Shareholder FAQ’S

Cobra is a Contract Manufacturing Organisation (CMO) listed on AIM that develops bespoke manufacturing solutions for biotechnology and pharmaceutical companies who are looking to take their medicinal products into human clinical trials (Phase I, II, and III) and to the public (market supply).

In excess of £12 million has been invested in both our Keele and Oxford facilities over the years.

We play a pivotal role in enabling clients to bring their medicinal products from the research stage into human clinical trials (Phase I, II, and III) and to the public (market supply).

Cobra manufactures biologicals such as antibodies, recombinant proteins, DNA, viruses and cell products for human clinical trials, to current Good Manufacturing Practice (cGMP), that can have the potential to slow down or cure cancers (breast cancer, prostate cancer etc), provide protection from diseases such as HIV, Malaria, Tuberculosis, or slow down the progression of genetic diseases.

Over 150 batches for Phase I, II and III clinical trials and over 90 different client products have been manufactured by Cobra.

The majority of our clients will have developed the medicinal product themselves at a laboratory scale but do not necessarily have the experience, expertise or capacity to take their product to the next step of clinical trials and beyond. In fact there are a number of steps that need to be undertaken which form the core part of Cobra's service offering.

Cobra can take the medicinal product and ensure that it is being produced in the right organism to generate the maximum amount of drug product. We will also look at the most suitable and scaleable process needed to produce a product which can be used in human clinical trials. The culmination of this work is the release (or permission) of the drug product to be used in human clinical trials by a Qualified Person (QP).

There are a number of benefits to outsourcing the manufacturing to Cobra which are listed below in no particular order.

• Well trained and experienced staff
• Equipment
• A quality standard required by regulatory authorities
• Flexibility with scale and timelines (avoids manufacturing being on the critical path)
• Improvement in productivity with access to in-house technologies (maxXpress, ORT and ORT-VAC)
• Clients can focus on core activities (research and development of new drug products, preparation for clinical trials and regulatory submission)
• Reducing risk and capital expenditure for clients (no need to build a facility)

We have developed excellent relationships with clients, supplying medicinal products for clinical trials on five continents: North America, Europe, Australia, Asia and Africa.

Cobra is making significant capital investments in disposable bioreactor and bioprocessing technologies to increase the mammalian cell secreted protein (antibodies and recombinant proteins primarily) manufacturing capacity. We are investigating the technologies currently available that are cGMP compliant that also provide maximum flexibility in terms of working volumes, process comparability and suite turnaround times, all of which will also increase the throughput capacity of the Keele and Oxford facilities.

In excess of £12 million has been invested in both our Keele and Oxford facilities over the years.

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A company that offers manufacturing services, with volume capabilities ranging from small amounts of medicinal product for preclinical R&D to larger volumes necessary for clinical trial purposes and market supply. In order to supply medicinal products for human clinical trials the CMO must comply with current Good Manufacturing Practice (cGMP).

Antibodies are part of the body's natural defence mechanism. Their task is to circulate in the body and to attach themselves to any foreign particles (antigens such as viruses) or abnormal cells (cancer, genetic diseases) which they may come across. Scientists have exploited this natural recognition mechanism by using antibodies to target some of the big killler diseases affecting us today such as cancer.

Proteins are essential constituents of living organisms. Proteins such as enzymes, structural constituents of cells and components of the immune system, are used as medicines and such products are under development by our clients to combat a number of critical and growing diseases such as cancer and infectious diseases including malaria and meningitis. Antibodies are proteins too.

DNA (Deoxyribonucleic acid) the physical carrier of genetic information in all living cells is being used in two main medical applications, gene therapy and vaccines. The focus for gene therapy has been in a number of genetic disorders and diseases such as cancer and cardiovascular disease. Potentially, DNA vaccines could provide protection against the big killer diseases including cancer, but also the infectious diseases such as HIV, herpes and hepatitis.

Viruses have a natural mechanism for entering cells. By taking advantage of this property, attenuated (live but inactivated) and genetically modified viruses may be exploited as medicines. Our clients are evolving revolutionary products capable of combating devastating diseases such as genetic disorders like Parkinson's and cancer for which there is an unmet clinical need.

Cells or micro organisms have evolved ways of entering the human body and cause infectious diseases such as food poisoning. Genetic engineering can be used to create attenuated strains which do not cause disease and yet retain the ability to enter the human body. Such strains, and in particular bacteria which can be administered orally, are used as carriers for the delivery of novel vaccines or therapeutic products. Oral delivery of vaccines to the gut will in many cases be far more potent than other routes of administration. Cobra and its client are developing novel products based on this approach.

