“Creativity is intelligence having fun”

– Albert Einstein

Our novel technology and unique culture allow us to discover and develop transformative therapeutics

Amunix aims to mitigate the toxicity of T cell engagers (TCEs) and cytokine therapies by creating drugs that are preferentially activated in the tumor microenvironment, thus driving tumor cell killing while minimizing on-target, off-tumor toxicity that can damage healthy tissues and/or cause CRS. 

Pro-XTEN

Protease-Releasable Masking Technology Designed to Safety Harness the Power of Potent Immune Modulators Through Preferential Activation in the Tumor Microenvironment by Tumor-Associated Proteases
Amunix Pro_XTEN illustration

Our Pro-XTEN technology exploits the intrinsically high protease activity of the tumor microenvironment to preferentially unmask and activate our product candidates in the tumor as compared to healthy tissues, thereby mitigating off-tumor toxicity. Importantly, we already have clinical validation of the key properties of our technology, including half-life extension, masking, protease-driven unmasking, and low immunogenicity, as over 200 patients have been treated with product candidates developed by partners who have licensed our technology outside of oncology.  We are now using this validated technology in a new way to create our proprietary oncology pipeline.

The two proprietary components of this technology are as follows:

  1. Universal, Tunable XTEN® Mask. Our XTEN mask is a polypeptide that serves a dual purpose: 1) it acts as a universal, tunable mask, and 2) it provides half-life extension, which we believe can enable more convenient dosing for patients. Our XTEN masks drive a next generation masking strategy that can be applied universally to a broad array of protein therapeutic modalities. In contrast to first-generation masks, our novel XTEN masks do not require customized and specific binding to a functional region of the drug, instead acting as spatial shields that occupy space around a functional region. This mechanism of spatial shielding allows XTEN masks to be universally applicable regardless of the sequence or characteristics of the protein being masked. The strength of the masking can be fine-tuned by adjusting the length, number, and position of XTEN masks on a protein.
  2. Protease-Cleavable Linker. Our protease-cleavable linker enables preferential unmasking and drug activation in the tumor microenvironment. We designed it to be universally cleaved across tumor types to drive efficacy, yet remain largely intact in systemic circulation and in healthy tissues to enable safety.

T Cell Engagers: XPATs

TCEs Activate T Cells, Driving Direct Tumor Cell Death and Initiating a Cytokine Amplification Cascade That Promotes Further Killing and Potential Long-Term Immunity
Immunotherapy illustration

Our Solution to TCE Toxicity: XPATs, XTENylated Protease-Activated T Cell Engagers
Amunix XPAT illustration

XPATs are designed to exploit the dysregulated protease activity in tumors to enable preferential activation in tumors as compared to healthy tissues. Our XPATs are designed to expand the therapeutic index through three mechanisms:

  • Masking of both TAA and CD3 targeting domains. As compared to unmasked or singly masked domains, masking of both domains significantly reduces the T cell-mediated cytotoxicity in vitro and improves the tolerability in vivo
  • Preferential unmasking and activation in the tumor microenvironment. Our proprietary protease-cleavable linker has been preclinically validated to be cleaved in tumor tissues, yet remain largely intact in circulation and healthy tissues
  • Rapid elimination of the unmasked, activated TCE. Our XPATs have long half-lives in circulation due to the half-life extension properties of XTEN, but the active forms lacking XTEN masks are rapidly cleared, thus minimizing potential toxicity arising from any low rate of unmasking in systemic circulation or healthy tissue

Cytokines: XPACs

Like T cell engagers, cytokines are extremely potent, yet their clinical utility has been hampered by dose limiting toxicity.  Cytokines are therefore well suited to masking with our Pro-XTEN technology to create XTENylated Protease-Activated Cytokines, or XPACs, which are preferentially activated in the tumor microenvironment. In addition to monotherapy use, XPACs can potentially be combined with our XPATs and other modalities, such as checkpoint inhibitors, to drive the immune system to kill tumors.

Our most advanced cytokine program is focused on IL-12.