Role of Big Data & Pharma Analytics in

Rescuing Failed or Shelved Compounds

Nandu Gattu, PhD
Vice President, GVK Biosciences

Pharma Business Analytics

Data + Science + Business = Pharma Business Analytics

11%

24%

24%

41%

Source: Everest group

December 21, 2015

GVK BIO Confidential

Pharma Business Analytics

Pharma Analytics
Research & Development
Sales & Marketing
Strategy
Patient & Care Giver
Supply Chain & Distribution

Research & Development Analytics

Identification of new drugs

Manufacturing Operations

Effective Pre-clinical exp

Better Clinical trial Design
Patient Stratification
Rescue the failed drugs
Recycle current drugs
December 21, 2015

GVK BIO Confidential

Drug Discovery & Development Process

Major Challenges:
$ 1.5 Billion
Soaring R&D Cost
14 years
Longer duration
High Attrition Rate or Lower Success Rate
Failures due to efficacy
Failures are mostly in the clinical phase only
December 21, 2015

GVK BIO Confidential

Pharma R&D Spend vs. Approvals

25 X

2X

December 21, 2015

GVK BIO Confidential

Pharma Strategy The Number Game

Company
Global Rank # of Drugs 10 Y R&D ($ M)
J&J
8
13
67624
GSK
6
11
57595
Pfizer
1
10
77786
Novartis
3
10
60727
Merck & Co
4
9
49133
BMS
12
9
30352
Roche
5
8
70928
Sanofi
2
6
60768
Bayer
16
5
33118
Amgen
14
5
21350
Genzyme
2
5
4814
AstraZeneca
7
4
38245
Eli Lilly
10
4
26710
Takeda
13
4
24132
Eisai
24
4
11534
Biogen Idec
33
4
9470
Genetech
5
4
6277
Forest
38
4
5184
Shire
32
4
3827
Wyeth
1
3
22702
Schering-Plough
4
3
18845
Astellas
18
3
12582
Gilead
21
3
5527
Baxter
22
3
4627
Novo Nordisk
17
2
9251
Celgene
27
2
7193
Teva
11
2
6763
Lundbeck
42
2
3527
Abbott
9
1
13183
UCB
33
1
4325
Yamanouchi
18
1
4321
Fujisawa
18
1
4286
Shionogi
36
1
3854
December 21, 2015

R&D per Drug ($ M)

5202
5236
7779
6073
5459
3372
8866
10128
6624
4270
963
9561
6678
6033
2884
2368
1569
1296
957
7567
6282
4194
1842
1542
4626
3597
3382
1764
13183
4325
4321
4286
3854

Global rank <50; 10 Y R&D spend; > $ 2B;

Drug Discovery &

Development Cost
$ 5 Billion &
14 Years
Per Drug

http://www.forbes.com/sites/matthewherper/2013/08/11/the-cost-ofinventing-a-new-drug-98-companies-ranked/

GVK BIO Confidential

Forbes 2013

Drug Discovery & Development

# of Projects for One Launch

http://www.phrma-jp.org/archives/pdf/profile/Profile_2010_FINAL.pdf
http://www.discoverymanagementsolutions.com/the-organization-of-biopharmaceutical-rd/common-goals-between-discovery-and-development/innovation/nmeoutput-versus-rd-expense-perhaps-there-is-an-explanation/

December 21, 2015

GVK BIO Confidential

Percent R&D Budget Spent

Decreased Pre-clinical Cost

Increased Clinical Cost

December 21, 2015

GVK BIO Confidential

Pharma Innovation Root cause for Failures

December 21, 2015

Forbes 2013

GVK BIO Confidential

Pharma Innovation Root cause for Failures

Retrospective Analysis
Phase II Failures (2008-2010)
(108 Failures)

Nature Reviews in DD, 2011, 10(5), 328

Retrospective Analysis
Phase III Failures (2007-2010)
(83 Failures)

Nature Reviews in DD, 2011, 10(2), 87

December 21, 2015

GVK BIO Confidential

10

Pharma Innovation Strategic step for Success

Drug Discovery &
Development Cost
$ 5 Billion
& 14 Years ?
Steep increase in
R&D Cost

