- Centers for Disease Control and Prevention (the "CDC")
reported 105,007 drug overdose deaths - with 90% involving
synthetic opioids like fentanyl
- Mazindol ER potentially offers a non-opioid alternative,
addressing the underlying neurochemical imbalances associated with
fentanyl addiction.
- Mazindol ER is patent protected beyond September 2038
ZURICH, Jan. 28,
2025 /PRNewswire/ -- NLS Pharmaceutics
Ltd. (NASDAQ: NLSP) (NASDAQ: NLSPW) ("NLS" or the
"Company"), a Swiss clinical-stage biopharmaceutical company
dedicated to developing therapies for rare and complex central
nervous system disorders, is proud to announce the launch of a
preclinical program evaluating Mazindol ER (Extended-Release) as a
novel treatment for fentanyl dependence. Fentanyl dependence is a
major global health crisis and was recently declared a national
public health emergency by the new Trump administration. In 2023,
the CDC reported 105,007 drug overdose deaths with 90% involving
synthetic opioids like fentanyl.
"The opioid epidemic, and specifically the rise of fentanyl
dependence, presents an urgent medical need for innovative,
non-opioid treatment approaches," said Alex
Zwyer, Chief Executive Officer of NLS. "We are committed to
exploring the unique pharmacological profile of Mazindol, which
targets multiple neurotransmitter systems implicated in opioid
addiction. This preclinical program represents an important step in
developing a potentially transformative therapy."
Highlights of the Preclinical Program
Mazindol, a tetracyclic compound with a distinct pharmacological
profile, has shown potential in mitigating opioid dependence by
acting on multiple neurotransmitter pathways, including:
- 5-HT1A receptor modulation: Regulates mood, anxiety, and reward
pathways, addressing psychological aspects of opioid
withdrawal.
- Mu-opioid receptor ("MOP") interaction: Provides partial
modulation of opioid effects, potentially reducing cravings and
withdrawal symptoms without reinforcing addiction.
- Orexin-2 receptor ("OX2R") partial agonist: Aids in restoring
sleep-wake cycles and enhancing cognitive stability, which are
significantly disrupted during opioid withdrawal.
Scientific Rationale
Fentanyl, a synthetic opioid that is up to 50 times more potent
than heroin, has driven a global health crisis due to its high
abuse potential and severe withdrawal symptoms. Traditional
treatments, such as methadone and buprenorphine, often come with
limitations, including risk of dependence and regulatory
hurdles.
Mazindol ER offers a potential non-opioid alternative,
addressing the underlying neurochemical imbalances associated with
fentanyl addiction while supporting recovery through its multimodal
action on neurotransmitter systems. The sustained-release
formulation provides a long-acting therapeutic effect, improving
patient compliance and minimizing withdrawal-related
disruptions.
Mechanism of Action of Mazindol ER
Mazindol's unique pharmacodynamic properties position it as a
promising candidate for opioid dependence treatment. Its mechanisms
include:
- Inhibition of dopamine and norepinephrine transporters,
restoring neurochemical balance and reducing cravings.
- 5-HT1A receptor modulation, potentially alleviating anxiety and
depressive symptoms associated with withdrawal.
- MOP agonist activity, which may help mitigate opioid withdrawal
symptoms while preventing full opioid reinforcement.
- Partial OX2R agonist activity, aiding in circadian rhythm
regulation and reducing the impact of opioid-induced sleep
disturbances.
Preclinical Study Objectives and Next Steps
The preclinical study, designated Study KO-943, will
focus on:
- Evaluating the safety and efficacy of Mazindol ER in fentanyl
dependence models.
- Assessing pharmacokinetics and pharmacodynamics in
opioid-exposed subjects.
- Exploring the impact of Mazindol ER on craving reduction,
withdrawal mitigation, and cognitive performance.
The study is expected to be completed within 12-18 months. Upon
successful results, NLS will potentially seek regulatory pathways
to advance to clinical development.
"We believe that Mazindol ER could offer a paradigm shift in
opioid addiction treatment," added Dr. Konofal, M.D./PhD, Chief
Scientific Officer of NLSP. "Our stepwise development plan
prioritizes early-stage investment to generate critical data that
will pave the way for larger-scale studies and potential
commercialization opportunities."
Existing Patent Portfolio
NLS Pharmaceutics has secured several patents supporting the
development of Mazindol ER:
- United States Patent No. 11,207,271: Covers oral
formulations containing immediate-release and sustained-release
layers of mazindol and their use in treating attention deficit
disorders ("ADHD") as well as sleep disorders.
