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Speaker spotlight - Dr John Elvin

Dr John Elvin, Associate Director, Scientific External Liaison for MedImmune – the worldwide biologics research and development arm of AstraZeneca – explains what biologic medicines are, why they are revolutionising healthcare and shows how a new biological medicine is taken from conception through to clinic.

Dr Elvin is giving a talk, Biologic therapeutics: what are they and how do we make them? on Thursday 17 March.  

CSF: Can you explain what biologic medicines are?

JE: Put very simply, biological medicines are those that must be made in living cells, as opposed to being synthesised using chemical reactions. Biologics are usually large complex molecules, such as proteins, which are encoded by DNA. MedImmune inserts the required DNA into cells and then transfers the cells to flasks and fermentation vessels, before extracting and purifying the medicine away from the cells.

At this stage, we can test the potential medicine further and, ultimately, work towards delivering it to patients. Because they are typically such large and complex molecules, biologics cannot usually be taken in a pill form but are instead delivered directly into the patients by, for example injection. Biologics have many useful properties, such as specificity and rare ‘off target’ toxicity, but they are also more sensitive to temperature, for example, which means they are not as robust as the small chemical medicines that are the focus of research elsewhere within the AstraZeneca organisation.

CSF: Why are biologics revolutionising healthcare?

JE: Biologics are revolutionising healthcare for a number of reasons. Biologics are exquisitely precise – and can be engineered to only bind to the target and not to other molecules. They are made using the body’s own building blocks of amino acids and therefore degrade in a fairly predictable way; also they can be used to interact with the body’s own immune system to affect their therapeutic benefit.

Biologics are very good at interacting with other large proteins that often are the targets, and in general have fewer side effects. Biologics also can be combined with smaller molecules and be engineered into a large range of forms with useful properties. By using biologic medicines physicians have acquired a new range of tools to treat diseases which they previously did not have.

CSF: Will biologic medicines eventually eradicate the use of chemical medicines?

JE: No. Both biologic and chemical medicines are necessary to treat and prevent illness. Although biologics have many advantages they also have limitations. For example, they have limited ability to reach molecular targets inside cells, or in some locations of the body, such as the eye, where the body restricts access of large molecules such as antibodies. In addition, because they are so complex, biologics will never be as easy to manufacture as small chemical medicines. Indeed, both AstraZeneca and MedImmune see a great potential in combining small and large molecule medicines and using the strengths of both types in future therapeutic regimens.

CSF: How are biologic medicines taken from concept to clinic? And how long can it take?

JE: Biologic medicines are discovered using a similar, but not identical, method to the modern small molecule medicines: there is an identified target associated with a disease which is able to be modified by a therapeutic molecule, which is optimised into a medicine using molecular engineering.

Different therapeutics take different lengths of time to develop but, as a rule of thumb, it takes 12-15 years from concept to final product, and about half to two thirds of this time is applied to the clinical testing phases.

CSF: What are the challenges to manufacturing biologic medicines?

JE: As proteins, biologics must be made within living cells. So, we have to make an individual manufacturing cell line for each medicine and then develop a customised process to purify and formulate it before it can be delivered to patients. The major challenge is that, due to their nature, biologics can be quite delicate and require careful handling, storing and shipping at all stages, including the environmental conditions, such as temperature. 

CSF: What have been MedImmune’s most significant innovations?

JE: With one of the largest, most sophisticated pipelines in the industry with more than 120 projects and product candidates in development, MedImmune is pioneering innovative research and exploring novel pathways across key therapeutic areas, including respiratory, inflammation and autoimmunity; cardiovascular and metabolic disease; oncology; neuroscience; and infection and vaccines.

In particular, MedImmune (and previously as Cambridge Antibody Technology) is known for its protein and antibody engineering and for the development of phage display technology. This was used to discover Humira* (used to treat a range of inflammatory diseases such as rheumatoid arthritis) and Benlysta** (used to treat lupus), and for the development of the attenuated live intranasal vaccine for influenza. 

CSF: Why is the Cambridge Science Festival so important for MedImmune?

JE: As a science-focussed company, MedImmune is committed to bringing life-changing medicines to patients.  For us to be successful now and in the future, it’s vital that there is a qualified workforce keen to get involved in biopharmaceutical research and, in line with this, we are committed to inspiring the next generation of scientists.

We fully support the aims of  the Festival in providing a meaningful opportunity for engagement with the Cambridge  community and are delighted to be able to put our commitment into action by participating in the event.   We’ve been involved with the Festival since 2009 and believe it provides a vital connection between science – both academic and industrial – and the residents of Cambridge and beyond. For MedImmune, it provides an opportunity to demonstrate our connection to Cambridge in a tangible way, and our staff volunteers willingly give their own time at the weekends to help with the hands-on activities. And, for the past couple of years, we have been delighted to work alongside our parent organisation, AstraZeneca, offering interactive opportunities across a wider range of drug development disciplines. 

CSF: How does MedImmune’s activity at the Festival relate to the work you do every day in your labs?

JE: For each Festival we pick an aspect of the process we use to discover a new biologic therapeutic: in the past we have focussed on our ‘phage display’ technology or on our bioprocessing expertise. For example, all biologic medicines need to be made in cells, and then recovered and purified.

For 2016, we are offering an activity designed to demonstrate our approach to developing new medicines to treat cancer. Traditionally cancers respond initially to treatment but after time can evolve resistance mechanisms. One way to try to overcome this resistance is to use combinations of medicines – it can be much more difficult for the cancer to adapt to two different attacks at the same time. However, medicines used in combination need to have certain properties for them to work correctly; the right combination of active components with the right formulation is necessary to create a successful medicine.

Our activity this year asks participants to make mixtures of four compounds (represented by simple fluids such as sunflower oil and water) and to use a test (based on pH indicator) to find which combination is the most effective and which also works well. The participants use real laboratory pipettes and tubes to measure out the compounds, mix, and analyse the results and draw conclusions as to which will be the best combination to use. The hand-eye skills and thought processes required for this are representative of those we use in our R&D every day.

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*Humira is a registered trademark of AbbVie Inc

** Benlysta is a registered trademark of GSK