With biotech flush with venture capital funding, it seems that every hot new area of biology research now comes with its own startup. The latest is Celsius Therapeutics, and the new technology is single-cell genomics—the study of genetic activity of individual cells. Celsius was founded by scientists from the Broad Institute and elsewhere, and the Cambridge, MA-based company now has $65 million in Series A funding from lead investor Third Rock Ventures and several other investors. It aims to use single-cell genomics to find new drug targets for autoimmune disease and cancer.
Scientists at the Broad Institute, including Celsius co-founder Aviv Regev (pictured left), have been leaders in developing technologies that allow researchers to drill down deeper into the biology of cells and disease by homing in on individual cells. Genetic studies of cells have traditionally involved taking a bunch of cells, mincing them up in a blender, extracting the DNA or RNA, and then sequencing that to come up with results that are averaged across different cells in that messy collection. Details about differences between individual cells, and how those cells interact, get lost in the blender.
But the founders of Celsius say that tiny subgroups of cells in that mix, which have so far remained hidden, could be key drivers of disease or drug resistance. To tease out these hidden cells, Celsius is using high-resolution sequencing technologies, licensed from the Broad, to zoom in and study the RNA at the level of individual cells. The goal is to learn about what those cells are doing in healthy people and in those with disease, how the cells differ from other cells, and which genes and biological pathways the disease-driving cells are using. That could lead to the discovery of new biological mechanisms of disease, and new drug targets, says Christoph Lengauer (pictured right), Celsius’s co-founder, president, and venture partner at Third Rock. “The power of the approach lies in the [high] resolution” of the single-cell technologies, he says.
A big part of the company’s approach is coming up with new machine learning algorithms to crunch the massive amounts of sequence data from millions of cells and pull out useful signals. Celsius co-founder Regev says this is no small feat for the company. “One key challenge is the analysis of data sets of unprecedented size and complexity to identify key cells and genes,” says Regev.
The company is doing early drug discovery on three new targets in autoimmune disease and cancer, according to Lengauer. Celsius is focused on these two disease areas because they come about through complex interactions between a variety of cell types in the immune system and other tissues. Lengauer says single-cell genomics allows researchers to probe those interactions, and see which ones might be the most important in a particular disease.
Lengauer has been watching the single-cell genomics field as more academic labs around the world started doing these sorts of studies. Both Science and Nature devoted special issues to the topic last year, and both featured articles from or about Regev. Lengauer says he started talking to Regev two years ago about working on a startup that would take advantage of all the technological advances in single-cell research. “We knew this had to be turned into a company,” says Lengauer. “The technology is so promising.”
Single-cell researchers in academia have worked mainly on cells from lab animals or healthy people. Some of that work is through big international research projects such as the Human Cell Atlas. That effort is co-chaired by Regev and is sequencing the RNA from every cell type in the human body to classify the cells and map their location.
Lengauer says his company will take a different tack by studying patient samples to look for drug targets. He says his team are analyzing cells from specific patient subgroups, such as people with a well-defined form of a disease, or who have developed resistance to a certain kind of treatment. The idea is that a drug developed from those samples would be targeted at that group.
Celsius, with 15 employees, is still in the earliest stages of drug discovery. Lengauer, who was chief scientific officer of Blueprint Medicines from 2012 to 2016 and remains a consultant there, says that the $65 million in funding will hopefully be enough to take Celsius into clinical trials sometime in the next five years.
For now, though, Lengauer says he wants his team to focus on disease biology first, and that means being “agnostic” about what types of drugs they will develop, whether it’s small molecules or antibodies or something else. Lengauer admits that this uncertainty adds to the already formidable challenge he has in trying to harness relatively new technology for drug discovery, but he adds, “That’s why I love it.”
Third Rock Ventures led the Series A round (Third Rock’s Alexis Borisy is pictured middle), with GV (formerly Google Ventures), Heritage Provider Network, Casdin Capital, Alexandria Venture Investments, and other investors joining in. The other scientific founders of Celsius are Jeff Bluestone, CEO of the Parker Institute for Cancer Immunotherapy at the University of California, San Francisco; Vijay Kuchroo at Brigham and Women’s Hospital; and Ramnik Xavier at Massachusetts General Hospital and the Broad Institute.