Amunix to Present Preclinical Data on HER2- and EGFR-Targeted T Cell Engagers at AACR Virtual Annual Meeting II
- Data demonstrate potential of Amunix’s XPAT platform to significantly widen therapeutic index, and address on-target, off-tumor toxicity that has hindered application of T cell engagers to treat solid tumors
- Prodrug XPATs demonstrated >1000 fold increase in tolerated exposures versus traditional T cell engagers
- Amunix’s lead program, AMX-818, an XPAT T cell engager targeting HER2+ solid tumors, continues to progress toward the clinic
MOUNTAIN VIEW, CA; June 22, 2020 – Amunix Pharmaceuticals, Inc. (“Amunix”), a biopharmaceutical company focused on developing prodrugs to bring the promise of potent immune-activating biotherapeutics to patients with solid tumor cancers, today announced that it will present preclinical data on two T cell engager programs: AMX-818, the company’s lead clinical candidate, which targets HER2, and a second targeting EGFR (EGFR-XPAT), an earlier stage discovery candidate, at the American Association for Cancer Research (AACR) Virtual Annual Meeting II taking place June 22 - 24, 2020.
“We are very excited to present for the first time preclinical data supporting our most advanced T cell engager programs, which we are developing for HER2- and EGFR-positive solid tumors,” said Angie You, CEO of Amunix. “These new data demonstrate the potential of our XPAT platform to significantly widen the therapeutic index of T cell engagers and overcome the challenge of on-target, off-tumor toxicity that has hindered the use of potent immune activators to treat solid tumors to date. We believe our platform and resulting pipeline of novel T cell engagers could finally deliver on the promise of this class for many patients.”
The poster presentation titled, “HER2-XPAT and EGFR-XPAT: Pro-Drug T Cell Engagers (TCEs) Engineered to Address On-Target, Off-Tumor Toxicity With Potent Efficacy in vitro and in vivo and Large Safety Margins in NHP,” showed, in a non-human primate model, that Amunix’s XPAT technology can improve the toxicity profile of T cell engagers while maintaining their potency against solid tumors. In vitro data showed that protease-activated XPATs had potent cytotoxicity against tumor lines with EC50s in the single-digit pM range, with masking reducing target-directed T cell cytotoxicity and T cell activation by up to 15,000-fold. In established xenograft models, both HER2 and EGFR XPATs induced protease-dependent tumor regressions with efficacious doses within an order of magnitude of the unmasked (active) T cell engager.
Safety data from cynomolgus monkeys demonstrated that XPATs significantly reduce CRS and increase tolerated exposures relative to an unmasked T cell engager, suggesting a favorable therapeutic index even for targets as broadly expressed as EGFR. In contrast to traditional unmasked T cell engagers which have cyno MTDs in the µg/kg range, HER2-XPAT can be safely dosed up to 42 mg/kg in cynos and EGFR-XPAT up to 1 mg/kg, representing >1000-fold and ~100-fold, respectively, increase in tolerated exposures from masking.
Poster Presentation Details
Title: HER2-XPAT and EGFR-XPAT: Pro-Drug T Cell Engagers (TCEs) Engineered to Address On-Target, Off-Tumor Toxicity With Potent Efficacy in vitro and in vivo and Large Safety Margins in NHP
Poster number: 3376
Abstract Number: 7667
Session: Therapeutic Antibodies 2 – E-Posters
Date: Monday, June 22, 2020 from 9:00AM – 6:00PM
A copy of the poster is available here.
About Amunix Pharmaceuticals
Amunix Pharmaceuticals, based in Mountain View, 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 selectively 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 discovery programs underway. By delivering breakthrough therapies that can safely harness the immune system, we aim to conquer cancer and save lives.
For additional information about the company, please visit www.amunix.com.
Director, Corporate Development