3CL Protease Inhibitor NLC-001 Added to COVID-19-focused Joint Venture Between Todos Medical and NLC Pharma

·       NLC-001 is a proprietary blend of plant extracts administered orally as dietary supplement

·       US FDA granted Certificate of Free Sale for NLC-001 on August 28, 2020

·       JV evaluating potential of NLC-001 to treat COVID-19 in clinical studies in Israel

·       Todos evaluating commercialization options for NLC-001 Worldwide

Rehovot, Israel – (NewMediaWire) – September 17, 2020 – Todos Medical Ltd. (OTCQB: TOMDF), an in vitro diagnostics company focused on developing and distributing comprehensive solutions for COVID-19, and developing blood tests for the early detection of cancer and Alzheimer’s disease, today announced that NLC Pharma has added the dietary supplement NLC-001 to its joint venture with Todos Medical. NLC-001 is an orally administered proprietary blend of plant extracts that includes a powerful potential 3CL protease inhibitor that could help support and maintain healthy immune function. The 3CL protease plays a vital role in the intracellular replication of coronaviruses, and 3CL protease inhibition is being evaluated as a potential therapeutic target for coronaviruses.

“In looking at the landscape for COVID-19, it is becoming clear that despite the large number of alternatives being investigated and used today, some of our best weapons may in fact be natural oral compounds that help to boost immunity or reduce excessive inflammation,” said Jorge Leon, Ph.D., Chief Medical and Scientific Officer for Todos Medical. “Using 3CL protease inhibitors to help support immune function against coronaviruses is based on sound science. The role of a 3C protease inhibitor could be to slow or stop viral reproduction. This could support and maintain healthy immune function by giving the body time to recognize a coronavirus and mount an immune response to terminate the virus.  Pfizer recently announced the development of such an inhibitor as a potential pharmaceutical drug for COVID-19. NLC Pharma had worked in parallel with Agouron (later acquired by Pfizer) for many years to identify 3C inhibitors for Human rhinovirus (HRV). We believe the NLC-001 3CL protease inhibitor may ultimately prove to help support and maintain healthy immune function against various strains of coronaviruses, as it is based on a fundamental mechanism that does not change within the coronavirus family.”

Under the terms of the agreement, Todos has been granted exclusive worldwide distribution rights for various formulations of NLC-001, excluding Israel, as well as a right of first refusal to develop pharmaceutical drugs based on the NLC technology. Todos is responsible for all commercial activities, including manufacturing, clinical testing, marketing and distribution outside of Israel. NLC will be responsible for the commercialization of NLC-001 in Israel. NLC-001’s active ingredient is on the Israel Ministry of Health’s authorized dietary supplement import list. The U.S. Food & Drug Administration (FDA) granted a Certificate of Free Sale for NLC-001 to the Joint Venture’s U.S.-based contract manufacturer on August 28, 2020. NLC-001 has not received FDA approval as a prophylactic or as a therapeutic intervention for COVID-19. The companies will work together to meet the remaining regulatory requirements to distribute branded versions of NLC-001 as a dietary supplement to help support and maintain healthy immune function in the United States. NLC Pharma has filed multiple patent applications covering the NLC-001 program worldwide.

“We started developing 3C protease inhibitors in 1987 as an antiviral against HRV and since early 2000, when SARS surfaced, we have been diligently advancing both our diagnostic and therapeutic understanding of the 3C protease,” said Dorit Arad, Ph.D., President & Chief Scientific Officer of NLC Pharma. “At a time when others are focused on a vaccine, we are targeting the reproduction mechanism of the coronavirus. Unlike vaccine targets, this mechanism does not change even when the virus mutates.  A safe dietary supplement that can help support and maintain healthy immune function by slowing or stopping viral replication, giving the body’s immune system time to mount an appropriate response, is the best route to re-open economies safely and achieve the desired herd immunity. For this strategy to be effective, screening and diagnostic technologies will become more important than ever, and because of this, we believed that Todos was the right partner for this potentially game-changing dietary supplement.”

“We are extremely excited to add NLC-001 to our joint venture with NLC Pharma due to its strong safety profile, as demonstrated by being granted a Certificate of Free Sale by the FDA,” said Gerald Commissiong, President & CEO of Todos Medical. “Selected dietary supplements represent some of the most accessible and close-to-market alternatives to improve immune function. NLC is advancing clinical studies at hospitals in Israel to evaluate the efficacy of NLC-001 in the treatment of hospitalized COVID-19 patients. We believe NLC-001 certainly warrants commercialization in the United States as a dietary supplement, without therapeutic claims. We are currently evaluating the best commercialization path for NLC-001.”

Key Scientific Publications related to potential of 3C Protease Inhibitors for COVID-19

Science Translational Medicine

3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice (https://stm.sciencemag.org/content/12/557/eabc5332 )

Abstract

Pathogenic coronaviruses are a major threat to global public health, as exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound 1 day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses.

International Journal of Microbial Agents

Potential of coronavirus 3C-like protease inhibitors for the development of new anti-SARS-CoV-2 drugs: Insights from structures of protease and inhibitors (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286838/ )

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), which belong to the same Betacoronavirus genus, induces severe acute respiratory disease that is a threat to human health. Since the outbreak of infection by SARS-CoV-2 began, which causes coronavirus disease 2019 (COVID-19), the disease has rapidly spread worldwide. Thus, a search for effective drugs able to inhibit SARS-CoV-2 has become a global pursuit. The 3C-like protease (3CLpro), which hydrolyses viral polyproteins to produce functional proteins, is essential for coronavirus replication and is considered an important therapeutic target for diseases caused by coronaviruses, including COVID-19. Many 3CLpro inhibitors have been proposed and some new drug candidates have achieved success in preclinical studies. In this review, we briefly describe recent developments in determining the structure of 3CLpro and its function in coronavirus replication and summarize new insights into 3CLpro inhibitors and their mechanisms of action. The clinical application prospects and limitations of 3CLpro inhibitors for COVID-19 treatment are also discussed.

