Preclinical data for MYTX-011, a cMET-targeting antibody-drug conjugates (ADC) leveraging Mythic Therapeutics’ innovative FateControl™ technology, confirms that the investigational drug demonstrated potent efficacy across a broad range of tumor xenograft models harboring clinically relevant mutations.
This finding further confirms the potential of MYTX-011 (see ADC Drugmap) to treat multiple tumor types, regardless of mutation status or cMET expression level.
The data were presented in a poster presentation at the annual meeting of the American Association for Cancer Research (AACR), held April 25 – 30, 2025 in Chicago, Illinois.[1]
“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,” Fiske added.
MYTX-011
MYTX-011 is a novel cMET-targeted ADC includes a pH-dependent anti-cMET antibody conjugated via a Cal-Cit (Valine–citrulline/vc) linker to monomethyl auristatin E (MMAE).
The antibody 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.[2]
incorporation of pH-dependent binding in the antibody component of a c-mesenchymal-epithelial transition (MET)-targeting ADC, the researchers demonstrated the possibility to overcome the requirement for high c-MET expression on tumors. an innovation that has the potential to benefit a broader population of patients [2]
The investigational agent is based on the company’s proprietary FateControl™ technology, considered the ‘next step beyond linker-payload technologies’ which is designed to manipulate the trafficking of an ADC in cells to increase uptake in the desired tissue while avoiding payload release in other, undesired tissues. This approach simultaneously increases therapeutic potency and improves the drug’s tolerability, thereby enabling our medicines to treat broader set of molecular targets and patient profiles with lower c-MET levels than previously possible.
The preclinical date shows that 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, a multicenter, first-in-human study in patients with previously treated, locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC).
Clinical trials
Clinical Study of Antibody-Drug Conjugate MYTX-011 in Subjects With Non-Small Cell Lung Cancer – ClinicalTrials.gov ID NCT05652868
Reference
[1] Kanojia D, Colombo F, Israelsen WJ, Ramesh V, Gera N, Chittenden T, Fiske BP. MYTX-011: A pH-dependent anti-cMET ADC exhibits potent activity in multiple epithelial tumor models with clinically actionable mutations and varying levels of cMET expression. In: Proceedings of the 116th Annual Meeting of the American Association for Cancer Research; 2025 April 25-30; Chicago, IL.: AACR; 2025. Abstract nr 2960 / 12
[2] Gera N, Fitzgerald KM, Ramesh V, Patel P, Kanojia D, Colombo F, Kien L, Aoyama S, Xu L, Jean J, Deshpande AM, Comb WC, Chittenden T, Fiske BP. MYTX-011: A pH-Dependent Anti-c-MET Antibody-Drug Conjugate Designed for Enhanced Payload Delivery to c-MET-Expressing Tumor Cells. Mol Cancer Ther. 2024 Jun 10:OF1-OF12. doi: 10.1158/1535-7163.MCT-23-0784. Epub ahead of print. PMID: 38853438.
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This article was firts published in ADC Review | Journal of Antibody-drug Conjugates. [Link]
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DOI
 leveraging Mythic Therapeutics’ innovative FateControl™ technology, confirms that the investigational drug demonstrated potent efficacy across a broad range of tumor xenograft models harboring clinically relevant mutations.This finding further confirms the potential of MYTX-011 (see ADC Drugmap) to treat multiple tumor types, regardless of mutation status or cMET expression level.The data were presented in a poster presentation at the annual meeting of the American Association for Cancer Research (AACR), held April 25 - 30, 2025 in Chicago, Illinois.){kind=link}