Big ticket & long

duration

High Odds 57:1

>50% Clinical Costs

De-risk the investments

Strengthen the portfolio

Identify New Indications

Repurpose the Failed Candidate

December 21, 2015

GVK BIO Confidential

Low success rate in

Clinical Phase

Efficacy is the main culprit

11

Drug Repurposing is real

DRUG ORIGINAL
Amphotericin
Aspirin
Bromocriptine
Finasteride
Gemcitabine
Methotrexate
Raloxifene
Duloxetine
Miltefosine
Retinoic acid/Tretinoin
Thioridazine
Imatinib
Propranolol
Botulinum Toxin A
Bosentan Monohydrate
Crizotinib
Galantamine
Plerixafor
Rituximab

INDICATION
B Fungal infections
Inflammation, pain
Parkinsons disease
Prostate hyperplasia
Viral infections
Cancer
Cancer
Depression
Breast Cancer
Severe acne
Schizophrenia
Chronic Myeloid Leukemia
Angina, Hypertension
Blepharospasm, Cervical dystonia
CHF
Anaplastic large-cell lymphoma
Pot-polio paralysis and Neuro Pain
HIV
Non-Hodgkins Lymphoma

http://thomsonreuters.com/products/ip-science/04_038/drug-repositioning-cwp-en.pdf

December 21, 2015

NEW INDICATION
Leishmaniasis
Antiplatelet, Colorectal Cancer
Diabetes mellitus
Hair loss
Cancer
Psoriasis, Rheumatoid arthritis
Osteoporosis
Detrusor Instability
Visceral Leishmaniasis
Acute promyelocytic leukemia
QTc prolongation, Antimicrobial agent
Gastrointestinal stromal tumor,
Migraine
Axillary hyperhidrosis
PAH
NSCLC
Alzheimers
Mobilization of hematopoietic stem cell
RA

J Clin Pharmacol. Nov 2007; 64(5): 563565; Journal of Market Access & Health Policy 2014, 2: 22813.

GVK BIO Confidential

12

Drug Re-purposing

Drug Re-Purposing: Identification of additional

therapeutics indications for existing marketed drugs
or clinical candidates
It is a strategic approach to drug development to
extract added value from prior Research and
Development investments
The Drug Re-positioning concept is not new; So far
more than 300 FDA approved repurposed drugs are
in the market
Repurposed drugs generated approximately $20
Billion annual sales in year 2012
All major pharmaceutical companies are interested
and invested in drug repurposing program
Drug Repurposing science is moving from
serendipitous discovery to data driven approach.

December 21, 2015

GVK BIO Confidential

Recycle

Reinvent
13

Why Drug Re-purposing ?

Approximately 200 Drug candidates per year are

placed in the shelve for variety of reasons
Majority of the Phase III compound are failing due
to efficacy only
Pharma companies looking for novel strategic ways
to build or strengthen the portfolio
Drug Development

Drug Repurposing

Cost

$1.5 B to develop

$300- $400 M to develop

Time for R&D

12-14 years

2-6 years

Experiments

Complete set

Significantly less

Cost Vs benefit

Lower

Higher

Success rate

Low

Relatively better

Complexity

High

Relatively less

Ph II to Market

10%

25%

Ph III to Market

50%

65%

Repurposed Drugs

Time and Money matters

December 21, 2015

GVK BIO Confidential

14

Sildenafil (Viagra) A Billion Dollar Repurposed Drug

The little blue pill

Revolutionized the lives of Millions of people

Pfizer discovered Sildenafil in 1992 for
cardiovascular diseases
Pfizer tried this drug for Hypertension and
Ischemic heart diseases
Drug had little effect on angina
REPURPOSED
In 1998, FDA approved Sildenafil for Erectile
Dysfunction
BECAME A BILLION DOLLAR DRUG
REPURPOSED AGAIN
In 2006, FDA approved this drug for Pulmonary
Arterial Hypertension

December 21, 2015

GVK BIO Confidential

15

Thalidomide A Billion Dollar Repurposed Drug

Thalidomide was synthesized in 1954
Hailed as wonder drug that provides safe,
sound sleep
Given to pregnant women to treat symptoms
associated with morning sickness
Thalidomide was a catastrophic drug with
tragic side effects
When thalidomide was taken during pregnancy
it caused birth defects short extremities

After 44 years
In 1998, Thalidomide was approved as
repurposed drug for Leprosy by FDA

After 52 years
In 2006, Thalidomide was approved as
repurposed drug for Multiple Myeloma by
FDA

A Billion Dollar Drug

December 21, 2015

GVK BIO Confidential

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Big Data Analytics in Pharma World

Big Data Analytics is crucial for Repurposing Data driven Science

December 21, 2015

GVK BIO Confidential

17

GVKBIO Repurposing Integrated Platform - GRIP

GRID
GVKBIO Repurposing Integrated Database

Repurposing Algorithms

Visualization Tools

Novel Repurposing Ideas

Analytic s Engine
December 21, 2015

GVK BIO Confidential

18

GVKBIO Repurposing Integrated Database (GRID)

