Todos Medical Ltd. together with its 3CL protease theranostic joint venture partner NLC Pharma Ltd. announced positive interim data for its Tollovir™ oral antiviral 3CL protease inhibitor Phase 2 clinical trial for the treatment of hospitalized (severe and critical) COVID-19 patients. Tollovir met its primary endpoint of reducing time to clinical improvement as measured by the National Emergency Warning System 2 (NEWS2) and met several key secondary clinical endpoints, including complete reduction in COVID-19 deaths. The Company has now formally closed the Phase 2 clinical trial due to positive interim efficacy data.

Lead clinical site share Zedek Medical Center now permits the use of Tollovir™ in hospitalized COVID-19 patients on a compassionate use basis. Study NLC-V-01 was a double blinded randomized placebo-controlled study designed to evaluate the safety and efficacy of NLC-V (Tollovir™) in adult patients with a confirmed diagnosis of SARS-CoV-2 infection, who are hospitalized due to the infection.  Approximately 78 patients were set to be randomized using a 1:1 ratio (approximately 39 per arm) and stratified by weight group (<70 kg, 70-100kg, and >100kg) to receive Tollovir or placebo, in addition to standard of care. Patients who need mechanical ventilation received the randomized treatment using Liquid Syrup.  The Company paused enrollment of the NLC-V-01 clinical trial after enrollment of 31 patients to perform an interim-analysis to evaluate the safety and efficacy profile of Tollovir.

Primary Objective: To evaluate the safety and efficacy of Tollovir in addition to Standard of Care (SOC) in adult patients hospitalized due to infection with a confirmed diagnosis of SARS-CoV-2. Endpoints: Time to clinical improvement, defined as a National Early Warning Score 2 (NEWS2) of = 2 maintained for 24 hours, in the treatment group (Tollovir) compared to the control group. Time elapsed from hospitalization (1st day) until hospital discharge in patients receiving Tollovir treatment. COVID-19 - related death(s) in the treatment group (Tollovir) compared to the control group.

Incidence of deterioration and need for mechanical ventilation in both treatment group (Tollovir) and control group. Incidence and duration of time on supplemental oxygen in both treatment group (Tollovir) and control group.  Number of Patients: 31 participants (adult patients with a confirmed diagnosis of SARS-CoV-2 infection, who are hospitalized due to the infection) were enrolled in the Tollovir Phase 2 clinical trial.  The study was executed in two cohorts (parts) as follows: Part 1: Tollovir Clinical Trial Part 1 (TCTP1) (N=11): Tollovir formulation 1 (TLVR1) + SOC (N=6) vs. Placebo + SOC (N=5).

This part of the study enrolled patients from December 2020 through February 2021 primarily during the Third COVID Wave (Alpha and Beta variants). Part 2: Tollovir Clinical Trial Part 2 (TCTP2) (N=20): Tollovir formulation 2 (TLVR2) + SOC (N=11) vs. Placebo + SOC (N=9). This part of the study enrolled patients from May 2021 through November 2021 primarily during the Fourth COVID Wave (Delta variant). All study design features were identical in Part 1 and Part 2, including enrollment criteria and statistical analysis plan.

The only difference between Part 1 and Part 2 cohorts was a change in formulation of the Tollovir botanical drug formula: in TCTP1 the active drug was TLVR1 and in TCTP2 the active drug was TLVR2. TLVR1 primarily consisted of the botanical extract identify as NLC-EXT-2, discovered by Dr. Dorit Arad in 2004 as a 3CL protease inhibitor with potent anti-cytokine activity. TLVR2 consists of a formulation that includes NLC-EXT-2 and NLC-EXT-1, a newly isolated compound first identified in January 2021 as part of raw material qualification experiments that was confirmed in April 2021 to have significantly more potent 3CL protease inhibitor than NLC-EXT-2. NLC-EXT-2 has a 3CL protease ICD50 binding affinity of 20mM vs.

NLC-EXT-1 that has a 3CL protease ICD50 binding affinity of 0.8mM. Going forward for the next phase of clinical trials and commercialization, Tollovir will consist exclusively of the TLVR2 formulation that contains both NLC-EXT-1 and NLC-EXT-2 in the proprietary ratio used in Part 2 of the study (TCTP2). The data was analyzed by independent biostatistical service contractor InCSD using SAS 9.4, and the data tables below were prepared by InCSD's President Dr. Luis Rojas.

Dr. Jules Mitchel, a key clinical advisor to the Company, oversaw the analysis.