Clinical Trial Update

Todos Medical And NLC Pharma Announce Primary And Secondary Endpoints Met In NLC-V-01 Phase 2 Clinical Trial Of Oral Antiviral 3CL Protease Inhibitor

January 28,2022 10:59 AM
- By Admin

Phase 2 Study NLC-V-01 closed early after interim data analysis due to positive clinical efficacy

§  Primary endpoint of time to clinical improvement reached with average reduction of 2.7 days in the Tollovir group vs. the placebo group

§  0% COVID-related deaths in Tollovir™ group vs. 22% COVID-related deaths in placebo group

§  Lead clinical site Shaare Zedek Medical Center now permits the use of Tollovir™ in hospitalized COVID-19 patients on a compassionate use basis

§  Company preparing Phase 2/3 clinical trial to support Emergency Use Authorizations

§  Company to host conference call today at 9:15am ET to discuss the positive Phase 2 trial results

§  Company to make a corporate presentation for Emerging Growth Conference today at 3:00pm ET

New York, NEW YORK, and Tel Aviv, ISRAEL, Jan. 27, 2022 (GLOBE NEWSWIRE) -- via NewMediaWire --Todos Medical Ltd. (OTCQB: TOMDF), a comprehensive medical diagnostics and related solutions company, together with its 3CL protease theranostic joint venture partner NLC Pharma Ltd., today 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 Shaare Zedek Medical Center now permits the use of Tollovir™ in hospitalized COVID-19 patients on a compassionate use basis.

The Company will host a conference call at 9:15am Eastern Time. The conference call link is: https://audience.mysequire.com/webinar-view?webinar_id=cd68df03-4911-4ded-a910-ba73d61afeeb.

The Company will also be presenting at Emerging Growth Conference at 3:00pm Eastern Time. The link to the presentation is: https://goto.webcasts.com/starthere.jsp?ei=1526304&tp_key=6e03917339

“It is extremely exciting to see the validation of Tollovir in a placebo-controlled trial which now allows us to continue on the clinical and regulatory path towards Emergency Use Authorization for the treatment of COVID-19 patients,” said Dr. Dorit Arad, Founder & CTO of NLC Pharma, Todos Medical’s 3CL science-based joint venture partner. “The data produced in this study closely mirrors data we generated in an Observational Clinical study conducted in 2020. The recent emergence of the Omicron variant has been pushing healthcare systems to the brink of collapse.  Tollovir could be an incredibly powerful tool to reduce death and stabilize patients faster, thereby reducing their recovery time from this debilitating disease. Tollovir will help flatten the curve by freeing up hospital capacity to see more patients and perform other more routine non-COVID related hospital treatments.”

“We are extremely pleased with the results from this clinical study in the hospital setting of our dual mechanism antiviral & anti-cytokine oral drug candidate Tollovir,” said Gerald E. Commissiong, President & CEO of Todos Medical. “We have already begun preparing manufacturing for commercial quantities of Tollovir so that we will be able to deliver shipments in jurisdictions where we expect to be granted accelerated Emergency Use Authorization (EUA), and are in the process of fine tuning our proposed Phase 2/3 clinical study protocol for hospitalized COVID-19 patients. The new protocol is the key document that will enable our regulatory team to engage with regulatory bodies worldwide, including US FDA. Our goal is to immediately target EUA in jurisdictions that will require limited additional clinical data. We are also preparing for the development of Tollovir for the treatment of: 

1) hospitalized pediatric COVID-19, 

2) moderate to severe adult COVID-19 in the outpatient setting, 

3) moderate to severe pediatric COVID-19 in the outpatient setting, 

4) the treatment of Long COVID in adults and 

5) the treatment of Long COVID in the pediatric setting.”

Study design:  

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:

(a)    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). 

(b)   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 we 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.

Table 1 and Table 2 below display the topline results for Part 2 and Part 1 (respectively) of the NLC-V-01 trial.