Inhibrx’s

Proprietary sdAb Platform

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With the goal of addressing unmet medical needs, we leverage our deep understanding of target biology and innovative protein engineering technologies to create therapeutic candidates with attributes and mechanisms of action that we believe are superior to current approaches and applicable to a range of challenging, validated targets with high potential.

Our proprietary sdAb platform allows us to address complex target biology where other biologic approaches have failed or are suboptimal. Our precision engineering enables the generation of therapeutic candidates with defined valencies and specificities, which we believe can result in optimal mechanisms of action. Initially, we’ve focused on applying these technologies to targets with clinically validated mechanistic rationales—but where prior approaches have lacked sufficient therapeutic activity or safety.

Our clinical pipeline is enabled by our protein and process engineering capabilities, and includes therapeutic candidates in the following categories:

  • INBRX-109 and INBRX-106 utilize our multivalent formats, for which the precise valency was optimized in a target-centric way to mediate appropriate agonist function;
  • The dual mechanism of action of INBRX-105 is enabled by a multi-specific format that combines potent blockade and conditional agonism; and
  • With INBRX-101, we’re seeking to maintain the natural function of AAT in a recombinant format, optimized for less frequent dosing and greater potential therapeutic activity as compared to pdAAT.

Our Platform Is Designed To Be:

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Versatile

Our formats enable validated complex target biology to be exploited.

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Highly Developable

Using standard manufacturing processes.

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Precisely Engineered

Smaller than conventional antibodies.

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Multivalent

Precise valency selection engineered to specific target biology.

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Multispecific

Our formats are engineered for optimal synergistic or co-dependent functionalities.

The Challenge

Conventional Antibodies & Their Limitations

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Antibodies are multifunctional, Y-shaped proteins, made up of a pair of interacting heavy and light chains to form a symmetric, dimeric molecule with four total protein chains. Each arm of the antibody contains an antigen-binding region (also referred to as the variable fragment, or Fv), which consists of both a heavy and light variable domain, or VH and VL, respectively, held together through interaction of constant domains.

The Fc portion of the heavy-chain constant domain extends the half-life of the antibody in circulation and has the potential to modulate the function of immune cells through interaction with various Fc receptors found on the surface of cells of the immune system.

Antibody Fv domains aren’t optimal building blocks for multispecific and multivalent therapeutics, due to the extensive protein engineering required to ensure the correct pairing of the appropriate VH and VL domains to construct functional Fvs.

One common approach used to achieve correct pairing is the production of single-chain variable fragments, or scFvs, which are generated by combining the VH and VL domain antigen-binding domains using a flexible linker. Despite the addition of this linker, VH or VL sequences within an scFv have the propensity to errantly pair with a neighboring scFv, and can lead to disruption of proper Fv formation or aggregation. This issue can be exacerbated in constructs that contain multiple scFvs, with each entity requiring significant up-front optimization. These formatting challenges may restrict broad applicability of this technology.

Conventional vs. sdAb Structure

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Our Solution

A Flexible & Versatile Platform

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To address these limitations, we’ve developed our sdAb platform to enable the streamlined production of protein formats with multiple antigen specificities. sdAbs are conceptually similar to the VH domain of a conventional antibody but neither contain nor require a paired VL domain, as shown in the “Conventional vs. sdAb Structure” graphic above.

Denoted as heavy-chain-only antibodies, sdAbs are half the molecular weight of an ScFv, but maintain specific target binding with an affinity range that is comparable to those achieved by conventional antibodies.

sdAbs are derived from heavy-chain-only antibodies that are naturally produced by animals in the camelid family, which includes camels, alpacas, and llamas. Unlike the antibody systems of other mammals, a subset of the camelid antibody repertoire is composed of heavy-chain-only antibodies that can be miniaturized into sdAbs. Modular in nature, they can be linked to a constant domain to capture half-life extending and immune cell modulating function.

We believe that the small size of sdAbs, along with their stable nature and simple structure, make them ideal building blocks to construct novel biologics with multiple specificities and functions.

Precisely Engineered Modular Formats

Our Multivalent formats

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Our Multispecific formats

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Pipeline of Therapeutic Candidates

Inbrx 109

INBRX-109

Our Tetravalent DR5 Agonist

INBRX-109, our most advanced program, is a precisely engineered tetravalent sdAb-based therapeutic candidate that agonizes DR5 to induce tumor selective programmed cell death.

Learn more clinicaltrials.gov
Inbrx 106

INBRX-106

Our Hexavalent OX40 Agonist

INBRX-106 is a hexavalent sdAb-based therapeutic candidate targeting OX40 that provides co-stimulation that promotes T-cell expansion, enhanced effector function and memory cell formation, and prevents activation-induced cell death.

Learn more clinicaltrials.gov
Inbrx 105

INBRX-105

Our PD-L1 x 4-1BB Tetravalent Conditional Agonist

INBRX-105 is a tetravalent sdAb-based therapeutic candidate that acts both as an antagonist of PD-L1 and a conditional agonist of 4-1BB.

Learn more clinicaltrials.gov
Inbrx 101

INBRX-101

Our Recombinant Alpha-1 Anti- trypsin Fc-Fusion Protein (AAT-Fc)

INBRX-101 is a recombinant human AAT-Fc fusion protein therapeutic candidate currently being evaluated for the treatment of AATD. We believe this therapeutic candidate supports a dosing schedule of every three weeks to achieve continuous normal AAT serum concentrations, a significant improvement from patients’ current regimen.

Learn more clinicaltrials.gov