Mythic Therapeutics Presents Promising Preclinical Data Demonstrating Broad Antitumor Efficacy of MYTX-011 at the 2025 AACR Annual Meeting
Mythic Therapeutics, a clinical-stage biotechnology company pioneering the next generation of antibody-drug conjugates (ADCs), today unveiled compelling preclinical data supporting the broad antitumor efficacy of its lead investigational therapy, MYTX-011, during a poster session at the American Association for Cancer Research (AACR) Annual Meeting 2025. The findings underscore MYTX-011’s potential to target a wide range of tumors expressing cMET, independent of mutational status or cMET expression level.
The presentation, held as part of the prestigious annual oncology research conference in Chicago, provided new insight into MYTX-011’s unique mechanism of action, as well as its potential to overcome limitations associated with earlier-generation anti-cMET ADCs. These data not only support the ongoing Phase 1 KisMET-01 clinical trial evaluating MYTX-011 in non-small cell lung cancer (NSCLC) but also suggest broader applicability across other difficult-to-treat tumor types.
A Novel ADC Engineered for Greater Tumor Selectivity and Payload Delivery
MYTX-011 represents a differentiated approach to antibody-drug conjugate therapy. It is a cMET-targeted DAR 2 vcMMAE ADC developed with Mythic Therapeutics’ proprietary FateControl™ technology platform. The antibody component of MYTX-011 is uniquely engineered to bind pH-dependently, enabling the drug to selectively internalize and deliver its cytotoxic payload with greater efficiency in tumor cells, while reducing uptake in healthy tissues.
This innovation addresses a key challenge in ADC development: striking the balance between therapeutic potency and safety. By designing MYTX-011 to bind more effectively within the acidic microenvironment of tumor cells, Mythic aims to optimize therapeutic index—achieving robust antitumor activity while minimizing off-target effects.
Summary of Preclinical Findings
The preclinical data presented at AACR 2025 highlighted MYTX-011’s efficacy in a series of xenograft models representing various tumor types and clinically relevant mutations. Notable findings include:
- Efficacy Across Mutation Profiles: MYTX-011 demonstrated potent antitumor activity in models harboring genetic alterations commonly associated with treatment resistance. This included:
- MET exon 14 skipping mutations, which drive oncogenesis and have been difficult to treat with existing targeted therapies.
- KRAS mutations, particularly KRAS G12C, which are found in a substantial proportion of NSCLC patients and have historically been resistant to ADC therapy.
- EGFR mutations, including EGFR T790M, a well-known resistance mutation to tyrosine kinase inhibitors (TKIs).
- Activity Independent of cMET Expression Level: Importantly, MYTX-011 was effective in low- to moderate-cMET-expressing tumors, expanding its potential patient population. This is a significant advancement, as most anti-cMET ADCs in development exhibit reduced efficacy in tumors with lower cMET levels.
- Superior Uptake and Internalization: In live-cell imaging studies, MYTX-011, equipped with FateControl™ modifications, demonstrated increased internalization into tumor cells compared to a non-engineered parent antibody. This led to enhanced payload delivery and cell death. In contrast, benchmark ADCs either failed to internalize effectively or showed minimal efficacy.
- Resistant Tumor Models: MYTX-011 achieved tumor regression in xenograft models previously shown to be unresponsive to standard-of-care therapies, including ADCs currently under development by other companies. This supports the drug’s potential role in overcoming resistance mechanisms that limit current treatment options.
These preclinical results suggest that MYTX-011 may be a viable therapeutic option for a broader population of cancer patients than previously considered for cMET-targeted ADCs.
Expert Commentary and Clinical Implications
Dr. Brian Fiske, Ph.D., Chief Scientific Officer and Co-founder of Mythic Therapeutics, commented on the significance of the data:
“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—genomic alterations that have historically shown limited response to other anti-cMET ADCs currently in development.”
“The robustness of MYTX-011 in preclinical models, including those with low cMET expression and resistance-driving mutations, reinforces our confidence in its clinical potential. We believe that this compound has the potential to shift the treatment paradigm for patients who currently have limited therapeutic options.”
Dr. Fiske added that the new data further validate the rationale for the KisMET-01 clinical trial and signal momentum in Mythic’s broader pipeline strategy.
Clinical Development: KisMET-01 Phase 1 Trial Progress
The promising preclinical profile of MYTX-011 is being translated into clinical evaluation through KisMET-01, an ongoing Phase 1, first-in-human dose-escalation trial in patients with advanced or metastatic non-small cell lung cancer. The trial is designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of MYTX-011, with a focus on patients whose tumors express cMET or harbor mutations associated with TKI resistance.
The trial, which launched in 2024, has thus far demonstrated encouraging tolerability and early signs of antitumor activity. Building on the 2024 interim update, Mythic Therapeutics plans to present new clinical data from KisMET-01 at a major upcoming medical conference later in 2025.
Expanding Opportunities in ADC Therapeutics
Antibody-drug conjugates continue to represent one of the most exciting areas of innovation in oncology. Despite recent approvals and clinical successes, many ADCs still suffer from a narrow therapeutic window, limited patient applicability, and challenges with efficacy in tumors expressing target antigens at moderate or low levels.
MYTX-011 seeks to overcome these limitations through next-generation ADC engineering. By combining pH-selective targeting, optimized payload delivery, and broad-spectrum activity across mutations, Mythic aims to advance MYTX-011 as a best-in-class therapeutic for difficult-to-treat solid tumors.
Beyond NSCLC, the company believes that MYTX-011 may have future applications in other cMET-expressing cancers, including gastric, colorectal, and head and neck cancers. These indications are being evaluated as part of preclinical expansion studies and may inform future clinical trial designs.
Mythic’s Broader Pipeline Strategy
While MYTX-011 leads Mythic Therapeutics’ clinical development pipeline, the company is also actively advancing additional ADC candidates leveraging its proprietary FateControl™ platform. This platform is designed to enhance intracellular delivery of cytotoxic agents and expand the utility of ADCs beyond conventional antigen-expressing populations.
Upcoming pipeline programs are expected to target other high-priority cancer antigens, with preclinical data anticipated in 2025 and early-stage clinical trials targeted for 2026.
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.
