Multi-Tissue Organoid Better Predicts Human Response to Drug Treatments: CellCipher

Katherine Rhodes, PhD ’21, CellCipher cofounder, presented at the George Shultz  Innovation Fund finals where the team was awarded $150,000.

CellCipher has developed a new type of organoid model that captures nearly 70 different cell types to enable drug discovery and personalized medicine.

In vitro human models, including organoids and other technologies, enable researchers to study human cells before testing them in humans. While this is done currently to some extent, safety studies rely heavily on animal models. In clinical trials, this leads to high failure rates due to unexpected toxicity in humans – toxicity that was not observed in animal models.

“There’s really a need for models that are going to do a better job of predicting how real humans are going to respond,” said Katherine Rhodes, PhD ’21, cofounder of CellCipher. And organoids are one of these promising models.

As typically described, organoids are a group of cells that model a single tissue, for example, the brain or gut. What is different about CellCipher’s model is that it doesn’t capture just a single tissue, but a diverse sample from across the human body of nearly 70 different cell types. Additionally, where the process of maturing cells to create these models can be long, sometimes lasting months, CellCipher can generate their models in as little as three weeks.

“What that means is you are getting a huge array of human cell types all growing in a single dish and in a really short time frame,” explained Rhodes. “We can provide a broad perceptive on human response to a drug treatment and how it’s affecting many cell types.”

This lets researchers ask new and interesting questions, such as how genetic variants affect drug response – examining these responses in detail that has not been possible before.

The team’s experiments to date have proven that the 68 cell types that comprise its MTOs align well with known gene expression patterns in human embryonic stem cells, fetal cells, and adult human tissues. With its machine learning classifier trained on data from its “MTO Drug Response Atlas,” CellCipher will be able to provide thorough toxicity profiles and predict off-target effects.

The startup will initially focus on preclinical toxicity testing, as it requires fewer resources to get up and running and can make a meaningful impact in the short term, Rhodes explained, noting that they have already seen interest from pharmaceutical companies about adopting the model.

Longer term, the goal is to add a precision medicine component, which would specifically draw on the unique expertise of its team.

Rhodes, who finished her PhD in human genetics at the University of Chicago in 2021, is a staff scientist in the lab of Yoav Gilad, a professor of medicine and dean for biomedical and health informatics at the University. Also a cofounder of CellCipher, Gilad is the section chief of genetic medicine and vice chair for research in the department of medicine. The duo is joined by a third cofounder, Alexis Battle, professor of biomedical engineering and computer science at Johns Hopkins. Both are experts in the fields of human genomics; Gilad specifically in developing models and Battle on new statistical and machine learning methods to understand genomic data types.

Applying this experience with CellCipher’s model and it becomes “a very exciting technology for precision medicine,” said Rhodes. It also could be applied to clinical trial recruitment and drug rescue or repurposing.

Stepping Outside Academia

Why a startup? In terms of the science, the team had completed most of the proof-of-concept work to understand the system’s ability to scale. The next question was what impact the model and the analytical methods could have outside of academia – importantly, for the benefit of society.

When Gilad suggested forming a startup, it was a clear “yes” from Rhodes, who was heavily involved in Polsky Center programming throughout graduate school. Before participating in the fall 2023 Innovation Fund, where the startup was awarded $150,000, she was an Innovation Fund Associate for a previous cohort, conducting due diligence on participating ventures. She also participated in the Polsky Center I-Corps program, first with a different technology, and most recently with her own work for the MTO system.

“All of that experience happened before I even considered being on the entrepreneurial side of things. It gave me a strong understanding of what it takes to make a viable technology and how to think about the earliest steps,” explained Rhodes.

One of these earliest steps for CellCipher was presenting at another Polsky programming event, the Collaboratorium, which unites UChicago students with researchers, technologists, and faculty who want to explore the commercialization opportunities and business applications of their work. It was here in 2022 that the team connected with an undergraduate student and Chicago Booth MBA candidate Jackson Finks.

“This was one of the best things that has come out of programming for us,” said Rhodes, speaking to getting “dedicated, smart people involved.”

Following on the recent investment, CellCipher aims to raise a $5 million seed round to move into a commercial labs space and take on initial customer contracts. In parallel, it will continue building out its internal biobank of cells from diverse individuals to set them up for population-scale studies as part of its precision medicine component.

// About the George Shultz Innovation Fund

Managed by the Polsky Center, the George Shultz Innovation Fund provides up to $250,000 in co-investment funding for early-stage tech ventures coming out of University of Chicago, Argonne National Laboratory, Fermilab, and the Marine Biological Laboratory. Learn more here. 

Article by Melissa Fassbender, senior associate director of external relations and science communications at the Polsky Center. Melissa is a former journalist and has held the role of editor at various global publications in the drug development, clinical trials, and design engineering space. Reach Melissa via email or on Twitter at @melfass.

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