Company: RVRC
Filing Date: 2025-10-03
Form Type: S-1/A
Source: 0001213900-25-096094
Chunk: 100

Company: Revium Rx.
Filing Date: 2025-10-03
Form: S-1/A
Chunk 100
---
: 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 treatment outcomes of existing therapies. Incorporating the nano-ARB
component is intended to assist in overcoming this barrier by normalizing the TME through decompression of tumor blood vessels and reprogramming
of fibroblasts. As a result, therapeutic penetration is expected to be significantly enhanced.

<div align='center'>63</div>

The diagram is hypothetical and conceptual
in nature. It is based on published scientific literature third party studies describing the role of ARBs in tumor stroma normalization
and on exploratory preclinical studies conducted in animal models, and is not derived from clinical data with our Nano-ARB (Nano-Candesartan)
product. As such, the diagram reflects management’s current development hypothesis as to treatment outcomes.

Previous clinical evidence from retrospective
analyses and early human trials conducted by third parties suggested that cancer patients receiving candesartan or other AT1 receptor
antagonists showed improved responses to treatments such as gemcitabine and other chemotherapies (1,2). The blood pressure–lowering
effect of ARBs is well documented and generally well tolerated in patients already using them as antihypertensives; however, it may raise
concerns in individuals not accustomed to anti-hypertensive (HT) medication. However, there can be no assurance that these results will
be replicated in large scale human clinical studies or future clinical trials will demonstrate an acceptable safety profile, or that
the product will be tolerated in patients, or that it will show clinically significant results.

<div align='center'>64</div>

With respect to combination therapy, findings
from a large population-based clinical study (1) demonstrated that ARB exposure after a pancreatic cancer diagnosis was significantly
associated with improved survival. These results suggest that ARBs may represent an important therapeutic consideration