Company: RVRC
Filing Date: 2025-12-12
Form Type: S-1/A
Source: 0001213900-25-121070
Chunk: 99

Company: Revium Rx.
Filing Date: 2025-12-12
Form: S-1/A
Chunk 99
---
 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.

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'>63</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 for pancreatic
cancer patients, particularly those with the poorest prognosis and limited treatment options. The results of the study are presented
below.

Figure 11: Kaplan– Meier curves for overall survival by treatment groups. The median overall survival was 15.1 months in the ACEI/ARB group, 8.9 months in the non-ACEI/ARB with hypertension group, and 9.5 months in the non- hypertension group (1)

In another clinical study evaluating the combination
of gemcitabine and candesartan (2), the investigators recommended a candesartan dose of 16 mg alongside gemcitabine for the treatment
of advanced pancreatic cancer. The study concluded that this regimen is both feasible and safe in