Company: RVRC
Filing Date: 2025-08-13
Form Type: S-1/A
Source: 0001213900-25-075747
Chunk: 93

Company: Revium Rx.
Filing Date: 2025-08-13
Form: S-1/A
Chunk 93
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 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 efficacy of existing therapies. Incorporating the nano-ARB component
helps overcome this barrier by normalizing the TME through decompression of tumor blood vessels and reprogramming of fibroblasts. As
a result, therapeutic penetration is significantly enhanced.

We believe that Nano-ARB not only has the
potential to reprogram cancer-associated fibroblasts (CAFs) by decompressing blood vessels and increasing tumor vascular permeability,
but also to enhance the delivery and retention of therapeutic agents within the tumor, leveraging the Enhanced Permeability and Retention
(EPR) effect, to ultimately improve clinical outcomes.

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Nano-ARB innovative approach focuses on encapsulating
a known ARB Candesartan within PEGylated nano-liposomes, an approach that offers several key advantages, such as:

| ● | Passive targeting. PEGylated                                                                       
 nano-liposomes can exploit the enhanced permeability and retention (EPR) effect allowing           
 for passive and selective targeting of tumors, without the need for