Glythera inks alternative antibody deal with Avacta

Under the agreement, Glythera will work with Avacta to develop and test specific Affimer Drug Conjugates (AfDCs) for an undisclosed drug target, with the aim of taking it into the clinic, or licensing to a larger partner, said Avacta’s CEO Alastair Smith.

The firms did not disclose financial details, but said Avacta would receive development milestone payments and royalties on sales of an approved drug.

The Affimer platform – used to develop non-antibody drug conjugates – is based on a small human protein that can be engineered to bind with high specificity and affinity to a wide range of protein targets.  

Smith told us Affimer molecules are smaller and more stable than antibodies: “They are relatively small, highly stable, engineered proteins, with high affinity binding surfaces.”​

“During the recombinant engineering development process, these non-antibody scaffold proteins have become stable, non-toxic and biologically neutral,” ​he said.

Further, size of antibodies is a limiting factor with regards to tissue penetration, he told us: “By using much smaller Affimer technology, the AfDC is likely to be able to penetrate the tumour far more readily and to a much deeper level.”​

According to Smith, Affimer AfDC technology has the potential to generate more effective therapeutics with fewer toxic side effects.

“In the proof-of-concept study, Avacta and Glythera showed that the Affimer technology could be combined with Glythera’s Permalink conjugation chemistry which provides what the companies believe could be a technically superior drug conjugate platform with shorter development times, simpler, more consistent production and greater chemical stability compared to ADCs,” ​he told us.

Smith said another limiting factor seen with ADC (antibody drug conjugate) technology is the potential for systemic exposure to the cytotoxic drug that increases the possibility of non-targeted toxic effects on healthy cells.

“With Affimers, the shorter half-life associated with their small size, greatly reduces the systemic exposure. This can be modulated during the structure optimisation programme, thereby modifying the therapeutic window,” ​he said.

In 2016, Avacta opened​ two UK facilities to support the development of Affimer proteins in Wetherby and Cambridge.