For information related to Todos Medical’s COVID-19 testing capabilities, please visit www.todoscovid.com

For testing and PPE inquiries, please email sales@todosmedical.com.

About NLC Pharma

NLC Pharma Ltd., an Israeli company, was founded by Dr. Dorit Arad, a leading physical organic chemist with more than 25 years of experience in the Life Science industry, specifically in research and development of infectious diseases. 

NLC is in the process of producing developing and commercializing a COVID-19 rapid detection kit, to prevent further spread of the pandemic. In addition, NLC aims to develop an antiviral solution for prevention and treatment of the disease. Both products – the rapid detection kit and the antiviral drug – are based on thorough extensive research and development performed on a crucial viral enzyme – the 3CLpro, a 3C-like protease that resembles the human Rhinovirus (HRV) 3C protease, which has a central role in the maturation of several coronaviruses, including the 2003 SARS-CoV and the recent SARS-CoV-2. These products can be globally deployed and serve as a platform to inhibit the spread of other viruses and infectious diseases. 

About Todos Medical Ltd.

Headquartered in Rehovot, Israel, Todos Medical Ltd. (OTCQB: TOMDF) engineers life-saving diagnostic solutions for the early detection of a variety of cancers. The Company’s state-of-the-art and patented Todos Biochemical Infrared Analyses (TBIA) is a proprietary cancer-screening technology using peripheral blood analysis that deploys deep examination into cancer’s influence on the immune system, looking for biochemical changes in blood mononuclear cells and plasma. Todos’ two internally-developed cancer-screening tests, TMB-1 and TMB-2, have received a CE mark in Europe. Todos recently entered into an exclusive option agreement to acquire U.S.-based medical diagnostics company Provista Diagnostics, Inc. to gain rights to its Alpharetta, Georgia-based CLIA/CAP certified lab and Provista’s proprietary commercial-stage Videssa® breast cancer blood test. The transaction is expected to close in the third quarter of 2020.

Todos is also developing blood tests for the early detection of neurodegenerative disorders, such as Alzheimer’s disease. The Lymphocyte Proliferation Test (LymPro Test™) is a diagnostic blood test that determines the ability of peripheral blood lymphocytes (PBLs) and monocytes to withstand an exogenous mitogenic stimulation that induces them to enter the cell cycle. It is believed that certain diseases, most notably Alzheimer’s disease, are the result of compromised cellular machinery that leads to aberrant cell cycle re-entry by neurons, which then leads to apoptosis. LymPro is unique in the use of peripheral blood lymphocytes as a surrogate for neuronal cell function, suggesting a common relationship between PBLs and neurons in the brain. In July 2020, Todos completed the acquired Breakthrough Diagnostics, Inc., the owner of the LymPro Test intellectual property, from Amarantus Bioscience Holdings, Inc. (OTC: AMBS).

Additionally, Todos has entered into distribution agreements with companies to distribute certain novel coronavirus (COVID-19) test kits. The agreements cover multiple international suppliers of PCR testing kits and related materials and supplies, as well as antibody testing kits from multiple manufacturers after completing validation of said testing kits and supplies in its partner CLIA/CAP certified laboratory in the United States. Todos has formed strategic partnerships with Meridian Health, Moto-Para Foundation to deploy COVID-19 testing in the United States.

For more information, please visit https://www.todosmedical.com/.

Forward-looking Statements

Certain statements contained in this press release may constitute forward-looking statements. For example, forward-looking statements are used when discussing our expected clinical development programs and clinical trials. These forward-looking statements are based only on current expectations of management, and are subject to significant risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements, including the risks and uncertainties related to the progress, timing, cost, and results of clinical trials and product development programs; difficulties or delays in obtaining regulatory approval or patent protection for product candidates; competition from other biotechnology companies; and our ability to obtain additional funding required to conduct our research, development and commercialization activities. In addition, the following factors, among others, could cause actual results to differ materially from those described in the forward-looking statements: changes in technology and market requirements; delays or obstacles in launching our clinical trials; changes in legislation; inability to timely develop and introduce new technologies, products and applications; lack of validation of our technology as we progress further and lack of acceptance of our methods by the scientific community; inability to retain or attract key employees whose knowledge is essential to the development of our products; unforeseen scientific difficulties that may develop with our process; greater cost of final product than anticipated; loss of market share and pressure on pricing resulting from competition; and laboratory results that do not translate to equally good results in real settings, all of which could cause the actual results or performance to differ materially from those contemplated in such forward-looking statements. Except as otherwise required by law, Todos Medical does not undertake any obligation to publicly release any revisions to these forward-looking statements to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events. For a more detailed description of the risks and uncertainties affecting Todos Medical, please refer to its reports filed from time to time with the U.S. Securities and Exchange Commission.

Investor Contact:

Kim Sutton Golodetz

LHA Investor Relations

Senior Vice President

(212) 838-3777

kgolodetz@lhai.com

Corporate Contact:

Daniel Hirsch

Todos Medical

+972.52.6420.126

Dan.h@todosmedical.com