- United States Patent No. 11,596,622: Granted for
the use of Mazindol ER in the treatment of heroin dependence,
providing a new therapeutic strategy for opioid use disorder.
These patents strengthen the Company's intellectual property
position and support the ongoing development of Mazindol ER for
various indications.
Future Outlook
NLS aims to utilize initial findings to expanded research and
potential commercialization of Mazindol ER in the treatment of
fentanyl dependence. Other pipeline candidates include:
- NLS-4 (Lauflumide): A wake-promoting agent with
applications in military and emergency response.
- NLS-11 (Benedin): A circadian rhythm modulator with
potential applications for space missions and the ultra-rare
Kleine-Levin Syndrome (KLS).
- NLS-3 (Levophacetoperane SR): A novel treatment for
ADHD and Autism Spectrum Disorders, with potential pro-drug
development.
About NLS Pharmaceutics Ltd.
NLS is a global development-stage biopharmaceutical company,
working with a network of world-class partners and internationally
recognized scientists, focused on the discovery and development of
innovative therapies for patients with rare and complex central
nervous system disorders who have unmet medical needs.
Headquartered in Switzerland and
founded in 2015, NLS is led by an experienced management team with
a track record of developing and commercializing product
candidates. NLS has recently filed a Registration Statement on Form
F-4 with the U.S. Securities and Exchange Commission (the "SEC"),
outlining the details of the proposed merger between NLS and
Kadimastem (the "Merger"). Kadimastem is a leading clinical stage
cell therapy company, developing "off-the-shelf", proprietary cell
products including human pancreatic islet-like cells capable of
secreting insulin to generate an innovative treatment intended for
the potential cure of type 1 diabetes.
Following the Merger, NLS and Kadimastem expect to continue
developing NLS's promising, first-in class Dual Orexin Agonist
platform within the combined company. The remaining NLS assets are
expected to be divested subject to a contingent value rights
agreement, the proceeds of which will be distributed entirely to
the current shareholders of NLS. For more information, please
visit www.nlspharma.com.
About Kadimastem
Kadimastem is a clinical stage cell therapy company, developing
"off-the-shelf", allogeneic, proprietary cell products based on its
technology platform for the expansion and differentiation of Human
Embryonic Stem Cells (hESCs) into functional cells. AstroRx®, the
company's lead product, is an astrocyte cell therapy in clinical
development for the treatment for ALS and in pre-clinical studies
for other neurodegenerative indications.
IsletRx is the company's treatment for diabetes. IsletRx is
comprised of functional pancreatic islet cells producing and
releasing insulin and glucagon, intended to treat and potentially
cure patients with insulin-dependent diabetes. Kadimastem was
founded by Professor Michel Revel, Chief Scientific Officer of
Kadimastem and Professor Emeritus of Molecular Genetics at the
Weizmann Institute of Science. Professor Revel received the Israel
Prize for the invention and development of Rebif®, a multiple
sclerosis blockbuster drug sold worldwide. Kadimastem is traded on
the Tel Aviv Stock Exchange (TASE: KDST).
Safe Harbor Statement
This press release contains expressed or implied forward-looking
statements pursuant to U.S. Federal securities laws. For example,
NLS is using forward-looking statements when it discusses the use
of Mazindol as a potential novel treatment for fentanyl dependence,
regulatory approval timelines, clinical trial outcomes, market
acceptance and its expected preclinical program. Further, NLS and
Kadimastem are using forward-looking statements when they discuss
the expected closing of the transaction and the potential benefits
of the transaction to NLS and Kadimastem and their respective
shareholders, as well as the expected strategic position of the
combined company following the merger, if completed. These
forward-looking statements and their implications are based on the
current expectations of the management of NLS and Kadimastem and
are subject to a number of factors and uncertainties that could
cause actual results to differ materially from those described in
the forward-looking statements. The following factors, among
others, could cause actual results to differ materially from those
described in the forward-looking statements: risks related to the
combined company's or NLS's ability to have future successful
meetings with the FDA; risks related to the companies' ability to
complete the merger on the proposed terms and schedule, including
risks and uncertainties related to the satisfaction of the closing
conditions related to the merger agreement and risks and
uncertainties related to the failure to timely, or at all, obtain
shareholder approvals for the transaction; unexpected costs,
charges or expenses resulting from the transaction and potential
adverse reactions or changes to business relationships resulting
from the announcement or completion of the proposed merger or
resulting from the trial or preclinical program and potential
adverse reactions or changes to business relationships resulting
