The Candidate

Our recombinant human AAT-Fc fusion protein.

INBRX-101 is a precisely engineered recombinant human AAT-Fc fusion protein with the potential to:

Extend the dosing range from weekly to every three weeks, while maintaining patients in the normal range of AAT exposure.
Overcome challenges of maintaining the function of recombinant AAT, while manufacturing at commercial scale.
Is engineered to maximize the functional activity of AAT, particularly in the lungs.
Complements RNAi approaches, but addresses all AATD patients.

INBRX-101 vs. Current Therapy

Predicted mean serum AAT levels:

120 mg/kg of INBRX-101 Every 3 Weeks

The current state and standard of care for people with AATD is suboptimal. Receiving plasma-derived AAT with weekly infusions doesn’t maintain normal serum AAT levels. AAT has proven difficult to develop recombinantly, often displaying loss of activity and experiencing accelerated degradation.

We believe our novel approach has the potential to overcome these challenges. Fusion of AAT to the Fc region allows for production using a standard antibody expression system, which, when combined with our proprietary AAT-function preserving purification process, generates substantial and potentially scalable yields of active recombinant AAT protein.

We believe that this extended exposure supports the potential for dosing every three weeks while maintaining patients in the normal range of AAT exposure, which in turn would reduce the frequency of annual infusions, eliminate lung decline from Alpha-1 Disease, and could significantly improve patient quality of life.

INBRX-101 Clinical Trials

Data from the Phase 1 multiple ascending dose study of INBRX-101 at 40, 80 and 120 mg/kg IV every three weeks, showed the expected accumulation of functional AAT levels and the ability to achieve fully normal functional AAT levels in severely deficient AATD patients. Based on PK modeling, accumulation is expected to continue following subsequent doses and reach steady state after a total of approximately five to six consecutive doses, administered every three or four weeks.

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.

Inhibrx plans to initiate a Phase 2 potentially registration-enabling clinical trial using functional AAT as a surrogate endpoint with the intent to submit for regulatory approval under the FDA’s Accelerated Approval Program.

Additionally, we believe there is an opportunity for INBRX-101 to be used as a treatment for aGvHD. It has the potential for a more sustainable dosing schedule and could provide a superior safety benefit coupled with greater efficacy.

We plan to explore this opportunity in acute GvHD in a potentially registration-enabling trial to begin during the second half of 2023.

clinicaltrials.gov