ExcepGen emerges from Y Combinator, taking aim at better proteins for drug discovery

Investigation of protein expression (Image: AstraZeneca)
ExcepGen is launching with three Big Pharma partnerships and eventually wants to create its own pipeline, “mostly in the biologics space." (AstraZeneca)

It’s no secret that drug discovery is a difficult business, with the vast majority of small molecules entering the clinic never coming out the other side. There’s no one cause for this failure rate—it comes from a mix of factors. Enter ExcepGen, which is taking aim at a historically challenging one: the way we make proteins for drug discovery. 

ExcepGen is officially launching out of Y Combinator with technology that uses an engineered human cell line to produce full-length human proteins for use in drug discovery. Its founders believe the approach could speed up discovery and even come up with protein targets previously thought to be undruggable. 

That seems like a no-brainer—to target human disease, why not test potential drug candidates against human proteins, and full-length ones at that? 

FierceBiotech Executive Breakfast

Getting Real: The Changing Tide on Real-World Evidence in Drug Development

Join FierceBiotech and a panel of industry experts for an executive breakfast at BIO. We will discuss the impacts of real-world evidence on drug development and address the important questions that companies are facing including where to find the right talent & technology and how to deploy it internally or with partners. Join us in Philadelphia on June 5th for this important discussion.

Scientists have struggled to do this because human cells have evolved not to produce proteins in the large amounts needed for drug R&D: “When human cells produce the wrong protein, or the protein in the wrong amount, this is where diseases usually come from. Our cells have had billions of years to specialize in fighting against this,” said Barbara Mertins, Ph.D., ExcepGen’s chief scientific officer and co-founder. 

RELATED: AI player twoXAR teams up with 1ST Biotherapeutics on glioblastoma 

To get around this problem, drug developers have turned to other sources to create proteins, such as insect or E. coli cell lines, said Tom Folliard, Ph.D., ExcepGen CEO and co-founder. Another method is to work with shortened versions of the protein. These approaches end up lengthening the whole drug discovery process: Companies must spend time figuring out which cell lines might work, or which truncations are needed to make to the protein. And after all that, the molecule under development may not end up working in humans. Creating a molecule that binds to an E. coli protein does not guarantee it will bind to the same protein in humans, Mertins said. 

ExcepGen eventually wants to create its own pipeline, “mostly in the biologics space,” Folliard said. But for the moment, it is partnering with three Big Pharma companies and hopes to get more on board. The biotech is launching with a lean team of three and will look to grow as it adds partners and customers. 

One of its partnerships is with AstraZeneca, which is “constantly on the lookout for new methods” to “express high levels of recombinant protein” for drug discovery, said Steve Rees, the company’s vice president of discovery biology. 

RELATED: Daphne Koller, A-list backers unite to create machine learning drug R&D startup 

“A specific problem common to the field is that it is very difficult to express larger full-length proteins and, for that reason, many companies, ourselves included, express the domains of the protein rather than the full-length protein to support screens,” Rees said. 

"We were recently introduced to ExcepGen; they have an exciting new platform that can rapidly express proteins in mammalian cells with the potential to successfully express these larger proteins. We’ve asked ExcepGen to express a small number of proteins we found difficult to express in-house. We asked the question, can they, using their system, successfully express those proteins? We are in the middle of that collaboration at the moment,” Rees said. 

It’s still early days for this collaboration, but Rees said AstraZeneca’s early data shows that ExcepGen’s technology is able to express proteins that the Big Pharma has had trouble expressing in-house. 

Suggested Articles

Yale researchers discovered that AstraZeneca’s anti-VEGF cancer drug cediranib may boost the effectiveness of PARP inhibitors.

The FBI has launched its own probe into some of the world’s largest medtech companies, stemming from a Brazilian corruption case, Reuters reports.

AbbVie became yet another biopharma learning that aggressive brain cancer glioblastoma is one of the toughest cancers out there.