World's only technology that consistently produces full-length, correctly folded, functional proteins - Sengenics
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Misfolded
proteins are
washed away
Only correctly
folded proteins
are immobilised
World’s only technology
that consistently produces full-length, correctly folded, functional proteins
Confidential © 2008–2021 Sengenics Corporation Pte Ltd
Agenda for today’s presentation 2
1. Company 2. Technology 3. Case Studies 4. Study Design
Cambridge roots Protein folding Autoantibodies Samples
Main collaborators Protein function Diagnostics Study design
Team Performance Response prediction Business case
Confidential © 2008–2021 Sengenics Corporation Pte Ltd
Sengenics is a 12-year old British biotech company with a solid global footprint 3
2020
2021 2008
A c q ui r ed b y
m u l t i - bi l l i on d o l l a r ,
l i f e - s c i enc e f o c used,
S w e di s h f i r m
C a m b r i dge s p i n - out
B o s t on R & D f a c i l i t y
2016
P r o t e i n p r o d uct i on a n d
h i g h- t hr oughput a s s ay f a c i l i t y i n A s i a
Confidential © 2008–2021 Sengenics Corporation Pte Ltd
Sengenics KREX immunoproteomics platform leveraged by 100+ institutions 4
9 o u t o f t o p 1 0 P h a r m a g lo b a lly
10 a c a d e m ic in s t it u t io n s
6 a c ad e m ic in s t it u t io n s
> 5 0 p r o je c t s
Member of Cancer, Inflammation
& Immunity, and Neuroscience
Steering Committees 2 7 a c a d e m ic in s t it u t io n s
> 2 00 p r o je c t s
I n d us t r i a l a d v i s or y
b o a r d m e mber
Confidential © 2008–2021 Sengenics Corporation Pte Ltd
Wide repertoire of research studies and IP 5
Type 1 Type 2 Type 3
Core Tech Patents Sero-diagnostics Drug ADR-Response
14 Granted 3 Filed 1 Filed
1 Filed 20+ Unfiled 16 Unfiled
2 Unfiled
Group 1 - Preparing protein arrays with Aging Sjogren’s Anti TNF
marker tag to immobilise proteins Oral Cancer Zika Anti IL
Group 2 - Protein Variant Arrays NSCLC Melanoma Anti CTLA-4
Group 3 - BCCP tag Type II Diabetes Malaria Anti PDL1
Group 4 - Cytosolic Accessory Proteins Parkinson’s Gastric Cancer Other drugs
Group 5 - Drug discovery Alzheimer’s Crohn’s
Prostate Cancer RA
Lupus Breast Cancer
Confidential © 2008–2021 Sengenics Corporation Pte Ltd
The core principle of our KREX protein folding technology 6
> BCCP: compact, inert, folding marker
> Biotin is attached ONLY to correctly folded proteins
> Misfolded proteins misfold BCCP
> BCCP loses its biotinylation activity
> Only correctly folded proteins are attached
Confidential © 2008–2021 Sengenics Corporation Pte Ltd
Unique surface chemistry 7
> No conventional purification:
Simultaneous purification and
immobilisation PROTEINS
> KREX proteins retain folded
structure and function in the behave as if
aqueous environment they are in
> Streptavidin tetramers
covalently bound to hydrogel free solution
layer COO-
COO-
> Single attachment point ensures COO-
consistent orientation of COO- COO-
proteins
> Proteins are immobilised onto
proprietary streptavidin-coated
HYDROGEL
> Proteins are projected 50
Angstroms from the glass
surface
Confidential © 2008–2021 Sengenics Corporation Pte Ltd
Immobilise various biomolecules associated with complex diseases on KREX arrays 8
PTM & complex protein
Bacterial protein Peptide
DNA
Viral protein
QC of KREX protein arrays demonstrates performance required for downstream assays 9
1. Biotinylated marker
15. Biotinylated marker
14. Control pPro10
8. No name
11. No name
4. SH3GL1
3. STAT5A
6. ERCC5
13. KRAS2
5. GPHN
7. GPC3
12. GAS7
9. HRAS
10. SAV1
2. SSX1
Spot diameter ~25nm
202+/-33 streptavidin units per mm2
Dual wavelength scan of an on-array c-Myc Distance between streptavidin units
assay: Red = Cy5-biotin BSA controls (red); 52.9+/-3.1 nm
Green = C-terminally c-myc-tagged antigens 40,000 binding units / 200mm2 spot
Western blot analysis Anti-c-myc assay Streptavidin density
Confidential © 2008–2021 Sengenics Corporation Pte Ltd
KREX arrays exhibit exceptional sensitivity, specificity and consistency 10
Very high specificity
High signal:noise ratio and clearly
interpretable hits
Obviates conventional
blood draw and cold chain
As little as
1µl Collect samples during
flare-ups
of serum
or plasma Leverages sensitivity of
sample
KREX platform
Highly reproducible Exceptional sensitivity
