Company: CERO
Filing Date: 2025-02-07
Form Type: 424B3
Source: 0001213900-25-011071
Chunk: 160

Company: CERO THERAPEUTICS HOLDINGS, INC.
Filing Date: 2025-02-07
Form: 424B3
Chunk 160
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 the tumor from the CAR or the display by the T cells of an exhaustion phenotype. Moreover, while engineered CAR-T cells have shown
remarkable potential in the treatment of hematological cancers, they have not demonstrated equivalent efficacy in the treatment of solid
tumors. Curative cell therapies for solid tumors currently do not exist and the importance of this limitation is underscored by the prevalence
of solid tumor malignances. The American Cancer Society estimates that solid tumor cancers accounted for more than 1.7 million of
the 1.9 million people newly diagnosed with cancer in 2021. Even in hematological malignancies with approved CAR-T cell therapies,
less toxic orthogonal treatment approaches are needed as cure rates for CD19-targeted CAR-T cell therapies do not exceed 60%.

Challenges to the use of
cellular therapy to address solid tumors often relate to difficulty in developing receptors directed towards targets expressed in high
frequency on cancer cells as well as overcoming the immunosuppressive microenvironments that contribute to ineffective immune responses.
The tumor stroma, made up of a dense fibrotic matrix, often surrounds solid tumors and acts as a physical barrier, which restricts CAR-T
cell access to the tumor. CAR-T cell activity may be further hindered by the tumor microenvironment (“TME”). In the TME,
multiple cell types which drive immunosuppression infiltrate solid tumors, including myeloid-derived suppressor cells, tumor-associated
macrophages, and regulatory T cells. The interaction of these cells and the tumor cells increases the expression of signaling molecules
that enable tumor cell proliferation while dampening the generation of co-stimulatory signals necessary for T cell expansion and persistence.
In addition, TME-associated immune dysfunction may result in a down regulation of MHC class I molecules, limiting proper antigen
presentation and T cell proliferation. Collectively, these attributes of solid tumors enable them to avoid normal immune surveillance.
Increased engagement of the endogenous host response is an important, if not critical, component of CAR-T cell therapy clinical success
as the recruitment into the tumor of bystander lymphocytes has been observed in tumor biopsies from patients with curative CAR-T cell
therapy. Enhancing the host’s own response to tumor cells offers an important opportunity to improve current CAR T cell responses.

<div align='center'>89</div>

CAR-T recipients may also
incur serious adverse events (“SAEs”), perhaps the most prominent of which is cytokine release syndrome (“CRS”). Believed
to be