
GPC1 expression in LNCaP XenograftsA. B.
15
Next Steps
Antibody Manufacturing Phase 1 StudyFurther Preclinical
GlyTherix Led Manufacturing Consortium
16
CSIRO/UTS(MAb Production)
GlyTherix(Industry Lead)
GE(Manufacturing & Imaging)
ANSTO(Clinical RIT production)
Auspep(Conjugation)
MQ/MMI(Clinical Delivery/Validation)
KeyGE: GE HealthcareCSIRO: Commonwealth Scientific and Industrial Research OrganizationUTS: Univ. of Technology, Sydney ANSTO: Australian Nuclear Science and Technology OrganizationMQ: Macquarie UniversityMMI: Macquarie Medical Imaging Mab: Monoclonal antibodyRIT: Radioimmunotherapy
Funded by Round 9 of the CRC-P Program
M1 M2 M3 M4 M5 M6 M7 M8 M9 M10 M11 M12 M13 M14 M15 M16 M17 M18
Indicative Gantt Chart for Antibody Manufacturing
17
Mab ProductionConjugation Production
Clinical Validation
Radiolabelling DevelopmentRadiolabelling for Trial
Cell Line Dev
ZIRLU Phase I Trial
18
TX DOSE 1177Lu-Miltuximab®
TX DOSE 2177Lu-Miltuximab®
TX DOSE 3177Lu-Miltuximab® FOLLOW UPSCREENING
185 MBq 89Zr-Miltuximab®
GPC-1 -ve
GPC-1 +ve370 MBq 555 MBq 1100 MBq
555 MBq 1100 MBq 1665 MBq
1100 MBq 1665 MBq 1665 MBq
1665 MBq 1665 MBq 1665 MBq
Cohort 1
Cohort 3
Cohort 4
Cohort 2
ProstateGlioblastomaPancreasBladder
177Lu-Miltuximab® Logistics for Patient Administration
19
Doctor meets patient - assessed eligible for drug
Radiopharmacy places order for drug and
177Lu with GlyTherix
ANSTO ships 177Lu to Radiopharmacy on scheduled dose date
177Lu-Miltuximab®product
GlyTherix ships Shake and Bake Kit containing DOTA-Miltuximab®
to Radiopharmacy and co-ordinates delivery of 177Lu
Patient infused and then monitored for 4 hours
Patient goes home
DOTA-Miltuximab®
stores at GlyTherix
Use of Funds – US$5M raiseClinical and Pre-Clinical Programs Stage Amount - AUD Outcome
Antibody engineering program GMP batchShake and Bake Kit 5.5M Humanized GMP Mab
Radio-immunotherapy program 89Zr/177LuProstate, pancreas, bladder, glioblastoma Phase I trial 6.5M Theranostic data
Pre-clinical studies Additional data 1.0M
Staff, space, KOLs, administration - 2 yrs Overheads etc 2.4M
Subtotal Sub Total 15.4M
Less
CRC-P Government Grant (non-dilutive) 3.0MR&D Tax Rebate @ 43.5% of 12.0 million (non-dilutive) 5.2M
Balance – to be funded by new equity 7.2M (5.0M USD)
20
• GlyTherix intends to commercialize its technology either by licensing or trade sale to a large pharmaceutical or biotech company capable of taking the drug through regulatory approvals and into the global market
• Alternatively, additional Clinical and Pre-Clinical data generated can be used to support a US IPO (c.2022)
• GlyTherix continues to engage with Key Opinion Leaders (KOLs) and potential licensees ensuring drug development meets clinical, commercial and patient expectations
• GlyTherix will produce sufficient clinical grade drug to commence US Phase 1 trial(s) - a compelling value proposition for potential licensees and partners
Pathway to Shareholder Returns
21
22
Company Profile PipelineIntellectual Property
• GlyTherix is a private immuno-oncology company spun out from Minomic International
• GlyTherix is based in the business parknext to Macquarie University campusand adjacent to Macquarie UniversityHospital (Sydney, Australia)
• Company has in place partnershipswith universities & research institutes(Univ. Qld, Qld Univ. Tech, Univ.Technology Sydney, Weill Cornell,Univ. Michigan)
Company Profile
8
GlyTherix History
24
2007-2014 2015 2016 2017 2018 2019 2020
Formation of GlyTherix (Cancer Tx Co.)
