INBRX-101: Recombinant AAT-Fc Fusion Protein
- Alpha-1 antitrypsin (AAT) deficiency is a genetically defined rare respiratory disease characterized by the progressive destruction of lung tissue leading to emphysema
- The standard of care, augmentation with human derived AAT, has remained unchanged for decades
- AAT deficiency is characterized by low AAT levels in the blood due to mutations in the AAT gene, mostly commonly AAT-Z, that lead to misfolding, impaired secretion and reduced inhibitory function of AAT
INBRX-101 is a recombinantly produced AAT replacement protein specifically designed to address the limitations of plasma derived AAT replacement therapy. The modifications introduced into INBRX-101 aim to improve the pharmacokinetic profile (PK) and neutrophil elastase inhibitory function. This could offer superior clinical activity to the current commercial plasma derived AAT by providing sustained enhanced serum concentration with a less frequent, monthly dosing regimen.
Patients with an AAT deficiency are currently treated with weekly infusions of AAT derived from human donor plasma. Due to the short half-life of these plasma derived products, the AAT concentrations often drop below the normal range by day 3 or 4, leaving patients at risk for lung destruction. The current market is over $1B annually, with 80% of sales in the U.S. and Canada.
Efforts to develop small molecule chaperone correctors of misfolded AAT-Z protein or gene therapy replacement of functional AAT face significant challenges due to the impaired inhibitory function of AAT-Z and the massive amount of AAT protein that is normally present in unaffected individuals that is required for effective protection against neutrophil elastase.
The Phase 1 study for INBRX-101 is enrolling and preliminary functional pharmacokinetic (PK) data from the single dose escalation portion of this trial is expected to be announced in the first half of 2020.