Flagship Pioneering launches start-up to suss out disease-state biomarkers

Flagship Pioneering has unveiled a new start-up that aims to find, then drug, targets that are specific to different states of diseases. The company, Etiome, will begin with metabolic, neurodegenerative, and inflammatory illnesses.

The venture firm has backed Etiome with $50 million, enough to give the start-up about a year and a half of runway, says Etiome cofounder and president Scott Lipnick, who also serves as an origination partner in Flagship’s Preemptive Health and Medicine Initiative. During that time, Etiome’s 20-person team aims to identify targets in all three disease areas and begin developing drugs for them, both internally and through partnerships with pharmaceutical companies.

“The diseases we want to work on are progressive diseases, where we have a long window of the disease and also where we have complex, evolving biology,” Lipnick says.

Etiome uses clinical data from electronic health records, as well as cellular and molecular data from other databases, to discern when certain proteins or genes change such that cells go from a healthy to diseased state, or from mildly to more severely ill. The company calls these “BioStage Markers;” the idea is to isolate a biomarker that’s specific to a stage of disease, thus allowing for better subgrouping of patients and in turn more targeted drug development.

“It’s really about finding those targets that are going to stop or reverse progression,” Lipnick says. “We’re about 30 years into the electronic health record revolution. We’re about 5–15 years into artificial intelligence making a huge impact on how we look at large data. So we can build probabilistic models, deep learning models from huge amounts of clinical data.”

Etiome’s first metabolic disease of interest is metabolic dysfunction–associated steatohepatitis, a liver disease better known as MASH. It is a chronic, progressive illness in which excess fat cells cause inflammation, which in turn damages the liver over time. Lipnick says MASH can be broken down into groupings based on disease state: from initial inflammation to fibrotic scarring and finally to cirrhosis, in which scar tissue has replaced healthy liver tissue and caused permanent damage.

“As the disease progresses, we have a very different profile of targets,” Lipnick says.

On the neurodegenerative side, Etiome is working in Alzheimer’s disease, an area where new biomarkers are beginning to yield better diagnostics, including for early-stage Alzheimer’s.

In particular, Etiome scientists are looking at targeting tau, a type of protein that often shows up in hyperphosphorylated tangles inside the neurons of people with Alzheimer’s disease. That would entail a different approach from existing Alzheimer’s medications, with are designed to reduce amyloid-β, another protein that misfolds and clumps on patients’ brains. Lipnick believes the tau-focused approach could promote resilience in neurons.

It might also be a smart regulatory play. The US Food and Drug Administration (FDA) has approved tau-based diagnostics and recently fast-tracked a tau-targeting drug candidate made by Johnson & Johnson.

“Because we’re kind of bullish on the idea of tau being a relevant readout that is related to neuronal health, we think that we can use an existing marker to actually get an FDA approval,” Lipnick says. “Then our biomarkers can be used more for signs of efficacy, potential patient subtyping, but we don't need to go through the whole process of getting FDA approval.”

Etiome is based in Cambridge, Massachusetts, where it’s leasing space from another Flagship-backed company.