Anti-cancer screening of herbal drugs using cancer patient cells

Case Studies of Testing Herbal Extracts & Drugs for Cancer
Patient Tissue- and Primary Cell-Based 2D & 3D Preclinical Models

Why Test Natural Extracts and Molecules
Since the 1980s, a total of 174 new anti-cancer compounds have been approved for
commercialization, of which 93 (53%) were natural products, or derived directly from plants
One of the most famous anti-cancer drugs, paclitaxel, used for the treatment of breast cancer, was
isolated from the bark of Taxus Brevifolia
There is tremendous opportunity to systematically investigate promising plants and extracts for their
anti-cancer activity and validate it rigorously in drug discovery campaigns. Even traditional plant-based
medicines that have been in use for years need more data to claim anti-cancer activity
We provide a platform to pharma and biotech companies for screening their plant extracts and
compounds directly on patient tumor-derived primary cancer cells (PDCs), in 2D and 3D assays, to
confirm and compare their activity from traditional cancer cell lines
11 July 2020 Sapien Biosciences
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Our Anti-Cancer Platform for Screening Activities and MOA
Breast Cancer
Glioma
Oral Cancer
AML
CLL
More in development
Cancer Cell type available
Patient derived primary
cancer cells (PDCs)
2D Assays
3D Assays
Cancer cell lines
Antiproliferation
Apoptosis assays
Analysis
of cancer
stem
cells
Toxicity
studies on
healthy
tissue, cells
or stem
cells
Cytokine
Analysis by
ELISA assay
Gene
expression
analysis by
IHC, FACS,
RT PCR
ROS assay
NOS assay
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Sapien Biosciences

SOLID TUMORS: Herbal Extracts in TNBC Breast Cancer Patient Cells
Dose response study of two natural extracts
Patient detail: PDC SB 30750
Age, Gender: 42-year Female
Histopathology: DCIS
Receptor status : ER-/PR-/Her2-,
TNBC
Tumor grade : I
TNM stage : T2N0Mx
Treatment details available
Standard of Care Drugs
(SOC) for Breast Cancer
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Sapien Biosciences

Screening in MDA-MB 231 TNBC Cell Line, part of NCI-60 Panel
Dose response study of two natural extracts
We also perform screening in cell lines
Here, the MDA-MB 231 cell line,
established from pleural effusion of a
Caucasian female with a metastatic
mammary adenocarcinoma, was used
Standard of Care Drugs for Breast Cancer (SOC)
Observation: Both the extracts showed better anti-cancer activity in TNBC patient-derived cells than in cell line
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11 July 2020
Sapien Biosciences

Screening of Extracts in ER+/PR+ HER2 equivocal Breast Cancer PDCs
Dose response study of two natural extracts
Patient detail: PDC, SB 45472
Age, Gender: 58-year Female
Histopathology: DCIS
Receptor status : ER+/PR+/Her2 equivalent
Tumor grade : II
TNM stage : T2N2
Treatment details available
SOC/ Standard Inhibitor
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Sapien Biosciences