'cGMP' stands for current Good Manufacturing Practice, a code of practise that ensures medicinal products are produced consistently and to the appropriate quality standards. In the UK, manufacturers of medicinal products require accreditation with the Medicines and Healthcare products Regulatory Agency (the MHRA). The Food and Drug Administration (FDA) is the equivalent regulatory body in the USA.

QP is a technical term used in European Union pharmaceutical regulation. The regulations specify that no batch of medicinal product can be released for sale or supply prior to certification by a QP that the batch is in accordance with the relevant requirements. The QP is typically a licensed biologist, who has several years experience working in pharmaceutical manufacturing operations, and has passed examinations attesting to his or her knowledge.

Clinical trials are conducted to allow safety and efficacy data to be collected for new drugs or devices. These trials can only take place once satisfactory information has been gathered on the quality of the product and its non-clinical safety, and Health Authority approval is granted in the country where the trial is taking place. Depending on the type of product and the stage of its development, clinical trials enroll heathly volunteers and/or patients into small studies initially, followed by larger scale studies in patients that often compare the new product with the currently prescribed treatment. As positive safety data are gathered, the number of patients is typically increased. Clinical trials can vary in size from a single centre in one country to multicentre trials in multiple countries.

Pre-clinical studies involve (test tube or laboratory) studies and trials on animal populations. Wide-ranging dosages of the study drug are given to the animal subjects in order to obtain preliminary information and to assist pharmaceutical companies in deciding whether it is worthwhile to go ahead with further testing.

Phase I trials are the first stage of testing in human subjects. Normally, a small group of 20-80 healthy volunteers will be selected. This phase includes trials designed to assess the safety and tolerability of a drug.

Phase II trials are performed on larger groups of approx. 20-300 and are designed to assess how well the drug works (efficacy), as well as to continue Phase I safety assessments in a larger group of volunteers and patients. When the development process for a new drug fails, this usually occurs during Phase II trials when the drug is discovered not to work as planned, or to have toxic effects.

Phase III trials are controlled on large patient groups approx. 300-3,000 or more depending upon the disease/medical condition studied and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment. Because of their size and comparatively long duration. Phase III trials are the most expensive, time-consuming and difficult trials to design and run.

Phase IV trials or post marketing surveillance trials involve the safety surveillance and ongoing technical support of a drug after it receives permission to be sold. Phase IV studies may be required by regulatory authorities or may be undertaken by the sponsoring company. The safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials. Harmful effects discovered by Phase IV trials may result in a drug being withdrawn from the market.

Medicinal drugs can be made in bacteria by inserting the information into them which codes for the drug. These bacteria then function as miniature factories producing the drug. But how do you know that the bacteria contain your product? The standard route is to insert the desired product together with a gene for antibiotic resistance. If the bacteria are flooded with the antibiotic then only those with the antibiotic resistance and hence the drug product information will survive. But there is one fundamental flaw - the possible transfer of the antibiotic resistance to other bacteria. Examples exist of bacteria that have developed resistance to certain antibiotics (MRSA).

ORT provides a simple and effective solution to the dilemma allowing the bacteria with the drug product to be selected without using antibiotics.

One of the reasons why a large number of drug products do not reach the market is because they cannot be delivered effectively. ORT-VAC allows oral administration of a drug product. The technology combines Cobra's ORT technology with the properties of certain bacteria which can pass through the stomach. Such technology could provide a simple and effective route for medicinal products targeting infectious diseases (e.g. HIV, tuberculosis, avian influenza, anthrax) and cancers.

Always one of the first hurdles when looking at producing a drug product in cells is how to ensure that the cells are producing the drug product at high enough levels to be commercially viable. The effort to identify high producing cells by traditional methods is very resource intensive and time consuming. The maxXpress service combines Cobra's expertise in cell line development with a technology (UCOE) which allows the rapid production of cells (mammalian) capable of producing high levels of the desired drug product. The service allows the rapid production of drug products to be used as therapies, vaccines or diagnostics.

Traditionally, recombinant therapeutics produced in mammalian cells have been produced in stainless steel  bioreactors. This technology requires significant labour and time to clean between operations to maintain the required standards for pharmaceutical operations. Also they make very high demands on energy, water usage and capital. Recent development in manufacturing technologies have made it possible to perform the same operations in single use disposable reactors. These units have significantly lower capital and operational costs with regards to labour and require minimal maintenance.

In line with a growing trend in the biopharmaceutical industry, Cobra sees these as the future platforms for the production of mammalian secreted products, such as monoclonal antibodies as well as more novel products such as recombinant viruses. Recent reports suggest that this can also be a more environmentally acceptable method of production due to the lower energy and water demands.