Duplicate samples exhibit exceptional performance Limit of detection is 10pg/ml range
and consistency Single digit µl levels of sample can be used
(Pearson correlation >0.97) Five orders of magnitude dynamic range
Confidential © 2008–2021 Sengenics Corporation Pte LtdProteins on KREX arrays have been functionally validated 11
> Kinases auto-phosphorylate and Kinase inhibition assays correlate with published data
> DNA binding proteins bind DNA – p53 mutant proteins exhibit differential binding of labelled oligo
> Indirect functional assays
Kinases autophosphorylate P53 mutants bind labelled Autoimmune disease hits
in the presence of ATP DNA oligo with different Kd values correlate with published data
Confidential © 2008–2021 Sengenics Corporation Pte LtdKREX proteins form multimers and are functional on the array 12
HETERODIMERS TRIMERS ON-ARRAY PTMs FUNCTIONAL ASSAYS
The detection of the 58 kDa Western blot analyses of expressed Quantifying the effect of post-translational On-chip phosphorylation of p53 by
hexahistidine-tagged β-subunit (lower HA variants protein. Two samples modifications on autoantibody casein kinase II (CKII)
boxes in red) and a band at ~90 kDa (denatured and non-denatured recognition: neoantigens in colorectal
(upper boxes in red) under semi-native proteins) of each HA variant were run cancer. Protein arrays were incubated in assay
conditions of all TCR proteins provides side-by-side on SDS-PAGE gels. buffer containing ATP in the presence
evidence for heterodimer complex Arginine deimidation to citrullene on chip and absence of CKII
formation during protein expression in using peptide arginine deimidase 4. Results: Specific phosphorylation of
insect cell. S392 was detected using residue
specific antiphosphoserine primary
Only the β-subunit was detected at ~58 antibody with detection by secondary
kDa under denaturing/reducing antibody-peroxidase conjugate and
conditions. chemiluminescence.
Mutations with “X” denote truncations
due to introduction of premature stop
codons and therefore lack S392
Confidential © 2008–2021 Sengenics Corporation Pte LtdKREX arrays exhibit exceptional consistency with CV% values of
Diverse microarray product & antigen range 14
High-throughput Quantification of Simultaneous screening of Multi-antigen,
autoantibody profiling autoantibodies to 200+ 100+ wild-type and multi-domain COVID-19
against 1600+ proteins clinically relevant CT antigens mutant p53 antibody test
Confidential © 2008–2021 Sengenics Corporation Pte Ltd15
Identify all the autoantigens and antigens that make up the
Using Orvar, the totality of all possible
autoantigens and neoantigens representing a
given disease and its sub-types can be identified
The total number of antigens if you add
all possible variants of human proteins,
splice variants of those human proteins
and neoantigens is in the millions
Use KREX to clone, express and attach every single
autoantigen or antigen on to a Sengenics protein array
Confidential © 2008–2021 Sengenics Corporation Pte LtdAutoantigens identified using Orvar are clinically relevant 16
Tissue from Colorectal Cancer (CRC) individuals (cancer and adjacent normal tissue) were characterised on Orvar:
Plasma samples from CRC and healthy individuals were screened against existing KREX proteins
KREX proteins
Positive on both platforms: Wild-type antigens
13.7% Positive on Orvar only: Neoantigens
9.8%
54.9%
New autoantigens
21.6%
Homologue autoantigens to KREX proteins which may contain
overlapping surface epitopes reactive to the bound autoantibodies
GO enrichment analysis:
Results indicate % of antigens with high significance
(adjusted p-values < 0.01)
Confidential © 2008–2021 Sengenics Corporation Pte LtdAutoantibodies are superior biomarkers compared to DNA, RNA and proteins 17
Confidential © 2008–2021 Sengenics Corporation Pte Ltd90% of autoantibodies bind to dis-continuous, conformational epitopes 18
Continuous Dis-continuous
Folding independent Folding dependent
Non-conformational Conformational epitope
1. *Barlow, D. J., Edwards, M. S., & Thornton, J. M. (1986). Continuous and discontinuous protein antigenic
determinants. Nature, 322(6081), 747–748;
2. *Van Regenmortel, M. H. V. (2006, May). Immunoinformatics may lead to a reappraisal of the nature of B cell
epitopes and of the feasibility of synthetic peptide vaccines. Journal of Molecular Recognition, 19(3), 183–187.
