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Nepkar – Executive Summary
Nepkar will revolutionize drug screening under contract to major pharmaceutical companies. Nepkar is a new company formed to apply yeast genetic engineering to the discovery of new drugs. Its core technology is in engineering human cell targets in yeast such that the yeast can respond to molecules, both natural and unnatural, that match the target. This allows us to make screens for new drugs that either block the target function (antagonists), or mimic the action of the natural ligand (agonists). The advantages of using yeast for screening as opposed to competing technologies such as membranes or mammalian cell lines are:
- Ultra-high throughput without the need for complex robotics – scaleable to millions of tests per week.
- Low cost per drug candidate.
- Simple defined mechanism devoid of other receptors – higher quality.
Receptor targets are membrane-spanning proteins which connect the inside of cells to the outside. Receptors have two important properties: they bind specific target molecules – ligands – outside the cell; and then transmit this information within the cell. As a result, they can affect the whole range of cellular activity, from metabolic activity to the choice between cell- death and division. Of the many receptor families, the most numerous and diverse are the G-protein linked receptors. They allow cells to detect a vast range of chemical stimuli ranging from nutrients to toxins, protein hormones to neurotransmitters and light to macromolecules. They are fundamental to life, and are found in most organisms.
Our initial targets, G-protein coupled receptors, (GPCRs) are a major focus of pharmaceutical drug discovery. Of the top 100 drugs, 18 are directed at GPCRs, and an estimated 60% of all commercial drugs act on GPCRs. Interest in them as targets is being further fueled by the human genome project, which is identifying hundreds of new “orphan” receptors, Overall there are probably about 4000 human GPCRs of pharmaceutical interest. There is therefore a critical need for new technologies that accelerate the development of new drug leads targeted at this class of receptor. Nepkar will not itself become involved in downstream pharmaceutical development, though it will retain royalty rights and form strategic alliances with researchers and combinatorial-chemistry companies to identify drug leads for licensing to pharmaceutical companies.
The research revenues will be used to fund the further development of yeast as a drug screening tool, broadening its application to other classes of drug target such as ion channels, nuclear receptors and components of cell signaling pathways. We will also develop further Nepkar’s proprietary technology relating to receptors with specificity for compounds of commercial (non-pharmaceutical) importance. These will be incorporated into first-generation biosensors using intact yeast cells, with application in the lucrative area of medical diagnostics and the rapidly growing field of environmental monitoring. Nepkar is entering negotiations with a large instrumentation company to completely fund biosensor development, with Nepkar retaining substantial revenue rights.
Nepkar seeks £1.5m to build a staff base and to fund operating expenditure for two years. At this point the Company should have a neutral cash flow from its rapidly expanding contract drug discovery operation, and a greatly expanded intellectual property portfolio. As a biotech investment opportunity, Nepkar is unusual in that it couples relatively low start-up and ongoing costs, an early revenue stream, and significant scope for growth in asset value based on its intellectual property and projected research contracts.
The founders of Nepkar are Andy Alias, who has an extensive track record in scientific management and product development, and Dr Mark Alias, who has successfully applied Biotechnology both in the food industry (for Nutrasweet), and the pharmaceutical industry (for British Biotech plc). Nepkar has been formed with the full support of British Biotech, who have committed to invest £250k of seed capital, and agreed a £250k research contract to develop a yeast-based GPCR screen. British Biotech will retain a minority stake in Nepkar (15%).
- Chemical compound which one seeks to detect or characterize in a complex mixture.
- The study of biological processes through the use of computing tools and databases to catalogue, analyze and match DNA and protein sequences.
- An analytical instrument containing a biological sensing element, typically an enzyme or antibody, in combination with a convenient readout.
- The large segments of DNA which allow a cell to organize its genome during cell division. Humans have about 6 x 109 base pairs (basic units) of DNA divided into 46 chromosomes (23 pairs). Bacteria typically have a single chromosome of about 4 x 106 base pairs.
- Combinatorial chemistry
- The simultaneous synthesis of large numbers of new chemical compounds through the sequential modification of a core structure with mixtures of modifying groups. A new technique, typically performed by automated robotics.
- The functional interaction of a receptor with the internal signaling machinery of a cell, allowing the receptor to work.
- Small region of a macromolecule, typically a protein, which is recognized by an antibody. Used for tagging and detecting purposes.
- Organism whose cells contain a nucleus. Ranges from single-celled organisms, such as yeast, to mammals. Distinct from prokaryotes (bacteria).
- Functional genomics
- Working out protein function starting from a gene sequence (often produced by the Human Genome Project). Often called reverse genetics.
- Collective name given to the components of a three-protein complex (a,b,g) that couples the cellular machinery to receptors. G-proteins are involved in other types of interaction, but all have in common the use of GTP degradation as a molecular switch.
- Sequence of hundreds to thousands of base-pairs of DNA which carries the information for directing the synthesis of a specific protein.
- The DNA content of a cell.
- Human genome project
- International project to map all the human chromosomes and ultimately to sequence them in their entirety.
- Ion channel
- Complex proteins which span the membranes of cells, providing controlled “gates” for the passage of ions in and out of the cell.
- A term used to describe a very large collection of compounds or DNA sequences. A key asset and tool of biotech companies.
- A substance (chemical or protein) that binds to (matches) a protein.
- Large biological polymer such as a protein, typically with molecular weight in the range of 1,000 to 100,000 Daltons.
- Small organic molecule used in cell-to-cell communication within the nervous system.
- Nuclear receptors
- Special class of receptor proteins which bind fat-soluble ligands which can cross cell membranes and hence gain access to the nucleus. This class of receptor can activate gene expression directly without the need for intermediate signaling pathways.
- Orphan receptor
- Receptor protein, typically identified from genomic sequencing, for which the natural ligand is unknown.
- A protein, usually spanning a membrane, which binds to a ligand of biological significance and transmits the information so that it can influence cellular behavior.
- Reporter gene
- A gene coding for an enzyme or other protein, the presence of which is readily detectable by virtue of cell growth, color reaction, fluorescence or light output.
- A robust test that can be used to identify chemical compounds that interfere with a biological activity. A high-throughput screen should be scaleable to test many thousands of compounds per day.
- Transmission of information within the cell by protein-protein or ligand-protein interactions, often in a cascade of reactions.
- Smart screen
- A drug screen that relies on modification of a reporter gene output rather than on simple receptor binding.
- A potential point of intervention for a new drug. Usually a protein or protein activity.
|Table of Contents||Appendices|
|1. Executive Summary
|All information herein is confidential and belongs to Nepkar.|