Data demonstrate higher internalization in cMET positive (cMET+) tumor cells and broader, more potent efficacy, including a greater than 3-fold increase in efficacy in mouse models of non-small cell lung cancer (NSCLC), as compared to other cMET-targeting ADCs

Data establish preclinical proof of concept for MYTX-011 in the treatment of a broader cMET+ patient population, including those whose tumors express moderate levels of cMET

WALTHAM, MA, USA I April 18, 2023 IMythic Therapeutics, a clinical-stage biotechnology company focused on the development of next-generation antibody-drug conjugate therapies for the treatment of a wide range of cancers, today announced preclinical data highlighting the potential of MYTX-011, its investigational cMET-targeting ADC, for treating a broader range of cMET+ cancers than other cMET-targeting ADCs in development. These data were presented today as a poster at the American Association for Cancer Research Annual Meeting.

“We are excited by the findings of this study, which demonstrate the potential of MYTX-011 to not only expand the use of ADCs to patients who have not been eligible for treatment due to their level of target expression or tumor type, but also increase ADC efficacy as compared to current cMET-targeting ADCs in development,” said Gilles Gallant, BPharm, PhD, FOPQ, Chief Development Officer at Mythic Therapeutics. “These data reinforce the continued evaluation of MYTX-011, not only through our ongoing Phase 1 KisMET-01 clinical trial in NSCLC, where cMET overexpression occurs in up to 70% of cases,1,2 but also for patients with other cMET-expressing cancers who are still in need of targeted treatment options.”

Details of the poster presentation are as follows:

Title: MYTX-011: A novel cMET-targeting antibody-drug conjugate (ADC) engineered to increase on-target uptake in and efficacy against cMET expressing tumors
Presenter: Nimish Gera, Ph.D., Vice President, Biologics at Mythic Therapeutics
Session Title: Targeting Protein Kinases and Phosphatases for Therapy 1
Session Date and Time: Today, April 18, 2023, from 1:30 PM – 5:00 PM
Location: Poster Section 17
Poster Board Number: 13
Published Abstract Number: 5000

MYTX-011 was designed using Mythic’s FateControl™ platform by introducing an optimized set of mutations into an anti-cMET antibody. This engineering is designed to allow MYTX-011 to bind cMET on the surface of cancer cells and be selectively freed once inside of cancer cells, increasing the delivery of a potent chemotherapy, MMAE, inside of cancer cells.

In this study, the efficacy of MYTX-011 was evaluated on 62 different cancer cell lines grown in vitro, including NSCLC, head and neck, gastric, pancreatic and other cancer types which are known to express cMET. The efficacy of MYTX-011 was also evaluated in mouse models of NSCLC that expressed moderate and high levels of cMET, as measured by an immunohistochemistry (IHC) test.

MYTX-011 demonstrated higher internalization in cMET+ tumor cells and broader, more potent efficacy, including a greater than 3-fold increase in efficacy in mouse models of NSCLC, as compared to other cMET-targeting ADCs. MYTX-011 also exhibited favorable pharmacokinetics in monkeys including increased half-life, reduced target-mediated drug disposition, and reduced release of free MMAE payload, as compared to other cMET-targeting ADCs. The toxicity profile of MYTX-011 in monkeys was consistent with other vcMMAE-based ADCs. No MYTX-011-related clinical toxicities were found, and the only findings included MMAE-related neutropenia and mild bone marrow toxicity, both of which were reversible.

Mythic recently announced that the first subject was dosed with MYTX-011 in its Phase 1 KisMET-01 multi-center, dose escalation and dose expansion clinical trial in subjects with NSCLC. More information about the clinical trial is available at (identifier: NCT05652868).

About MYX-011

MYTX-011, a cMET-targeting ADC, leverages Mythic’s innovative FateControl™ technology, which allows ADCs to actively navigate inside of cells to potentially increase 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.

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.

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1 Lee YJ, Han JY, Lee GK, et al. C-MET overexpression as a resistance biomarker to epidermal growth factor receptor tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer. J ClinOnc. 2016;34:15_suppl, e20660-e20660.
2 Moosavi F, Giovannetti E, Saso L, Firuzi O. HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers. Critical Rev Clin Lab Sci. 2019;56(8):533.

SOURCE: Mythic Therapeutics