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 Stockholder,
In mid-June, I wrote to update you on the status
of our Company and our respective investments.
In that letter, I provided an update regarding
the Company’s clinical development plans, which remained on track
then, and continue to remain on track today. As a reminder, 180
Life Sciences was founded on the belief that novel
anti-inflammatory biologics that are already approved, such as
anti-tumor necrosis factor (TNF), or adalimumab, could have the
potential to address large unmet needs for a variety of additional
indications. Currently, we have an active clinical development
program that includes Phase 2a and Phase 2b proof-of-concept data
which we believe demonstrates that anti-TNF therapy can prevent the
progression of Dupuytren’s disease in its early stages, as well as
plans for two additional Phase 2 studies, one in frozen shoulder
which has recently commenced, and the other in post-operative
cognitive delirium (POCD), for which we just received grant
funding. The POCD grant will allow 180LS to determine if
administration of an anti TNF antibody, just prior to surgery,
either reduces or eliminates the cognitive delirium often seen
following surgery. This will be a randomized controlled clinical
trial using Remsima, an anti TNF antibody supplied by Celltrion. We
think all three indications share a similar underlying mechanism of
being critically dependent on TNF. (1-3).
Fibrosis of the hand, known as Dupuytren’s
disease, is a common chronic, progressive condition that causes the
fingers to curl irreversibly into the palm and can be very
disabling. In the early stage of the disease, TNF and other
pro-inflammatory cytokines, recruit myofibroblasts that lead to
fibrosis and the formation of a tiny lump, or nodule, in the palm
of the hand. The nodule is the site where the cells which drive the
disease reside. Approximately 20-35% of patients with a palmar
nodule progress to finger contractures. (4). Patients with
comorbidities, such as smoking and diabetes, are more likely to
experience disease progression. Roughly 12 million patients in the
U.S., 2.5 million in the U.K. and 22 million in the EU have
Dupuytren’s disease.(5). Currently, there is no approved treatment
for early-stage disease and patients must wait until the disease
progresses with loss of hand function before undergoing surgery or
treatment with collagenase. More than 50% of patients will
experience a recurrence of Dupuytren’s disease within five years of
non surgical intervention (6) and about 6 % after surgery (7). As
such, there is a very large unmet need for patients with
early-stage Dupuytren’s disease.
In April, we announced that positive Phase 2b
data from our trial in Dupuytren’s disease had been published in
The Lancet Rheumatology. As discussed in that publication, through
extensive research of published medical literature, as well as
direct clinical and drug development experience, Dr. Nanchahal,
Chairman of the 180LS Clinical Advisory Board , believes that the
treatment for Dupuytren’s disease is most effective during the
early nodular stage of the disease, to prevent the development of
cords and progression to finger contractures. Dr. Nanchahal’s
investigation of anti-TNF therapy in Dupuytren’s disease in a small
Phase 2a study(8) found, that intranodular injection of 40
milligrams (mg) of adalimumab in 0.4 milliliter (ml) resulted in
down-regulation of the myofibroblasts that are responsible for
fibrosis and the formation of the nodule in the early stage of
Dupuytren’s disease.
Based upon the Phase 2a findings, he determined
that a rigorous randomized, double-blind, placebo-control Phase 2b
was warranted in order to attempt to further demonstrate that
repurposing anti-TNF therapy for Dupuytren’s disease could be an
effective treatment for early-stage disease and prevent
progression. Based upon published medical literature, clinical
experience and the findings from our Phase 2a study, we believed
that a primary endpoint of nodule hardness and a secondary endpoint
of nodule size could be effective indicators, or surrogates, of
long-term disease progression in the absence of a clinical trial
with a 10-year follow-up. The trial met its primary endpoint of
nodule hardness and, importantly, also the secondary endpoint of
nodule size. These were specified before the clinical trial was
performed. The results were statistically significant when compared
to placebo. Further there is published information indicating that
module size correlates with eventual finger contraction (9). The
significant and persistent reduction in nodule size as seen in the
2B trial (1) would be expected to delay or eliminate the
progression to finger contraction.
This brings us to where we are today. We have a
scheduled meeting during Q4 2022 with the U.K.’s Medicines and
Healthcare products Regulatory Agency (MHRA) regarding our Phase 2b
data in Dupuytren’s disease, based on the initial determination by
MHRA that our chosen endpoints need further validation. At this
meeting, we plan to submit evidence to the MHRA that supports our
chosen endpoints. Once this data is submitted, we expect further
discussions with the MHRA, in which they are expected to provide
final guidance regarding the regulatory approval pathway of an
anti-TNF therapy in early-stage Dupuytren’s disease. Knowing that
this could take several months, we expect to gain clarity from the
MHRA by late first quarter of 2023.
We also continue to remain in discussions with
potential partners, and/or licensees for our Dupuytren’s
program.
