TL1A ImmunoPET
Ga-68–NOTA–Fab TL1A Tracer for IBD
Overview
Response to biologics in IBD is heterogeneous; no pathway-specific imaging exists to select TL1A-high patients or directly measure target engagement for anti-TL1A drugs. Major deals: Merck–Prometheus ($10.8B) and Roche–Telavant ($7.1B) signal massive interest in the TL1A pathway.
Unmet Medical Need
Need for pathway-specific imaging to: (i) enrich trials for 'TL1A-high' patients most likely to benefit, and (ii) demonstrate target engagement by showing post-dose blocking of tracer binding.
Therapeutic Hypothesis
Same-day immunoPET tracer using human Fab vs TL1A, conjugated with p-SCN-Bn-NOTA and labeled with Ga-68. Fab format enables rapid clearance and high contrast within hours. Use baseline vs blocked scans and post-therapy scans to measure expression and occupancy.
Computational Work Performed
- AF-Multimer-class complex modeling of TL1A trimer with 12 Fab clones
- PRODIGY contact-based ΔG/KD prediction on top-ranked complexes
- Aggrescan3D hotspot mapping for developability
- Conjugation modeling: solvent-accessible Lys SASA analysis
- 3 leads identified: Fab07, Fab09, Fab03 with predicted sub- to low-nM affinity
Next Milestones (Success Criteria)
- 1≥2 Fabs with KD ≤10 nM by SPR/BLI and ≥50% DR3-Fc competition
- 2NOTA-Fab with DAR 1-2, IRF ≥70% (Lindmo-type)
- 3RCP ≥95% for [⁶⁸Ga] product per USP <823>
- 4DSS colitis PET: colon TBR ≥1.5 and ≥50% blockade
Competitive Landscape
Anti-TL1A mAbs in Ph2/3 (RVT-3101, afimkibart)—no disclosed clinical TL1A imaging agent. Active development of fragment-based and nanobody tracers for same-day imaging in other indications.
Key Differentiation
- First-in-class TL1A immunoPET CDx
- Directly supports multi-billion-dollar anti-TL1A programs
- Same-day imaging: Fab + Ga-68 enables within-hours readouts
- Direct PD readout: baseline/post-dose scans deliver occupancy data
Interested in This Asset?
Contact our licensing team to discuss partnership opportunities, access detailed data packages, and explore collaboration terms.