Series A Capital Raising Commences to fund:
• Phase 1 trial• GMP manufacture of
antibody
Development of Miltuximab®
(chimeric version of mouse antibody)
First in Human Trial of Miltuximab® Commences
First in Human Trial of Miltuximab® Concludes:
• No drug related adverse events observed• tumor targeting observed
Acquisition1 of the exclusive MIL-38 Antibody Licence for Tx use
and Companion Dx from Minomic1. IP cost $8.1M satisfied by issue of shares
- 5,000,000
10,000,000 15,000,000 20,000,000 25,000,000 30,000,000
2014 2015 2016 2017 2018 2019 2020
Cumulative Capital Raised AUD
Note: more detailed information upon request
Minomic’s In-licence of MIL-38 parent
mouse monoclonal antibody,
identification of antigen and epitope
2007 - 2014
GlyTherix Executive Management
25
Dr Yanling Lu (CMC Manager) - Yanlingcompleted her PhD in Physical Biochemistry atthe University of Nottingham in collaborationwith Cambridge Antibody Technology and UCB-Celltech. Thereafter she joined Medimmune as aSenior Research Scientist in BioprocessDevelopment leading formulation, analyticalmethod development and stability testing.Yanling is conversant with regulatoryrequirements and is passionate in CMC projectmanagement.
Dr Maria Lund (Preclinical Manager) - Mariacompleted her PhD in Immunology at theUniversity of Technology Sydney. Her doctoralwork identified a novel peptide therapeutic forautoimmune disease, which led to the spin outof a company to commercialise this therapy. Shehas extensive background in early stage drugdevelopment and preclinical testing, includingdevelopment of an antibody therapy now inPhase 2 clinical trials.
Dr Brad Walsh (CEO) - founded Minomic raising over A$26 millionto commercialize its first major product, MiCheck, as well asdeveloping a pipeline of new diagnostics for other cancers. He hasa PhD in protein chemistry and has led research groups ingovernment agencies, universities and hospitals. He played a keypart in establishing a major national research facility beforeforming Minomic in 2007. He has a long history ofcommercialization and his products are being sold by majorcorporations, such as Bio-Rad Laboratories.
David Burdis (CFO / Company Secretary) - is a seasoned financialprofessional having worked in the telecommunications, chemical,and financial services industries. He has held various senior/boardpositions, for both listed and unlisted companies, in Australia, theUK and Hong Kong, including Swire Blanch Limited and OAMPSLimited. His extensive consulting background includes provision ofservices to industry and government as well as expert witnessevidence.
Dr Douglas Campbell (Head of Research and Development) -leads Minomic’s scientific team. He has been instrumental inbuilding Minomic’s intellectual property estate and designing allthe clinical trials. He has nearly 20 years of experience inbiomedical research with a particular focus on oncology. Prior toMinomic he was involved in the development of a novel antibody(MDX-1097) from pre-clinical to Phase 2 clinical trials.
Addressable Indications, Unmet Need, GPC-1 Role
26
Cancer 2018 New Cases Diagnosed
% All Cancers*
% Mortality Rate Per Annum GPC-1 Key Reference
Prostate 1,276,106 7.1 28.1 Russell et al Cancer Immunol. Immunother. (2004) 53: 995-1004
Breast 2,088,849 11.6 30.0 Matsuda et al Cancer Res 2001;61:5562-69
Bladder 549,393 3.0 36.4 Walker et al, J Urol. (1989) 142: 1578-83
Pancreas 458,918 2.5 94.2 Lu et al, Cancer Medicine (2017) 6:1181
Glioblastoma 154,362 1.6 81.2 Saito et al J. W.Neurosurg.(2017) 105: 282
Esophagus 572,034 3.2 88.9 Harada et al Oncotarget (2017) 8:24741
Ovary 295,414 1.6 62.6 GlyTherix data
Total 5,242,151Source: http://gco.iarc.fr/today/home *excl. non-melanoma skin cancers
Miltuximab® Pipeline Development Stage
27
Pre-Clinical Development
Clinical Phase I
Clinical Phase III
First In Human
Clinical Phase II
Indication
Prostate
Bladder
Pancreas
Glioblastoma
Breast
Ovary
Esophagus Published data
Pipeline Molecule Development
28
• Serial filing of primary and dependent patent claims via PCT track• Countries to be lodged in include : US, EU, AU, Canada, Japan, China, Singapore and Korea• IP counsel: Cooley LLP (Washington DC office, US), Spruson & Ferguson (Sydney office AU)
• Related guidance is that company has assembled robust patent portfolio• Assuming all granted, patent coverage will run to 2035
An Expanding Patent Estate with Robust, Multilayered Claims
29
Patent Family Stage of Development
1. Cell Surface Prostate Cancer Antigen for Diagnosis Registered US, CN, SG, EU, JP. National Phase process continuing: AU, CA, HK, KR
2. Monoclonal ANTI-GPC-1 Antibodies and Uses Thereof Registered US, EU National Phase process continuing: AU, CN, CA, HK, JP, KR and SG
3. Glypican Epitopes and Uses Thereof Registered EU National Phase process continuing: AU, CN, CA, HK, JP, KR, SG and US
4. Therapeutic antibodies and Uses Thereof National Phase process continuing: AU, CN, CA, EU, HK, JP, KR, SG and US