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AxioMx Continues Work on Speeding Antibody Development After Acquisition by Abcam


NEW YORK (GenomeWeb) – Since being acquired last year by Abcam, antibody firm AxioMx has continued to develop its rapid antibody generation pipeline and is currently incorporating new technology that will shave an additional two to three weeks off the process.

The technology is a new system that allows for more rapid conversion of the single-chain variable fragment (scFv) antibodies screened during phage display to a full-length IgG antibody that can be used for validation. Named pMINERVA, and detailed in a recent paper in the Journal of Immunological Methods, the system brings the time required to move from scFvs to IgGs down from around two weeks to one day, which, in addition to speeding the development process also allows for a larger number of candidate IgGs to be evaluated and validated.

"The research and development [for the method] is complete, and we are beginning to incorporate it into our pipeline," Michael Weiner, a founder of AxioMx and vice president of molecular sciences at Abcam, told GenomeWeb, adding that the company was currently building out a new cell culture facility in which it will be implementing the new approach.

The incorporation of the pMINERVA system is the latest step in AxioMx's, and now Abcam's, long-running goal of significantly bringing down the time and expense of antibody development.

The company launched in 2012 with the goal of making antibodies more comparable to genomic technologies in terms of cost and speed, Weiner told GenomeWeb in a 2015 interview.

"You can get your genome sequenced in a day; you can get oligos overnight," he said. "So, the challenge [we] saw was, how come for antibodies it still takes four to six months and costs $15,000?"

AxioMx is the second antibody outfit founded by Weiner — who also helped invent 454 sequencing and RainDance Technologies' microfluidics systems, and co-founded genomics firm GnuBio — in recent years. In 2008, he, along with Stanford University researcher Michael Snyder (then at Yale University), Yale researcher Sherman Weissman, and Elm Street Ventures partner Mike Sherman, launched the biotech firm Affomix, which similarly aimed to shorten antibody production timescales while increasing quality.

Affomix was acquired by Illumina in 2010. Five years later, AxioMx was acquired by Abcam, which purchased the company last November for $45 million — $20 million upfront along with performance-based payments totaling up to $25 million to be made over the next five years based upon successful completion of commercial and technical milestones.

Abcam was interested in AxioMx's streamlined antibody production process in general, Weiner noted, but has to date employed its newly acquired technology largely for going after antibodies that are difficult to generate using Abcam's traditional rabbit-based methods.

For instance, in vivo systems are limited when it comes to generating antibodies to highly toxic antigens, he said, citing ricin as one target they have taken on. Likewise, if a human protein target is too similar to the rabbit version, the rabbit will not generate antibodies to it, making it difficult to produce reagents in this way.

"I think what [Abcam] is trying to do is have the ability to get at affinity reagents no matter what the immunogen is," Weiner said. "And so there are limitations in phage display, and there are limitations to rabbit, but [combining the two] allows you to go after a larger immunogen space."

Phosphorylated proteins, which were a primary area of concentration for AxioMx prior to the acquisition, have also remained a point of focus, Weiner said.

"We have developed specialized libraries and methods to go after phosphor-specific proteins," he said. "Epigenetics and post-translational modifications are areas of high interest in the scientific and biological world, so those are areas that continue to be of interest to Abcam as a reagent supply company."

And, of course, there is the matter of speed. Weiner said he believed one factor contributing to Abcam's decision to acquire AxioMx was the fact that the company was able to deliver an antibody three weeks after being given the target.

"I think one of the things that may have impressed them is we were able to deliver an antibody to them within three weeks of them handing us the immunogen, and that antibody was validated for immunohistochemistry," he said. Typically, Weiner added, delivery of such a reagent would take between six and 12 months.

From AxioMx's perspective, a major boon of the acquisition has been having Abcam's resources for better validating their antibodies, Weiner said. "They have a huge infrastructure for validating antibodies that we never had. They are able to do immunocytochemistry, immunohistochemistry, sandwich ELISAs — things we weren't able to do where we had to instead rely on our customers for doing the end validation."

This includes knockout validation, which Abcam began last year, inking an exclusive agreement with Horizon Discovery Group, which uses CRISPR gene-editing technology to provide the company with haploid knockout cell lines (in which the target protein has been removed) for validation of its reagents.

AxioMx's ultimate goal, he said, is to move towards a system where the entire antibody-antigen screening process is done upfront, allowing the company to more or less provide antibodies on demand as customers order them.

To do this, Weiner and his colleagues are applying a variety of the molecular biology techniques, from next-generation sequencing to emulsion-based reactions, he has worked on in previous positions at 454 Life Sciences and Raindance Technologies.

Such a system would be emulsion-based to allow for the screening of billions of individual antigen-antibody pairs at once followed by next-generation sequencing to identify the sequence of antibodies that are particular hits for a given antigen.

"Then when somebody comes to you with the need for a particular antigen you just use your database to figure out which of those microdroplets had [the antibody] that was of interest [regarding that antigen]," he said. "That is kind of the ultimate dream of mine."

In fact, Weiner said that he believes such a platform is feasible within the next two to four years, noting that it is primarily a matter of integrating existing technologies into a single workflow.