#United States #Chicago #Myeloid Therapeutics #ASCO 2025 #RNA-based CAR

Myeloid Therapeutics Unveils Groundbreaking In Vivo mRNA CAR Therapies at ASCO 2025

In a remarkable development for immuno-oncology, Myeloid Therapeutics, Inc. has revealed exciting initial findings from its in vivo mRNA CAR therapies at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago from May 30 to June 3, 2025. This clinical-stage immunology company, dedicated to advancing RNA therapeutics, has showcased its pioneering products, MT-302 and MT-303, which aim to revolutionary the treatment of solid tumors.

Transforming Cancer Treatment

Daniel Getts, PhD, Co-founder and CEO of Myeloid Therapeutics, expressed optimism at the conference, stating, "Our presentations at ASCO demonstrate the clinical translation of our proprietary mRNA-LNP platform for in vivo immune cell engineering." This innovation allows Myeloid to transcend traditional CAR therapies, eliminating the often challenging ex vivo manipulation to furnish powerful tumor-specific immune activation for patients grappling with advanced solid tumors.

The studies reveal an exciting possibility of repeatedly administering lipid nanoparticle (LNP)-encapsulated mRNA therapies. "This exciting data illustrates that we can deliver repeated doses of LNP-mRNA, allowing CAR-programmed myeloid cells to penetrate solid tumors effectively and alter the tumor microenvironment," explained Dr. Matt Maurer, Chief Medical Officer at Myeloid. He highlighted the potential for these therapies to yield enhanced clinical benefits compared to existing treatments.

Key Highlights of MT-302 and MT-303

MT-302: Targeting Epithelial Tumors

MT-302 emerges as the first intravenous mRNA-based CAR therapy to enter the clinical trial phase and targets TROP2, overexpressed in many epithelial tumors while showing minimal expression in healthy tissues. A correlative biomarker analysis from the Phase 1 study illustrated promising immune activation with significant CAR expression in myeloid cells and a marked increase in pro-inflammatory gene signatures across various tumor types.

Key findings from MT-302 include:

• - Immune Activation: Single-cell RNA sequencing verified selective CAR expression in myeloid cells, demonstrating solid immune activation.
• - Target Engagement: Pharmacodynamic markers confirmed successful delivery and CAR expression post-systemic administration.
• - Continued Dose Escalation: The dose escalation continues with an optimized linear mRNA formulation showing expression durability for over 12 days.

The results from MT-302 were presented by lead author Dr. Charlotte Lemach during a session at ASCO on June 2, 2025.

MT-303: Hepatocellular Carcinoma Innovation

MT-303, which specifically targets glypican-3 (GPC3) expressed widely in hepatocellular carcinoma (HCC), utilizes a unique mechanism to enlighten the potential of in vivo CAR therapy. The ongoing multicenter Phase 1 trial follows a Bayesian Optimal Interval (BOIN) dose escalation approach, focusing on adults with advanced solid tumors expressing GPC3.

Major points from the MT-303 clinical trial include:

• - Trial Design: The trial features an open-label design and aims to reprogram Fc receptor gamma chain-expressing myeloid cells to identify and eliminate GPC3+ tumor cells.
• - Mechanism: The mRNA used encodes for a GPC3-targeted CAR construct regulated by CD89, inherently confining expression to myeloid cells.

Lead author Dr. Timothy Humphries highlighted these findings during the session on May 31, 2025, showcasing the promising developments within Myeloid's innovative therapeutic landscape.

Future Implications

Myeloid expects to provide additional clinical translation results in subsequent medical meetings following the completion of the ongoing Phase 1 studies of MT-302 and MT-303. Their strategy (including presenting tumor neoantigens to stimulate a full immune response) aims to revolutionize how solid tumors are treated, offering a more accessible, potentially tolerable, and targeted therapeutic option, breaking the confines of conventional cell therapies.

As Myeloid Therapeutics propels forward in the oncology sphere, the implications of these therapies could drastically change the treatment regimen for many patients battling advanced solid malignancies.

This innovative approach positions Myeloid Therapeutics at the forefront of cancer research, driven by their commitment to reprogram immune cells and provide hope to patients who urgently need transformative treatment options.