§ 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 -- January 27, 2022 --
InvestorsHub NewsWire -- 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.
Table 1: Top line
Clinical Trial Results (Part 2)
Endpoint/Statistics |
Tollovir™(TLVR2)
N = 11 |
Placebo
N = 9 |
Difference
(Tollovir vs. Placebo) |
Time (days) to clinical improvement as measured by NEWS
2 |
|
|
|
n |
11 |
9 |
|
Mean |
8.3 |
11.0 |
-2.7 |
Median |
8.0 |
15.0 |
-7 |
|
|
|
|
Time (days) in the hospital |
|
|
|
n |
11 |
9 |
|
Mean |
10.6 |
17.8 |
-7.2 |
Median |
8.0 |
8.0 |
0 |
|
|
|
|
Time (days) to discharge from the hospital |
|
|
|
n |
10 |
6 |
|
Mean |
9.7 |
8.3 |
1.4 |
Median |
8 |
8 |
0 |
|
|
|
|
No. of Patients Deterioration to Mechanical Ventilation,
n(%) |
1 (0.09) |
3 (0.33) |
-24% |
|
|
|
|
No. of Deaths related to COVID-19 while on Treatment, n(%) |
0 (0.00) |
2 (0.22) |
-22% |
|
|
|
|
Total Deaths, n(%) |
1* (0.09) |
3 (0.33) |
-24% |
|
|
|
|
Need for supplemental oxygen, n(%) |
8(0.73) |
8 (0.89) |
-16% |
|
|
|
|
Time on supplemental oxygen |
|
|
|
n |
8 |
8 |
|
Mean |
3.8 |
5.8 |
-2 |
Median |
3.0 |
7.0 |
-4 |
|
|
|
|
C-Reactive Protein at Day 10 |
|
|
|
n |
7 |
3 |
|
Mean |
3.44 |
14.79 |
-11.35 |
Median |
1.16 |
9.98 |
-8.82 |
|
|
|
|
Interleukin-6 (IL-6) at Day 10 |
|
|
|
n |
4 |
3 |
|
Mean |
24.6 |
36.23 |
-11.63 |
Median |
10.95 |
13.8 |
-2.85 |
|
|
|
|
D-Dimer at Day 10 |
|
|
|
n |
5 |
2 |
|
Mean |
2,55.8 |
29,554.0 |
-29,298.2 |
Median |
779.0 |
29,554.0 |
-28,775.2 |
* A patient had a stroke prior receiving study
treatment. The patient received the study treatment for
the 10 days via feeding tube and achieved COVID-19 clinical
improvement as measured by NEWS2, 9 days after stopping the study
treatment (on day 19) the patient expired. |
Part 2 Conclusion:
The data from part 2 indicates that patients exposed to Tollovir
(TLVR2) + SOC showed better overall clinical improvement (as
measured by the endpoints described in Table 1 above) as
compared to patients who were treated with placebo + SOC.
Table 2: Top line Clinical Trial Results (Part
1)
Endpoint/Statistics |
Tollovir™(TLVR1)
N = 6 |
Placebo
N = 5 |
Difference
(Tollovir vs. Placebo) |
Time to clinical improvement as measured by NEWS 2 |
|
|
|
n |
0 |
0 |
|
Mean |
N/A |
N/A |
N/A |
Median |
N/A |
N/A |
N/A |
|
|
|
|
Time (duration) in the hospital |
|
|
|
n |
5 |
5 |
|
Mean |
7.2 |
6.2 |
1 |
Median |
9.0 |
6.0 |
3 |
|
|
|
|
Time to discharge from the hospital |
|
|
|
n |
3 |
4 |
|
Mean |
6.0 |
5.5 |
1 |
Median |
4.0 |
5.5 |
-1.5 |
|
|
|
|
Deterioration to Mechanical Ventilation, n(%) |
0 |
0 |
0% |
|
|
|
|
Deaths related to COVID-19 while on Treatment, n(%) |
0 |
0 |
0% |
|
|
|
|
Total Deaths, n(%) |
0 |
0 |
0% |
|
|
|
|
Need for supplemental oxygen, n(%) |
4 (0.67) |
4(0.8) |
13% |
|
|
|
|
Time on supplemental oxygen |
|
|
|
n |
4 |
|
|
Mean |
2.5 |
3.8 |
-1.3 |
Median |
1.5 |
4.0 |
-2.5 |
|
|
|
|
C-Reactive Protein at Day 10 |
|
|
|
n |
1 |
0 |
|
Mean |
6.2 |
N/A |
N/A |
Median |
6.2 |
N/A |
N/A |
|
|
|
|
Interleukin-6 (IL-6) at Day 10 |
|
|
|
n |
0 |
0 |
|
Mean |
N/A |
N/A |
N/A |
Median |
N/A |
N/A |
N/A |
|
|
|
|
D-Dimer at Day 10 |
|
|
|
n |
1 |
0 |
|
Mean |
3.84 |
N/A |
N/A |
Median |
3.84 |
N/A |
N/A |
Part 1 Conclusion:
Based on the data available in Part 1, there is not enough
evidence to assume possible differences in terms of efficacy
between Tollovir (TLVR1) + SOC vs. Placebo + SOC.
