Matinas BioPharma Holdings, Inc. announced that the independent Data and Safety Monitoring Board of the EnACT trial has completed a prespecified review of the third cohort and unanimously recommended progression to the fourth and final cohort of patients. Enrollment in the next randomized EnACT cohort, with 40 active-treatment patients, is expected to begin early first quarter 2022. EnACT is a Phase 2 prospective, randomized, open-label, sequential cohort study, financially supported by the National Institutes of Health, evaluating the safety, tolerability and efficacy of MAT2203 in approximately 100 HIV-infected patients with cryptococcal meningitis . MAT2203 utilizes the Company’s LNC platform delivery technology to orally deliver the traditionally IV-only fungicidal drug, amphotericin B. The EnACT trial includes a total of four cohorts of patients, with the first two cohorts testing MAT2203 as early stepdown therapy following initial treatment with IV amphotericin B during the induction period, and the second two cohorts testing MAT2203 as potential monotherapy. The induction period for all patients in each cohort is 14 days, followed by an additional four weeks of treatment during a consolidation/maintenance period. All patients in the induction period of EnACT receive background therapy of flucytosine, also known as 5-FC, which is specifically recommended to be used with amphotericin B as standard-of-care treatment during induction in patients with CM. During the consolidation/maintenance period, all patients receive 800 mg/day of fluconazole. An independent DSMB oversees the safety of the study and reviews all available data from each cohort for both safety and efficacy and makes a recommendation on whether to proceed to the next cohort of patients. In the MAT2203 arm of Cohort 1, 10 patients received IV amphotericin B for the first five days of induction, followed by ten days of oral MAT2203 . In the MAT2203 arm of Cohort 2, 40 patients first received IV amphotericin B for two days, followed by thirteen days of oral MAT2203 . In both Cohorts 1 and 2, treatment with MAT2203 was continued after induction during the next four weeks of consolidation/maintenance treatment, administered with 800 mg/day of fluconazole. In the MAT2203 arm of Cohort 3, 10 patients received 5 days of oral MAT2203, followed by 10 days of IV amphotericin . In the MAT2203 arm of Cohort 4, 40 patients will receive MAT2203 for the entire 14-day induction period. In both Cohorts 3 and 4, treatment with MAT2203 will continue after induction during the next four weeks of consolidation/maintenance treatment, administered alongside 800 mg/day of fluconazole. The primary efficacy endpoint for EnACT is the quantitative microbiologic clearance rate of Cryptococcus yeasts from CSF, termed Early Fungicidal Activity . This is a quantitative measurement of the efficacy of antifungal agents as well as a key surrogate marker for survival. The primary EFA endpoint is measured from the first CSF culture with 3-4 repeated cultures obtained over the first two weeks of treatment. The prespecified endpoint threshold was achieving EFA >0.20 log10 CFU/mL/day, recognizing that EFAs of less than 0.20 are strongly associated with significantly higher mortality and worse clinical outcomes. Standard of care active control HIV patients with cryptococcal meningitis are included in EnACT, primarily to assess patient safety. The control arms for Cohorts 1, 2 and 3 included 4, 17 and 4 patients, respectively, and expect that the control arm for Cohorts 4 will include 16 patients. In the control arms, patients receive IV amphotericin for 7 days, followed by a high dose of oral fluconazole for 7 days, and then transition to 800 mg/day of fluconazole for the 4-week consolidation phase. Either amphotericin B deoxycholate or liposomal amphotericin B can be used in the control arm. EnACT was not powered to formally test comparisons with the control arm standard of care. The FDA has designated MAT2203 as a Qualified Infectious Disease Product with Fast Track status for four indications, specifically, the prevention of invasive fungal infections due to immunosuppressive therapy, and the treatment of invasive candidiasis, invasive aspergillus and cryptococcal meningitis. In addition, the FDA has granted orphan drug designation to MAT2203 for the treatment of cryptococcosis.