Crestone Reports Positive Phase 2 Results for CRS3123 in Treating C. Difficile Infections

Crestone, Inc., based in Boulder, Colorado, has reported promising topline results from its Phase 2 clinical trial of CRS3123, a novel drug candidate for treating Clostridioides difficile infection (CDI). This drug, which has shown a narrow spectrum and minimal disruption to normal gut microbiota in earlier studies, was evaluated in 43 patients within the primary intent-to-treat (ITT) analysis population. The clinical cure rates at the day 12 test-of-cure visit were high and comparable across all treatment groups. Specifically, 97% of patients receiving one of two dosages of CRS3123 achieved clinical cure, compared to 93% in those receiving vancomycin.

Notably, the trial revealed significantly lower recurrence rates of CDI in patients treated with CRS3123. By day 40, the recurrence rate was 4% for CRS3123, much lower than the 23% observed in the vancomycin group. Furthermore, CRS3123 was well tolerated with no serious treatment-emergent adverse events reported. Crestone intends to present these findings at an upcoming medical conference.

CDI is recognized as the most prevalent hospital-acquired infection in the U.S. and has become increasingly common in community settings, including among younger individuals. The infection affects nearly half a million people annually in the U.S. and results in approximately 30,000 deaths each year.

Dr. Thomas Louie of the University of Calgary, the principal investigator for the study, highlighted the urgent need for treatments that spare normal gut microbes to help reconstitute the microbiome and prevent further recurrences of CDI. He emphasized that the study's findings support further development of CRS3123 as a potential therapeutic agent.

Dr. Mark Wilcox from the University of Leeds, who also played a significant role in the study, noted that the ability to curb C. difficile while preserving healthy intestinal flora is a key goal for CDI therapeutics. He stated that the Phase 2 study outcomes reinforce this objective.

Dr. Jon Bruss, Acting Chief Medical Officer of Crestone, expressed satisfaction with the results, acknowledging the challenges posed by the pandemic on healthcare and thanking all those involved in the study for their contributions.

Following these positive results, the National Institute of Allergy and Infectious Diseases (NIAID) has exercised an option under an existing agreement to provide $4.5 million in new funding for microbiome analyses, manufacturing process optimization, and other supporting studies in Phase 2. This funding is part of a larger project financed with federal funds from NIAID.

Dr. Urs Ochsner, co-Founder, Vice President of R&D, and CEO of Crestone, expressed gratitude for the scientific input and financial support from NIAID, noting that the total funding for the Phase 2 development of CRS3123 now exceeds $28 million. He looks forward to further discussions with the FDA, development partners, and investors to accelerate pivotal CDI studies with CRS3123.

The Phase 2 trial was a randomized, double-blind, comparator-controlled, multicenter study that assessed the safety and efficacy of two dosages of CRS3123 (200 mg and 400 mg) administered twice daily compared to vancomycin 125 mg administered four times daily. The study enrolled 43 adults diagnosed with either a primary episode or first recurrence of CDI across sites in the U.S. and Canada. The treatment duration was 10 days for all groups. The primary endpoint was the clinical cure rate at day 12 in the ITT population, while secondary and exploratory endpoints included recurrence rates, global cure rates, time to resolution of diarrhea, and the impact of CRS3123 on gut commensal bacteria.

CDI, identified by the Centers for Disease Control and Prevention (CDC) as an urgent threat, presents with symptoms such as painful diarrhea, mental anguish, and potentially life-threatening conditions like toxic megacolon. Current treatments using broad-spectrum antibiotics often fail to prevent recurrences, leading to high morbidity and mortality rates. An effective therapy that treats CDI while preventing recurrence remains critically needed.

CRS3123, a small molecule, inhibits a specific bacterial methionyl-tRNA synthetase, making it effective against C. difficile without affecting human cells or other beneficial gut bacteria. It also blocks toxin production and spore formation. The FDA has granted QIDP and Fast Track designations to CRS3123 for CDI treatment. Crestone, Inc. is focused on developing novel antimicrobial drugs, with CRS3123 being a key candidate in their pipeline. The company has received over $50 million in research and development grants and contracts, supporting its efforts to bring innovative treatments to market.

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