INBRX-101 Shows Favorable Safety Profile in Patients with Alpha-1 Antitrypsin Deficiency and Demonstrates Potential to Achieve Normal Functional Alpha-1 Antitrypsin Levels with Monthly Dosing

Inhibrx Inc. announced topline results from a Phase 1 clinical trial evaluating the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of INBRX-101, an optimized recombinant human AAT-Fc fusion protein, in patients with alpha-1 antitrypsin deficiency (AATD). Data from this multi-country Phase 1 study are from 31 patients with AATD: 26 with the ZZ genotype, 3 with the SZ genotype and 2 with the MZ genotype of the SERPINA1 gene, the underlying cause of AATD. Treatment was well tolerated with no severe or serious adverse events related to the study drug.

Drug-related adverse events were predominantly mild and those few that were moderate in severity were all transient and reversible, with minimal or no symptomatic care. No safety-related or PK/PD-related signs of neutralizing anti-drug antibodies were observed. Dose-related increases in maximal and total INBRX-101 exposure occurred across the entirety of the single and multiple ascending dose ranges.

Data from the multiple ascending dose cohorts of INBRX-101 at 40, 80 and 120 mg/kg IV every three weeks showed the expected accumulation of functional AAT levels. Based on PK modeling, accumulation is expected to continue following subsequent doses and reach a steady-state after a total of approximately five to six consecutive doses, administered every three weeks. The current standard of care, plasma-derived AAT, dosed once weekly at 60 mg/kg, achieves a Cavg of functional AAT of 17.8 µM over the weekly dosing interval as calculated from steady-state area under the curve ("AUC") values reported in Stocks et al.

BMC Clinical Pharmacology 2010, 10:13. INBRX-101 achieved a mean Cavg of functional AAT of 40.4 µM over the 21-day dosing interval following the third 80 mg/kg dose. To date, bronchoalveolar lavage fluid samples have been processed from two 80 mg/kg multiple ascending dose cohort individuals and confirm the presence of INBRX-101 in the lung fluid.

Additionally, functional AAT levels were measured in plasma samples from 65 normal MM genotype individuals. This analysis revealed the 5th and 95th percentiles of functional AAT levels in the normal MM genotype individuals were 23 and 57 µM, respectively, with a median of 38 µM.