Myeloid Therapeutics, Inc. (“Myeloid”), a clinical stage mRNA-immunotherapy company, today announced its presentation of two posters at the American Association for Cancer Research (AACR) Annual Meeting, being held in Orlando, Florida.
“At AACR 2023, we are pleased to present late-breaking research on our in vivo engineering capabilities and clinical data from our Phase I IMAGINE study of MT-101 in PTCL patients,” said Daniel Getts, Ph.D., Chief Executive Officer of Myeloid. “These data demonstrate the power of myeloid cells to orchestrate broad immune responses. We look forward to advancing our platform and expanding our clinical portfolio of in vivo programming candidates and ATAK™ CAR cell therapy candidates.”
Details of the poster presentations are below:
Title: “In vivo delivery of novel CD89 fusion receptor to myeloid cells by mRNA activates anti-tumor immunity”
Session: Late-Breaking Research: Experimental and Molecular Therapeutics 1
Session Date and Time: Sunday April 16, 2023, 1:30 PM – 5:00 PM
Location: Poster Section 35
Poster Board Number: 19
Abstract Presentation Number: LB027
- Myeloid illustrates with this poster its ability to engineer circulating and tumor-penetrating myeloid cells so that these cells are activated within the tumor setting and elicit anti-tumor adaptive immunity. This approach is an attractive, novel manner to harness systemic anti-tumor immunity.
- Myeloid has applied its engineering insights to overcome challenges of specifically targeting and activating myeloid cells in vivo.
- Myeloid has developed a novel in vivo myeloid cell engineering platform, in which a chimeric antigen receptor (CAR) is generated by fusing a tumor recognition scFv with the alpha chain of human Fc receptors (CD89). The stable expression and function of these receptors requires the endogenously expressed common Fc receptor gamma chain (FcRg), which expression is mostly restricted to myeloid cells.
- For in vivo engineering, the construct is encapsulated and delivered in lipid nanoparticles (LNP).
- Myeloid’s most-advanced in vivo programming candidate is a candidate referred to as MT-302, targeting trophoblast cell surface antigen 2 (TROP2) on cancer cells. TROP2 is overexpressed in most human solid epithelial cancers, as compared to low expression in corresponding normal tissue. Increased TROP2 expression has been linked to increased tumor growth and has been implicated as a prognostic marker in these cancers, supporting the development of earlier therapies targeting TROP2.
- Within immunodeficient xenograft models of hepatocellular carcinoma and triple negative breast cancer, delivery of LNP mRNA encoding GPC3-CD89 or TROP2-CD89 fusion proteins resulted in anti-tumor efficacy, confirming the ability of this approach to program myeloid cells. Repeat dosing studies showed significant anti-tumor efficacy following bi-weekly administration of TROP2-CD89.
- These studies highlight the potential of in vivo delivery of CD89 fusion proteins to program myeloid cells to recognize and kill cancer, thus providing a novel, promising approach to treating cancer.
Title: “Initial Preclinical and Clinical Experience of Autologous Engineered Monocytes in T cell Lymphoma Patients”
Session Category: Clinical Trials
Session: Phase I Clinical Trials in Progress
Session Date and Time: Monday April 17, 2023, 1:30 PM – 5:00 PM
Location: Poster Section 46
Poster Board Number: 19
Published Abstract Number: CT131
- Myeloid developed the first engineered monocyte cell product, by engineering autologous monocytes to express a novel chimeric antigen receptor (CAR). This CAR contains a tumor recognition domain that is fused to a CD8 hinge domain, Fcγ and PI3K intracellular signaling domains. In addition to imparting tumor specificity, the Fcγ and PI3K signaling domains promote phagocytosis, cytokine production and antigen presentation upon activation.
- In a rodent model of melanoma (gp75+ B16/F10-OVA), Ly6C+ monocytes engineered with this receptor were able to phagocytose tumor cells and cross present antigen in vitro. In vivo infusion of engineered monocytes was associated with significant suppression of tumor growth. FACS analysis of tumor-infiltrates demonstrated that engineered monocytes preferentially infiltrated tumors and differentiated into antigen presenting cells.
- Based on these promising data, MT-101 is being assessed in humans in the Phase 1, open-label, first-in-human trial in patients with refractory or relapsed T cell lymphoma, IMAGINE trial (NCT05138458). The primary objective is the assessment of safety and tolerability at Day 28, following 3 weekly cycles of 2 infusions. Secondary objectives include assessment of correlative markers of response, pharmacokinetics, and efficacy.
- In the first 3 subjects, MT-101 was well-tolerated, with no evidence of CRS, ICANS, or infusion reactions. Examination of biomarkers by CyTOF in one subject showed changes in circulating leukocytes, including B cells. In this subject, survival has been greater than 10 months, while the median overall survival of patients with R/R PTCL is 5.5 months.
Abstracts and full session details can be accessed through the AACR meeting planner: AACR Annual Meeting 2023 | Meetings | AACR.
About Myeloid’s ATAK™ CAR receptors and in vivo mRNA Programming
Myeloid’s novel class of CARs, known as ATAK™ Receptors, combine tumor recognition with multiple proprietary innate-immune signaling domains. Myeloid scientists have screened multiple unexplored combinations of innate-immune signals and uncovered optimal multi-signal pathways. The combination of cancer recognition binders with these novel intracellular signaling domains allows myeloid cells to be reprogrammed with previously unexplored combinations of immune signals, leading to tumor killing and broad systemic anti-tumor responses.
Myeloid’s novel in vivo engineering platform specifically targets and activates myeloid cells to elicit broader anti-tumor adaptive immunity. Through this approach, Myeloid demonstrates that delivery of lipid-nanoparticles (LNPs) encapsulating mRNA results in selective uptake and expression by myeloid cells in vivo, leading to potent tumor killing in multiple cold tumor models. These data demonstrate the potential for Myeloid’s technology to program cells directly in vivo.