Markets

The markets for Pastel's InVenio™ technology are likely to develop in a similar manner to those of NGS with use starting in academic R&D labs, moving to applications within pharma and biotech companies for incorporation into their drug discovery programmes but then rapidly progressing to use in clinical settings.

Pastel however recognises that InVenio™ technology and its InVenio™ biomarker discovery & validation platform have many applications in other areas including diagnostics, and in particular blood bank screening, in the discovery of emerging and unknown pathogenic organisms, e.g. SARS and avian flu viruses, and in civil protection programmes through its role as a monitor of biowarfare agents.

Components of the technologies being developed may also be applicable separately (capture molecules as drug candidates, uHTP screening platform) and Pastel is looking to leverage the value of these to shareholders through out-licensing and collaborations. These are addressed in the Technology section.

Biomarker Discovery

Understanding of the human proteome enables scientists to identify differences in protein expression patterns that occur between healthy and diseased cells or tissues which can then be used as biomarkers. These are playing an increasingly important role in basic R&D, the drug discovery process and diagnostics.

Biomarkers are increasingly important for drug discovery as they can be ...
⇨ key in identifying novel biochemical pathways and disease mechanisms from which new drug "targets" can be identified;
⇨ integrated into the early drug development phases to assess cellular responses and toxicity issues in both in vitro and in vivo models;
⇨ used in clinical trials for the selection of patient cohorts that are likely to respond positively to a new drug; and
⇨ employed as surrogate end-points in clinical trials reducing timeframes and costs.

Biomarkers are increasingly important for diagnostics as they can be ...
⇨ used to predict whether a person is likely to develop a specific disease and its likely progression;
⇨ used in the diagnosis or prognosis of a specific disease within a person who is exhibiting symptoms; and
⇨ employed in the development and evaluation of therapeutic interventions (companion diagnostics) - the identification of patients who will respond positively to a specific drug treatment or equally important, those that will not exhibit serious adverse reactions.

Until recently a single protein or gene biomarker was generally considered to be sufficient to indicate a particular disease. With the advent of proteomics and the move to personalised medicine it is now recognized that the identification and quantification of multiple proteins may provide far more detailed and accurate information about a particular disease, its stage of development, aggressiveness, response to drug treatment, and both short and long term prognosis.

Thus, to be useful in the fight against human diseases, proteomics requires technologies for large-scale protein separation and identification so that particular proteins can be identified within a clinical sample as a detectable and measurable biomarker. However, while there are now advanced technologies to simply and rapidly map all of the genes within the genome of an organism, there is no such equivalent for the proteome. InVenio™, Pastel's unique biomarker discovery and validation platform will provide just such a technology.

Pharma

High and rising clinical development costs, coupled with declining drug discovery success rates and slowing corporate earnings growth have forced pharmaceutical companies to re-evaluate their drug development process in order to reduce attrition rates, shorten drug development timescales and remain competitive. Over the next decade biomarkers are expected to radically alter the way in which pharmaceutical companies determine the economic viability of their drug discovery process. The use of biomarkers to aid the discovery of promising products will:
⇨ create an enhanced understanding of the clinical development process and
⇨ help to facilitate the shift towards 'personalised' medicine.

InVenio™ technology will be a key tool that enables pharmaceutical and biotechnology companies to:
1. Make a step change in the discovery of novel drug targets - the identification of new protein biomarkers may be the entry point for new drug discovery programmes:
⇨ a protein biomarker may present a target for a new drug entity to be created to impact upon progress of a disease;
⇨ unravelling the biochemistry behind the particular levels of protein biomarkers can provide significant insight into the underlying mechanisms of the disease process and allow scientists to intervene with a therapeutic drug at the correct point in the disease's progression.