For more information, please visit www.todosmedical.com. For more
information on the Company’s CLIA/CAP certified lab Provista
Diagnostics, Inc. please visit www.provistadx.com.
About Dr. Dorit Arad
Dr. Dorit Arad is a D.C. in physical organic chemistry from the
Technion who has more than 25 years of experience in the life
science industry as an international researcher, executive and
entrepreneur. Dr. Arad is a pioneer in the discovery and
development of 3CL protease biology related products and product
candidates. Dr. Dorit Arad is an interdisciplinary scientist with
expertise in computer assisted drug design, biotechnology,
mechanism-based drug design, diagnostics, infectious disease and
cancer.
About Tollovir®
Tollovir® is a 3CL protease inhibitor and anti-cytokine
therapeutic candidate for the treatment of the nidovirus
subcategory of coronaviruses that includes SARS-CoV-2, COVID-19,
SARS-CoV-1, MERS and 229E. Tollovir is made from ingredients that
are qualified to ensure strong inhibition of the 3CL protease in
vitro, as well as strong anti-cytokine activity. Tollovir has
successfully completed a Phase 2 clinical trial in Israel for the
treatment of patients hospitalized with COVID-19. Tollovir will be
developed for the treatment of hospitalized COVID-19 (severe and
critical), moderate COVID-19, long-haul COVID and potentially
pediatric COVID-19. Todos has licensed rights for Tollovir to
T-Cell Protect Hellas S.A. for the Greek market.
About Todos Medical Ltd.
Founded in Rehovot, Israel with offices in New York City, Todos
Medical Ltd. (OTCQB:
TOMDF) engineers life-saving diagnostic solutions for the early
detection of a variety of cancers. In 2021, Todos completed the
acquisition of U.S.-based medical diagnostics company Provista
Diagnostics, Inc. to gain rights to its Alpharetta, Georgia-based
CLIA/CAP certified lab currently performing PCR COVID testing and
Provista's proprietary commercial-stage Videssa® breast cancer
blood test. 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 is
focused on the commercialization of Videssa and will bring the TBIA
tests to market thereafter.
Todos has entered into a joint venture with NLC Pharma targeting
diagnostic and testing solutions to address the COVID-19 pandemic.
The Joint Venture is pursuing the development of diagnostic tests
targeting the 3CL protease, as well as 3CL protease inhibitors that
target a fundamental reproductive mechanism of coronaviruses. The
Company’s proprietary therapeutic candidate Tollovir™ is currently
in a Phase 2 clinical trial to treat hospitalized COVID-19 patients
in Israel, and is preparing to initiate Phase 2/3 clinical trials
for both hospitalized and non-hospitalized patients in Israel.
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.
Todos is also distributing certain (COVID-19) testing materials
and supplies to CLIA-certified labs in the United States. The
products cover multiple suppliers of PCR testing kits, extraction
kits, automation materials and supplies, as well as COVID-19
antibody and antigen testing kits.
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.
Todos Corporate Contact:
Daniel Hirsch
CFO
Todos Medical
917-983-4229 x 104
Dan.h@todosmedical.com
Todos Investor Relations Contact:
Eric Ribner
LifeSci Advisors
Email: eric@lifesciadvisors.com
646-751-4363
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