A Platform to Uncover Biological Complexity to Target Virtually Any Disease

Company to Watch – Cellarity

In the second of four features on Cellarity, Big4Bio spoke with CEO Fabrice Chouraqui about the company’s unique platform, initial pipeline, and plans moving forward.

by Marie Daghlian

Cellarity aims to discover medicines that can resolve human disease, potentially any disease. To do this it has developed a cell-centric platform for understanding the complexity of biology at the cellular level, using powerful single cell sequencing and machine language tools to map the changes as cells move from health to disease and find and optimize interventions that can move it back to a healthy state.

Cellarity’s lab in Boynton Yards, Cambridge, Mass.

“When we better know the rules of biology, drugs are essentially the instructions we can give against those rules,” says Fabrice Chouraqui.

Timing is a key part of Cellarity’s success, says Chouraqui. The advent and maturation of single cell technologies to generate vast amounts of multi omics digital data that didn’t really exist at the same scale five years ago, and the use of artificial intelligence and machine learning tools to interpret vast amounts of data, has allowed the company to build mathematical models that increasingly replicate key biological systems.

Cellarity reasons that most diseases stem from dysfunction at the cellular level, and thus its approach is applicable to almost any disease, allowing the company to develop treatments that would not have been identified if they had started from a single target.  Cellarity also reasons that its approach is more likely to translate into clinical success because the cell is a fuller representation of disease compared to an individual target.

“With recent advances in high-resolution data, single cell technologies, and machine learning, we can now computationally model the changes that occur between health and disease and fundamentally rethink the way we create medicines,” says Chouraqui.

Using a three-step process, Cellarity first identifies the set of cellular changes that underlie the start and progression of a disease, then uses AI and machine learning to model computationally the changes that occur in these systems when they move between health and disease.  Cellarity then models the actions of various pharmacologic interventions and purposefully engineers therapies that address this broader set of changes.

During the first step, the company begins by analyzing diseased tissue and collects – at the single cell level – transcription profiles of cells in that tissue. From these inputs they build a Cellarity Map, revealing cells that make up a tissue and illustrating the diversity of underlying behaviors and relationships. Next, Cellarity evaluates how cells transition from a state of health to disease. It then compares a Cellarity Map of diseased tissue to one of healthy tissue to identify cellular dysfunction, or the set of transcriptional changes that occur as individual cells move from health to disease.

Addressing the cellular dysfunction is the second step, for which Cellarity uses its Intervention Library, a proprietary purpose-built resource that links various interventions with the changes they induce in different cells in different contexts.

“At this point we have two things,” says Chouraqui. “One, our Cellarity Maps tell us the cellular dysfunction we are trying to address. Two, our Intervention Library tells us what changes different interventions produce in different cells. We now combine them by searching in the library to see which interventions would be most likely to address the changes we see in cellular dysfunction.”

Cellarity then uses machine learning to pick from thousands of interventions and by doing so, also draws from its experience not just in this specific disease, but by leveraging all previous forms of cellular dysfunction it has investigated. The company then tests what its algorithms predict.

CEO Fabrice Chouraqui at Cellarity’s office

“We use machine learning models to predict changes from interventions and then test those interventions in vitro to verify or refine our models. We modify and repeat this iterative process and strive to converge our in silico and in vitro models,” Chouraqui explains.

Cellarity believes it can apply its platform to virtually any disease. But as the company looked at the enormity of what to tackle, how would they choose initial programs when they could do anything but not everything?

Chouraqui said the company identified certain “vanguard” and “follow-on” programs that could maximize the platform’s value creation opportunities. Vanguard programs are specific conditions that when successfully conducted, can unlock a meaningful understanding of a broader group of cell types and follow-on programs. Using an internal tool the company developed, Cellarity selected those vanguard programs that would maximize value creation opportunities of related follow-on programs.

“We selected vanguard programs that differ in complexity of cell type and behavior so we could demonstrate the platform’s range,” said Chouraqui. “They range from diseases with a specific cellular dysfunction found in one cell type – like sickle cell disease – to diseases with multiple forms of dysfunction across multiple cell types – such as certain metabolic diseases. Regardless of complexity, each vanguard disease enables multiple follow-on programs.”

The company currently has seven programs underway in metabolic disease, hematology, immuno-oncology, and respiratory disease and raised $123 million from a series B financing in July 2021 to advance these programs.

That financing has allowed Cellarity to prove that its platform works and to identify compounds that engender a desired cell behavior change in disease areas of initial focus, says Chouraqui.

“During the year that followed, we’ve been able to validate those compounds in higher species,” he notes. “In two of our programs, we were able to demonstrate translation to higher species, which illustrated the power of this unique approach to creating drug. The goal now is to advance our first programs into the clinic and expand our platform into new modalities and the use of new data types to increase the sophistication of what we are doing.”

Cellarity is also actively pursuing collaborations as the platform has piqued the interest of large biopharmaceutical companies. The company is in active discussions with potential partners to explore research collaborations that could allow it to uncover new biology and new treatments in other disease areas.

Cellarity has big plans moving forward: expanding its platform to new therapeutic modalities and adding new data types; progressing its lead programs into the clinic; expanding its exploratory pipeline; and unlocking new disease systems.

“We are fundamentally changing how we create drugs,” Chouraqui says. “Our goal is to make Cellarity the next generation biotech company that is driving a new age in therapeutic research.”


NEXT: Podcast on Cellarity history, growth and more

This is part of the Big4Bio Company to Watch program for March 2022: Cellarity
For more information on the series, click here