BOULDER, Colo.--(BUSINESS WIRE)--Crestone, Inc. (“Crestone”) today announced positive topline results from the Phase 2 clinical trial evaluating CRS3123 in patients with Clostridioides difficile infection (CDI). CRS3123 is a novel drug candidate that has demonstrated narrow spectrum and minimal disruption of normal gut microbiota in preclinical and Phase 1 studies. Among the 43 patients in the primary intent-to-treat (ITT) analysis population, clinical cure rates at the day 12 test-of-cure visit were comparable in all three treatment groups, including 28/29 (97%) in patients receiving one of two dosages of CRS3123 versus 13/14 (93%) in those receiving vancomycin. There were no clinical failures at the day 12 time point; the results in two patients were indeterminate.
Importantly, rates of CDI recurrence were considerably lower in those patients who received CRS3123. For example, at day 40 recurrence rates were 4% for CRS3123 versus 23% for vancomycin. CRS3123 was well tolerated, with no serious treatment-emergent adverse events. Crestone plans to present the results from the Phase 2 trial at an upcoming medical conference.
CDI is the most common hospital-acquired infection in the U.S. and is now even more prevalent in the community, including in younger patients. In the U.S. there are almost half a million infections each year and approximately 30,000 deaths.
Dr. Thomas Louie of University of Calgary, Canada, principal investigator for this study, stated: “Treatment of C. difficile infection remains in urgent need of agents that spare normal gut microbes, so they can reconstitute the microbiome and prevent further recurrences of CDI. The findings of this study support CRS3123 as such a candidate for further development.”
Epidemiology analysis and toxin testing for this study were performed at the University of Leeds. Dr. Mark Wilcox, Professor at Leeds Teaching Hospitals and University of Leeds and Lead on CDI for UK Health Security Agency, stated: “It is now abundantly clear that curbing C. difficile while preserving healthy intestinal flora is what we want in a CDI therapeutic. The outcome of this phase 2 study further reinforces that goal.”
“We are very pleased with these results,” said Dr. Jon Bruss, Acting Chief Medical Officer to Crestone. “This was a challenging study to execute given pandemic disruptions to healthcare. We want to sincerely thank all the patients, families, clinicians and collaborators who contributed to the generation of these important data.”
The company also announced that, based upon the results of this study, the National Institute of Allergy and Infectious Diseases (NIAID) has exercised its option under an existing agreement with Crestone to provide $4.5 million in new funding for microbiome analyses, manufacturing process optimization and other phase 2 supporting studies. This project has been funded with federal funds from NIAID, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93019C00056.
“We very much appreciate NIAID’s scientific input and the more than $28 million in funding for phase 2 development of CRS3123,” said Urs Ochsner, PhD, co-Founder, Vice President of R&D and CEO at Crestone. “With these topline data and further data to come in the next few months, we look forward to discussions with the FDA and prospective development partners and investors about accelerating into pivotal CDI studies with CRS3123,” said Dr. Ochsner.
About the Phase 2 Clinical Trial of CRS3123
The Phase 2, randomized, double-blind, comparator-controlled, multicenter study evaluated safety and efficacy of two dosages of CRS3123 (200 mg and 400 mg) administered twice-daily compared with vancomycin 125 mg administered four times daily in 43 adults diagnosed with a primary episode or first recurrence of CDI. The duration of treatment for all study treatment arms was 10 days. Patients with clinically documented, toxin-positive CDI were enrolled at sites in the U.S. and Canada. The primary endpoint was defined as the rate of clinical cure at day 12 in the ITT population. Secondary and exploratory endpoints included rates of recurrence and global cure, time to resolution of diarrhea and the effect of CRS3123 on commensal bacteria in the gut.
About C. difficile Infection
CDI has been identified by the Centers for Disease Control and Prevention (CDC) as an “urgent” threat. CDI is an infection of the gut with symptoms of painful diarrhea, associated mental anguish and sometimes toxic megacolon or death. Currently, most patients are treated with suboptimal, broad-spectrum antibiotics that prevent healthy gut microbiota from recovering, contributing to CDI recurrence rates of 20-40%. Once CDI recurs, it is more likely to recur again and again even after further treatment with existing therapeutics, leading to substantially increased morbidity and mortality. 30-day CDI mortality rates ranging from 6% to 11% have been reported by CDC and multiple other sources. Among Medicare beneficiaries over 65 with a first CDI episode, mortality from all causes within 12 months was between 35% and 45%. An effective therapy that treats CDI while preventing recurrent CDI continues to be urgently needed.
About CRS3123
CRS3123 is a small molecule that selectively inhibits one form of the bacterial methionyl-tRNA synthetase, which is the mechanistic basis of its narrow spectrum. This target is not present in human cells, nor in other important bacterial species that are part of the normal microbiota of the gut. As a protein synthesis inhibitor, CRS3123 blocks not only C. difficile growth, but also toxin production and spore formation. In Phase 1 trials in healthy subjects and in this Phase 2 trial in CDI patients, CRS3123 achieved high intestinal concentrations, low systemic exposure and was generally safe and well tolerated. The FDA has granted QIDP and Fast Track designations to CRS3123 for the treatment of CDI.
About Crestone, Inc.
Boulder, Colorado-based Crestone, Inc. is a clinical stage biopharmaceutical company focused on inventing and developing novel mechanism of action, small molecule antimicrobial drugs. Its pipeline includes CRS3123 in clinical development to treat CDI and under investigation to treat symptoms of autism spectrum disorder, symptoms of Pitt Hopkins Syndrome (a rare genetic disease), prevention of graft versus host disease (GvHD) and other indications. The pipeline also includes CRS0540 to treat resistant Gram-positive infections such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), and other programs directed at nontuberculous mycobacterial (NTM) disease and other bacterial and viral diseases. The company has been funded primarily through multiple research and development grants and contracts worth more than $50 million, including two ongoing NIAID contracts for CRS3123 and CRS0540, respectively. The company is owned by its scientific founders and staff and currently retains worldwide, royalty-free rights to both programs.