Confidential © 2008–2021 Sengenics Corporation Pte LtdSengenics apps: use protein array technology to diagnose and stratify patients 19
CANCER AUTOIMMUNE NEURO
CANCER AUTOIMMUNE
Early diagnosis of diseases using Predict response and ADRs
autoantibodies for cancer and autoimmune
drugs using autoantibodies
Diagnosis and screening
of infectious diseases
MICROBES
Confidential © 2008–2021 Sengenics Corporation Pte LtdAutoantibody assay protocol 20
Microarray Scanner
1. Add sample – 1 to 10μl
(Serum, Plasma, CSF, Lung lavage,
Tissue homogenate)
2. Autoantibodies in sample
bind quantitatively to proteins
on array
3. Scan to Quantify
Autoantibody signal by adding
anti-IgG secondary antibody
Confidential © 2008–2021 Sengenics Corporation Pte LtdORVAR autoantigen discovery work flow 21
Autoantigens from
tissue source
aAb from
patient serum
1. Use ORVAR to identify the auto-proteome of
interest using patient tissue source and serum
2. Use KREX to clone, express and attach
every single autoantigen on to a
Sengenics protein array
3. High-throughput quantification of
autoantibodies for intra-disease stratification
Confidential © 2008–2021 Sengenics Corporation Pte LtdCase Study Cancer diagnostics in Melanoma 22
> Stage I/II Melanoma patients (n=124) vs controls (n=121) profiled on Sengenics Immunome arrays
“The test, billed as a world first, is designed to make it easier to spot the skin cancer
before it becomes fatal, according to researchers.” - BBC, 18 July 2018
139 biomarkers based on cut-off of positive score >5. A panel 10 biomarkers was selected based on a Biomarkers appear primarily related to general
VEGFb, p53, MITF, KIT and MLANA have previously been random forest and classification tree analysis, resulted a cancer pathways, including apoptosis,
associated with cancer and Melanoma combined sensitivity 84% and specificity 79% and an AUC of pathways associated with the immune
0.828. Biomarkers Panel : ZBTB7B, PRKCH, TP53, PCTK1, response and cell cycle, p53 signaling and the
PQBP1, UBE2V1, IRF4, MAPK8_tv2, MSN and TPM1 MAPK signalling pathway, the main pathway
associated with melanomagenesis
Zaenker, Pauline et al. 2018
Confidential © 2008–2021 Sengenics Corporation Pte LtdCase Study Stratification of Melanoma patients to Pembro using autoantibodies 23
250000 CTAG2
24A
200000
Average RFU
NY-ESO-1 24B
> Study Design: 150000
24C
100000
> Metastatic melanoma, BRAF mutant patients, treated 24D
50000
with either Pembrolizumab (anti-PD-1) 24E
0
COL6A1
DDX53
ITGB1
SPANXC
NANOG
PBK
TYR
BAGE4
DPPA4
GAGE1
GAGE5
MAGEA4v2
MAGEA5
MAGEB6
MAPK3
TPTE
PRKCZ
SILV
CDC25A
CDK7
CTAG2
p53 Q136x
p53 S46A
ROPN1
SPO11
CALM1
CXorf48.1
FES
LIP1
NY-CO-45
p53 K382R
AKT1
MAGEA11
5T4/TPBG
CSAG2
GDF3
OIP5
SPAG9
SSX2A
XAGE3av1
SYCP1
> Patient sera collected at different points of treatment
(baseline, post-treatment 1, 2 etc.)
