Despite all the advances in drug research, bringing a new molecule into clinical testing today is still very much a roll of the dice, said Adrian “Ad” Rawcliffe, CEO of new company Etcelera. About half the time, a molecule fails. Rawcliffe contends the high failure rate comes from insufficient understanding of biology.
Cambridge, Massachusetts-based Etcelera aims to improve the odds with science. The recently formed startup combines three portfolio companies of startup creator Flagship Pioneering. Each Flagship company is built around a platform technology. While Etcelera’s three predecessors had different technologies, Rawcliffe said the thread connecting them was a shared goal of seeking a better understanding of the biology of disease to reduce the risks of drug development. Put another way, the three startups were trying to improve the chances of clinical trial success.
“If you can do that, then you can solve the problem of attrition in drug development because your clinical trials then stop being experiments in humans and they start being validation of predictions that you make before you go into humans,” said Rawcliffe, whose 30 years of industry experience includes senior roles at GSK and Adaptimmune.
Rawcliffe is relatively new to Flagship. At the start of the year, he joined Flagship as CEO-partner and CEO of Etiome, one of the Flagship companies that is now part of Etcelera. Etiome’s technology analyzes gene expression to identify patterns and changes over time as a disease progresses. The goal was not only identifying the right patients for a drug, but also identifying the stage of a disease that’s best for intervention. Rawcliffe said that as that research continued, he looked at what other companies in the Flagship portfolio were doing.
Cellarity, with its platform that applies machine learning to biology, was similar to Etiome, albeit with a focus on analyzing cells to learn about disease biology. Like Etiome, Cellarity’s analysis yields “maps” of disease progression. Empress Therapeutics brings a suite of multi-omic analysis tools that enable complex perturbation experiments, tests in which changes or disturbances are introduced to see how the biology responds, such as knocking out multiple genes simultaneously to see what happens. Rawcliffe said the ability to do such tests at scale will bring Etcelera closer to understanding cause and effect in biology.
The endeavor led Flagship to coin a new term: causal intelligence. Rawcliffe describes it as the ability to not only predict what happens in complex biological systems, but also to understand and explain it. These predictions and explanations exceed human capabilities and can only be done in the context of machine learning, he said.
The biggest impact of understanding cause and effect in biology should be economic — reducing the failure rate in clinical trials. Rawcliffe acknowledges that other companies with AI and machine-learning technologies share a similar goal, but he believes Etcelera’s technologies put it in a good position to achieve it.
Rawcliffe said the billions of dollars it can take to bring a drug from discovery through commercialization is the sum of all the things scientists tried in order to find the one thing that succeeds. Understanding cause and effect should bring those costs down, which in turn would change the economics of drug discovery, he said.
Diseases previously considered prohibitively expensive to pursue could become more economically feasible. As an example, Rawcliffe pointed to rare cancers and rare diseases where companies can’t see a way to recoup what it would cost to develop a drug. Causal intelligence could make these diseases economically attractive, he said. It could also change investment strategies. With better understanding about cause and effect, money for clinical trials might no longer be viewed as high-risk capital, potentially opening the door to more investment in early-stage projects.
Etcelera has a way to go prove its approach can yield the research and economic changes Rawcliffe describes. But it’s not the first time that Flagship has combined two or more of its portfolio companies in pursuit of an ambitious new strategy. Sail Biomedicines, developer of programmable RNA medicines, formed from the 2023 merger of Laronde and Senda Biosciences. Senda itself was a combination of several Flagship companies.
Etcelera inherits the mostly preclinical pipelines of its predecessors, which spans hematology, immunology, and metabolic fibrotic conditions. Cellarity’s CLY-124, a small molecule in early clinical development for sickle cell disease, is being spun out into a separate company. Two pharma partnerships in metabolic dysfunction-associated steatohepatitis (MASH), one Novo another with an undisclosed pharma company, will continue with Etcelera.
The funding backed Etcelera’s predecessors will continue to support the new company. Additional money could come from new partnerships. Building on the existing collaborations, Rawcliffe said he plans to pursue more alliances in 2027.
Etcelera is in the process of combining the three technology platforms. Exactly how they’ll be used in drug research will depend on the particular challenge or problem that needs to be solved, Rawcliffe said. Diseases characterized by cellular changes will lean more heavily on Cellarity’s components while diseases with a longitudinal pattern will rely more on Etiome’s contributions. In all cases, perturbation experiments will leverage Empress’s contributions.
“The whole is greater than the sum of its parts, but you can still see the component parts within the overall platform,” Rawcliffe said.
Photo: Bulat Silvia, Getty Images
