In developing new drugs for cancer, researchers have been aided by the identification of numerous genetic mutations which spur tumor growth and can be targeted therapeutically.
By contrast, fewer genetic markers exist to guide drug development in inflammatory diseases, such as ulcerative colitis or Crohn's.
"There's no obvious mutation you can point to in a patient who has inflammatory bowel disease that's driving their disease," said Tariq Kassum, CEO of Celsius Therapeutics, a Cambridge, Massachusetts-based biotech launched last year with $65 million in Series A funding.
The search for a better way to identify biomarkers in inflammatory disease led Johnson & Johnson's Janssen unit to partner with Celsius, which specializes in single-cell RNA sequencing.
Under a research deal announced Tuesday, Celsius will hunt for predictive biomarkers in data generated by a Phase 2a clinical trial run by Janssen in patients with ulcerative colitis. Financial terms were not disclosed for the partnership, Celsius' first since its 2018 launch.
What sets Celsius apart is its focus on single-cell genomics, which gives the biotech a window into how cellular dysfunction and communication between cells can cause disease. Typically, genomic sequencing reports averages and therefore can miss the role played by specific cell types, according to Celsius.
"We have a very limited understanding right now of why some patients respond and some don't," said Kassum, who joined the biotech in early June from Obsidian Therapeutics, in an interview with BioPharma Dive.
"With a single-cell approach, high resolution and a large number of samples, we've got a fighting chance to unpack some of these differences."
For Celsius, that large number of samples is what makes the collaboration with Janssen compelling. The trial in question, which is testing J&J's drugs Tremfya and Simponi in combination, is set to enroll 210 patients with ulcerative colitis, according to clinicaltrials.gov.
"No one has ever looked at 100 different patients with ulcerative colitis on a single cell level," said Kassum, speaking broadly about the study, called VEGA.
"It's entirely conceivable that we can learn that different patients have different drivers for their disease on a cellular level," he added. "Maybe the inflammatory symptoms are the final common pathway for a number of different sub-diseases, for example."
According to Kassum, the largest single cell study conducted to date in ulcerative colitis involved 17 people, seven of whom had the disease and 10 who were healthy. The investigation, led by researchers at the Broad Institute of MIT and Harvard including Celsius co-founder Aviv Regev, is currently available as a preprint, and has not yet been peer reviewed.
In it, researchers built an "atlas" of more than 115,000 cells from mucus membranes of participants' colons. Among those cells, the investigators identified 51 different cell subsets, including some they claimed as "previously uncharacterized."
By mapping gene expression to cells in either healthy or inflamed mucus membranes, such studies could help identify markers of disease, drug response and resistance.
Under the partnership with Janssen, Celsius will use its single-cell approach to attempt to identify predictive biomarkers of response, collecting patient data from VEGA.
"We believe combination therapy may break through the monotherapy efficacy ceiling seen in many immune-mediated diseases," said David Lee, Janssen's therapeutic area head for immunology, in a statement provided to BioPharma Dive.
"Historically, safe and effective combinations have been challenging to develop because of the complexity of the immune system."
Partnering with Celsius, he added, would help guide Janssen as it works to develop combination treatments across different immune system pathways.
In return, Janssen will pay Celsius undisclosed sums as well as potential milestones based on how biomarkers identified via the collaboration are used.
The collaboration is the result of a "natural evolution" of discussions between Janssen and Celsius, Kassum said, rather than broad outreach on the part of the smaller biotech.
Still, "we're definitely looking forward to doing more of these," the CEO said, "and we're having a number of different conversations with a lot of different pharma partners."