Drug development history is full of efforts to get small molecules to target individual proteins. While some of those programs succeeded, countless others fell short. Zachary Sweeney, CEO of startup Interline Therapeutics, contends many of those failures are because a focus on single proteins is an incomplete way to do drug discovery.
Cells are crowded with proteins, and the way that they interact with each other matters, Sweeney said. Technological advances are now helping scientists to better understand how proteins interact as a community and Interline is translating this biology into new drugs. On Thursday, the startup unveiled its approach along with $92 million in funding. This combination of seed funding and Series A financing was co-led by Foresite Capital and ARCH Venture Partners.
The concept that proteins interact within communities is not new, but until recent years, it’s been poorly understood, Sweeney said. In the past decade, technological advances have given scientists new tools to understand protein communities as they’re found in cell type of interest—a capability that was limited by earlier technologies. Further analysis helps scientists understand how proteins in these communities interact and how they change when drugged. They are not just enzymes in isolation, Sweeney said. They are molecular machines that are interacting.
“I worked in neurodegenerative diseases for many years,” said Sweeney, former chief scientific officer of neuro drug developer Denali Therapeutics. “Many [drugs] failed. Some made them worse. I would argue that’s because we didn’t have a sufficient understanding of the proteins we’re going to target.”
Interline’s protein communities approach is interdisciplinary. The company employs genomics, high-throughput proteomics, machine learning, structural biology, and computational chemistry. With those tools, Interline is building a map of protein communities. This map reveals the genetic variants that alter protein communities and, in turn, drive disease.
Interline identifies the specific molecular mechanisms these genetic variants use to change a protein community. With that understanding, the company then discovers small molecules capable of drugging these protein communities, correcting the dysfunction in a community that leads to disease.
Interline was founded in Foresite Labs, the life sciences incubator of Foresite Capital. Don Kirkpatrick, a Genentech veteran who is now Interline’s chief technology officer, co-authored a paper published last year in Nature describing protein communities and their responses to drugs.
Proteomics, the study of proteins, is becoming fertile ground for a growing number of startups. Seer Biotechnology of Redwood City, California, raised $55 million last year to support the development of its suite of products and tools for protein analysis. Seattle-based Nautilus Biotechnology is going public in a merger deal that will infuse it with $350 million for its protein analysis technology. Both companies aim to provide their services and products to support the drug research of others, rather than discover their own drugs.
Though Interline may leverage its technology platform into drug discovery partnerships with larger companies in the future, Sweeney said the focus now is on advancing the startup’s internally discovered pipeline. The Interline research could apply to many therapeutic areas, but the first targets are inflammatory diseases and cancer. Interline currently has six preclinical programs for undisclosed diseases.
In a turnabout from the approach that many drug discovery startups take, Sweeney said Interline won’t be going after rare diseases. The company aims to develop new medicines for common diseases based on new genetic information that the company’s technology has revealed.
Nick Galli, a former Denali business development executive who is now Interline’s chief operating officer, estimates the new cash will finance work on the startup’s six programs until 2024. By then they should have enough data to support another round of financing, he said.
Interline is preparing to move its dozen employees from Foresite Labs into physical lab and office space in South San Francisco. Galli expects the company will grow to 20 by midyear, and 35 by the end of the year. Foresite Labs will continue to provide Interline with its expertise in data science and genomics. The startup also has collaborations with the University of California San Francisco and Memorial Sloan Kettering Cancer Center.
Photo by Interline Therapeutics