We often think of proteins as isolated targets for drugs, says Zach Sweeney, Ph.D., a drug discovery veteran who most recently was chief scientific officer at Denali Therapeutics.
JAK inhibitors block enzymes in the JAK family, for example, while PD-1 blockers target a specific cell surface receptor. But it’s more complicated than that—enzymes and other proteins don’t exist in a vacuum and altering one protein affects a whole community of other proteins.
Enter Interline Therapeutics, which launches out of Foresite Capital’s incubator with $92 million from Foresite and Arch Venture Partners to develop drugs that alter protein communities to treat disease. With Sweeney at the helm, the company will use the capital to double its team, expand its platform and drive six programs through preclinical development.
“We hope to understand the complex relationships that exist between proteins: physical, functional and spatial relationships,” said Don Kirkpatrick, Ph.D., chief technology officer of Interline, who joined Interline after a 13-year run at Genentech. “That’s what defines cellular dysfunction. We think if we understand them in detail, we’ll be able to develop specific drugs that will impact, improve and correct protein communities in a way that can impact genetically validated disease.”
It’s an opportunity Sweeney has been waiting his whole career for.
“I’ll take us back to 1996 when I was trying to decide what to do with my career … It was also the year that people understood the mechanism by which people were protected from HIV,” he said. “It was the first time, in my understanding at least, there was a genetic variant protecting people from a common disease.”
If scientists could pinpoint those protective variants, they could develop treatments that mimic their effects, Sweeney figured. There are some drugs work this way, such as PCSK9 inhibitors to lower cholesterol, but drug developers didn’t have the right kind of data at the time to discover this type of drug in a systematic and prospective way, he said.
The kind of data linking protein communities and common diseases has only emerged in the last few years, Sweeney said. Couple that with advances in technologies like mass spectrometry, computational structural biology and machine learning, and the time is ripe for a company like Interline, Sweeney and Kirkpatrick said.
The company’s strategy rests on three pillars: mining genetic information for variants that drive disease by altering protein communities; identifying how those genetic variants change the structure and dynamics of protein communities; and discovering drugs that can reshape those communities.
“We have collaborations in each of those areas,” Sweeney said, including partnerships with the University of California, San Francisco and Memorial Sloan Kettering Cancer Center.
Interline thinks the approach can be applied to many different disease areas, but it’s starting with immunology and precision oncology. Six programs are underway at the moment, but Interline plans to be “at a steady state between eight and 10 programs,” Sweeney said.
The company has inked a few academic partnerships around specific targets and hopes to be in the clinic within two to three years, Kirkpatrick said.
As Interline advances the programs and platform, the team will expand, too. At about 12 staffers now, the company hopes to reach 30 to 35 by the end of the year.