British biotechs team up to apply Nobel laureate's chemistry to immuno-oncology

A pair of British biotechs are pooling their resources and capabilities to have a crack at development of immuno-oncology drugs. The joint venture, Avvinity Therapeutics, is underpinned by technology, derived from the work of Nobel laureate Kary Mullis, that is designed to overcome the difficulties of treating wild-type expression and lower-frequency mutation cancers.

Horizon Discovery CEO Darrin Disley

Horizon Discovery (LON:HZD) and Centauri Therapeutics are the biotechs behind the new company. The Alphamer technology at the heart of the venture is being provided by Centauri, which has spent the past four years working to apply it to the treatment of infectious diseases. Around 15 months ago, Horizon began talking to Centauri about the potential for the technology in immuno-oncology, ultimately leading to the creation of Avvinity, a virtual biotech that is starting life with a £5.3 million ($7.5 million) commitment from its founders and plans to pursue three targets.

The Alphamer technology, which Avvinity has exclusively licensed in cancer for at least three years, is made up of an aptamer that binds to the target and an outward-facing component that attracts antibodies. "You can get very high, very tailored affinity with an aptamer," Horizon CEO Darrin Disley told FierceBiotech. "You get that to bind to the receptor on the surface and then you use this very clever, tunable linker chemistry that you can moderate, pretty much tailor it on demand, to the point where it can then recruit naturally-occurring antibodies."

While traditional monoclonal antibody approaches require high-affinity interactions with the target, the tactic being pursued by Avvinity is as dependent on avidity, the accumulated strength of multiple binding interactions. The team envisages up to tens of antibodies directed against alpha-gal latching on to each Alphamer, resulting in an immune response that takes down the cancer cell. 

"You could literally recruit two, four, 8, 16, 32, 64 different antibodies per Alphamer molecule," Disley said. "So, you can tailor the avidity, which means that you're going to be able to have much more impact on things that are naturally lower affinity, so for example wild-type expression cancers or cancers that are relatively low frequency mutations … where conventional antibody immunotherapies are having more difficulty." 

Avvinity has spent the past year testing this idea against an as-yet-undisclosed target. Having secured a £5.3 million commitment from Horizon, the first £2.5 million tranche of which is already in its bank account, and agreements to source services at cost from its parent companies, Avvinity is now working to advance this program to in vivo proof-of-concept while starting to develop drugs against two more novel targets.

Disley, who is overseeing Avvinity alongside three other executives from Horizon and Centauri, expects to make a decision about the second tranche of funding in around 18 months, by which time the lead candidate may have advanced to the point at which Avvinity is ready to seek external funding.

"If the program that's most advanced develops as well or better than expected, we will have reached a value inflection point and we may elect at that stage … to go out and raise a Series B round in the 20, 30, 40 million sort of range," Disley said.

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