Myeloid Therapeutics to Present on MT-303 at SITC 2024 for Advanced HCC

Myeloid Therapeutics, Inc., a clinical-stage company focused on immunology, recently announced a significant presentation at the Society for Immunotherapy in Cancer (SITC) 2024 annual meeting in Houston, Texas. The event spans November 6-10, 2024. Dr. Matthew Maurer, the Chief Medical Officer of Myeloid, is set to discuss the company’s latest advancements, particularly the development of MT-303.

MT-303 is Myeloid's second in vivo mRNA CAR program to reach clinical trials from its innovative pipeline of immune cell programming therapies. This program is pioneering as it represents the first time a CAR encoded from mRNA and encapsulated in lipid nanoparticles has been evaluated in patients with hepatocellular carcinoma (HCC). Given the limited treatment options available for HCC, this development is noteworthy.

MT-303 targets Glypican-3 (GPC3), a protein overexpressed in many cancers, including the majority of HCC cases, while maintaining limited expression in normal tissues. Elevated GPC3 levels are associated with aggressive tumor growth and poor prognosis, making it an attractive target for therapeutic intervention.

Myeloid Therapeutics employs a unique approach that focuses on selective in vivo programming of immune cell subsets using off-the-shelf mRNA-encoded CAR technologies. These candidates, such as MT-303, are administered without the need for preconditioning. MT-303 arms myeloid cells with a proprietary chimeric antigen receptor that specifically targets GPC3-expressing cancers. This strategy not only enables the myeloid cells to directly attack the cancer but also orchestrates a coordinated adaptive immune response, characterized by the expansion of new T cell clones.

Dr. Maurer highlighted the rapid advancement of MT-303 into first-in-human testing as part of their second in vivo CAR clinical program. Current dose escalation for both MT-303 and another program, MT-302, shows promising biological indications of proof-of-mechanism, along with early signs of safety and efficacy. These clinical observations extend the promising results seen in preclinical studies, which demonstrated selective activation of CAR myeloid cells and robust anti-tumor activity in mouse models of HCC.

The oral presentation detailing the preclinical development of MT-303 will provide deeper insights into the innovative nature of this therapy. Scheduled for November 8, 2024, the presentation titled "Preclinical Development of MT-303, a Novel LNP-Formulated GPC3-Specific CAR mRNA, for in vivo Programming of Monocytes to Treat Hepatocellular Carcinoma" will be part of the session on Protein and Cellular Engineering Strategies.

Myeloid's platform integrates validated antibody/antigen binding with novel myeloid signaling domains coded within simple mRNA, which can be repeatedly delivered using lipid nanoparticles (LNPs). This platform’s flexibility supports a wide range of signaling domains and immune cell types, making it suitable for combination approaches. This proprietary approach aims to deliver personalized therapy efficiently and cost-effectively by eliminating the need for ex vivo handling of patient cells and complex neoantigen sequencing.

Liver cancer poses a significant challenge globally, with over 850,000 new cases diagnosed each year and limited treatment options available, especially for those resistant to first-line treatments. Myeloid aims to address this unmet medical need by providing new CAR therapies capable of orchestrating a durable and coordinated immune response against advanced disease. The MT-303 Phase 1 study is designed to investigate its safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy in adults with advanced or metastatic HCC that overexpresses GPC3.

MT-303 continues to demonstrate potential as a monotherapy, showing tumor-fighting efficacy in preclinical models even in the absence of T cells. This candidate has shown a favorable safety profile in both rodent and non-human primate studies and aims to elicit a comprehensive immune response by presenting tumor neoantigens to stimulate T cells.

Myeloid Therapeutics is committed to advancing cancer treatment through innovative RNA technology and immune cell programming, operating from its base in Cambridge, MA.