Company: RVRC
Filing Date: 2025-02-14
Form Type: S-1
Source: 0001213900-25-013823
Chunk: 67

Company: Revium Rx.
Filing Date: 2025-02-14
Form: S-1
Chunk 67
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s 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.

Nano-ARB is expected to reprogram CAFs by decompressing blood vessels and making tumor vasculature hyperpermeable. This would allow for enhanced permeability for therapeutic agents, as well as their retention within the tumor, known as Enhanced Permeability and Retention (EPR) effect; and allow for better clinical outcome.

Nano-ARB innovative approach focuses on encapsulating ARBs 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 
 specific ligands or receptors.                                                            |

| ● | Selective                                                                                           
 release. Specially engineered liposomes can release ARBs selectively within tumors, avoiding        
 systemic effects on blood pressure while achieving TME normalization. The nano-ARB liposomal        
 specific characteristics might trigger the release of ARBs in response to the acidic or proteolytic 
 environment of the TME.                                                                             |

<div align='center'>41</div>

| ● | Safety.                                                                                                  
 PEGylated nano-liposomes have a track record of safety, as they can evade the recognition                
 and clearance by the reticuloendothelial system (RES), prolong the circulation time, and                 
 reduce the toxicity and immunogenicity of the encapsulated drugs. ARBs have also been in                 
 clinical use for years, with a well-established safety and tolerability profile. Safety proof-of-concept 
 experiments were conducted in mice. As opposed to Valsartan, which caused reduction in the               
 blood pressure 2h after injection, the nanoparticles-based ARB at similar doses showed no                
 effect on MBP, demonstrating correctness of the working hypothesis.                                      |

| ● | Efficacy:                                                                                     
 Prof. Barenholz’s team has demonstrated initial feasibility and potential of the ARB          
 approach in preclinical studies using animal models of several solid cancers, such as breast, 
 lung, colon