Proprietary Databases
GOSTAR (SAR Database with 6 M compounds)
GOBIOM (Biomarker database)
CTOD (Clinical Trial Outcome Database)

GVKBIO
Repurposing Integrated Database (GRID)

Disease

Target

Public Databases
More than 40+ Public database

Drug

Understanding the relationship among

Drug Disease Target is key to identify new alternative Indications

December 21, 2015

GVK BIO Confidential

19

Drug Repurposing Integrated Database

Drugs
Pathway
Diseases
Biomarkers
Target/EC50, IC50 etc..
Tissue specific expression
Gene expression drugs, disease
Transcription factor
Clinical trial info
Marketed drugs
Target-Target interactions

Gene
Pathway
Diseases
Biomarkers
Target/EC50, IC50 etc..
Gene expression
Transcription factor
Clinical trial info
Marketed drugs
Adverse events
Drug-protein interactions

Drug

Target

Disease
Gene
Pathway
Drugs
Biomarkers
Gene expression
Clinical trial info
Disease gene relationship

December 21, 2015

GVK BIO Confidential

20

Drug Repurposing Algorithms

Structural
similarity
Literature
Mining

Genome
Wide
Association

Adverse
Events

Drug
Repurposing
Algorithms

Gene
Expression

Clinical
Trials

Interactome

Pathways

December 21, 2015

GVK BIO Confidential

21

Drug Repurposing Modalities

December 21, 2015

GVK BIO Confidential

22

Drug Repurposing Flow Chart

Binning and Profiling

Drugs /Targets/Disease

List of Drug Disease

Associations
(17040)

MESH tree
MESH term
CARDIOVASCULAR DISEASES
ACUTE CORONARY SYNDROME
CARDIOVASCULAR DISEASES
ACUTE ISCHEMIC STROKE
CARDIOVASCULAR DISEASES
HEART FAILURE
PHYSIOLOGICAL PHENOMENA
AGING
ENDOCRINE SYSTEM DISEASES
HYPERALDOSTERONISM
CARDIOVASCULAR DISEASES
HYPERTENSION
UROGENITAL ABNORMALITIES
NEPHRITIS, HEREDITARY
RESPIRATORY TRACT DISEASES
ALVEOLITIS, EXTRINSIC ALLERGIC
LIVER DISEASES
NONALCOHOLIC STEATOHEPATITIS
HEMIC AND LYMPHATIC DISEASES
ANEMIA
CARDIOVASCULAR DISEASES
ANGINA PECTORIS
CARDIOVASCULAR DISEASES
AORTIC VALVE STENOSIS
NERVOUS SYSTEM DISEASES
ALZHEIMER DISEASE
CARDIOVASCULAR DISEASES
ATHEROSCLEROSIS
CARDIOVASCULAR DISEASES
CARDIOMYOPATHIES
CARDIOVASCULAR DISEASES
CORONARY ARTERY DISEASE
NUTRITIONAL AND METABOLIC DISEASESDIABETES MELLITUS
UROLOGIC DISEASES
DIABETIC NEPHROPATHIES
EYE DISEASES
DIABETIC RETINOPATHY
NERVOUS SYSTEM DISEASES
BIPOLAR DISORDER
NEOPLASMS
URINARY BLADDER NEOPLASMS
CARDIOVASCULAR DISEASES
BRADYCARDIA
NERVOUS SYSTEM DISEASES
BRAIN EDEMA
NERVOUS SYSTEM DISEASES
BRAIN INFARCTION
CARDIOVASCULAR DISEASES
HYPERTROPHY, LEFT VENTRICULAR
NEOPLASMS
CARCINOMA, ENDOMETRIOID
UROLOGIC DISEASES
KIDNEY FAILURE, CHRONIC
CARDIOVASCULAR DISEASES
MYOCARDIAL INFARCTION
NUTRITIONAL AND METABOLIC DISEASESOBESITY
CARDIOVASCULAR DISEASES
ATRIAL FIBRILLATION
NERVOUS SYSTEM DISEASES
BRAIN ISCHEMIA
NEOPLASMS
BREAST NEOPLASMS
UROLOGIC DISEASES
CARDIO-RENAL SYNDROME
CARDIOVASCULAR DISEASES
CAROTID STENOSIS
NERVOUS SYSTEM DISEASES
CEREBRAL HEMORRHAGE

