AMX-818, an HER2-targeted T cell engager (TCE), is the lead program in Amunix’s XPAT® (XTENylated Protease-Activated TCE) platform designed to improve the therapeutic index of TCEs for the treatment of patients with solid tumors.

The collective preclinical data indicate that AMX-818 is effective in driving anti-tumor responses, yet has significantly lower toxicity than its unmasked HER2 TCE counterpart. This profile is enabled by proprietary protease-releasable masking technology that is preferentially cleaved off in the tumor microenvironment to yield active drug.

Amunix expects to file a Clinical Trial Application (CTA) for AMX-818 by the end of 2021.

SOUTH SAN FRANCISCO, CA, USAI October 07, 2021 I Amunix Pharmaceuticals, Inc. (Amunix), an immuno-oncology company leveraging its proprietary, clinically validated Pro-XTEN technology platform to discover and develop transformative T cell engagers and cytokine therapies for patients suffering from cancer, today announced that preclinical data from its lead program, AMX-818 (HER2-XPAT), were presented at the AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics. The collective data indicate that AMX-818 is effective in driving anti-tumor responses, yet has significantly lower toxicity than its unmasked HER2 TCE counterpart. AMX-818 is largely stable in plasma and healthy tissue, yet efficiently cleaved to yield an active TCE in the tumor microenvironment. Amunix expects to file a CTA for AMX-818 by the end of 2021.

“These data show the promise of our Pro-XTEN protease-cleavable masking technology and showcase the work we did to select our preferred protease-cleavable linker, which indicates significant stability in circulation and healthy tissues, and efficient cleavage in tumors,” said Angie You, Ph.D., Chief Executive Officer of Amunix. “We are excited about the potential of this technology to improve the therapeutic indices for both T cell engagers and cytokines, and we are building a pipeline using this modular, plug and play technology.”

In the established HER2-high BT-474 and HER2-low HT-55 xenograft models, AMX-818 induced protease-cleavable linker-dependent tumor regressions comparable to its unmasked TCE counterpart. Preferential cleavage of AMX-818 was demonstrated in patient-derived xenograft tumors (across seven tumor types) relative to healthy organs, with an average of 24% of the XPAT in tumors cleaved to the fully unmasked TCE form.

In non-human primates, AMX-818 demonstrated a wide safety margin, achieving a >400-fold higher Cmax at its maximum tolerated dose of 42 mg/kg relative to that achieved with its unmasked HER2 TCE counterpart. Only 1-3% of singly-cleaved XPAT metabolites were detected in plasma from NHPs treated with high doses of AMX-818 (25 and 42 mg/kg), while the fully unmasked TCE form was undetectable at <0.1% of total masked species.

In vitro studies in which AMX-818 was incubated for seven days at 37oC (conditions which over-represent the potential accumulation of metabolites in vivo) in plasma from healthy and diseased NHPs and humans indicate[s] that AMX-818 is stable in plasma. There is a similar and low amount of fully unmasked TCE form generated between species. The similar rates of cleavage between species, and the strong safety margin observed with AMX-818 in NHPs, suggest limited risk of significant systemic accumulation of active, unmasked HER2 TCE in cancer patients.

Poster Presentation Details
Title: AMX-818, a Protease-Activated T Cell Engager Targeting HER2 with Potent T Cell Activation, Proteolytic Cleavage and Efficacy in Xenograft Tumors, and Wide Safety Margins in Non-Human Primates
Poster Number: P193

A copy of the poster is available here.

About Amunix’s Platform
Amunix is leveraging its proprietary Pro-XTEN technology platform to create potent immune modulator drugs that are preferentially activated in the high protease milieu of the tumor microenvironment to drive tumor cell killing while minimizing toxicity elsewhere in the body. The technology comprises two proprietary components: 1) a universal, tunable mask, which is an unstructured polypeptide (XTEN®) clinically validated to have low immunogenicity, that functions via steric hindrance and confers half-life extension, and 2) a protease-cleavable linker that enables release of the mask and hence drug activation, by tumor-associated proteases. Amunix’s proprietary molecules are called XTENylated Protease-Activated T cell engagers (XPATs®) and XTENylated Protease-Activated Cytokines (XPACs™).

About Amunix Pharmaceuticals
Amunix Pharmaceuticals, based in South San Francisco, CA, is focused on developing masked T cell engagers and cytokines to bring the promise of these potent immune-activating biotherapeutics to patients with solid tumor cancers. The company is leveraging its proprietary XPAT® and XPAC™ platforms to advance a pipeline of novel drugs that are preferentially activated in the tumor microenvironment and designed to overcome toxicity challenges that have hindered other T cell and cytokine therapies. Amunix’s proprietary masking technology has been clinically validated to extend drug half-life with limited immunogenicity. The company’s initial product candidate is AMX-818, an XPAT® T cell engager targeting a variety of HER2-expressing solid tumors, which is currently in IND-enabling studies. Along with several other T cell engager programs, Amunix is also applying its proprietary masking technology to its first masked, protease-activated cytokine program, IL12-XPAC™, which is in lead optimization.

For additional information about the company, please visit

SOURCE: Amunix Pharmaceuticals