Emerging from the Company’s proprietary ATAK™ CAR receptor library, 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 uptake and selective expression by myeloid cells in vivo, leading to potent tumor killing in multiple cold tumor models.

The Company’s lead in vivo program, MT-302, is a TROP2-targeting in vivo CAR designed for expression within the myeloid compartment. TROP2 is a tumor associated antigen expressed widely on epithelial tumors, including some of the most difficult to treat cancers. Treatment with MT-302 has demonstrated monotherapy activity in a TROP2/TNBC model, confirming the potency of programmed myeloid cells in the absence of T cells. Myeloid believes that MT-302 has significant advantages over TROP2-ADC approaches through its ability to engage the full immune response. Myeloid has initiated a Phase 1 clinical study with MT-302 for patients with TROP2-expressing tumors.

MT-302 Study

MT-303 represents the first candidate in a new therapeutic modality targeting hepatocellular carcinoma (HCC). Liver cancer is a prevalent and challenging cancer with over 850,000 new cases diagnosed globally each year, and the third leading cause of cancer death. The clinical candidate is a first-in-class, GPC3-FcA-LNP, with a strong preclinical profile supporting its advance into this first-in-human trial. GPC3 is overexpressed in most human hepatocellular carcinomas, with limited expression in corresponding normal tissues. Increased GPC3 expression has been linked to tumor growth.

Treatment with MT-303 as a monotherapy demonstrates activity in a GPC3/HCC preclinical model, confirming the tumor-fighting potency of programmed myeloid cells even in the model’s absence of T cells. MT-303 has demonstrated strong expression in myeloid cells and a favorable safety profile in rodents and non-human primates. Unlike other therapies, MT-303 brings the potential advantages of eliciting a full immune response by also presenting tumor neoantigen to stimulate T cells.

MT-303 represents Myeloid’s second in vivo CAR clinical program, building on the company’s innovative approach to cancer treatment through immune cell programming.

MT-303 Study

Retrotransposons are genetic elements that replicate through reverse transcription of an RNA transposition intermediate. Retrotransposons contribute to structural changes and more importantly, to gene regulation. Myeloid’s RetroT™ technology relies on a single-strand mRNA to deliver genetic sequences and integration enzymes. This breakthrough technology offers the potential to deliver gene-sized pieces of DNA into the genome in a virus-free manner. The payload realizable with RetroT™ is larger than currently possible with all known existing gene editing technologies. As a result, the Company’s RetroT™ platform holds the potential to significantly expand the type and scope of genetic errors that can be reversed in situ. In March 2022, Myeloid entered into an exclusive option and research collaboration agreement with Prime Medicine, Inc. to develop and accelerate RetroT™.