TB-001 is a biologic designed to intervene across the key biochemical axes linking the gut microbiome to chemoresistance in colorectal cancer. Fusobacterium nucleatum-induced immune shielding of the tumor microenvironment is the primary target. GI mucositis is a secondary indication. A defined, scalable therapeutic with a systems biology foundation.
TB-001 is a defined biologic built from microbial biology, designed to intervene across multiple axes simultaneously. Scalable. Not dependent on live organisms.
Chemoresistance in colorectal cancer is a multi-pathway failure involving the tumor microenvironment, immune evasion, and microbial biology. Our approach maps these convergence points and intervenes strategically.
TB-001 targets F. nucleatum-induced chemoresistance in colorectal cancer as its primary indication. GI mucositis, a dose-limiting toxicity in irinotecan and 5-FU regimens, is a secondary indication. Focused. Addressable. Unmet.
| Program | Target / mechanism | Stage |
|---|---|---|
| TB-001 Primary: F. nucleatum-induced chemoresistance · Colorectal cancer Secondary: GI mucositis · Irinotecan & 5-FU | Multi-axis biologic: β-glucuronidase modulation, butyrate/HDAC, AhR/IL-22, PXR/IPA, FXR/TGR5 via UDCA | Pre-clinical |
| Microbiome Map Systems biology model · CRC microbiome-immune axis | Mechanistic network model of the gut-tumor immune axis in colorectal cancer — target identification and biomarker discovery platform | Discovery |
Each axis in TB-001 addresses a distinct biological node in the gut-tumor immune network. These mechanisms are exploratory and under active investigation. Together they form the basis for TB-001's activity across both primary and secondary indications.
Bacterial β-glucuronidase in the gut lumen reconverts SN-38-glucuronide back to the active, toxic SN-38, the primary driver of irinotecan-induced intestinal damage. TB-001 modulates this enzyme activity to reduce luminal SN-38 exposure and downstream epithelial injury.
Indole-3-propionic acid, a tryptophan-derived microbiome metabolite, activates the pregnane X receptor (PXR) to upregulate tight junction proteins and suppress pro-inflammatory NF-κB signaling. A critical barrier restoration signal disrupted under cytotoxic chemotherapy.
Indole metabolites activate the aryl hydrocarbon receptor (AhR), driving IL-22 production from innate lymphoid cells. IL-22 is a master regulator of intestinal epithelial regeneration and antimicrobial peptide production, both critically depleted during mucositis.
Short-chain fatty acid butyrate inhibits histone deacetylases (HDACs), promoting colonocyte survival, mucosal Treg differentiation, and IgA class switching. Simultaneous GPR41/43 signaling reinforces barrier function and mucosal immune balance disrupted by chemotherapy.
Ursodeoxycholic acid (UDCA) activates both FXR and TGR5 receptors, modulating bile acid composition, reducing intestinal inflammation, and supporting colonocyte survival. Bile acid dysregulation is a documented consequence of chemotherapy-induced microbiome disruption.
Chemotherapy drives mucosal immune dysregulation, depleting regulatory T cells and secretory IgA at the intestinal surface. TB-001's SCFA and butyrate components work in concert to restore Treg populations and support IgA production, preventing secondary immune-mediated barrier damage.
Fecal microbiota transplant introduces undefined microbial communities with variable composition, donor-dependent safety risks, and significant regulatory barriers. TB-001 is a defined biologic that eliminates the risk of pathogen transfer and the need for cold chain.
Probiotics rely on viable organism colonization in an intestinal environment actively destroyed by chemotherapy. TB-001 delivers the downstream effector metabolites directly, bypassing the need for engraftment and operating effectively even in a disrupted gut ecosystem.
Current standard of care for GI mucositis is reactive: dose modification, antidiarrheal agents, supportive hydration. None prevent mucosal damage. TB-001 is designed for co-administration with chemotherapy, an upstream intervention that addresses sid effects proactively.