R3*
Allosteric Modulation of Transglutaminase 2 to Treat Progressive Pulmonary Fibrosis
Prof. Ulf Simonsen, Aarhus University; Dr Gökay Albayrak, Aarhus University
Kitchen, Aarhus University (TechTransferOffice)
Challenge
Progressive Pulmonary Fibrosis (PPF) is a fatal fibrotic lung disease with poor prognosis and limited treatment options. Current standard-of-care therapies (nintedanib, pirfenidone) only slow disease progression and do not reverse fibrosis. Many PPF patients develop secondary pulmonary hypertension due to vascular dysfunction, leading to right heart failure and death. There is a critical unmet medical need for disease-modifying therapies addressing both fibrosis and vascular pathology.
Technology
We have developed first-in-class, reversible allosteric modulators of Transglutaminase 2 (TG2) that promote the closed conformation of the enzyme. Our ESTUS compounds inhibit pathological TG2 transamidase activity while preserving physiological function. Uniquely, they combine anti-fibrotic and vasoprotective effects, inducing vasorelaxation in small pulmonary arteries and preventing fibrosis. This dual mechanism differentiates our approach from irreversible TG2 inhibitors and current antifibrotic therapies.
Commercial Opportunity
- Orphan Drug Designation and potential for accelerated regulatory pathways
- Global PPF treatment market: ~USD 4.0B (2025) → ~USD 8.2B (2035), ~7.3% CAGR
- Pricing benchmark: ~USD 112k–113k per patient/year (current standards)
- Initial target markets: US (~188k) and EU (~191k) patients
- Partnering ask: investment + strategic collaborations to reach in vivo PoC and IND enabling
Development Status
The project is currently at TRL 3. In vitro and ex vivo PoC studies have demonstrated antifibrotic and vasorelaxant activity. A lead compound is close to selection. The next milestone is in vivo PoC and DMPK/toxicity studies.
Patent Situation
ESTUS compounds are protected under EP3833354B1, and a WIPO application is under process, covering TG2 modulators for medicinal use.
Further Reading
- Pinilla et al., Hypertension, 2021
- Engholm et al., British Journal of Pharmacology, 2016
- Marcon et al., Int J Environ Res Public Health, 2021