from the announcement of the trial or preclinical program; changes
in technology and market requirements; either or both companies may
encounter delays or obstacles in launching and/or successfully
completing their clinical trials; the companies' products may not
be approved by regulatory agencies; their technologies may not be
validated as they progress and their methods may not be accepted by
the scientific community; either of both of the companies may be
unable to retain or attract key employees whose knowledge is
essential to the development of their products; unforeseen
scientific difficulties may develop with the products being
advanced by the companies; their products may wind up being more
expensive than anticipated; results in the laboratory may not
translate to equally good results in real clinical settings;
results of preclinical studies may not correlate with the results
of human clinical trials; the companies' patents may not be
sufficient; their products may harm recipients; changes in
legislation may adversely impact either or both of the companies;
inability to timely develop and introduce new technologies,
products and applications; and loss of market share and pressure on
pricing resulting from competition, which could cause the actual
results or performance of candidate products to differ materially
from those contemplated in such forward-looking statements. Except
as otherwise required by law, neither Kadimastem nor NLS undertakes
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. More detailed information about the risks and uncertainties
affecting NLS is contained under the heading "Risk Factors" in
NLS's annual report on Form 20-F for the year ended December 31, 2023, filed with the SEC, which is
available on the SEC's website, www.sec.gov, and in subsequent
filings made by NLS with the SEC, including under the heading "Risk
Factors" in NLS's registration statement on Form F-4, filed with
the SEC on December 27, 2024.
No Offer or Solicitation
This communication is not intended to and shall not constitute
an offer to buy or sell or the solicitation of an offer to buy or
sell any securities, or a solicitation of any vote or approval, nor
shall there be any sale of securities in any jurisdiction in which
such offer, solicitation or sale would be unlawful prior to
registration or qualification under the securities laws of any such
jurisdiction. No offering of securities shall be made, except by
means of a prospectus meeting the requirements of Section 10 of the
Securities Act of 1933, as amended.
Additional Information about the Transaction and Where to
Find It
In connection with the proposed transaction, NLS has filed a
Registration Statement on Form F-4, including a proxy
statement/prospectus, with the SEC. NLS may also file other
relevant documents with the SEC regarding the proposed transaction.
This document is not a substitute for the proxy
statement/prospectus or any other document that NLS may file with
the SEC. The proxy statement (if and when available) will be mailed
or delivered to shareholders of NLS and Kadimastem. INVESTORS AND
SECURITY HOLDERS ARE URGED TO READ THE PROXY STATEMENT/PROSPECTUS
AND ANY OTHER RELEVANT DOCUMENTS THAT MAY BE FILED WITH THE SEC, AS
WELL AS ANY AMENDMENTS OR SUPPLEMENTS TO THESE DOCUMENTS, CAREFULLY
AND IN THEIR ENTIRETY IF AND WHEN THEY BECOME AVAILABLE BECAUSE
THEY CONTAIN OR WILL CONTAIN IMPORTANT INFORMATION ABOUT THE
PROPOSED TRANSACTION. Investors and security holders will be able
to obtain free copies of the proxy statement/prospectus (if and
when available) and other documents containing important
information about NLS and Kadimastem and the proposed transaction,
once such documents are filed with the SEC through the website
maintained by the SEC at http://www.sec.gov. Copies of the
documents filed with the SEC by the Company will be available free
of charge on NLS's website at www.nlspharma.com.
Participants in the Solicitation
NLS, Kadimastem, and certain of their respective directors and
executive officers may be deemed to be participants in the
solicitation of proxies from NLS and Kadimastem shareholders in
respect of the proposed transaction. Information about the
directors and executive officers of NLS, including a description of
their direct or indirect interests, by security holdings or
otherwise, is set forth in NLS's Annual Report on Form 20-F for the
fiscal year ended December 31, 2023, which was filed with the
SEC on May 15, 2024. Other information regarding the
participants in the proxy solicitation and a description of their
direct and indirect interests, by security holdings or otherwise,
will be contained in the proxy statement/prospectus and other
relevant materials to be filed with the SEC regarding the proposed
merger when such materials become available. Investors should read
the proxy statement/prospectus carefully when it becomes available
before making any voting or investment decisions. You may obtain
free copies of these documents from NLS Pharmaceutics using the
sources indicated above.
NLS Contacts:
InvestorRelations@nls-pharma.com
www.nlspharma.com
Kadimastem Contacts:
Sarah Bazak, Investors
relations
s.bazak@kadimastem.com
www.kadimastem.com
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