180 Life Sciences Corp. (NASDAQ: ATNF, “180 Life Sciences” or
the "Company"), a clinical-stage biotechnology company today
released the following letter to stockholders from its Chief
Executive Officer, Dr. James Woody.
Dear Fellow Stockholders,
After our press release press of last week,
which included a synopsis of the letters received from the UK
Medicine and Healthcare products Regulatory Agency (MHRA) and the
US Food and Drug Administration (FDA), we received numerous
requests from our stockholders to clarify our plans at 180 Life
Sciences for developing a novel therapy for patients with
early-stage Dupuytren’s disease and I would like to take this
opportunity to bring you up to date.
Our overall aim continues to be to develop new,
patented uses for anti-tumor necrosis factor (TNF) therapy for
major unmet medical needs. To achieve this, we plan to:
(1) Perform innovative “translational” clinical
research to improve medical care for important unmet medical needs;
and (2) Execute on our business objectives to bring beneficial
therapies to patients, and thus deliver value for our
investors.
Due to the determination, dedication, and
expertise of our consultant Prof. Jagdeep Nanchahal, who leads our
clinical trials, we have been able to complete the first
large-scale trial for early-stage Dupuytren’s disease, which was
able to continue due to Prof. Nanchahal’s leadership, unlike many
other trials that were closed due to the COVID-19 pandemic.
Early-stage Dupuytren’s disease (DD) affects millions of patients
in the US and Europe and for which there is currently no approved
therapy. Importantly, there are no randomized, placebo-controlled
trials to support other possible treatments, including the use of
radiotherapy or corticosteroids. Therefore, at present, patients
have to wait until their fingers are curled into the palm of the
hand before being offered relief via surgery or collagenase, both
of which have shortcomings, including the risk of recurrence of the
disease.
A problem to overcome when aiming to fulfil
unmet needs is the need to design new trials for conditions where
there are no previously validated endpoints. Our endpoints for
early-stage Dupuytren’s disease, nodule hardness and size, were
selected so as to obtain quantitative information in a reasonable
timeframe, i.e., 1-2 years, as opposed to a trial that followed
patients for a much longer period. For example, a trial using
clinical endpoints based on finger contraction or loss of hand
function would take about 10 years. We believe that our expert,
Prof. Nanchahal, who led our blinded randomized (meaning that
patient and medical staff do not know what treatment a patient
received) placebo controlled trial, chose innovative, insightful
and practical endpoints based on his deep knowledge of the biology
and clinical course of this disease.
Our trial met its primary endpoint, the hardness
of the injected nodules and, importantly, also the secondary
endpoint of nodule size. These were pre-specified before the
clinical trial was started, so there is no ‘cherry-picking’ of
data. The nodule in patients with early-stage Dupuytren’s disease
is the site where the cells which drive the disease process reside
and in our trial the nodule was injected four times over nine
months with adalimumab, an inhibitor of TNF, or the placebo,
saline. The results were highly statistically significant, and were
published in The Lancet Rheumatology in April 2022, and
subsequently announced. This Phase 2b trial followed on from a
prior Phase 2a trial which established the optimal dose of
adalimumab to inject into the nodule.
Since statistical significance is not understood
by all, allow me to explain that in layman’s terms. The
conventionally accepted threshold for statistical significance,
which means the possibility that the results obtained might be due
to random chance, is less than one in 20. This is summarized as a
‘p’ or probability value of less than 0.05, which is written as
p<0.05. Only a p value of less than 0.05 is considered
significant. Furthermore, the lower the p value, the greater the
statistical significance. In our trial for nodule hardness, the
statistical significance at 12 months was p=0.0002 (which is 250
times less than the accepted minimum, and hence much more
significant, meaning there was only 1 chance in 5,000 that this
result might have occurred by chance), and for nodule size (area),
the statistical significance was p=0.0025 (20 times less than the
minimum threshold for statistical significance) at 12 months.
Importantly, both parameters continued to progressively decrease
further for 9 months after the last injection, (p<0.0001 for
both nodule hardness and nodule size, i.e., 500 times less than the
minimal threshold for statistical significance). Thus, we can infer
that the local injections of adalimumab were having highly
statistically significant and lasting effects.
