Human intestinal epithelium, from real donors, for DMPK, tox and IBD. Where Caco-2 and animal data stop predicting, we start. Durham, NC. RepliGut®
Joined January 2025
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4,272 genes separate Caco-2 from primary human intestinal epithelium.
No goblet cells. No MUC2. CES1 where the human gut runs CES2.
Your permeability number is only as human as the cells that made it.
PROTACs break the standard permeability assay. Low Papp and poor recovery.
Next week at #ISSX2026 in SF, we're presenting PROTAC permeability in primary human jejunum epithelium. The trends follow in vivo oral absorption.
Come find us.
Happy Labor Day! Today we celebrate the dedication and hard work of professionals across every industry, especially those in the lab and office who push the boundaries of drug discovery every day. Enjoy a well-deserved break! 🛠️🔬 #LaborDay #AltisBiosystems #ScienceAtWork
We model human intestinal absorption using cells from a colon tumor. And then we're surprised when the data doesn't translate.
Caco-2 comes from a 1974 colorectal adenocarcinoma biopsy.
But most drug absorption happens in the small intestine — a completely different tissue.
Different cell types.
Different transporter expression.
Different mucus architecture.
This isn’t a small detail. It’s the biology.
To be fair, Caco-2 solved a real problem.
It gave the field a reproducible, standardized assay when nothing else existed.
That mattered.
But the field has moved.
Human intestinal stem cell technology now lets us the actual tissue — not a proxy.
Same cell types.
Same transporter expression.
Same architecture.
The original problem Caco-2 solved now has a biologically accurate answer.
We owe the next generation of drugs better than a 50-year-old cancer cell line.
#DrugDevelopment #NAMs #Toxicology #Pharma #InVitroModels
Add activated immune cells to a healthy human gut barrier and you can watch it start to fail in real time.
We’ve been running primary human epithelium alongside immune cells and tracking barrier integrity as the two interact. The breakdown isn’t subtle and it isn’t slow.
What’s more interesting is what comes next. Pull the immune pressure back and the epithelium tries to repair itself. That repair, the actual return of barrier function, is what mucosal healing means to a patient. Most assays never see it, because they were never built to look past a cytokine readout.
If you’re screening for barrier protection or repair, what are you measuring it against right now?
A look at what we’re seeing: hubs.ly/Q04sYVdT0
#IBD #Immunology #DrugDiscovery #MucosalImmunology
In the intestinal epithelium, position is function.
Stem cells at the base. A proliferative zone above them. Differentiated enterocytes and goblet cells along the axis.
The biology that drives IBD - barrier integrity, mucus production, epithelial turnover - lives in that organization.
That’s why RepliGut Crypt was built to preserve the spatial architecture that matters:
→ EdU+ proliferative cells anchored in defined zones
→ APL+ mature enterocytes forming functional barriers
→ MUC2+ goblet cells producing the mucus layer pathogens actually engage with
All from human stem cells. All accessible to high-content imaging, and reproducible screening at scale.
The next generation of IBD therapeutics demands models that recapitulate the right biology, not just the right cells.
#IBD #DrugDiscovery #Organoids #IntestinalModels #NAMs #PreclinicalResearch #GutBiology #InVitroModels
Incretin biology begins in the gut. Yet many therapies bypass it.
As oral GLP-1s and next-generation incretins reshape the field, understanding the human intestinal epithelium isn't just interesting, it's foundational.
#GLP1 #Incretin #DrugDiscovery
Caco-2 myth: "it's the gold standard for permeability."
Reality: it's one cancer cell line, from one donor, missing most of the cell diversity of a real gut.
Gold standard, or just the standard we got used to?
How we measure permeability in human-relevant tissue:
altisbiosystems.com/in-vitro…
Complex drug modalities are changing the pipeline. Permeability models need to keep up.
At #GRCDrugMetabolism today, Liz Boazak will present how Altis is advancing RepliGut Models for new modalities and complex mechanisms.
#DMPK #ADME #NAMs
9 out of 10 drugs that reach trials still fail. A lot of that failure is baked in at the preclinical bench, where a 40-year-old cancer cell line stands in for the human gut.
You cannot predict human biology with something that was never human.
We run this as a human, stem cell-derived DMPK study. Happy to walk a team through how it compares to what you're getting from Caco-2. Details here:
altisbiosystems.com/in-vitro…