Orforglipron
The oral GLP-1 weight-loss candidate — two chiral indole fragments, capacity prepared ahead of launch
Orforglipron — project profile
- Therapeutic area
- Metabolic (obesity / type 2 diabetes)
- Mechanism
- Oral small-molecule GLP-1 receptor agonist (non-peptide)
- Commercial status
- Phase 3 positive · NDA submitted to FDA (under review)
- Originator
- Eli Lilly and Company
Why this project, right now
Only publicly disclosed facts: regulatory approvals, clinical data, supply-chain moves
- ✓Lilly reported ATTAIN-1 results in August 2025: at week 72 the highest dose (36 mg once daily) delivered mean weight loss of 12.4% (27.3 lb). ATTAIN-2, in people with type 2 diabetes, showed 10.5% mean weight loss and a 1.8% mean HbA1c reduction.
- ✓In December 2025 Lilly announced it had submitted the obesity NDA to the FDA — the programme shifts from clinical to commercial, and that transition is exactly when supply chains are built.
- ✓Being a non-peptide oral small molecule, it does not depend on solid-phase peptide synthesis or cold-chain injection pens. Cost structure is therefore highly sensitive to intermediate pricing — which is where China-based fragments win most directly.
- ✓The molecule carries an (S)-2,2-dimethyltetrahydropyran side chain and an oxadiazolone-substituted chiral cyclopropane: both fragments are chiral, with a clearly defined process barrier.
Public regulatory and clinical milestones
| Date | Event |
|---|---|
| 2025-08-07 | ATTAIN-1 Phase 3 meets primary endpoint: 12.4% mean weight loss at 72 weeks |
| 2025-08-26 | ATTAIN-2 positive in type 2 diabetes: 10.5% weight loss, 1.8% HbA1c reduction |
| 2025-12-18 | Lilly announces FDA submission of the obesity NDA |
Key intermediate list
2 key intermediates
| CAS No. | Chemical name | Fragment role | Action |
|---|---|---|---|
| 2212021-79-7 | (S)-5-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-N-methyl-N-phenyl-1H-indole-2-carboxamide | Indole-2-carboxamide fragment bearing the (S)-2,2-dimethyltetrahydro-2H-pyran chiral side chain Process note：Construction and ee control of the chiral side chain dominate cost | |
| 2212021-83-3 | 5-[(S)-2,2-Dimethyltetrahydro-2H-pyran-4-yl]-1-[(1S,2S)-2-methyl-1-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)cyclopropyl]-1H-indole-2-carboxylic Acid | Indole-2-carboxylic acid core fragment with the oxadiazolone-substituted chiral cyclopropane Process note：Two contiguous stereocentres plus an oxadiazolone ring — cyclopropane construction and ring stability are the focus |
How we support this project
Both fragments developed on one line and available as a package — from gram-scale route validation through kilogram-scale scale-up
Chiral methods (ee / diastereomers) and genotoxic-impurity assessment delivered to ICH conventions
Registration packages prepared for your target market: starting-material justification, process description, impurity limit rationale
Common capabilitiesThe same delivery capability backs every campaign project
- ✓Route design and process development: hands-on scale-up experience with fluorinated, chiral, boronate and heterocyclic fragments at partner plants
- ✓Scale continuity: gram-scale validation → hundred-gram → kilogram → commercial, without a route change
- ✓Analytics: chiral ee, related substances, residual solvents, elemental impurities and genotoxic-impurity assessment to ICH conventions
- ✓Registration support: DMF feasibility assessment, starting-material justification, stability study design
- ✓Confidentiality: customer projects run under NDA; no cross-disclosure between plants and end customers
Supply scope and compliance note
Most of the target drugs above are originator products still under patent. The intermediates listed here are supplied for research use, and for markets where the patent has expired or a valid licence is in place. The buyer is responsible for confirming patent status and registration requirements in the target market and for the resulting compliance obligations. Third-party brand names and trademarks belong to their respective owners and are referenced here only as a technical cross-reference.
Intermediate lists (CAS and chemical names) are taken from the Division II 2026 Key Projects source sheet. Regulatory and clinical information comes from originator press releases and public FDA material. Fragment roles are neutral descriptions derived from the chemical structure and do not represent the originator patent route. Chinese drug names are common industry transliterations, not official registered names.
Data version 2026-09