bioinformatics-decoding drug discovery with it...integrates with their discovery strategy and guides...

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BIOINFORMATICS-DECODING DRUG DISCOVERY WITH IT

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BIOINFORMATICS-DECODING DRUG DISCOVERY WITH IT | APRIL 2014

TABLE OF CONTENTSABSTRACT 3

INDUSTRY TRENDS 4

MARKET SIZE 4

IT – A CATALYST IN DRUG DISCOVERY 5

REFERENCES 8

ABOUT THE AUTHOR 9

ABOUT HCL 10



ABSTRACTThe Pharma industry is passing through a turbulent phase, the industry has been witnessing a drastic dip in R&D productivity and revenue streams are under threat from near expired drug patents. In the near future there is an estimated loss of US $ 16 billion of revenue of marketed products.

There have been various challenges leading to decline in R&D productivity, to enlist a few:

y Inaccurate target identification

y Lack of exhaustive information on potential drug and drug combinations

y Lack of insights into late stage drugs failure causes, other than safety related failures.

y Lack of comprehensive in-silico tools/applications being used to develop drug candidates

In order to mitigate the risk of late stage drug failure, pharmaceutical companies had to find new technologies to replace the old “hand-crafted” synthesis and testing NCE approaches. Application of Bioinformatics has started playing a significant role in decreasing rate of drug failure during late stage clinical trials and in catalyzing target identification.

Consequently, industry leaders are using integrated technology platforms in R&D processes to connect disparate data, information and technology. Most of the big pharma companies have established an Information Technology (IT) strategy that integrates with their discovery strategy and guides activities such as registration, compound management, and the capture of chemical and biological activity information. In addition, they are integrating genomics, proteomics and other technologies to improve target identification and enhance lead optimization.

In the coming years, the industry will continue to undergo a paradigm shift in the fundamental approach to R&D and externalization, especially in the early discovery phase. These changes are propelled by new breakthroughs in genomics, technology and research and the rapid evolution of patient-centric eco system that demands improved therapies and at an affordable cost. As drug discovery gets more technology-focused, many software companies are already functioning as “lab-less” pharmaceutical companies. This provides tremendous scope for IT companies to play significant role in drug discovery.



INDUSTRY TRENDS Bioinformatics have gained high importance in recent years because of its ability to generate rapid clinical research through its variety of applications like Molecular science and Gene therapy. Most pharmaceutical companies are now adopting automated technologies for manufacturing effective drugs and therapies due to rising concerns towards drug safety and strict regulations governing clinical trials for drug discovery.

The spectrum is segmented based on the approach namely, molecular medicine, gene therapy, drug discovery & development and preventive medicine

As major pharmaceutical and genome-based biotech companies make serious investments in software, Indian IT companies have a great business opportunity to offer complete database solutions to major pharmaceutical and genome-based biotech companies in the world.

R&D spend in the biotech industry has been increasing exponentially and an estimated 36 percent was spent in R & D in the last decade. The need to curtail the spiraling R&D costs while channelizing their energies on the core competency of hard core research will deter the Biotech companies from developing propriety software like in the past and they will rather outsource the same to a software vendor.

Since the cost and domain expertise are the key drives for running such development programs, Indian IT companies have a great business opportunity to offer end to end services starting from hardware, database solutions, implementation and customization.

MARKET SIZEAccording to a new market report published by Transparency Market Research on “Bioinformatics Market” - Global Market Share, the global bioinformatics market is estimated to reach USD 9.1 Billion by 2018 at a CAGR of 25.4%. Similarly, the global market for bioinformatics services is expected to reach $8.3 billion over the year 2014 at the CAGR of 24.8%.

The bioinformatics platform/tools holds the significant market share and it is estimated to account for nearly 50% of the total Bioinformatics market share. Currently services have a relatively smaller market share but it is expected to increase considerably over that of the forecasted period.

The Bioinformatics market growth and potential is propelled by increased use across various industries. Key sectors driving it are Biotechnology, Pharmaceuticals R&D, Agriculture and other life-sciences related industries.

The demand across genomics, and wide application in the medical and biological information sector, is driving the demand for bioinformatics platforms and services in the global market.



Developed economies like US and Europe are the largest consumers of this market and this trend is supported by increasing demand for sequencing platforms with growing research in the field of life sciences using the techniques like gene expression analysis, protein expression analysis, and sequence analysis.

This trend is further supported by the increasing externalization of some of their core early discovery and pre-clinical activities by global pharma companies.

IT – A CATALYST IN DRUG DISCOVERYAs discussed above, outsourcing R&D has proven to be an increasingly popular strategy of innovator companies. Externalization, especially in the early discovery phase (which is time consuming and has dependencies on IT systems) for Lead identification and target identification is on the rise.