> Sera screened on the KREX arrays for the
quantification of autoantibodies towards CT antigens 25000 p53 S15A
p53 S46A
20000
> Figures show autoantibody profiles across 3
Average RFU
p53 K382R
15000 p53
p53 L344P
C141Y
patients treated with Pembro whom were reported P53 T18A
10000
to have; 47A
5000 47B
> complete response (top)
0
> disease progression (middle)
COL6A1
DDX53
ITGB1
MAGEA4v2
MAGEA5
MAGEB6
TYR
PBK
BAGE4
DPPA4
GAGE1
GAGE5
MAPK3
SPANXC
NANOG
TPTE
CDK7
CTAG2
PRKCZ
FES
ROPN1
SILV
CALM1
CDC25A
SPO11
AKT1
5T4/TPBG
CSAG2
CXorf48.1
GDF3
LIP1
MAGEA11
NY-CO-45
OIP5
p53 K382R
p53 Q136x
p53 S46A
SPAG9
SSX2A
SYCP1
XAGE3av1
> initially stable and then disease progression
(bottom)
300000 DDX53
> Differences in autoantibody signatures observed 250000
suggest the platform’s potential in providing a 200000 MAGEB6
MAGEB1
Average RFU
CTAG2 NY-ESO-1
practical route to patient stratification prior to 150000 51A
100000
treatment 51C
50000
0 51D
COL6A1
DDX53
ITGB1
BAGE4
DPPA4
MAGEA4v2
MAGEA5
MAGEB6
GAGE1
GAGE5
PBK
SPANXC
MAPK3
NANOG
TPTE
TYR
CDK7
CTAG2
FES
ROPN1
CALM1
PRKCZ
SILV
CDC25A
SPO11
AKT1
CSAG2
CXorf48.1
GDF3
LIP1
MAGEA11
NY-CO-45
p53 K382R
p53 Q136x
p53 S46A
5T4/TPBG
OIP5
SPAG9
SSX2A
SYCP1
XAGE3av1
Source: Unpublished data in collaboration with ONCJRI
Confidential © 2008–2021 Sengenics Corporation Pte LtdCase Study Diagnostic biomarkers in SLE 24
> Two independent studies both identified well-known SLE autoantigens TROVE2 (Ro60) and SSB (La) showing the most significant
difference between SLE and healthy cohorts. (Study 1: 86 SLE patients vs 90 matched healthy individuals Study 2: 10 SLE patients
vs 10 healthy individuals)
> These studies also identified previously reported SLE autoantigens such as PRM1 (U.S. Patent Application No. 14/418,700). The
array also validated other previously reported SLE autoantigens PSME3 (also known as Ki) (M. Matsushita, 2004)
Volcano plot summarising the results from a comparison analysis of 86 SLE Comparison analysis of 10 SLE patients VS 10 matched healthy samples run on the
patients VS 90 matched healthy samples run on the Sengenics Immunome Sengenics Immunome array in Study 2
array in Study 1
Lewis, M. J., et. al. 2018
Confidential © 2008–2021 Sengenics Corporation Pte LtdCase Study Autoimmune patient stratification in Lupus 25
> Autoantibody profiles stratify SLE patients significantly based on disease trajectories – potential therapeutic targets based on severity
> Identified autoantigens cluster into functional groups, hinting at differing underlying pathogenic mechanisms and possibly at differing treatments
for the SLE subgroups
> 13 of the novel antigens directly implicated in SLE pathogenesis
B
Unsupervised clustering of the autoantibody repertoire revealed Two key themes emerged: cluster 2 autoantigens centred around
four distinct SLE clusters (1a, 1b, 2, 3) in discovery and validation SMAD2 and SMAD5 were linked to TGF-b/Wnt/BMP signalling;
cohort. These clusters represent distinct molecular subtype of SLE cluster 3 autoantigens were implicated in TLR/NF-kB signalling,
and different response to treatment apoptosis regulation, and B and T lymphocyte development.
Lewis, M. J., et. al. 2018
Confidential © 2008–2021 Sengenics Corporation Pte LtdCase Study Autoimmune patient stratification in Lupus 26
> Autoantibody profiles stratify SLE patients significantly based on disease trajectories – potential therapeutic targets based on severity
> Identified autoantigens cluster into functional groups, hinting at differing underlying pathogenic mechanisms and possibly at differing treatments
for the SLE subgroups
> 13 of the novel antigens directly implicated in SLE pathogenesis
Red = subgroup 1a
Purple = subgroup B-cell-directed therapies?
