Arrevus is focusing development efforts on immune-compromised patients as they may benefit most from new anti-infective therapies that can be life-saving and life-prolonging. Given the unacceptably high mortality rates, increasing hospitalizations and frequent infections, our current development efforts are to target infections in cirrhotic patients.
- Spontaneous bacterial peritonitis – Cirrhosis is a leading cause of death globally with mortality having increased by almost 50% since 1990, mirroring the similar increase in cirrhosis-related hospitalizations. Cirrhotic patients have a compromised immune response with a consequent increase in infections; Spontaneous bacterial peritonitis (SBP) is one of the most frequent causes. SBP patients face mortality rates > 30% at 30 days with relapse rates > 20%. Our lead compound, ARV-1502, is active against common SBP pathogens (both antibiotic-sensitive and antibiotic-resistant), both in vitro (E. coli and K. pneumoniae) as well as in mouse animal models.
- Bacteremia – Bloodstream infections can complicate and prolong hospital stays potentially resulting in mortality (exceeding 30% in many studies). These outcomes are worse in cirrhosis patients due, in part, to their dysfunctional immune status. As with SBP, Gram-negative organisms (both antibiotic-sensitive and antibiotic-resistant) comprise a large proportion of these infections including A. baumanii and K. pneumoniae to which ARV-1502 already has demonstrable activity, both in vitro and in animal models. Arrevus has been awarded NIH grant funding to further evaluate ARV-1502 activity in bacteremia.
- Wound infections – Wound infections are a frequent challenge for cirrhosis patients due to immune dysfunction as well as circulatory compromise. Early intervention can prevent local extension of such infections as well as more systemic consequences. Prior studies have demonstrated ARV-1502 activity against carbapenem-resistant A. baumanii and methicillin-resistant S. aureus (MRSA) in mouse models. Outcomes in these studies included not only wound reduction in bacterial load but far quicker wound healing with a significant reduction in wound size. Arrevus has been awarded NIH grant funding to further evaluate ARV-1502 activity in wound infections.
- Urinary tract infection – Urinary tract infection is a very common infection related to cirrhosis hospitalizations and are frequently caused by multi-drug resistant pathogens that can subsequently result in kidney damage and life-threatening sepsis. Bacteria that are commonly associated with such infections include E. coli and K. pneumoniae, organisms to which ARV-1502 has well-characterized activity. Arrevus has been awarded NIH grant funding to further evaluate ARV-1502 activity in UTI.