11.07.2020 Views

Anti-cancer screening of herbal drugs using cancer patient cells

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 prior to testing in xenograft and PDX models.

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 prior to testing in xenograft and PDX models.

SHOW MORE
SHOW LESS

Create successful ePaper yourself

Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.

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

2


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

3

11 July 2020

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

4

11 July 2020

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

5

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

6

11 July 2020

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

7


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

11 July 2020 8


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

9

11 July 2020


Screening is also done in

Hematopoietic Tumor Patient Cells

10

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

11

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

12


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

13

11 July 2020

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

15


About Us

16

11 July 2020

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

17


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

11 July 2020 Sapien Biosciences

18


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

11-Jul-20 19

Sapien Biosciences

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!