Preclinical data highlighting the differentiating properties of Mythic Therapeutics‘ investigational cMET-targeting antibody-drug conjugates (ADC), MYTX-011, published in April 30, 2024 edition of Molecular Cancer Therapeuticsa journal of the American Association for Cancer Research (AACR), demonstrated that this novel ADC which leverages Mythic’s innovative FateControl™ technology, actively navigated inside of cells, potentially increasing delivery of anti-cancer agents to tumor cells with less impact on healthy cells.

These outcomes confirm that 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.

Enhancing payload delivery
“The potential of novel ADC technologies to enhance payload delivery to tumors is relatively under-explored compared to advances in linker-payload technology and target selection,” said Nimish Gera, Ph.D., lead author of the paper and Scientific Co-founder, Vice President of Biologics at Mythic.

“We believe that engineering pH-dependent binding could be a particularly compelling strategy for ADCs targeting medium to low levels of cMET expression in patients. We’re pleased to publish this study illustrating how the properties of MYTX-011, including its potential for increased on-target potency, enhanced tolerability, longer half-life and higher efficacy, may enable this therapy to serve patients with a broad range of cMET expression who otherwise have limited treatment options. We look forward to continuing to evaluate MYTX-011 in our ongoing Phase 1 clinical trial,” Gera noted.

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Based on the outcomes of the study, the researchers concluded that that incorporation of pH-dependent binding in the antibody component of a cMET targeting ADC can overcome the requirement for high cMET expression on tumors, an innovation that has the potential to benefit a broader population of patients with lower cMET levels.

The study results demonstrated that MYTX-011 drove four-fold higher net internalization than a non-pH engineered parent ADC in non-small cell lung cancer (NSCLC) cells and showed increased cytotoxicity against a panel of cell lines from various solid tumors, including head and neck, gastric, pancreatic, esophageal, bladder, kidney and skin cancer. A single dose of MYTX-011 showed at least three-fold higher efficacy than a benchmark ADC in mouse xenograft models of NSCLC ranging from low to high cMET expression. Additionally, MYTX-011 showed improved pharmacokinetics over parent and benchmark ADCs. In a repeat dose toxicology study, MYTX-011 exhibited a toxicity profile similar to other MMAE-based ADCs.

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).

Clinical trials
Clinical Study of Antibody-Drug Conjugate MYTX-011 in Subjects With Non-Small Cell Lung Cancer – ClinicalTrials.gov Identifier: NCT05652868

Reference
[1] 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-cMET antibody-drug conjugate designed for enhanced payload delivery to cMET expressing tumor cells. Mol Cancer Ther. 2024 Apr 30. doi: 10.1158/1535-7163.MCT-23-0784. Epub ahead of print. PMID: 38684230.

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