Inhibrx Announces Dosing of First Patient in Phase 1 Dose-Escalation Study of INBRX-105

Inhibrx announced dosing has begun in a Phase 1 dose-escalation clinical trial of INBRX-105. INBRX-105 is a novel, multispecific antibody therapeutic candidate that is both an antagonist of PD-L1 and a conditional agonist of 4-1BB in development for the treatment of PD-L1 expressing tumors, including those that are resistant to approved checkpoint inhibitor therapies. The clinical trial aims to determine the safety profile of INBRX-105 in humans, as well as the recommended therapeutic dose level for future clinical development.

"INBRX-105 was designed to achieve a mechanistic concept we have termed 'checkpoint inversion', wherein the therapeutic candidate acts as an adaptor to convert a PD-L1-mediated immune-suppressive signal into an immune-stimulatory response through localized 4-1BB agonism," said Brendan Eckelman, Chief Scientific Officer and EVP, Corporate Strategy of Inhibrx.

"We are excited to advance INBRX-105 into clinical development, as we believe this therapeutic candidate has the potential to provide a benefit to patients beyond checkpoint inhibition alone, including those refractory or relapsed from approved checkpoint inhibitors," said Mark Lappe, Chief Executive Officer of Inhibrx.

INBRX-105 is a tetravalent bispecific antibody that was developed using the Inhibrx sdAb platform. It is comprised of four binding domains, two targeting PD-L1 and two targeting 4-1BB, yet is about one-third smaller in size than a conventional bivalent antibody. The number and positioning of the binding domains within INBRX-105 were designed to allow for potent and sustained PD-L1 blockade, as well as robust and conditional 4-1BB agonism in the presence of PD-L1, a target enriched in the tumor microenvironment and associated lymphoid tissues.

Inhibrx utilizes diverse methods of protein engineering in the construction of therapeutic candidates that can address the specific requirements of complex target and disease biology. A tool for this effort is the Inhibrx proprietary sdAb platform, which enables the development of therapeutic candidates with attributes superior to other monoclonal antibody and fusion protein approaches. This platform enables the construction of molecules that contain multiple binding units with defined valency or multiple specificities. These novel antibodies can be combined to create therapeutic candidates with the potential to achieve enhanced cell signaling or conditional activation. Importantly, these optimized, multi-functional entities can be manufactured using the established processes that are common in the production of therapeutic proteins.

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