Dose Response of Known Herbal Extracts in Brain Cancer primary PDCs
125
100
75
50
25
0
Ashwagandha derivative Internal Standard Turmeric derivative
IC50: 6.2 ug/ml
-25
0.1 1 10 100
Cpd conc [ug/ml]
IC50:
N1: 743 nM,
N2: 221 nM,
N3: 175nM
125
100
75
50
25
0
IC50: 12.5 ug/ml
0.1 1 10 100
Cpd conc [ug/ml]
Patient detail: PDC, SB 30771
Age/gender: 74 yr Male
Tissue Histology:
Glioblastoma
WHO Tumor grade: IV
Treatment details
available
1. Inhibition shown by Temozolomide (SOC) in above expt @ 300uM: 20 %
2. N1, N2 and N3 are 3 independent experiments performed on different days
3. There are a few publication that have done similar work with medicinal herbal extracts with
similar results as shown by us:
• IC50 value of an Ashwagandha extract in GBM primary cells: 4.2uM (J Neurooncol. 2016; 126: 253-64)
• IC50 of a turmeric extract in two GBM primary cells: 46 uM & 78 uM. (J Cancer Res Ther 2016;12(2)
11 July 2020
Sapien Biosciences
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IC50 Determination of Known Herbal Extracts in Glioma cell line
125
100
75
50
Ashwagandha derivative A
125
100
75
50
Ashwagandha derivative B
The U87 MG cell line was
established from a male
glioblastoma (GBM) patient
(ATCC)
25
0
IC50: 4.1 ug/ml
-25
0.1 1 10 100
Cpd conc [ug/ml]
25
0
IC50: 0.25 ug/ml
-25
0.01 0.1 1 10 100
Cpd conc [ug/ml]
Inhibition showed by Temozolomide (SOC)
in this expt. @ 300uM: 28 %
*Published literature:
125
100
75
50
25
0
Internal standard
IC50: 4.5 uM
10 -8 10 -7 10 -6 10 -5 10 -4 10 -3
Cpd conc [uM]
125
100
75
50
25
0
Turmeric extract
IC50: 8.7 ug/ml
0.1 1 10 100
Cpd conc [ug/ml]
IC50 of Ashwagandha derivatives in
U87 MG cell line - 1.4 uM and 0.15
ug/ml (J Neurooncol. 2016; 126: 253-64).
IC50 of a Turmeric derivative in U87 MG
cell line - 37 ug/ml. (J Evid Based
Complementary Altern Med 2015 Apr;20(2):109-19
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IC50 Determination of an Ashwagandha derivative in 2D vs 3D Neurospheres
in U87 MG
2D assay
3D assay
125
125
100
100
75
75
50
50
25
0
IC50: 0.25 ug/ml
25
0
IC50: 6 ug/ml
-25
0.01 0.1 1 10 100
Cpd conc [ug/ml]
-25
0.01 0.1 1 10 100
Cpd conc [ug/ml]
*Published literature: IC50 of an Ashwagandha derivative in U87 MG cell line in 2D proliferation assay - 0.15
ug/ml (J Neurooncol. 2016 Jan; 126 (2): 253-64), whereas in 3D proliferation assay – 0.31 ug/ml (J Neurooncol. 2016 Jan; 126(2):
253–264)
*All experiments have been done with duplicate or triplicates and illustrative data has been shown here
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11 July 2020

Screening is also done in
Hematopoietic Tumor Patient Cells
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11 July 2020
Sapien Biosciences

Screening of Herbal Extracts in AML Patient Cells
Dose response study of two natural extracts
Extract S: IC50 determination
IC50: 19.5 ug/ml
SOC/ Standard Inhibitor
Patient detail: PDC SB 33866
Age & Gender: 76 year Female
Diagnosis: AML M4 subtype,
Detailed diagnostic report
available
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11 July 2020
Sapien Biosciences

Screening of Herbal Extracts in CLL PDCs
Dose response study of two natural extracts
Extract X: IC50 determination
% Inhibition of cell proliferation
IC50: 22 ug/ml
11 July 2020
SOC/ Standard Inhibitor
Patient detail: PDC, SB 31713
*Inhibition showed by Ibrutinib (SOC) on same CLL PDCs @ 60uM: 45 %
Age/gender: 77-year Male
Diagnosis: CLL, detailed report
available
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Our Model of Working
We are working on drug discovery programs for US-based clients already to analyze the
anti-cancer property of their plant-based natural extracts, their mechanism of action and
toxicity determination in actual cancer patient tissue-derived cell models. This is being
done to validate their extracts prior to taking them for animal efficacy and into human
trials since patient samples have higher translation to clinical activity
We work as a CRO to design and execute the whole experimental plan to help clients for
their drug evaluation, strategic development plan in vivo, publication and/or patent
review and indications for clinical trials. IP belongs to the client.
We also consider collaborative projects on a case-by-case basis.
We are flexible and work as per each client’s requirement
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Sapien Biosciences

Ask about our Other Sample Types, Assays and Services
Tissue types
• Healthy or cancer PBMCs
• FCR characterized PBMCs
for ADCC assays
• Dendritic cells
• Keratinocytes
• Fibroblasts, CAFs
• Primary Cancer cells
• Normal human skin
Assays/ Readouts
• Proliferation / Apoptosis
• DC-MLR assay
• Immunogenicity assays
• ADCC assay
• Skin air-liquid assay
• ELISAs – LDH, Cytokines
• Cancer stem cells
• IHC, IF, FACS
11-Jul-20
Please write at : research@sapienbio.com