Unique list of indications (442)

ACUTE CORONARY SYNDROME
ACUTE ISCHEMIC STROKE
HEART FAILURE
AGING
ALDOSTERONISM PRIMARY
HYPERTENSION
ALPORT SYNDROME
ALVEOLITIS
NONALCOHOLIC STEATOHEPATITIS
ANEMIA
ANGINA PECTORIS
AORTIC VALVE STENOSIS
ALZHEIMER'S DISEASE
ATHEROSCLEROSIS
CARDIOMYOPATHY
CORONARY ARTERY DISEASE
DIABETES MELLITUS
DIABETIC NEPHROPATHY
DIABETIC RETINOPATHY
BIPOLAR DISORDER
BLADDER CANCER
BRADYCARDIA
BRAIN EDEMA
BRAIN INFARCTION
HYPERTROPHY, VENTRICULAR
CARCINOMA ENDOMETRIOID
KIDNEY FAILURE, CHRONIC
MYOCARDIAL INFARCTION
OBESITY
ATRIAL FIBRILLATION
BRAIN ISCHEMIA
BREAST NEOPLASMS
CARDIORENAL SYNDROME
CAROTID ARTERY STENOSIS
CEREBRAL HEMORRHAGE

Adverse EventsClinical trialsInteractome

Literature MiningPathwaysStructure Similarity
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
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Y
Y
Y
Y
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Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
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Y
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Y
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Y
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Y
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Y
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Y
Y

Frequency table

Relevancy check at
vertical levels and
removing duplicates

Drug Disease
Associations
(888)
December 21, 2015

Indications with
Preclinical
evidence

Standardization with MESH terms

Removing general indications
Unifying synonyms/alias

Drug Disease
Associations
(447)

GVK BIO Confidential

Indications with
clinical
evidence

Indication with no
evidence

145 indications
Ignored all
kinds of
hypertensions
Ignored CNS
indications
Focused on
partner
interest
Based on
target
mechanism

Priority indications
(10 indications)

23

Drug Repurposing Live Case Study with

Major Japanese Global Pharma
6 Stalled
Compounds from
Major Pharma

Provided leads to
Improve the pipeline!
Patent new use cases!!
Rescue the failed compounds!!!
Possible additional revenue of millions of dollars !!!!

GRIP

Initiated Pre-clinical Proof of concept experiments

5 out of 6

6 months

December 21, 2015

GVK BIO Confidential

24

Failed Compound Case Study

December 21, 2015

GVK BIO Confidential

25

Drug Repurposing Case Study In-silico Predictions

Compound is shelved due to lack of efficacy (safety profile is good)
Like to repurpose..
Identify novel
Therapeutic utility
& create IP

Compound with focus on

__________ disease

Proposed for TB
New Mechanism of
Action
Possible first in class
treatment

Received the following:

Compound Info
Target Info
Original therapeutic focus
Received certain Internal data

GRID & Well trained

MS/PhD level scientists
with drug discovery
experience

Structural Similarity

Interactome

Adverse Events

Literature Mining

GWAS

Pathways

Clinical trial mining

Gene Express

Internal Data

GVKBIO Repurposing Integrated Platform (GRIP)

December 21, 2015

Current Status
Pre-clinical
Stage

GVK BIO Confidential

Proposed for
Pulmonary
Hypertension
New Mechanism of
Actions
Possible first in class
treatment
3 independent MOA to
intervene the pathophysiology
26

Repurposing of Client Compound for PAH Pre-clinical Exp

Protocol

Validation of monocortaline (MCT) induced

pulmonary arterial hypertension (PAH) model in
SD rats with marketed drugs

Repurposing of Client compounds for PAH

Hemodynamic parameters

December 21, 2015

GVK BIO Confidential

Cpd Client Compound

27

Repurposing of Client Compound for PAH Pre-clinical Exp

Hemodynamic parameters
75.000000
75.000000

RVP

50.000000

25.000000

25.000000

mmHg

mmHg

50.000000

RVP

RVP

50.000000

mmHg

75.000000

25.000000

0.000000

0.000000

0.000000
45.00000
seconds

Vehicle

20.00000
seconds

5.00000

10.00000
seconds

MCT

MCT+cpd 10mg/kg

Systemic blood pressure

Cpd Client Compound

December 21, 2015

GVK BIO Confidential

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Drug Repurposing Portal

http://www.drugrepurposingportal.com
Sponsored & Maintained by GVKBIO

December 21, 2015

GVK BIO Confidential

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Thank You