1b (e.g. Rituximab)
Green = subgroup 2
Blue = subgroup 3
Non-B-cell-directed therapies?
(e.g. cyclophosphamide)
Lewis, M. J., et. al. 2018
Confidential © 2008–2021 Sengenics Corporation Pte LtdPublication Anti-TROVE2 Antibody Determined as a Predictive Marker for Adalimumab 27
Immunogenicity and Effectiveness in RA Good responders
Anti-drug antibody (ADAb) positive vs negative patients at
baseline and at week 24 of adalimumab therapy
> Results:
> Panel of top 8 biomarkers identified: autoantibodies
Heat map showing clear
against TROVE2, SSB, NDE1, ZHX2, SH3GL1, CARD9, distinction between poor
PTON20, and KLHL12 and good (purple box)
> Combined discriminatory power with: responders to adalimumab
therapy
> Sensitivity = 77%
> Specificity = 81%
Panel: 8 biomarkers
Mean sensitivity: 0.774
Mean specificity: 0.806
Mean distribution plot from Mean accuracy: 0.790
random forest analysis showing a
panel consisting of 8 biomarkers
resulting in the most stable
performance
Anti-TROVE2 had the highest individual discriminating
ability, and may serve as a novel predictor of
adalimumab immunogenicity. Plasma autoantibody
levels against TROVE2 correlated positively with ADAb
titres and negatively with drug levels
Chen, P. K. et. al., 2021
Patent no. 10202011473Y
Confidential © 2008–2021 Sengenics Corporation Pte LtdProposed study design and phases to validation and commercialisation 28
Pilot study Validation Custom Clinical
Matched samples Training and Signature ID FDA process
Time points Validation set +Orvar proteins Regulatory
6 weeks 8 weeks 12 weeks
2500
2000
1500
1000
500
0
Samples Proteins
Confidential © 2008–2021 Sengenics Corporation Pte LtdStudy design is dependent on disease type and heterogeneity 29
Percentage of
Sample Size Estimation and Power Calculation for Various Diseases Category Type of Disease Power (%) Biomarkers
2% 1%
800
90.00% 153 250
Rheumatoid Arthritis 95.00% 189 309
Number of sample size estimation
700
99.00% 267 437
600
Autoimmune
90.00% 128 221
Sjogren’s syndrome 95.00% 149 256
500
99.00% 191 329
400 90.00% 91 116
Gastric Cancer 95.00% 113 143
300
99.00% 159 203
Cancer
200 90.00% 57 90
Non-small-cell lung
95.00% 66 104
100
carcinoma (NSCLC)
Statistical 99.00% 85 134
Power
0
90.00% 160 182
Metabolic
0.9 0.95 0.99 0.9 0.95 0.99 0.9 0.95 0.99 0.9 0.95 0.99 0.9 0.95 0.99 0.9 0.95 0.99 Type 2 Diabetes (T2D) 95.00% 186 211
Disorder
NSCLC Gastric Cancer T2D Sjogren Rheumatoid Parkinson 99.00% 239 271
Syndrome Athritis 90.00% 357 427
Neurological Parkinson 95.00% 442 528
Percentage of Biomarkers 2% 1%
99.00% 624 746
Confidential © 2008–2021 Sengenics Corporation Pte LtdSengenics publications 30
Autoantibodies Targeting TLR and SMAD Pathways Define New Subgroups in Systemic Lupus Erythematosus
Lewis, Myles J. et al. 2018
Identification of Novel Native Autoantigens in Rheumatoid Arthritis
Poulsen, Thomas B. G. et al. 2020
A U T O I M M U N E
Detection of Putative Autoantibodies in Systemic Lupus Erythematous using a Novel Native-conformation Protein Microarray Platform
Mak, Anselm. et al. 2020
Anti-TROVE2 Antibody Determined by Immune-Related Array May Serve as a Predictive Marker for Adalimumab Immunogenicity and Effectiveness in RA
Chen, Der-Yuan et al. 2021
Functional Protein Microarrays for Parallel Characterisation of P53 Mutants
Boutell, Jonathan M. et al. 2004
Seromic Analysis of Antibody Responses in Non-Small Cell Lung Cancer Patients and Healthy Donors Using Conformational Protein Arrays
Gnjatic, Sacha et al. 2009
Protein Function Microarrays: Design, Use and Bioinformatic Analysis in Cancer Biomarker Discovery and Quantitation
Duarte, Jessica et al. 2013
