pH-dependent binding of MYTX-011 translated to potent efficacy regardless of mutation status or level of cMET expression
Anti-tumor activity demonstrated in EGFR mutant, KRAS mutant and MET exon 14 skipping xenograft models
Mechanism and impact of FateControl™ to increase ADC uptake further defined by live cell imaging and confocal microscopy
Mythic Therapeutics, a clinical-stage biotechnology company developing next-generation antibody-drug conjugate (ADC) therapies for the treatment of a wide range of cancers, today presented preclinical data demonstrating the potential of MYTX-011 to treat multiple tumor types, regardless of mutation status or cMET expression level, in a poster session at the AACR Annual Meeting in Chicago, Illinois.
“These findings highlight the broad therapeutic potential of MYTX-011 across a variety of cMET-expressing cancers and the opportunity to expand the treatable patient population to patients with EGFR, KRAS and MET mutations, which have shown reduced response rates in clinical studies of other anti-cMET ADCs in development,” said Brian Fiske, Ph.D., chief scientific officer and co-founder of Mythic. “These preclinical data reinforce our confidence in the ongoing Phase 1 dose escalation trial of MYTX-011. Building on last year’s promising preliminary data, we remain highly optimistic and eagerly await additional readouts.”
MYTX-011 is a novel cMET-targeted DAR 2 vcMMAE ADC with an antibody that has been engineered to have pH-dependent binding, which results in higher internalization and payload delivery to tumor cells with a range of cMET expression.
In the study, pH-dependent binding of MYTX-011 translated to potent efficacy in tumor xenografts regardless of mutation status, including models harboring MET exon 14 skipping, KRAS and EGFR mutations. Notably, MYTX-011 demonstrated anti-tumor activity in low or moderate cMET-expressing non-small cell lung cancer (NSCLC) KRAS G12C xenografts as well as tyrosine kinase inhibitor-resistant xenografts bearing EGFR T790M mutations. Additionally, live cell imaging studies demonstrated how FateControl™ technology drives increased uptake of MYTX-011 antibody in cMET-expressing tumor cells compared to a non-engineered parent antibody. In previous studies, a benchmark ADC was either inactive or had greatly reduced efficacy.
These findings support the continued clinical advancement of MYTX-011, which is currently being evaluated in the ongoing Phase 1 KisMET-01 trial in NSCLC.
The Company will present additional data from its Phase 1 KisMET-01 study at an upcoming major medical conference.
About MYTX-011
MYTX-011, an investigational cMET-targeting ADC, leverages Mythic’s innovative FateControl™ technology which is designed to allow ADCs to actively navigate inside of cells, potentially increasing delivery of anti-cancer agents to tumor cells with less impact on healthy cells. This breakthrough approach takes the next step beyond linker-payload technologies and is designed to improve ADC efficacy against a broad set of molecular targets and patient profiles. MYTX-011 is currently being evaluated in the Phase 1 KisMET-01 clinical trial, a first-in-human, open-label, multi-center, dose escalation and dose expansion study enrolling patients with locally advanced, recurrent or metastatic NSCLC (NCT05652868).
About Mythic Therapeutics
Mythic Therapeutics is a product-platform company developing a pipeline of antibody-drug conjugates (ADCs) designed to exhibit unparalleled therapeutic index and efficacy. The Company’s FateControl™ technology aims to enhance ADC uptake in targeted tissues by manipulating the fate of the ADC within the cell, thereby expanding the diseases and patient profiles that could be treated with Mythic’s ADCs. The company’s major investors include Venrock, Viking Global Investors, and First Round Capital.
For more information, visit: www.mythictx.com and follow on LinkedIn.
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