Amunix to Present Preclinical Data on Protease-Activated HER2- and EGFR-Targeted T Cell Engagers at ESMO Virtual Congress 2020
Data demonstrate potential of Amunix’s XPAT platform to mitigate on-target, off-tumor toxicity that has hindered success of T cell engagers in treating solid tumors
Masked prodrug XPATs demonstrate efficacy at doses within an order of magnitude of the unmasked, active TCE form, yet have between ~200 to ~500-fold higher tolerated exposures
Amunix’s lead program, AMX-818, an XPAT T cell engager targeting HER2+ solid tumors, continues to progress toward the clinic
EGFR-XPAT, which is in lead optimization, offers unique opportunity in difficult to treat KRAS mutant tumors
MOUNTAIN VIEW, CA; September 17, 2020 – Amunix Pharmaceuticals, Inc. (“Amunix”), a biopharmaceutical company developing prodrugs of potent immune-activating biotherapeutics for the treatment of 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), which is in lead optimization, at the European Society for Medical Oncology Virtual Congress taking place September 19 - 21, 2020.
“We are very excited to present progress on our most advanced T cell engager programs,” said Angie You, Ph.D., CEO of Amunix. “Both programs 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 is limiting the use of potent immune activators to treat solid tumors. For our HER2-XPAT clinical candidate, AMX-818, we have initiated IND-enabling studies. We are also excited to share progress with EGFR-XPAT, which offers a potential orthogonal approach to small molecule kinase inhibitors to target KRAS mutant tumors. As we progress these two most advanced programs, we are also leveraging our plug and play platform to rapidly develop XPATs against additional tumor targets such as PSMA and TROP2.”
Amunix will present two posters at ESMO, titled, “HER2-XPAT, A Novel Protease-Activatable Pro-Drug T Cell Engager (TCE), Engineered to Address On-Target, Off-Tumor Toxicity and Provide Large Predicted Safety Margins in Non-Human Primate (NHP)” and “EGFR-XPAT, A Novel Pro-Drug T Cell Engager (TCEs) Engineered to Address On-Target, Off-Tumor Toxicity and an Orthogonal Approach for Cancer Immunotherapy in EGFR, KRAS/BRAF Cancers”. Both posters show 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 XPATs showed potent cytotoxic activity against tumor cell lines with EC50s in the single-digit pM range. For both molecules, masking reduced target-directed T cell cytotoxicity and T cell activation by ~5,000 to >10,000-fold. In established xenograft models, both HER2-XPAT and EGFR-XPATs induced complete tumor regressions with efficacious doses within an order of magnitude of the unmasked (active) T cell engager. Importantly, EGFR-XPAT showed strong in vitro cytotoxicity in a KRAS mutant and BRAF mutant setting, as well as potent in vivo anti-tumor xenograft activity in a BRAF mutant background.
Safety data from cynomolgus monkeys demonstrate that masked XPATs have a markedly lower risk of CRS and enable a significant increase in maximum tolerated exposures relative to unmasked, active forms. 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 and EGFR-XPAT up to 1 mg/kg, representing ~500-fold and ~200-fold, respectively, increases in tolerated exposures from masking. Combined with the potency of XPATs in xenograft models, these data suggest a favorable therapeutic index even for targets as broadly expressed as EGFR.
Poster Presentation Details
Title: HER2-XPAT, A Novel Protease-Activatable Pro-Drug T Cell Engager (TCE), Engineered to Address On-Target, Off-Tumor Toxicity and Provide Large Predicted Safety Margins in Non-Human Primate (NHP)
Poster number: 1060P
Abstract Number: 2472
Session: Virtual On-Demand Poster Display
Date: Sep 17, 2020
Title: EGFR-XPAT, A Novel Pro-Drug T Cell Engager (TCEs) Engineered to Address On-Target, Off-Tumor Toxicity and an Orthogonal Approach for Cancer Immunotherapy in EGFR, KRAS/BRAF Cancers
Poster number: 1062P
Abstract Number: 3054
Session: Virtual On Demand Poster Display
Date: Sep 17, 2020
Copies of the posters are 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 earlier programs underway. Their second most advanced program, EGFR-XPAT, is in lead optimization, and two earlier XPAT programs targeting TROP2 and PSMA, are approaching lead selection. 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.
Director, Corporate Development