Amunix Presents Preclinical Data on AMX-818, a Protease-Activated HER2-Targeted T Cell Engager Prodrug, at SABCS 2020
- Category: Antibodies
- Published on Thursday, 10 December 2020 18:15
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– Data demonstrate potential of Amunix’s XPAT (XTENylated Protease-Activated T cell engager) platform to mitigate on-target, off-tumor toxicity that has hindered success of T cell engagers in treating solid tumors –
– Lead program AMX-818, an XPAT prodrug targeting HER2, demonstrates potent efficacy with ~500-fold improved safety relative to unmasked, active form, and no evidence of CRS –
– AMX-818 is effective in both HER2-high and HER-low tumor models, and continues progress toward clinic –
SOUTH SAN FRANCISCO, CA, USA I December 09, 2020 I Amunix Pharmaceuticals, Inc. (“Amunix”), a biopharmaceutical company developing prodrugs of potent immune-activating biotherapeutics for the treatment of patients with solid tumors, today shared new data on AMX-818 (HER2-XPAT), the company’s lead clinical candidate T cell engager which targets HER2. Data was presented at the 2020 San Antonio Breast Cancer Symposium.
“We continue to be excited by progress of AMX-818 and its strong efficacy and safety data package,” said Angie You, Ph.D., CEO of Amunix. “New in vivo results demonstrating AMX-818 efficacy in a HER2-low tumor model support the potential to treat the significant population of patients with HER2-low and –medium tumors who are not currently served by any HER2-targeting agents. In addition, because our universal masking technology is plug and play, we have been able to rapidly drive progress on two additional XPAT programs targeting PSMA and TROP2.”
Amunix presented a poster at SABCS, titled “HER2-XPAT, A Novel Protease-Activatable Prodrug T Cell Engager (TCE), Engineered to Address On-Target, Off-Tumor Toxicity and Provide Large Predicted Safety Margins in Non-Human Primates”. The poster shows that Amunix’s XPAT technology can improve the toxicity profile of T cell engagers while maintaining their potency against solid tumors. In vitro, protease-activated HER2-XPAT showed potent cytotoxic activity against tumor cell lines with EC50s in the single-digit pM range, while masking reduced target-directed T cell cytotoxicity and T cell activation by >10,000-fold. In established xenograft models, HER2-XPAT induced complete tumor regressions with efficacious doses within an order of magnitude of the unmasked (active) T cell engager. The ability to shrink large tumors was evident even after a single dose of HER2-XPAT, and the drug remained stable in circulation of tumor-bearing mice. Importantly, AMX-818 was also able to induce complete responses in xenograft tumors expressing low levels of HER2. This suggests the drug could have utility beyond HER2-high expressing cancer patients, addressing a large patient population that is not served by current HER2-targeting agents.
Safety data from cynomolgus monkeys demonstrate that the masked XPAT prodrug has a markedly lower risk of CRS and enables a significant increase in maximum tolerated exposures relative to the unmasked, active form. In contrast to traditional unmasked T cell engagers, which have MTDs in the µg/kg range, HER2-XPAT can be safely dosed up to 42 mg/kg in cynos, representing a ~500-fold increase in tolerated exposures from masking. Combined with the potency of XPATs in xenograft models, these data suggest a favorable therapeutic index for AMX-818.
Poster Presentation Details
Title: HER2-XPAT, A Novel Protease-Activatable Prodrug T Cell Engager (TCE), Engineered to Address On-Target, Off-Tumor Toxicity and Provide Large Predicted Safety Margins in Non-Human Primates
Abstract Number: PS17-11
Session: Virtual Poster Hall
Date: Available for Viewing Starting Dec 9
Copies of the posters are available here.
About Amunix Pharmaceuticals
Amunix Pharmaceuticals, based in South San Francisco, CA, is focused on developing prodrugs to bring the promise of potent immune-activating biotherapeutics to patients with solid tumor cancers. The company is leveraging its proprietary T cell engager (XPAT) and cytokine (XPAC) platforms to advance a pipeline of novel prodrugs that are preferentially activated in the tumor microenvironment. Both platforms utilize Amunix’s prodrug technology that has been clinically validated to extend drug half-life with limited immunogenicity. Amunix is advancing its lead development candidate, AMX-818, an XPAT T cell engager targeting HER2+ solid tumors, toward the clinic, and has several earlier programs underway, including programs targeting PSMA and TROP2. Amunix is also working on their first protease-activated masked cytokine program, IL12-XPAC, which is in discovery.
For additional information about the company, please visit www.amunix.com.