Amunix Presents Preclinical Data at American Academy of Cancer Research (AACR) Annual Meeting from Lead Program AMX-818 Demonstrating Robust Efficacy in HER2 Tumor Models and Enhanced Safety
AMX-818 is the lead program in Amunix’s XPAT® (XTENylated Protease-Activated T cell engager) platform designed to improve the toxicity profile of T cell engagers for the treatment of HER2-expressing solid tumors
In vivo, preferential cleavage of AMX-818 was demonstrated in xenograft tumors relative to healthy organs (average % unmasked AMX-818 was 25.2% in tumors vs. 1.6% in combined other organs), corroborating the protease-cleavable mechanism of action
Amunix expects to file a Clinical Trial Application (CTA) for AMX-818 by the end of 2021
SOUTH SAN FRANCISCO, CA; April 12, 2021 – Amunix Pharmaceuticals, Inc. (“Amunix”), a biopharmaceutical company focused on developing masked, protease-activated immune-oncology therapeutics to bring the promise of these potent therapies to patients with solid tumor cancers, today announced data were presented from its lead program AMX-818 (HER2-XPAT), at the AACR Annual Meeting. The data demonstrate that AMX-818, a masked T cell engager (TCE) that targets HER2 expressing tumors, is preferentially activated, as designed, in the protease-rich tumor microenvironment leading to robust tumor regression in HER2 tumor models and in non-human primates (NHP) achieved concentrations approximately 450 times higher than the unmasked TCE without causing cytokine release syndrome (CRS) or systemic T cell activation characteristic of T cell engagers.
“These data demonstrate the potential of our Pro-XTEN protease-releasable masking technology applied to our XPAT platform that expands the utility and safety profile of T cell engagers,” said Angie You, Ph.D., chief executive officer of Amunix. “Notably, we observed substantial tumor regression with AMX-818 treatment in both HER2 high and HER2 low expressing tumors, with the latter being an area of significant unmet need with no approved HER2 therapies. We are progressing this program towards the clinic and look forward to bringing the potential of this drug to patients, in particular to those with tumor types where cancer immunotherapies have failed to date.”
Amunix expects to file a CTA for AMX-818 by the end of 2021.
The studies presented at AACR demonstrate the potential for a wide safety margin with 400-fold higher protection against in vitro cytotoxicity for AMX-818 relative to the unmasked version. A 450-fold higher maximum tolerated exposure compared to the unmasked version was observed in non-human primates (NHP) -- cytokine release was dose limiting in the unmasked version and not observed at doses up to 50mg/kg.
In vivo, preferential cleavage of AMX-818 was demonstrated in established HER2high BT-474 xenograft tumors relative to healthy organs (average % unmasked AMX-818 was 25.2% in tumors vs. 1.6% in combined other organs), corroborating the protease cleavable mechanism of action (MOA). Crucially, in contrast to the cleavage observed in tumors, stability studies have shown minimal cleavage to the unmasked version in plasma from healthy humans or cancer/inflammatory disease patients, similar to what is seen in NHP. Furthermore, in toxicology studies in NHP, peripheral stability of AMX-818 was demonstrated in extreme inflammatory conditions to further support the MOA of minimal cleavage in circulation. Finally, in vitro, normal human cardiomyocytes which express HER2 show no cytotoxicity to AMX-818 up to 1uM. Collectively, these data provide strong support for the MOA of peripheral stability with tumor specific cleavage and tumor cytotoxicity while sparing normal HER2 expressing cells.
In HER2low HT-55 xenograft models, AMX-818 induced protease-dependent tumor regressions that were comparable to the unmasked (active) TCE, but required higher doses. With the wide safety margins demonstrated in the preclinical models, AMX-818 has the potential to expand into HER2 lower expressing tumors.
Poster Presentation Details
Title: HER2-XPAT, A Novel Protease-Activated Prodrug T Cell Engager (TCE) With Potent T Cell Activation and Efficacy in Solid Tumor Models and Large Predicted Safety Margins in Non-Human Primates
Abstract Number: 1824
Session: Therapeutic Antibodies, Including Engineered Antibodies
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 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 release site 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 masked 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 pipeline includes 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 discovery stage.
For additional information about the company, please visit www.amunix.com.
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