Targeting slippery cell-membrane proteins using antibody fragments.
CEO: Cedric Ververken, Ph.D.
Based: Ghent, Belgium
Clinical focus: Drugging GPCRs to treat fibrotic, metabolic and neurological diseases
The scoop: VHH fragments have already given rise to one breakout Belgian biotech, Ablynx. Now, they are fueling the rise of another one, Confo Therapeutics. Whereas Ablynx used the antibody fragments as drugs, resulting in a business that Sanofi valued at $4.8 billion, Confo is using them to stabilize G protein-coupled receptors (GPCRs), giving it a new way to find candidates against a large group of membrane proteins.
What makes Confo fierce: Confo has hoovered up talent from Benelux biotech success stories. Toon Laeremans, one of Ablynx’s first employees, helped to get Confo off the ground and now heads up technology at the startup. Laeremans is joined at the top of the company by another ex-Ablynx employee, Cedric Ververken, Ph.D., and the former director of medicinal chemistry at Galapagos, Christel Menet, Ph.D.
Working with Laeremans, Ververken and Menet, respectively the CEO and CSO of Confo, are using the proceeds of a €30 million ($33 million) series A round to advance three priority programs toward candidate selection. The three programs, which target fibrotic diseases plus orphan metabolic and neurological indications, are underpinned by tools to crack the challenge of drugging GPCRs.
“GPCRs are flexible proteins and they function through conformational changes to transmit a signal inside the cell. That makes them difficult to isolate and do drug discovery using biophysical methods,” Ververken said.
Other companies have tried to overcome the challenge through high-throughput screening, exposing GPCRs to vast compound libraries in the hopes of getting a hit. However, this approach requires the coverage of the right chemical space and, even then, Ververken thinks it has weaknesses.
“Even if you have a very successful screening you can get quite a lot of false positives because you’re looking at something three, four steps downstream of the receptor,” the Confo CEO said.
Confo’s approach uses VHH fragments, which it calls ConfoBodies, to stabilize GPCRs in their active state. This, according to Ververken, allows Confo to set up highly sensitive biophysical, competition and biosensor-type screening assays, enabling it to find hits in a library of around 3,000 small molecule fragments.
“With that relatively small library we’ve always been able to find hits,” Ververken said.
Confo is also using ConfoBodies to help determine GPCR structures. By giving that information to its medicinal chemists, Confo expects to accelerate the discovery of therapeutic compounds, providing it with another way to find drugs against GPCRs.
The potential of these approaches enabled Confo to expand its investor syndicate beyond the group of local specialists that provided seed funding. That done, Confo has gone on a hiring push, adding staff from lab technicians up to group leaders with industry experience. Confo has focused the first wave of the hiring push on areas such as structural biology and in vitro pharmacology, with a move into in vivo pharmacology and translational medicine set to follow as the lead programs advance.
Through the hiring, Confo hopes to establish a team capable of getting one of three priority programs IND-ready by late 2021 or early 2022. Then, Confo will get a chance to establish itself as the next breakout star of Belgian biotech.
Investors: BioGeneration Ventures, Wellington Partners, Fund+, Perceptive Advisors, Capricorn Venture Partners, MINTS, PMV, Qbic, V-Bio Ventures and VIB