CRS3123 / Crestone, National Institute of Allergy and Infectious Diseases - LARVOL DELTA

CRS3123 prodrugs for enhanced treatment of Helicobacter pylori infections (ESCMID Global 2026) - No abstract available

Infectious Disease

CRS3123, a novel narrow-spectrum methionyl-tRNA synthetase inhibitor, for prevention of vancomycin-resistant Enterococcus (VRE) infections in high-risk immunocompromised patients (ESCMID Global 2026) - No abstract available

Clinical • Infectious Disease

Novel tRNA Synthetase Inhibitors Increase Healthspan, Lifespan, and Autophagic Flux in C. elegans. (PubMed, Biomolecules) - "We previously demonstrated that the tRNA synthetase inhibitors mupirocin and borrelidin extend lifespan in C. elegans and S. cerevisiae and that tRNA synthetase inhibition enhances autophagy in mammalian cells. In this study, we identify four additional tRNA synthetase inhibitors, REP8839, REP3123, LysRS-In-2, and halofuginone, that extend both healthspan and lifespan in C. elegans...These phenotypes partially depend on the conserved transcription factor ATF-4. Our findings further establish tRNA synthetase inhibition as a conserved mechanism for promoting increased lifespan and now healthspan, with potential implications for therapeutic interventions targeting age-related decline in humans."

Journal • ATF4

Safety and efficacy of CRS3123 in adults with a primary episode or first recurrence of Clostridioides difficile infection: a phase 2, randomised, double-blind, multicentre, vancomycin-controlled study. (PubMed, Lancet Infect Dis) - P2 | "Both doses of CRS3123 were deemed safe and well tolerated and showed efficacy similar to vancomycin at the TOC visit, with lower rates of recurrence. Together, these data support further development of CRS3123."

Journal • P2 data • Allergy • Gastroenterology • Gastroesophageal Reflux Disease • Immunology • Infectious Disease • Pain • Pneumonia • Respiratory Diseases • Xerostomia

Repurposing antibacterial drugs identifies ridinilazole and CRS3123 as promising candidates against vancomycin-resistant enterococci. (PubMed, Sci Rep) - "In vivo studies using the C. elegans model confirmed potent efficacy, with CRS3123 reducing both E. faecium and E. faecalis burden similar to linezolid while ridinilazole were effective against E. faecium only. These findings support ridinilazole and CRS3123 as promising candidates for further VRE therapeutic development."

Journal

New investigational agents for the treatment of clostridioides difficile infections. (PubMed, Expert Opin Investig Drugs) - "Ibezapolstat, CRS3123, and ridinilazole were identified with unique mechanisms of action and narrow spectrums of activity that result in gut microbiome preservation and reduced recurrent CDI (rCDI) rates...Some have the ability to restore the microbiome (VE303) or preserve intestinal integrity (e.g. REC-3964, LMN-201, AQ)...CDI is a significant burden to the healthcare system and the quality of life for patients who suffer from CDI and rCDI. Further development of these investigational agents to prevent this cycle are of upmost importance."

Journal • Review • Infectious Disease

Microbiome Analysis of Fecal Samples Collected in a Phase 2 Clinical Trial Comparing CRS3123 vs. Vancomycin to Treat C. difficile Infection (ASM Microbe 2025) - "These findings suggest that CRS3123 exerts a more microbiome-sparing effect compared to vancomycin, particularly in preserving microbial diversity and protecting beneficial taxa. Ongoing and future analyses will integrate metagenomics, short-chain fatty acid (SCFA) profiling, bile acid quantification, and immune marker data to further elucidate the clinical implications of these microbial shifts."

Clinical • Late-breaking abstract • P2 data • Infectious Disease

Evaluation of the Potential Impact of a High-fat Meal on the Pharmacokinetics of CRS3123 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: Crestone, Inc | Active, not recruiting ➔ Completed

Trial completion

Evaluation of CRS3123 vs. Oral Vancomycin in Adult Patients With Clostridioides Difficile Infection (clinicaltrials.gov) - P2 | N=43 | Completed | Sponsor: Crestone, Inc | Active, not recruiting ➔ Completed | N=108 ➔ 43

Enrollment change • Trial completion • Infectious Disease

A Phase 1, Open-Label, Randomized, Single-Dose Crossover Study to Evaluate the Potential Impact of High-fat Meal on the Pharmacokinetics of CRS3123 200 mg Capsule in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Crestone, Inc

New P1 trial

Evaluation of CRS3123 compared to vancomycin for the treatment of Clostridioides difficile infection (CDI) (ESCMID Global 2025) - No abstract available

Infectious Disease

Evaluation of CRS3123 vs. Oral Vancomycin in Adult Patients With Clostridioides Difficile Infection (clinicaltrials.gov) - P2 | N=108 | Active, not recruiting | Sponsor: Crestone, Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease

Novel drug candidates against antibiotic-resistant microorganisms: A review. (PubMed, Iran J Basic Med Sci) - "This review focuses on the resistance mechanisms of the top five threatening pathogens identified by the World Health Organization's global priority pathogens list: carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin, vancomycin-resistant Staphylococcus aureus...The novel drugs against carbapenem-resistant bacteria include LCB10-0200, apramycin, and eravacycline, while for Enterobacteriaceae, the drug candidates are LysSAP-26, DDS-04, SPR-206, nitroxoline, cefiderocol, and plazomicin. TNP-209, KBP-7072, and CRS3123 are agents against E. faecium, while Debio 1450, gepotidacin, delafloxacin, and dalbavancin are drugs against antibiotic-resistant S. aureus. In addition to these identified drug candidates, continued in vitro and in vivo studies are required to investigate small..."

Journal • Review

Antibiotics with novel mode of action as new weapons to fight antimicrobial resistance. (PubMed, Eur J Med Chem) - "Today, the pipeline of potential new treatments with these characteristics includes promising compounds such as gepotidacin, zoliflodacin, ibezapolstat, MGB-BP-3, CRS-3123, afabicin and TXA-709, which are currently in clinical trials, and lefamulin, which has been recently approved by FDA and EMA. In this review, we report the chemical synthesis, mode of action, structure-activity relationships, in vitro and in vivo activities as well as clinical data of these eight small molecules listed above."

Journal • Review • Oncology

The Urgent Threat of Clostridioides difficile Infection: A Glimpse of the Drugs of the Future, with Related Patents and Prospects. (PubMed, Biomedicines) - "Many possible drugs of the future for CDI, with diverse mechanisms of action, are in development in the form of microbiota-modulating agents (e.g., ADS024, CP101, RBX2660, RBX7455, SYN-004, SER-109, VE303, DAV132, MET-2, and BB128), small molecules (e.g., ridinilazole, ibezapolstat, CRS3123, DNV3837, MGB-BP-3, alanyl-L-glutamine, and TNP-2198), antibodies (e.g., IM-01 and LMN-201), and non-toxic strains of CD (e.g., NTCD-M3). The development of some therapeutic agents (e.g., DS-2969b, OPS-2071, cadazolid, misoprostol, ramoplanin, KB109, LFF571, and Ramizol) stopped due to failed clinical trials or unknown reasons...The current pipeline of anti-CDI medications appears promising. However, it will be fascinating to see how many of the cited are successful in gaining approval from drug regulators such as the US FDA and becoming medicines for CDI and r-CDI."

Journal • Review • Developmental Disorders • Infectious Disease