Product & Services Offered by Sapien to Diverse R&D Enterprises
R&D
Products,
Platforms &
Services
R&D Platforms using Patient OR Healthy Human Samples
and Associated Medical Data
OncoBloc OncoPrime OncoData TruCell TruScreen TruSkin
Fixed & fresh
frozen samples
collection
Cancer Patients
tissue derived live
cells
Cancer Patients’
Treatment &
Outcomes Data
Non-cancer
Diseased OR
Healthy cells
NCD Diseaserelevant
functional assays
Healthy human
Skin from
cosmetic surg
Current
Offerings
Breast Cancer,
Glioma, Head &
Neck cancers etc.
AML, Breast Ca,
CLL, Glioma, Oral
Ca etc.
RWE in cancers:
Breast, Lung,
Renal, Oral, CRC
PBMCs, B/T cells,
CD34+, Dendritic,
Fibroblasts, k’cytes
Cytokine release,
Apoptosis, Gene
exprn, MLR, ADCC
Air-liquid
interphase skin
health model
Drug Disc
Applications
Personalized
Medicine
Applications
ID & validation of
novel drug targets
& biomarkers
Dev & validation
of novel targets,
diagnostic markers
Lead-optimization
of novel canceractive
molecules
Identify anticancer
drugs,
herbal extracts &
companion Dx
Patient
stratification,
marketing strategy
Optimization of
treatment
paradigms
Providing service
to companies to
perform in vitro
assays on-site
Validation of drugs
prior to clinical
trials
Phenotypic
screening of
drugs, extracts,
nanoformulations
Drugs, companion
marker dev &
validation
Screening drugs,
formulations, skin
markers by IHC IF
Skin penetration,
toxicity, health,
chemokines
Addressable
Market
Pharma, Biotech,
Diagn, Reagents
Equipment co
Pharma, Biotech,
Herbal,
Formulations co
MNC Pharma,
AI/ML Digital
Path Diagn co
Pharma, Biotech,
academics
Pharma, Biotech,
Nutraceutical,
Herbal co
Cosmeceutical,
Derma-focused
co, Formulations
www.sapienbio.co.in
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About Us
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Sapien Biosciences

Sapien- India’s Largest, Most Diverse Biobank
Data Associated With Our Samples
Active sites:
Ahmedabad
Bangalore
Bhubaneswar
Chennai -2 hospitals
Delhi
Hyderabad
Kolkata
Mysuru – 11-Jul-20 in process
Inventory has >0.2 Million samples
Jain J et al. 2015. ISBER. Building a Disease-Agnostic Sustainable Biobank
in India with Apollo Hospitals: Ethical and Regulatory Hurdles in
Conducting Human Biospecimen-Enabled Research and Development
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The ‘Essence’ of Our Enterprise
Unmet Need : Rigorous, scientific evidence for the efficacy of most herbal medicines is still lacking and
hence their development to meet regulatory approval and adoption by patients has been a challenge
Our Vision:
To provide actual Patient-derived primary cell (PDC) based screening platforms for real time
prediction of efficacy and safety of herbal extracts and drugs
To evaluate anti-cancer activity of herbal extracts in 3D organoid models and establish in vivo
PDX animal models, which enable judicious design for successful clinical trials
Our Mission:
To bring safe and affordable herbal anti-cancer drugs in the Indian and global markets through
our scientific rigor and expertise in physiologically relevant preclinical models
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We have a Highly Capable and Globally Experienced Team
• Molecular & cell biologist experienced in the use of primary human samples for
target/biomarker validation, diagnostics & drug discovery
• PhD in Genetics (Cambridge, UK), Post-doc immunology (Harvard Med , USA)
• >27 years of experience across cancer, autoimmune, inflammatory diseases at Vertex
Pharma (USA) and Sapien/Saarum. Led biology teams through target discovery & IND
filings for many molecules.
• Extensive R&D leadership experience and proven track record of forging several
successful R&D collaborations
Dr. Jugnu Jain
Co-Founder & CEO
Dr. Soma Chatterjee
Director,
Biobank operations
• Cancer biologist with post PhD >15
years of experience in ethical tissue
sourcing and cell biology applications.
• PhD in Molecular Endocrinology from
Chonnam National Univ, South Korea.
Executive diploma in International
Business Strategy from Indian
Institute of Foreign Trade, New Delhi.
• Track record of successful
collaborations, licensing deals &
alliances
• Led & managed Biobanks including
sample sourcing at Lonza for over 10
years.
Dr. Bhawana Gupta
Sr. Principal Scientist
MVSc, PhD with 15 yrs of experience in
cell biology and in-vitro drug discovery at
TCG Lifesciences and Sapien Biosciences
Dr. Mukesh Gandhari
Sr. Principal Scientist
PhD from Germany, Postdoc at NIH
>15 years experience in research post PhD in
drug discovery & biopharmaceuticals at Sun
Pharma, GVK Biosciences, Saarum Sciences
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Sapien Biosciences