Serologic Autoantibodies as Diagnostic Cancer Biomarkers — A Review
Zaenker, Pauline et al. 2013
C A N C E R Development Of A Novel, Quantitative Protein Microarray Platform for the Multiplexed Serological Analysis of Autoantibodies to Cancer-Testis Antigens
Beeton-Kempen, Natasha et al. 2014
Novel Potential Serological Prostate Cancer Biomarkers Using CT100+ Cancer Antigen Microarray Platform in a Multi-Cultural South African Cohort
Adeola, Henry A et al. 2016
Autoantibodies May Predict Immune-Related Toxicity: Results from a Phase I Study of Intralesional Bacillus Calmette–Guérin followed by Ipilimumab in Patients with Advanced
Metastatic Melanoma
Da Gama Duarte, Jessica et al. 2018
A Diagnostic Autoantibody Signature for Primary Cutaneous Melanoma
Zaenker, Pauline et al. 2018
B cells and Antibody Production in Melanoma
Da Gama Duarte, Jessica et al. 2018
Confidential © 2008–2021 Sengenics Corporation Pte LtdSengenics publications 31
Augmentation of Autoantibodies by Helicobacter pylori in Parkinson’s Disease Patients May Be Linked to Greater Severity
N E U R O
Suwarnalata, Gunasekaran et al. 2016
Autoantibody Profile of Patients Infected with Knowlesi Malaria
Liew, Jonathan et al. 2015
Identifying Protein Biomarkers in Predicting Disease Severity of Dengue Virus Infection Using Immune-Related Protein Microarray
Soe, Hui Jen et al. 2018
M I C R O B I A L
COVID-19 Antibody Testing: From Hype to Immunological Reality
Blackburn, Jonathan M et al. 2020
Quantitative, Epitope-specific, Serological Screening of COVID-19 Patients Using a Novel Multiplexed Array-based Immunoassay Platform
Blackburn, Jonathan M et al. 2020
A Novel Method to Identify Autoantibodies against Putative Target Proteins in Serum from beta-Thalassemia Major: A Pilot Study
Sumera, Afshan et. al. 2020
O T H E R
Potential Novel Proteomic Biomarkers for Diagnosis of Vertebral Osteomyelitis Identified using an Immunomics Protein Array Technique
Chen, Chang-Hua et al. 2020
Protein Function Microarrays for Customised Systems-Oriented Proteome Analysis
Blackburn, Jonathan M, and Shoko, Aubrey 2011
Advances in the Development of Human Protein Microarrays
Duarte, Jessica G, and Blackburn, Jonathan M 2017
T E C H N O L O G Y
Autoantibody-Based Diagnostic Biomarkers: Technological Approaches to Discovery and Validation
Aziz, Farhanah et al. 2018
Applications of Functional Protein Arrays for Detection and Development of Autoantibody-based Diagnostics and Therapeutics
Aziz, Farhanah et al. 2018
Confidential © 2008–2021 Sengenics Corporation Pte LtdImpact and benefits of using KREX and Orvar technologies 32
Use KREX protein arrays to discover high-accuracy autoantibody signatures
Diagnose cancers/autoimmune diseases earlier Predict irAEs at baseline for IO and autoimmune drugs
High PPV/NPV drug response prediction Intra-disease stratification
Confidential © 2008–2021 Sengenics Corporation Pte LtdSEROMAX blood collection kit 33
How to use SEROMAX
1. Wipe alcohol swab across your fingertip 3. Prick finger by pushing lancet firmly down 5. Gently drip blood onto all 4 circles of the
2. Twist off the cap from the lancet with your other hand blood card
4. Press finger lightly towards the puncture 6. Insert blood card into the biohazard bag
site to obtain blood before posting the box back to your service
provider
Sample collection kit which only requires a pin-prick amount of blood for
quantifying antibodies or autoantibodies
Obviates conventional blood draw and cold chain
Leverages sensitivity of KREX platform
Enables sample collection during flare-up events
Confidential © 2008–2021 Sengenics Corporation Pte LtdThank You
You can also read