In terms of additional progress, we recently
disclosed that the first patient in the preventative frozen
shoulder trial, also funded by a National Institute for Health and
Care Research (NIHR) grant, had received an injection in the trial.
There are five active sites, and we will be observing how quickly
patients can be enrolled in this trial to gain information on the
potential use of anti-TNF agents to reduce or eliminate the need
for surgical intervention in this debilitating disease. For the
POCD trial, we are gathering all the regulatory approvals necessary
to initiate patient treatment, anticipated by Q1 2023, or
earlier.
In terms of the further development of
intellectual property, we continue to make novel discoveries and
file new patents. Most recently we discovered another pro fibrotic
mechanistic pathway and showed that by blocking the protein
interleukin-33 (IL-33) and TNF receptor 2 (TNF R2), the expression
of the pro-fibrotic genes in myofibroblasts could be inhibited. The
patent was issued earlier this year.
In closing, we continue to work diligently and
efficiently to deliver treatment options for one of the largest
drivers of disease, inflammation. Our active clinical development
program currently consists of three potential indications and our
clinical development plans for all ongoing programs remain on
track. We believe that the successful execution of our current
clinical development plans over the long-term could enhance
stockholder value.
Sincerely,
/s/ James Woody MD, PhD
CEO, 180 Life Sciences
About 180 Life Sciences
Corp.
180 Life Sciences Corp. is a clinical-stage
biotechnology company driving ground-breaking studies into clinical
programs which are seeking to address major unmet medical needs.
The Company’s primary platform is a novel program to treat several
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 U.S. Food and Drug
Administration (FDA) and MHRA; the timing and outcome of the
Company’s planned meeting with MHRA, including the Company’s
ability to persuade MHRA that such chosen endpoints do not require
further validation; timing to complete required studies and trials,
and timing to obtain governmental approvals; 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, increases in interest rates which may make borrowing more
expensive and increased inflation which may negatively affect
costs, expenses and returns; 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 are not predictive of future results or 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’s securities 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; and the effect of economic downturns and
recessions. 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 June 30, 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
References:1. Anti-tumor necrosis factor therapy for early-stage
Dupuytren’s disease (RIDD): a phase 2b, randomized, double-blind,
placebo-controlled trial. Jagdeep Nanchahal, Catherine Ball, Ines
Rombach, Lynn Williams, Nicola Kenealy, Helen Dakin, Heather
O’Connor, Dominique Davidson, Paul Werker, Susan J Dutton, Marc
Feldmann, Sarah E Lamb. Lancet Rheumatology Vol 4 June 20222. Smith
SP, Devaraj VS, Bunker TD. The association between frozen shoulder
and Dupuytren's disease. Journal of Shoulder and Elbow Surgery.
2001;10(2):149-51.3. Tumor necrosis factor-α triggers a cytokine
cascade yielding postoperative cognitive decline; Niccolò
Terrandoa, Claudia Monacoc, Daqing Mab, Brian M. J. Foxwellc, Marc
Feldmann, and Mervyn Mazea, PNAS 107, 2010 pg;205194. Reilly RM,
Stern PJ, Goldfarb CA: A retrospective review of the management of
Dupuytren’s nodules. J Hand Surg Am. 2005; 30(5): 1014–8.5. The
worldwide prevalence of the Dupuytren disease: a comprehensive
systematic review and meta-analysis. Nader Salari1, Mohammad Bagher
Heydari, Masoud Hassanabadi, Mohsen Kazeminia, Nikzad Farshchian,
Mehrdad Niaparast, Yousef Solaymaninasab, Masoud Mohammadi ,
Shamarina Shohaimi and Alireza Daneshkhah . Journal of Orthopedic
Surgery and Research (2020) 15:4956. Van Rijssen AL, ter Linden H,
Werker PM. Five-year results of a randomized clinical trial on
treatment in Dupuytren's disease: percutaneous needle fasciotomy
versus limited fasciectomy. Plastic & Reconstructive Surg 2012;
129:469–77.7.Rodrigues JN, Zhang W, Scammell BE, et al.: Functional
outcome and complications following surgery for Dupuytren’s
disease: a multi-center cross-sectional study. J Hand Surg Eur Vol.
2017; 42(1): 7–17.8. Anti-Tumor Necrosis Factor Therapy for
Dupuytren's Disease: A Rand McCann, Marisa Cabrita, Jennifer
Swettenhama, Neil J. Cahoonb, Bethan Copsey c, E. Anne Francis
Peter C. Taylor a, Joanna Black c, Vicki S. Barber c, Susan Dutton
c, Marc Feldmann, Sarah E. Lamb E-Biomedicine 33 (2018) 282–2889.
Clusters in Short-term Disease Course in Dupuytren’s Participants
With Primary Dupuytren Disease Rosanne Lanting, MD, PhD, Edwin R.
van den Heuvel, PhD, Paul M. N. Werker, MD, PhD J of Hand Surgery
Am Vol 41: 2016
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