Implications of the Human Genome Project (HGP):

With the completion of the Human Genome Project and advances in genetics, drug research today is being driven by “Biology” rather than “Chemistry” with molecular genetics, genomics, and bioinformatics and the scenario seem to have reversed from compounds looking at targets to a plethora of targets looking for compounds. There is an emergence of Direct-to-Consumer (DTC) genomic industry that can be traced back directly to the wealth of information provided by the HGP (Human Genome Project). The customer is then provided with a wealth of genomic information such as susceptibility to various inherited diseases and past ancestry. While our current understanding of many fundamental mechanisms of cellular function is ambiguous, there is strong thrust in areas of practical application such as pharmacogenomics to deliver improved patient outcomes compared to the “trial-and-error” approaches of traditional pharmacology.

In a nutshell, HGP has opened the doors for IT broadly in the areas of:

y Data Computing and Integration

y Data Analysis and Interpretation

Data Computing and Integration

To make meaningful information from the large datasets generated by Next Gen Sequencing, there is an obvious need for computational algorithms and software capable of performing large-scale informational integration. Consequently, multi-disciplinary tools such as pathway network analysis and theories such as the graph theory (from computer science and pure mathematics) will be useful to design regulatory networks, and interactions in drug related biological pathways.

Handling huge sets of data and performing specific analytics/scientific computation at good speed has always been a challenge starting from combinatorial chemistry to genomics. The potential for a docking algorithm to be used as a virtual screening tool is based on both speed and accuracy. As a result, speeding up the programs



available for drug design using recent advances in HPC (High performance computing) technology is one of the important applications in this space.

Cloud computing solutions will serve as a good alternative to in-house computational infrastructure. The major advantage of using the cloud solution is the availability of supercomputing power without having to install and maintain expensive supercomputing hardware. Moreover, the pay-per-use pricing of Cloud services makes it competitive and affordable for an average user

Data Analysis and Interpretation

Genomic data gives information about the sequence but does not give information about the function. Predicting the actual 3-D structure of proteins still has many challenges. Development of tools that help predict correct folding patterns of proteins will aid in drug design research substantially. Deep understanding of the domain and software expertise is required to write algorithms, develop applications/tools using existing algorithms, manage databases, and during the final stage of drug discovery.

The other key areas are computational biology and bioinformatics, where a significant level of IT skills in conjunction with good domain understanding will help in the development of bespoke applications, which can integrate with disparate databases, simulations, molecular images, docking programs etc.

The scientific fraternity has used the principles of the network theory to develop software tools and databases capable of displaying complex biological interactions such as KEGG, Cytoscape etc. These exchanges are designed based on the data congregated from extensive review of empirical biological data and current scientific literature which is extremely dynamic and refreshed to reflect the advancements in the knowledge database.

Several pharma companies have begun experimenting in the areas of personalized medicine and pharmacogenomics, but they are cautious regarding its validity and predictive ability. Given that there is a good amount of genetic variations among individuals and would need personalized treatment and tailored drugs. However, many pharma companies are still struggling for a viable approach to finding druggable targets.

Using bioinformatics, several organizations are finding a large number of In silico targets. This is a big step forward for the industry to improve the success rate of clinical trials through use of patient subsets with specific genetic risks and reduced chances of toxicities and side effects. This genetic profiling can reduce clinical trial costs and increase the success rates of drugs. Pharma companies need to exploit this opportunity by leveraging genetic profiling of individuals into personalized medicine, thus making a significant shift in their strategy of trying to search for blockbuster drugs to higher-value individualized drugs.



Flow of Information in Drug Discovery process

DNA S Disease E i i lGenomics/ ProteomicsDNA Sequencesand Maps

Gene expression analysis

Genomics Database

Targetgenes Protein

In vivo cell biology

Disease Selection

Animal disease models

Empirical Medicine

Genomics/ Proteomicsbioinformatics

Physiology database analysis

ReceptorIdentification

Protein Structure Prediction and analysis

Database genes Protein data Database

Diseasebiology

Disease model

y gyMedical research databaseNucleotide Sequence

Information

LTSComputational Chemistry

Disease Characterization

Clinical Trials

Lead Identification and Optimization

Predictive ADME

Rational drug design

Preclinical Trials

M T

OX

Preclinical and Experimental data

HTS

g g

Clinical Trails

ADE

Clinical DataPhysical Chemistry

MedicinalChemistry

Molecular diversityChemical descriptions

Pharmacogenomics

Source: Modern Methods in drug discovery WS 11/12

Friend and Ideker propose a personalized health model based on the integration of multiple sources of data which include clinical, molecular, environmental and social data which are then integrated using tools of graph networks in a personalized healthcare setting. In their model, future clinicians will use multiple data networks to infer a patient’s medical condition and choose a personalized treatment approach. In the future treatment patient at the clinic will be based on a seamless integration of biological databases from a network analysis of multitude “omics” sources personalized to each patient. The versatility of next generation sequencing to provide data regarding the epigenetic makeup of a patient in near real time provides the most promising window into such a personalized healthcare future

