ARV-1801 (Taksta™, fusidic acid)
ARV-1801 (Taksta™, fusidic acid) has been in clinical use outside the United States for over 50 years. It is the only member of the fusidane antibiotic class and inhibits bacterial protein synthesis by binding to elongation factor G. Fusidic acid has > 90% bioavailability after oral administration and has a narrow spectrum of activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA).
Increasing rates of antibiotic resistance is resulting in more limited options for patients with bone & joint infections, including prosthetic joint infections. Fusidic acid, compared to typical antibiotic classes, has comparatively high bone penetration which makes oral administration for failing treatment regimens an opportunity to expand treatment options.
ARV-1502, is an engineered Host Defense Peptide (HDP) with proline-rich antimicrobial peptide (PrAMP) sequences to provide broad-spectrum Gram-negative activity. ARV-1502 acts as a bacterial chaperone protein inhibitor, specifically, bacterial DnaK, dysregulating bacterial proteostasis. The inhibition of DnaK has been linked to a decrease in virulence of bacterial pathogens as displayed by an inability to form biofilms and overcome antibiotic insults. Several studies have described the involvement of DnaK in antibiotic resistance and have shown that, in the absence of functional DnaK, MDR bacteria are sensitive to several classes of antibiotics, including fluoroquinolones and β-lactam antibiotics.
Arrevus has been awarded a Fast Track NIH grant to evaluate ARV-1502’s activity in multi-drug resistant bloodstream infection. Bloodstream infections can be life-threatening, complicating and prolonging hospital stays, and resulting in high mortality rates, exceeding 30% in many studies with a need for newer therapies that are active against the growing threat of antibiotic resistance. 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 is expanding the success of ARV-1502 into the first platform of bacterial DnaK inhibitors, the Insect Derived Anti-Infective (IDEA) platform that will permit screening of activity against other clinical pathogens.
ARV-1803 (allo-aca) is a second generation (optimized) leptin receptor (ObR) antagonist. Allo-aca binds selectively and tightly to ObR at Site III ObR binding site; sequences of human, rat and mouse Site III are 100% identical, thus rodent models well represent interactions in human tissue. The efficacy of Allo-aca has been proven in a mouse model of triple-negative breast cancer when administered subcutaneously and inhibits leptin-dependent proliferation of ObR-positive GBM cells in a concentration-dependent manner. Allo-aca can also penetrate the blood brain barrier after systemic administration.
Glioblastoma multiforme (GBM) is the most malignant primary tumors of the central nervous system. The standard therapy for GBM involves surgery, radiotherapy and chemotherapy. However, despite significant advances in surgical procedures, radiotherapy and advanced chemotherapeutic regimens, the prognosis of patients with GBM remains very poor. Numerous clinical trials have explored the use of targeted biologic agents (e.g., antiangiogenic, tyrosine kinase and metabolic inhibitors) but these attempts have not translated into clinically significant improvement in patient survival. Thus, the identification of new biotargets and development of innovative clinical regimens remains a critical unmet need in GBM management. Exploring the combination of ARV-1803 with cytotoxic chemotherapy and radiotherapy could yield new therapeutic options.