Next, I would like to discuss the process of
interacting with the regulatory agencies in order to gain marketing
approval for drugs and biologics, whether they be in the United
Kingdom, European Union, or with the FDA here in the US. This
process is complex. It is always lengthy and iterative, meaning
that questions and responses relating to the requirements for
eventual approval go back and forth over many months. Therefore, it
may take us the rest of the year or longer to come to an agreement
with the UK’s MHRA and maybe even longer with the FDA as to what is
necessary to gain UK and US marketing authorization. It is always
difficult to encapsulate these discussions in a brief press
release. Therefore, while we will periodically provide updates as
important details become resolved, we will not be commenting on all
of our interactions with the regulatory agencies moving
forward.
We also believe that there are other points in
the MHRA letter that were not emphasized in the press release from
last week that we believe are worth mentioning for
clarification.
- First, the MHRA did not require us
to produce any non-clinical data to support the use of anti-TNF in
patients.
- Second, the MHRA agreed that
statistical methods used to analyze the data from the trial were
appropriate and that the results were highly statistically
significant.
- Third, the MHRA noted that the
safety profile of adalimumab for early-stage Dupuytren’s disease is
likely to be more favorable than the approved indications based on
the lower frequency of injections. It is important to note that
adalimumab has been used in millions of patients with inflammatory
diseases.
- Fourth, the MHRA indicated that
they would not require another trial for the use of an adalimumab
biosimilar for early-stage Dupuytren’s disease.
It is important to note that none of the
foregoing represents final definitive positions – the agency
reserves the right to come to different determinations in the
future.
In response to the questions surrounding our end
points, we will be making a case to the MHRA to support our
position that nodule size is a relevant ‘surrogate marker’, meaning
a proxy for clinical disease progression, based on existing
published data linking nodule size and eventual finger
contraction.
While the choice of selecting relevant endpoints
for the Dupuytren’s trial is complicated because the disease
progresses slowly and no such trial had ever been done before, the
future trials in frozen shoulder and post-operative delirium that
the Company plans to conduct do not face the same challenges,
because these disorders develop over much shorter time scales. The
planned trials in patients with frozen shoulder and post-operative
delirium will assess the feasibility of conducting phase 3 clinical
trials with what we believe will be validated registration
endpoints acceptable to the regulatory agencies. As always, whether
and when the Company conducts any such additional trials will
depend on regulatory authorizations, resources, including available
funding and various other factors.
It is worth noting that for Dupuytren’s disease
and frozen shoulder, Prof. Nanchahal and the team working with him
have been awarded peer reviewed grants from public agencies to
support a significant part of the costs of these trials. We believe
this is noteworthy as this testifies to the perceived quality and
competitiveness of the work, which provides non-dilutive funding,
as only a very small percentage of proposals are funded.
To summarize, 180 Life Sciences continues to
progress with its innovative clinical development program. We are
working diligently and efficiently in order to deliver our aims for
the benefit of patients and our investor community. We look forward
to providing you future updates as our development program
continues to mature.
I also want to thank you, our stockholders, for
your continued support of 180 Life Sciences Corp.
Sincerely,
James Woody MD, PhD
CEO, 180 Life Sciences
About 180 Life Sciences
Corp.
180 Life Sciences Corp. is a clinical-stage
biotechnology company. The Company is driving groundbreaking
studies into clinical programs, which are seeking to develop
treatments for major unmet clinical needs. The Company’s primary
platform is a novel program to treat inflammatory disorders using
anti-TNF (tumor necrosis factor).