In the revolutionary arena of personalized medicine, there is an enormous increase in the amount of genomic data collected on large study populations. This in combination with new informatics approaches that needs to conjugate with many kinds of data from various sources with genomic data. This integration can catalyze drug research, allowing researchers to understand the genetic bases of drug response and diseases. IT companies can play a crucial role by providing high quality analytics/ KPO services to pharma companies, which in turn can help them design drugs efficiently.

In addition, to the opportunities mentioned above, IT companies can also play a major role in:

y Improving content and utility of databases.

y Developing better tools for data generation, capture, integration and annotation.



y For complete functional studies developing and improving tools and databases.

y Developing and improving tools for representing and analyzing sequence similarity and variation.

y Creating mechanisms to support effective approaches for producing robust, software that can be widely shared.

Bioinformatics may revolutionize the nature of the discovery process and it is up to the Pharma companies having a vision and strategy to embrace these new technology approaches and adapt to the re-segmentation of drug markets based on genetic information and exploit the emerging opportunities to have a significant competitive advantage in the market.

REFERENCEShttp://bioinformaticsweb.net/bioindia.html

http://articles.economictimes.indiatimes.com/keyword/bioinformatics/featured/3

http://www.nature.com/nrd/journal/v6/n1/full/nrd2229.html

http://www.policymed.com/2012/02/critical-issues-affecting-the-pharmaceutical-industry-in-2012.html

http://www.bionity.com/en/whitepapers/48748/alliances-in-drug-discovery-the-chemical-element.html

http://www.bionity.com/en/whitepapers/99167/outsourcing-r-d-innovation-takes-on-new-meaning.html

http://www.bionity.com/en/whitepapers/48748/alliances-in-drug-discovery-the-chemical-element.html

http://www.prweb.com/releases/2013/11/prweb11357325.html



ABOUT THE AUTHORVijai Krishna joined HCL family in June 2010. He has over 10 years of experience and over 5 years of experience in Pharma R&D IT especially in eCTD, SPL, DMS and Oracle suite of Life Sciences products.

Vijai started his career as a professional sales representative for Fulford India (an affiliate of Schering Plough) before moving to Life Sciences IT product sales in the capacity of Business Development Manager handling sales for the entire South India.

In HCL, Vijai is a part of the Life Sciences business solution group. He is responsible for analysing and identifying white spaces to building business propositions in pharma R&D space.

Vijai holds a Bachelors’ Degree in Pharmacy, P.G. Dip in Bioinformatics and P.G. Dip in Marketing Management.

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HCL Technologies is a leading global IT services company working with clients in the areas that impact and redefine the core of their businesses. Since its emergence on global landscape after its IPO in 1999, HCL has focused on ‘transformational outsourcing’, underlined by innovation and value creation, offering an integrated portfolio of services including software-led IT solutions, remote infrastructure management, engineering and R&D services and Business services. HCL leverages its extensive global offshore infrastructure and network of offices in 31 countries to provide holistic, multi-service delivery in key industry verticals including Financial Services, Manufacturing, Consumer Services, Public Services and Healthcare & Life sciences. HCL takes pride in its philosophy of ‘Employees First, Customers Second’ which empowers its 90,190 transformers to create real value for the customers. HCL Technologies, along with its subsidiaries, had consolidated revenues of US$ 5.2 billion, as on 31st March 2014 (on LTM basis). For more information, please visit www.hcltech.com

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HCL is a $6.4 billion leading global technology and IT enterprise comprising two companies listed in India – HCL Technologies and HCL Infosystems. Founded in 1976, HCL is one of India’s original IT garage start-ups. A pioneer of modern computing, HCL is a global transformational enterprise today. Its range of offerings includes product engineering, custom & package applications, BPO, IT infrastructure services, IT hardware, systems integration, and distribution of information and communications technology (ICT) products across a wide range of focused industry verticals. The HCL team consists of over 95,000 professionals of diverse nationalities, who operate from 31 countries including over 505 points of presence in India. HCL has partnerships with several leading global 1000 firms, including leading IT and technology firms. For more information, please visit www.hcl.com

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bioinformatics-decoding drug discovery with it...integrates with their discovery strategy and guides...

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