Company: RVRC
Filing Date: 2025-12-12
Form Type: S-1/A
Source: 0001213900-25-121070
Chunk: 98

Company: Revium Rx.
Filing Date: 2025-12-12
Form: S-1/A
Chunk 98
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 tumor
cells, as well as induce apoptosis and autophagy. ARBs may also modulate the immune response by affecting the polarization and activation
of macrophages, T cells, and natural killer cells.

By “combination therapy” we refer
to the administration of nano-candesartan with other oncology agents, such as approved chemotherapy drugs and/or immune checkpoint inhibitors
(immunotherapy agents such as Keytruda).

<div align='center'>62</div>

Novel formulation of Nanoparticles-based ARB
(nano-ARB) was designed to improve the therapeutic outcome of chemotherapy and biological treatments, such as antibodies and immune checkpoint
inhibitors for solid cancers. Solid cancers, such as breast, lung, colon, pancreas and prostate cancers, present a formidable challenge
to oncologists, as they are often resistant to existing treatments and have poor prognosis. One major obstacle lies in the complex tumor
microenvironment (TME), which consists of various cellular and non-cellular components that interact with each other and with the tumor
cells. The TME creates a physical and immunological barrier that impairs the delivery and effectiveness of anti-cancer drugs. For example,
the tumor blood vessels are leaky and irregular, resulting in poor perfusion and hypoxia. The extracellular matrix (ECM) within the TME
is dense and fibrotic, making it difficult for drugs to penetrate and reach their intended targets. The TME also contains various immune
cells, such as macrophages, T cells, and natural killer cells, that can either suppress or enhance the anti-tumor immune response, depending
on their polarization and activation state.

To overcome the challenges posed by the TME,
nano-ARB is targeting one of the key cellular structures in the TME: cancer-associated fibroblasts (CAFs). CAFs are fibroblasts that
are recruited or transformed by tumor cells. CAFs have a multifaceted role in cancer progression, influencing everything from tumor mechanics
to the immune system. CAFs secrete various growth factors, cytokines, chemokines, and ECM components that can promote tumor growth, angiogenesis,
invasion, metastasis, and drug resistance. CAFs can also modulate the immune response by attracting or repelling immune cells, or by
inducing immunosuppression or immune activation.

As illustrated in the diagram below, the tumor
microenvironment (TME) hinders drug delivery and diminishes the