In Profile: Alastair Smith, Avacta Life Sciences

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Alastair Smith, Avacta Life Sciences, outlines the company’s work developing engineered alternatives to antibodies

Who are you and what do you do?

Avacta Life Sciences was established in 2012 (as part of the Avacta Group) to develop and commercialise its Affimer technology. Affimers - an engineered alternative to antibodies – can be used in scientific research, diagnostics and in the development of therapeutics.

Up until now the Avacta Group has raised £37million to invest in the commercialisation of Affimers over the next few years. This investment is being used for a range of projects including product development and a 13,000 sq ft laboratory production and logistics space which is due for completion in April 2016.

What have you focussed on recently?

Affimers have been engineered to have all of the benefits of antibodies, without the limitations. They have high affinity, exquisite specificity, are small, stable, robust and new Affimers can be generated, expressed and validated just seven weeks after receipt of target material - compared to 6–12 months for equivalent high quality antibodies.

They can be used in a range of applications. However, our strategy is to address important gaps in life sciences where the right affinity reagents aren’t available and to provide life scientists with powerful tools to open up new avenues of research and discovery. At present our focus is on creating new tools to study the ubiquitin proteasome system and cell signalling, as well as providing a number of general toolkit Affimers.

What is you latest service / innovation?

We are currently focussing on creating tools to support research into ubiquitin and the ubiquitin proteasome system. The covalent addition of ubiquitin to a target protein is now known to modulate most key processes in a cell. This is a relatively new area of biology and the tools, specifically antibodies, are not yet available to allow researchers to do the fundamental biology research that is required. There are several classes of proteins involved in this system: Ligases that add the ubiquitin to a target protein (~300 different ligases), DUBs which remove ubiquitin chains and then the ubiquitin chains themselves. We now provide Affimer binders that recognise specific di-ubiquitin chains. There are seven of these types of di-ubiquitin and each type is thought to have a different function in terms of the fate of the protein they are attached to. For some of the chain types the function is quite well understood and this is the only chain to which a good quality antibody exists. We have Affimers in our catalogue that are entirely unique - no equivalent antibody exists – and customer feedback has been phenomenal. Our K33 and K6 ubiquitin binders, for example, have proved very popular.

How can you benefit the pharmaceutical sector?

We are excited about the potential applications of Affimers as therapeutics. Having already signed an exciting licensing partnership with Moderna Therapeutics to provide exclusive access to Affimers against certain targets, the potential of Affimers is now being recognised by the industry.

One example of where Affimers are being used in an exciting application is around the modulation of blood clotting. Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in the developed world. Fibrin clot structure and fibrinolysis can determine predisposition to CVD and manipulating the prothrombotic environment can reduce the risk of vascular events.

Affimers have been created that bind to fibrinogen and have been shown to interfere with clot formation in some cases, and in other cases to promote clot lysis.  Affimers that reduce clot formation could be used to treat thrombotic disorders and those inhibit clot lysis show promising potential for the treatment of pathological hemorrhagic disorders, or for stopping bleeding following trauma.

Future plans?

We will continue our combined focus on research reagents and therapeutic applications. In the near term we will focus on providing tools for the study of the ubiquitin proteasome system and cell signalling. We are also about to launch an exciting data pack around PD-L1 inhibitors, which has huge potential for oncology.

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