1. The core problem: proteolysis, polarity, and the “500-Dalton rule”
Classic GLP-1 agonists (semaglutide, tirzepatide) are ~4 kDa peptides. Swallow them and gastric/brush-border proteases shred the amide backbone long before portal-vein absorption; any fragments that survive still face a passive-diffusion ceiling of ≈500 Da. Oral bioavailability of unprotected GLP-1 analogs is typically < 0.5 %.
2. Marsland’s workaround: sub-lingual, not enteric
- Administration site: wafer dissolves against 100–200 µm ventral-tongue epithelium, an environment with minimal peptidase activity and rapid systemic access.
- Cargo selection: delivers an endogenous secretagogue tripeptide (MW ≈ 390 Da) plus a permeation enhancer—both below the 500-Da cut-off, enabling paracellular slip.
- Formulation science: trehalose (stabilizer) + GRAS bile-salt derivative (1.8 % w/w) boost flux 5.2-fold across porcine sublingual tissue in Franz-cell assays, consistent with recent nanoliposomal GLP-1 work showing 10–13 % transmucosal efficiency.
3. Early human signal vs. benchmark injectables (90-day interim)
- Mean body-weight change
- Mean A1C change (T2DM subset)
- Nausea / vomiting incidence
- Treatment discontinuation
Take-home: while peak efficacy still favors high-dose oral small-molecule GLP-1s, Triglutide’s tolerability and adherence profile already surpasses most injectable and oral comparators.
4. Manufacturing physics — why Rochester matters
- Bioreactor yield: Pichia pastoris fermentation hits ~2.4 g L⁻¹ after 48 h; downstream cation-exchange + lyophilization give a 38 % overall recovery.
- Cost of goods: $0.44 ± 0.05 per 2 mg wafer; ambient shipping adds $0.03, versus $1.12 cold-chain logistics for a semaglutide pen.
- Facility location: Building 319, Eastman Business Park (Rochester, NY)—a $20 M GMP retrofit completing Q3 2025.
5. Risk register still in play
- Regulatory pathway: August FDA workshop will decide 505(b)(2) vs. full NDA.
- Durability: need ≥12-month data to rule out receptor desensitization.
- Capacity cliff: second 10 m³ fermenter slated for summer 2026 to move beyond 4 M doses/month.
Why the science matters for the spreadsheet
- Lower molecular weight → higher mucosal flux → smaller dose → cheaper COGs.
- Ambient wafer → retail pharmacy & mail-order → broader commercial reach.
- U.S. bioprocessing → de-risked supply under new federal incentives.
If next-spring readouts keep efficacy within 25–30 % of injectables, Marsland’s platform could under-price incumbents by an order of magnitude while preserving margins solid enough to entice payers, employers, and strategic partners eyeing Rochester’s stainless forest.
Rigour isn’t a headline; it’s the moat.