NEW YORK(GenomeWeb) – Antibody development company AxioMx said this week that it has received a Phase I Small Business Innovation Research grant from the National Institute of General Medical Sciences.
According to Founder and CSO Michael Weiner, the company will use the one-year, $250,000 grant to fund development of a new screening technology that will enable it to simultaneously screen multiple antibodies against multiple antigens.
Ultimately, Weiner said, AxioMx aims to screen libraries of 10 billion antibodies against libraries of 10,000 antigens, which, he noted, would allow the company to potentially develop reagents against "a whole proteome in one shot."
Currently, phage display methods like that used by AxioMx and other antibody firms screen libraries consisting of billions of M13 phages, each displaying a different antibody against single protein or peptide antigens, to identify good antibodies to that particular target.
AxioMx will instead screen these large M13 libraries against libraries consisting of thousands of protein targets, each expressed on the outside of an individual cell, which will allow it to simultaneously identify antibodies to large numbers of antigens.
The screening technology is a key part of AxioMx's larger goal of dramatically driving down the cost and time required to produce antibodies.
"You can get your genome sequenced in a day; you can get oligos overnight," said Weiner. "So the challenge [CEO] Chris [McLeod] and I saw was, how come for antibodies it still takes four to six months and costs $15,000?"
Launched in March 2012, AxioMx began offering custom recombinant antibody services in November of that year. Currently, the company can, in its own internal work, produce a new antibody in roughly 20 days, a timescale it aims to drive down to 10 days this summer, Weiner said.
A new AxioMx antibody currently costs around $5,000, he said, adding that the company's ultimate goal is to bring this down to the $2,000 range, competitive with mouse monoclonals.
AxioMx is the second antibody outfit founded by Weiner 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, and two years later Weiner – who also helped invent 454 sequencing and RainDance Technologies' microfluidics systems, and co-founded genomics firm GnuBio – launched Axiomx with a similar goal of making antibodies more broadly available for proteomics research.
A lack of good quality antibodies to a large number of targets has bedeviled protein research and life sciences research more generally.
In the proteomics world, this has led many to look to mass spec as the future tool for protein identification and quantitation, but there is no doubt that a process for rapidly producing antibodies to a wide variety of targets would be of great use to the research community.
As Weiner told GenomeWeb in an earlier interview regarding the company's technology – "People say, 'There's no PCR for proteins. And so I think people … say that that's why nucleic acids took off [and proteins haven't.] But I think that the PCR for proteins is antibodies."
Antibody development has seen relatively little innovation over the last few decades, he told GenomeWeb this week.
"Reagent supply companies are using technologies developed 30, 40 years ago." he said. "They are using phage display, and they've focused on automating it but not reengineering it. So what we have done is looked at every step in the process and said, 'how can we make it faster and cheaper?'"
"You look at DNA, you are trying to go from a $1,000 genome to a $100 genome," he added. "But in the proteomics world, we are trying to go from a $15,000 antibody to a $2,000 antibody. So there is a lot of room to try to drive down the price and improve the speed."
AxioMx has streamlined the antibody production process in several ways aside from its multiplexed screening efforts.
For instance, it uses an all-liquid approach for its affinity screening process, which enables it to automate this work on liquid handling systems, speeding it while also reducing opportunities for human error.
Additionally, the company uses an AXM mutagenesis approach for its affinity maturation process. Affinity maturation uses error-prone PCR to create variations on initial hits with the aim of developing molecules that bind their target better than the original hit. Typically in this process the new PCR products must be ligated into a vector and then transformed into Escherichia coli. The AXM mutagenesis, on the other hand, selectively degrades one of the strands of the error-prone PCR product, allowing it to be hybridized, eliminating the need for the ligation step, which increases throughput and lowers costs.
With regard to the multiplexed screening process, one important step is developing a system for display of the antigen library. AxioMx plans to approach this by expressing individual target antigens in E. coli cells, with the expressed antigens then being displayed on the cell surface where they can come into contact with the phage-displayed antibodies.
Weiner said the company has demonstrated that it can effectively screen antibodies against antigens displayed in this way. They next key, he noted, is figuring out a way to compartmentalize the many billions of potential binding events in a way that allows researchers to identify specific hits.
"The problem in the past has been that if you do 1,000 [antigens] times a billion [antibodies], then things get lost," he said. He added that AxioMx has established a method for doing this, though he declined to provide specific details for print. The company then plans to use next-generation sequencing to identify the antibody-antigen pairs.
"So that's the concept of a library versus a library," Weiner said. "In two days you can do all the screening and then spend a couple days trying to deconvolute which antibodies hit against which antigens."
He added that while he was personally excited by the idea of generating antibodies to an entire proteome in one go, from a business perspective, a more likely application would be generating antibodies to drug targets for pharma research. For instance, he said, AxioMx could in theory rapidly synthesize antibodies against every linear epitope of a druggable protein.
"I think that has tremendous pharmaceutical value," Weiner said.
He cited infectious disease as another area where the approach could prove very useful.
"Imagine having an emerging infectious disease of some sort and being immediately able to sequence it in a day," he said. "Then we would synthesize all the epitopes in a day and so why not be able to produce all the antibodies to it? In one or two weeks you could have antibodies against everything in [the organism]."