A Cell Centric Drug Discovery Platform to Transform Therapeutic Development

Company to Watch – Cellarity

In the first of four features on Cellarity, Big4Bio spoke with CEO Fabrice Chouraqui about how and why the company was founded, and how it is uncovering the complexity of human biology and changing the paradigm of classic drug discovery to bring new treatments to patients. The second feature will provide an in-depth focus on its technology and pipeline, and plans moving forward.

by Marie Daghlian

Late in 2017 in a world increasingly governed by machines and computers, several partners at biotech venture firm Flagship Pioneering sat brainstorming and observed that human biology is the most sophisticated and complicated computer system ever built.

“What if we could model human biology in order to understand biology at a whole new level?” they asked themselves. They realized that if they could know the rules of biology, they could develop drugs that are essentially the instructions they can give against those rules.

Cellarity CEO, Fabrice Chouraqui

The thinking was: “What if we could actually represent biology mathematically?” says Cellarity CEO Fabrice Chouraqui, who is also a partner at Flagship. “Today our understanding of the transition from health to disease is still very limited and it is the main barrier to finding curative medicines. So, we found that by taking our understanding of biology to a whole new level we could better understand this transition from health to disease and address it by uncovering pharmacological interventions that would allow us to unlock many diseases. Many fields have been transformed by computational modeling. It is time for this to happen to drug discovery.”

Thus, the seed was sown to pioneer Cellarity, named for a complete focus on the whole cell and its behavior in healthy and diseases states as targets for new medicines. Flagship Pioneering Founder and CEO Noubar Afeyan, Partner Avak Kahvejian, and Senior Associate Nick Plugis recognized that with the new biological and computational technologies they could perturb and quantify cell behavior in healthy and disease states and generate the data necessary to unravel biological complexity. In 2020, Flagship armed Cellarity with $50 million in a series A financing round and brought in Chouraqui, who previously headed Novartis’ U.S. pharmaceutical division, to lead the new company.

Cellarity combines high-resolution data, single cell technologies, and machine learning to encode biology, simulate interventions, and design breakthrough medicines. The company’s “cell-first” paradigm is an entirely new approach, Chouraqui says. While many companies are using AI and machine learning to make the classic target-based drug discovery paradigm more efficient, what distinguishes Cellarity is its cell-centric approach—targeting the whole cell and its behavior.

“We solve for a functional readout combined with a cell behavior we wish to change, not a proxy, like hitting a molecular target or a phenotypic change,” says Chouraqui. “This approach allows us to understand and address diseases with previously undiscovered mechanisms and even complex multicellular origins. Modeling biology, testing interventions, and programming medicines — Cellarity is the only one doing this.”

The advantage of targeting cell behavior, the cellular changes that underlie disease, rather than an individual molecular target is that it can uncover new biology and treatments that are applicable to many disease areas. “Our target-agnostic approach lets us look for more, see more, and do more as we address disease,” Chouraqui says.

He explains it as a three-step process. Starting by analyzing diseased human tissue and collecting transcription profiles of single cells in that tissue, the company builds a Cellarity Map, a high-resolution digital model to measure and define the cellular dysfunction underlying the disease process. Then, using Machine Learning and its Intervention Library, a database of drugs and the change that these drugs induce in different cells in different types of contexts, it can identify drugs that address the cell dysfunction of interest and engender a desired cell change.

This is the stage where Cellarity can uncover novel biology overlooked by target-based approaches, says Chouraqui. Finally, the company’s Drug Design Studio creates new chemical entities by learning from features of effective interventions and optimizing their activity, producing an entirely novel chemical entity at its conclusion.

There’s little limit to the number of diseases that Cellarity’s platform can tackle since virtually every disease stem from a disorder at the cellular level. However, the company has to prioritize so it has chosen to start work in four areas: metabolic, hematology, immune-oncology, and respiratory.

“We wanted to target different cell types in different disease systems that had very limited overlap to demonstrate the breadth of the application of our platform,” Chouraqui says as the reason for choosing these disease areas.

Beyond these areas, the company has chosen what it calls Vanguard indications because they can open new opportunities in other areas, which are linked to either the cell-cell type or the cell-cell behavior that it is trying to type—an iterative process where the learning from one disease is applicable to another disease through the type of cellular behavior that it is trying to tackle or the type of cell it is focusing on.

Chouraqui, who spent most of his career in Big Pharma, says Cellarity’s transformative approach to drug discovery is what attracted him to the company. “The fact that we focus on the cell gives us the opportunity to look at a biological system in full and not through the proxy of a target or a pathway. By adopting this much wider approach we are able to identify the cellular processes that underly the start and progression of the disease,” he says. “And because the cell is a much fuller representation of disease than a single target, our platform is designed to drive much higher clinical success.”

NEXT: A Special Look at Cellarity’s technology

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