WHEN “IT WORKS IN CELLS” ISN’T ENOUGH
How Sitryx found confidence in a complex tissue
AT A GLANCE
Sitryx had a promising compound for a novel target in asthma. Cell assays said it worked. But would it get past the mucus barrier, reach the right cells in the lung, and engage the target where it actually matters?
Advancing without proof would have been a multimillion-dollar gamble.
CETSA® delivered the evidence that turned uncertainty into a confident go/no-go decision.
The Challenge: Prove target engagement in lung tissue
The Stakes: Go/no-go decision on inhaled delivery route
The Solution: CETSA® measured genuine binding in real tissue
The Outcome: Clear evidence = confident progression
THE ROADBLOCK
You know the feeling. Your compound is working beautifully in every controlled assay. The chemistry is solid. The cell data looks great. Your team is excited.
And then someone asks the question you’ve been dreading:“But does it actually work in tissue?” .
Jon Ellery, Director of Biology at Sitryx, and his team were working on a novel target in asthma, with little precedent and almost no tools. Enzyme assays and cell models suggested the compound engaged the target… but that’s not enough when the next step is a costly decision whether to move ahead or pivot away.
Listen to Jon talk about the project HERE
Confidence is built in vitro, but it’s not confirmed,” Ellery explains. “In complex systems like tissues, you’re often only inferring what’s really happening.
The Sitryx team needed a clear view of how their drug would function in real life.
Could it penetrate the mucus barrier? Would it actually engage the target in therapeutically relevant lung cells? Or would they only discover the truth after burning through budget, timeline, and investor confidence?
Decisions demand evidence, not inference. And Ellery knew one thing for sure: Assumptions are expensive. Proof is cheaper.
REPLACING INFERENCE WITH EVIDENCE
CETSA® does what traditional assays can’t: it measures direct, unmodified compound–target binding in the biological systems that actually matter – cells, tissue, lysates. No labels. No proxies. No guesswork.
The Pelago team worked with Sitryx to develop a protocol that translated from cellular systems to tissue.
First, they confirmed target binding in cells – a “fantastic thermal shift” as Ellery describes it – which gave them the confidence that the compound hit and stabilized the target. Then they applied the same method to lung tissue from animal models.
CETSA® revealed:
- Specific, on-target binding in lung tissue
- Penetration past the mucus barrier into therapeutically relevant cells
- Quantifiable engagement (~100% target occupancy at peak dose)
- Reversible, time-dependent kinetics aligned with expected behaviour
This was a go/no-go decision point for the project,” Ellery says. “CETSA®resolved the question mark of whether the compound could get through the mucus barrier and into the cells of importance.
CONFIDENT DECISION-MAKING
If the data had gone the other way then Sitryx would have pivoted their research focus, saving time, money, and scientific credibility. Either outcome was valuable – what mattered was knowing.
It was crucial to have the confidence that our compound engaged its target in a complex system to avoid costly late-stage failures, says Ellery.
Jon Ellery is an expert in analytical pharmacology, translational research, and early-stage drug development. With experience at Takeda, Cancer Research UK, and Sitryx, he specializes in optimizing small molecule drug discovery strategies to enhance clinical success.
CETSA® provided far more than just a dataset. It gave the Sitryx leadership decision-ready,
defensible evidence – the kind they could take to the board without caveats or crossed fingers.
KEY OUTCOMES
Early clarity – no downstream surprises
Validated route of administration
Decision-ready data for leadership
Reduced risk for investors and stakeholders
STOP GUESSING. START KNOWING.
Decisions this big deserve data this good. CETSA® gives you direct, biologically relevant proof of target engagement in the systems that actually matter.
Make the call with confidence – not crossed fingers. Explore what certainty looks like for others, or chat to our team to see how CETSA® could provide the clarity you need.
Want to learn more?
Watch our webinar to hear Jon Ellery talk in more detail about the project.
