Aiming for Earlier Intervention, Flagship Startup Etiome Emerges to Define ‘Biostages’ of Disease
Disease is often viewed in a binary way — you either have it or you don’t. Biology doesn’t work that way, of course. Years before a diagnosis, molecular changes are underway leading to the development and progression of a disorder. Therapeutic interventions come after the condition has advanced, which means they may not be effective, said Scott Lipnick, co-founder and president of biotech startup Etiome.
Etiome takes a longer view. The company’s platform technology characterizes a disease and its progression over time. With that insight, it develops drugs appropriate for particular a point of a disease, in some cases before symptoms show. The goal is stopping or even reversing disease.
“If we just say this group is healthy and this group is a bit sick, it creates a very bad math problem,” Lipnick said. “But if we actually give people appropriate labels of how far along in progression they are, how far from a diagnosis, we’re really moving things to a continuous measure of disease progression that allows us to be much more precise.”
Cambridge, Massachusetts-based Etiome has been developing its technology for the past four years. The young company emerged from stealth Thursday, revealing its technology along with a preclinical pipeline that includes programs for liver and brain disorders.
The concept of earlier intervention based on an identifiable biomarker is not a new one. As an example, Lipnick points to high levels of cholesterol, which is a known risk factor for cardiovascular disease. It’s common now to measure cholesterol in patients to gauge their heart health; patients at high risk can take medicines that lower cholesterol to preempt cardiovascular disease. What Etiome is doing is taking this concept further by defining different points of disease progression, which it calls biostages.
Etiome incubated in the labs of startup creator Flagship Pioneering, the same firm whose research spawned messenger RNA company Moderna. Lipnick, who is also a Flagship Pioneering origination partner, said the concept for the company came together after watching the progress of Moderna’s mRNA vaccines for infectious disease, including its Covid-19 vaccine. The idea was to make a similar impact on chronic and progressive diseases by taking a preemptive approach. But first, Etiome needed better understanding of who is getting sick and when they are getting sick.
The formation of Etiome followed advances in artificial intelligence technologies and increased access to electronic health records, said Lipnick, whose experience includes work as a data scientist at Harvard and PatientsLikeMe, a UnitedHealth Group subsidiary. The startup’s technology, named Temporal Biodynamics, finds patterns in data. These patterns define signals that help predict rates of change.
At the molecular level, the technology looks for protein changes in tissues and cells to understand how they transition across stages of health and disease. Using probabilistic models to identify who is getting sick and when they are getting sick, Etiome’s supervised AI technology generates labels with a temporal component. Labeling patient subgroups into different biostages gives scientists a continuous representation of a disease, Lipnick said.
Etiome is focusing on developing treatments for metabolic, neurodegenerative, and autoimmune diseases as well as pre-cancer. In metabolic disease, the startup is working on biostaged drugs for metabolic dysfunction-associated steatohepatitis (MASH) and non-alcoholic fatty liver disease. These disorders have clearly identifiable stages of disease progression with measurable indicators such as fat percentage, fibrosis, and inflammation. The company takes a similar approach to brain disorders. In Alzheimer’s disease, the company measures levels of beta amyloid and tau proteins.
“There are different substages of disease as well as different subtypes of people who might progress into those stages differently, and so it’s ultimately allowing us to say who’s going to likely respond best to which medicine, and when during the progression will that be the case,” Lipnick said.
Depending on the disease, there could be a different medication for each biostage. As an example, Lipnick pointed to Parkinson’s. By the time this disease is diagnosed, the patient’s brain is already damaged. There may be targets that are relevant in the first years of progression that are no longer relevant in advanced stages. That means treatment in the first 10-year window of Parkinson’s will look different than when a patient has heavier disease burden.
Etiome’s approach works with many types of drugs, and Lipnick said the choice of modality will depend on the disease and the biostage. In the liver, the startup is developing small molecules. For the brain, Etiome is researching small molecules and genetic medicines. Some of the programs are being studied as standalone therapies. But Lipnick said Etiome is also exploring combinations with existing therapies to potentially treat different stages of disease simultaneously, which could have a significant impact on disease reversal. Combinations may offer a way to build back functional capabilities of a disease-damaged organ, he explained.
Longer term, Etiome aims to develop drugs for novel targets. But since drugs are already available for some of the indications Etiome is researching, the company is exploring how its temporal approach can apply to already known and validated disease targets. Etiome’s technology has revealed more information about when those targets are active. That insight can help other companies. Lipnick noted that some programs failed because they weren’t tested in the right patient population at the appropriate disease stage. If Temporal Biodynamics can identify the appropriate stage for a drug, that insight can help derisk existing programs or even resurrect failed ones. This capability is drawing interest from pharmaceutical companies and Lipnick said partnership discussions are ongoing.
Etiome is backed by $50 million in financing from Flagship, which is the customary amount that the firm provides its startups at launch. Lipnick said it’s too early to talk about when its programs might reach human testing. Regarding the timing of Etiome’s launch, Lipnick said it comes ahead of partnership and pipeline developments he expects this summer. The company is also getting ready to demonstrate more of its technological capabilities.
“We take it for granted that people are just different, they progress at different rates and we just say that’s normal human humanity,” Lipnick said. “I just don’t think that’s the case, and what our data is showing us is that we can actually find a very strong source of that signal just by looking at how diseases progress molecularly and giving higher resolution to who we are.”
Photo: malerapaso, Getty Images
