Acurx Pharmaceuticals announced its lead product candidate, ACX-362E, has successfully completed the 68-subject, double-blind, placebo-controlled, multiple-ascending dose Phase 1 clinical trial of ACX-362E in healthy volunteers. The Phase 1 clinical trial was first-in-man for a new class of antibiotics which work by inhibiting DNA synthesis in certain bacterial cells (pol IIIC inhibitors). Pol IIIC is required for DNA replication of many Gram-positive pathogens, including Clostridioides as well as Enterococcus, Staphylococcus, and Streptococcus. Multiple dose levels up to 450 mg BID for 10 days were shown to be well tolerated. Any adverse events attributed to ACX-362E were mild, transitory, and did not interrupt treatment in any subject. Blood levels of ACX-362E show low systemic exposure, indicating poor oral absorption and desirable in treating CDI. Additionally, fecal concentrations of ACX-362E at higher dose levels rapidly exceeded the concentrations known to inhibit C. difficile by several hundred-fold and were sustained for the duration of the 10-day treatment period.

ACX-362E is a novel, oral antibacterial agent for the treatment of Clostridioides difficile infection (CDI), an acute, serious, potentially life-threatening, intestinal infection. This Phase 1 study included a 6-subject vancomycin treatment arm (the current standard of care for CDI) for comparative microbiome analysis by Dr. Kevin Garey, Professor, University of Houston College of Pharmacy and Principal Investigator for this aspect of the trial. ACX-362E effects on the fecal microbiome were compared to those produced by vancomycin over the 10-day treatment course. The results demonstrate that while vancomycin significantly disrupts Bacteroidetes and Firmicutes, deemed to constitute more than 80% of the favorable microbiota in the gastrointestinal tract, ACX-362E had minimal impact on the Bacteroidetes and Firmicutes. Specifically, vancomycin treatment resulted in a 3-4 log reduction in Bacteroides while ACX-362E doses of 300 or 450 mg BID showed minimal effect.

"The safety data are impressive with fecal concentrations comparable to those observed with precedent products that have advanced to demonstrate clinical success," Dr. Garey said. "For example, Bacteroides is one of the predominant species in the normal gut microbiome, and one of the most important in preventing colonization with C. difficile. Bacteroides represents the Bacteroidetes family of bacteria, which along with Firmicutes comprise the predominant portion of the normal gut flora often reported to exceed 80% of the microbiome." He stated further, "The minimal disruption to the healthy gut microbiome identified in this Phase 1 study population should offer advantages over other therapeutic options for an initial episode of CDI if these salutary effects on the gut microbiome translate into the clinical benefit of reducing recurrent infection."

"We are very encouraged by these data showing that at well-tolerated doses ACX-362E reaches concentrations in the colon that are anticipated to have a highly favorable therapeutic index for patients with CDI," said Robert J. DeLuccia, Co-Founder and Managing Partner of Acurx. "The safety, fecal concentration, low systemic exposure and, most importantly, the minimal impact on the healthy gut microbiome provide data to guide selection of our Phase 2 dose and improve the probability of success and timeline efficiency of our Phase 2 clinical trial program."

The Phase 1 trial was a double-blind, placebo-controlled study to determine safety, tolerability, pharmacokinetics and fecal concentrations of ACX-362E in healthy volunteers conducted in the U.S. A total of 68 subjects, of which 44 were given active drug, were enrolled in 3 parts: Part 1, Single-ascending dose (n = 32); 6 active/2 placebo per dose cohorts of 150, 300, 600, and 900 mg; Part 2: Food-effect crossover at 300 mg (n = 8); Part 3: Multiple-ascending dose (n = 22); 6 active/2 placebo per dose cohort; BID dosing x10 days; 30-day follow-up visit for microbiome sampling; dose cohorts of 300 and 450 mg. Additionally, it included an "Active" control group for microbiome studies, oral vancomycin q6H x10 days (n = 6)

Safety information was analyzed through assessment of adverse events and other standard safety measures, while concentrations of ACX-362E were determined in both the blood and the feces, the latter being the critical site of drug delivery for treating CDI. In addition, Acurx partnered with Dr. Kevin Garey's laboratory at the University of Houston to perform state-of-the-art microbiome testing of gastrointestinal flora in trial subjects.

FDA granted Fast Track Designation to ACX-362E in January, 2019. FDA Fast Track Designation is a process designed to facilitate the development and expedite the regulatory pathway of new drugs to treat serious or life-threatening conditions and that fill a high unmet medical need. ACX-362E is a novel, first-in-class, orally administered antibacterial. It is the first of a novel class of DNA polymerase IIIC inhibitors under development by Acurx to treat bacterial infections. Acurx acquired ACX-362E from GLSynthesis, Inc. in February 2018.

ACX-362E is a Qualified Infectious Disease Product (QIDP) for the oral treatment of patients with Clostridium difficile infection (CDI). Under QIDP designation, ACX-362E will now be eligible to benefit from certain incentives for the development of new antibiotics provided under the Generating Antibiotic Incentives Now Act (the GAIN Act). These incentives include Priority Review and eligibility for Fast Track status, the latter of which Acurx has already applied for and been granted by FDA. Further, if ultimately approved by the FDA, ACX-362E is eligible for an additional five-year extension of Hatch-Waxman marketing exclusivity. ACX-362E is being developed as a targeted, narrow spectrum oral antibiotic for the treatment of patients with CDI. Acurx is planning to advance ACX-362E into a Phase 2 clinical trial in first quarter 2020. The CDC (Centers for Disease Control & Prevention) has designated Clostridium difficile bacteria as an urgent threat highlighting the need for new antibiotics to treat CDI.

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