Design ankyrin repeat proteins (DARPins) have the potential to be a major disruptive technology in biologics-based therapy.
A relatively new phenomenon in the pharmaceutical industry, they were originally developed from ankyrin repeat proteins, natural receptor binding and cell signalling molecules.
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Molecular Partners developed the new technology based off these proteins, and was able to design them to bind specific targets of interest.
This has opened up the prospect of using these proteins as therapeutics, as an alternative to monoclonal-antibody-based therapies.
Advantages
DARPins offer many advantages over antibodies, ranging from desirable pharmacokinetic properties to more efficient production.
DARPins are around 14–21kDa – significantly smaller than antibodies, allowing greater tissue penetration.
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By GlobalDataThey have also demonstrated significant potency, stability and solubility1, 3.
However, the characteristic that is arguably the most exciting from a commercial point of view is the capability of producing them in simple cellular systems.
Recombinant antibodies are commonly produced in mammalian cell systems such as Chinese hamster ovary cells, which is expensive.
DARPins can be manufactured in E.coli cells at considerably less cost, meaning they have the potential to offer a significantly cheaper alternative.
What’s the next step?
Molecular Partners has shown interest in partnering with other firms to continue development of the technology.
For example, it has collaborated with Allergan to develop the drug Abicipar, which is expected to become the first marketed DARPin-based therapy.
Abicipar is being developed for the treatment of macular degeneration – a condition that leads to loss of sight and other ophthalmological disorders.
It is currently undergoing Phase III trials, having shown promising signs during earlier studies, in which a 2mg dose was shown to be effective at improving vision over 16 weeks of treatment with no major side effects.
MP-02050 represents another promising therapy in development.
It is a cancer treatment, established solely by Molecular Partners, and is currently in Phase I/II trials for the treatment of Kahler disease, a type of blood cell cancer6.
40 patients are expected to be enrolled, and safety will be assessed, with survival rates at 24 months used to determine efficacy.
Promise for the future?
Although DARPins are yet to reach the market, they have huge potential due to their pharmacokinetic properties, flexibility, and potential to be significantly cheaper than current therapies.
All of these factors make this technology a very attractive option for new drug development.
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