Forward-Looking Statements
This press release includes “forward-looking
statements”, including information about management’s view of the
Company’s future expectations, plans and prospects, within the safe
harbor provisions provided under federal securities laws, including
under The Private Securities Litigation Reform Act of 1995 (the
“Act”). Words such as “expect,” “estimate,” “project,” “budget,”
“forecast,” “anticipate,” “intend,” “plan,” “may,” “will,” “could,”
“should,” “believes,” “predicts,” “potential,” “continue” and
similar expressions are intended to identify such forward-looking
statements. These forward-looking statements involve significant
risks and uncertainties that could cause the actual results to
differ materially from the expected results and, consequently, you
should not rely on these forward-looking statements as predictions
of future events. These forward-looking statements and factors that
may cause such differences include, without limitation, statements
about the ability of our clinical trials to demonstrate safety and
efficacy of our product candidates, and other positive results; the
uncertainties associated with the clinical development and
regulatory approval of 180 Life Science’s drug candidates,
including potential delays in the enrollment and completion of
clinical trials, issues raised by the FDA and MHRA, timing to
complete required studies and trials, and timing to obtain
governmental approvals; the potential that earlier clinical trials
and studies may not be predictive of future results; 180 Life
Sciences’ reliance on third parties to conduct its clinical trials,
enroll patients, and manufacture its preclinical and clinical drug
supplies; the ability to come to mutually agreeable terms with such
third parties and partners, and the terms of such agreements;
estimates of patient populations for 180 Life Sciences planned
products; unexpected adverse side effects or inadequate therapeutic
efficacy of drug candidates that could limit approval and/or
commercialization, or that could result in recalls or product
liability claims; 180 Life Sciences’ ability to fully comply with
numerous federal, state and local laws and regulatory requirements,
as well as rules and regulations outside the United States, that
apply to its product development activities; the timing of filing,
the timing of governmental review, and outcome of, planned
Investigational New Drug (IND) applications for drug candidates;
current negative operating cash flows and a need for additional
funding to finance our operating plans; the terms of any further
financing, which may be highly dilutive and may include onerous
terms; statements relating to expectations regarding future
agreements relating to the supply of materials and license and
commercialization of products; the availability and cost of
materials required for trials; the risk that initial drug results
will not be able to be replicated in clinical trials or that such
drugs selected for clinical development will not be successful;
challenges and uncertainties inherent in product research and
development, including the uncertainty of clinical success and of
obtaining regulatory approvals; uncertainty of commercial success;
the inherent risks in early stage drug development including
demonstrating efficacy; development time/cost and the regulatory
approval process; the progress of our clinical trials; our ability
to find and enter into agreements with potential partners; our
ability to attract and retain key personnel; changing market and
economic conditions; our ability to produce acceptable batches of
future products in sufficient quantities; unexpected manufacturing
defects; manufacturing difficulties and delays; competition,
including technological advances, new products and patents attained
by competitors; challenges to patents; product efficacy or safety
concerns resulting in product recalls or regulatory action; changes
in behavior and spending patterns of purchasers of health care
products and services; changes to applicable laws and regulations,
including global health care reforms; expectations with respect to
future performance, growth and anticipated acquisitions; the
continued listing of the Company on The NASDAQ Stock Market;
expectations regarding the capitalization, resources and ownership
structure of the Company; expectations with respect to future
performance, growth and anticipated acquisitions; the ability of
the Company to execute its plans to develop and market new drug
products and the timing and costs of these development programs;
estimates of the size of the markets for its potential drug
products; the outcome of current litigation involving the Company;
potential future litigation involving the Company or the validity
or enforceability of the intellectual property of the Company;
global economic conditions; geopolitical events and regulatory
changes; the expectations, development plans and anticipated
timelines for the Company’s drug candidates, pipeline and programs,
including collaborations with third parties; access to additional
financing, and the potential lack of such financing; and the
Company’s ability to raise funding in the future and the terms of
such funding. These risk factors and others are included from time
to time in documents the Company files with the Securities and
Exchange Commission, including, but not limited to, its Form 10-Ks,
Form 10-Qs and Form 8-Ks, and including the Annual Report on Form
10-K for the year ended December 31, 2021 and Quarterly Report on
Form 10-Q for the quarter ended March 31, 2022, and future SEC
filings. These reports and filings are available at www.sec.gov and
are available for download, free of charge, soon after such reports
are filed with or furnished to the SEC, on the “Investors”—“SEC
Filings”—“All SEC Filings” page of our website at
www.180lifesciences.com. All subsequent written and oral
forward-looking statements concerning the Company, the results of
the Company’s clinical trial results and studies or other matters
and attributable to the Company or any person acting on its behalf
are expressly qualified in their entirety by the cautionary
statements above. Readers are cautioned not to place undue reliance
upon any forward-looking statements, which speak only as of the
date made, including the forward-looking statements included in
this press release, which are made only as of the date hereof. The
Company cannot guarantee future results, levels of activity,
performance or achievements. Accordingly, you should not place
undue reliance on these forward-looking statements. The Company
does not undertake or accept any obligation or undertaking to
release publicly any updates or revisions to any forward-looking
statement to reflect any change in its expectations or any change
in events, conditions or circumstances on which any such statement
is based, except as otherwise provided by law.
Investors:Jason AssadDirector of IR180 Life Sciences Corp(678)
570-6791Jason@180lifesciences.com
Suzanne MessereStern Investor Relations, Inc.(212)
698-8801Suzanne.Messere@sternir.com
Media Relations:David SchullRusso
Partners (212)
845-4271 David.Schull@russopartnersllc.com
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