2. Reduce the costs of drug discovery and clinical trials and shorten drug development times translating into higher sales associated with longer patent protection in the market by:
⇨ streamlining the drug discovery process by identifying whether a potential drug will be effective on a significant proportion of the population and eliminating those that will not be from the discovery pipeline earlier than can be achieved with current technologies.
⇨ reducing the size and timescales of clinical trials by identifying biomarkers that can be used as surrogate end-points for clinical trials thus reducing the number of patients required per clinical trial and/or the length of the clinical trial and hence both increasing the speed of a drug to market and reducing the costs of clinical trials.

3. Improve the regulatory success rate for market approval and develop combined drug/diagnostic tests needed for personalised prescribing - for example, if it can be demonstrated that a drug will be effective for patients that have a specific protein biomarker, but not for those without this, it would be possible to provide a test for the specific biomarker that could be taken before a specific drug was prescribed, hence significantly increasing the effectiveness of the drug.

Diagnostics

The ability to identify specific groups of patients and/or stages of disease progression for which a new drug will be effective generates substantial potential cost savings by reducing the use of therapeutics that are either ineffective or cause adverse reactions: for the UK healthcare system alone this could result in possible savings of between 23% and 54% and may equate to saved costs in excess of £2.4bn and £5.6bn per annum.

Regulators, such as the FDA, are increasingly looking for improvements in the demonstrated effectiveness of a drug before approval is given and are consequently recognising the need for and, in certain instances, requiring that diagnostic tests be available before a drug can be marketed - so-called companion diagnostics. This then generates a need for the industry to:
⇨ find ways to identify those patients most likely to respond positively in the clinical trials, increasing likelihood of drug approval
⇨ develop simple diagnostics tests that can be used to pre-select patients who will respond positively to the therapy.

Biomarkers, almost by definition, can be used as a diagnostic for a given disease and in many instances are now being developed as a prognostic of the likely disease progression.

Drivers for growth include:
⇨ demands of doctors and clinicians for new and improved tests.
⇨ recognised cost savings to healthcare systems, such as the NHS in the UK and Medicare in the US, as a result of earlier diagnosis and intervention.
⇨ regulatory drivers to achieve more cost effective treatment through the use of 'personalised' medicine, where more specific drug therapies can be used on the basis of the more detailed information being delivered by the newer biomarker assays.

Emerging Pathogens

The appearance of the previously unidentified SARS virus in 2002, the current concerns of pathogenic strains of the Avian flu virus and even the identification of HIV as the causative agent of AIDS back in 1985 highlight the fact that there is still a lack of understanding as to the numbers, nature, epidemiology and identification of emerging and undiscovered pathogenic organisms. While those that are of major concern are pathogenic for humans the identification of agents which may devastate commercially sensitive livestock or arable crops should be of equal importance.

There are many technologies available that are able to quickly identify with good sensitivity and specificity known organisms and their derived markers, usually proteins or DNA. There are however, very few technologies or assays that are able to identify markers which have not been previously identified.

Pastel has, through its bioinformatics, shown that if InVenio™ technology had been available in 2002 it would have been able to detect many, if not all, of the SARS proteins and this set of newly identified proteins distinguishable from all the human proteins could have acted as a rapid biomarker and diagnostic for this disease. Pastel has also extended this by taking 600 viral and bacterial protein sequences not employed in determining the data-set of capture molecules to be used as well as creating random protein sequences and then demonstrating that almost all of these would be identifiable with InVenio™ technology.

Biodefense

While the detection of conventional biowarfare agents, for example anthrax, may be difficult it is nevertheless achievable as the organisms and their component proteins and DNA are well documented and have been studied for years. Of far greater concern is the detection of genetically engineered biological agents which may be totally different from anything presently known. Current assay technologies generally rely on antibodies directed against known proteins but a genetically engineered organism may be completely different.

These biowarfare agents may in a certain sense be regarded in a similar manner to the unknown pathogenic organisms described in the previous section. Pastel has shown how its technology can be effective in uniquely identifying unknown proteins and it is anticipated that Pastel's InVenio™ technology and InVenio™ biomarker discovery & validation platform could prove to be a significant tool in the detection of biowarfare agents.