Академический Документы
Профессиональный Документы
Культура Документы
11%
24%
24%
41%
Manufacturing Operations
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
25 X
2X
http://www.forbes.com/sites/matthewherper/2013/08/11/the-cost-ofinventing-a-new-drug-98-companies-ranked/
Forbes 2013
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/
Forbes 2013
Retrospective Analysis
Phase III Failures (2007-2010)
(83 Failures)
10
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
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.
12
Drug Re-purposing
Recycle
Reinvent
13
Drug Repurposing
Cost
$1.5 B to develop
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
14
15
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
16
17
GRID
GVKBIO Repurposing Integrated Database
Repurposing Algorithms
Visualization Tools
18
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
19
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
20
Structural
similarity
Literature
Mining
Genome
Wide
Association
Adverse
Events
Drug
Repurposing
Algorithms
Gene
Expression
Clinical
Trials
Interactome
Pathways
21
22
Drugs /Targets/Disease
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
Frequency table
Relevancy check at
vertical levels and
removing duplicates
Drug Disease
Associations
(888)
December 21, 2015
Indications with
Preclinical
evidence
Drug Disease
Associations
(447)
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
Provided leads to
Improve the pipeline!
Patent new use cases!!
Rescue the failed compounds!!!
Possible additional revenue of millions of dollars !!!!
GRIP
6 months
24
25
Proposed for TB
New Mechanism of
Action
Possible first in class
treatment
Structural Similarity
Interactome
Adverse Events
Literature Mining
GWAS
Pathways
Gene Express
Internal Data
Current Status
Pre-clinical
Stage
Proposed for
Pulmonary
Hypertension
New Mechanism of
Actions
Possible first in class
treatment
3 independent MOA to
intervene the pathophysiology
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Hemodynamic parameters
27
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
28
http://www.drugrepurposingportal.com
Sponsored & Maintained by GVKBIO
29
Thank You