NLSP

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READ THE INVESTOR PRESENTATION HERE

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*****BREAKING NEWS THIS MORNING

NLS Pharmaceutics and Kadimastem Enter into a Definitive Merger Agreement

PUBLISHED

NOV 4, 2024 7:00AM EST

ZURICH, SWITZERLAND and NESS ZIONA, ISRAEL / ACCESSWIRE / November 4, 2024/ NLS Pharmaceutics Ltd. (NASDAQ:NLSP) ("NLS"), a biopharmaceutical company, and Kadimastem Ltd. (TASE: KDST.TA") ("Kadimastem"), a clinical-stage cell therapy company developing and manufacturing "off-the-shelf" allogeneic cell products for the treatment of neurodegenerative diseases and potential cure of diabetes, announced today that they have entered into a definitive merger agreement (the "Merger Agreement") to combine the two companies to focus on advancing NLS' promising, first-in class Dual Orexin Agonist platform ("DOXA") and Kadimastem's allogenic cell therapy program with its clinical assets (mainly targeting diabetes and amyotrophic lateral sclerosis (ALS), with Phase 2a studies that are planned to be initiated in the U.S.following the closing of the transaction). Following the closing of the transactions contemplated by the Merger Agreement (the "Closing"), NLS intends to divest its other legacy assets (including the Mazindol ER but excluding the DOXA platform), and the net proceeds of any such disposition, after deducting certain costs, fees, and expenses as set forth in a contingent value agreement (the "CVR Agreement"), will be distributed to NLS's shareholders and warrant holders, subject to the terms of the Merger Agreement and the CVR Agreement. At the Closing, pursuant to the terms of the Merger Agreement, NLS will issue shares of its common stock to Kadimastem's shareholders based on an initial target fully diluted share split, post transaction, of 85% to Kadimastem stakeholders and 15% to NLS stakeholders, in exchange for 100% of Kadimastem's issued and outstanding shares. The target fully diluted share split of 85% / 15% is subject to adjustment pursuant to the terms of the Merger Agreement, including as a result of estimated closing cash of NLS and Kadimastem and estimated closing indebtedness of NLS. Based on the cash balance of NLS following its most recent successful financing transaction, the parties currently estimate the fully diluted share split at the Closing will be 80% to Kadimastem stakeholders and 20% to NLS stakeholders. The boards of directors of Kadimastem and NLS have unanimously approved this transaction and expect it to close in January 2025, pending approval of each of NLS' and Kadimastem's shareholders, as well as other customary closing conditions, including Nasdaq approval.

‟I believe that the merger is an outstanding opportunity to progress our proprietary DOXA platform and help to enhance Kadimastem's portfolio of neurodegenerative and diabetes candidates,″ said Alex Zwyer, Chief Executive Officer of NLS. "This transaction represents NLS' commitment to delivering value to its shareholders by preserving the value of our legacy assets, including Mazindol, through the contingent value rights agreement, while also providing the opportunity for upside in the combined company with a promising cell therapy technological platform."

Ronen Twito, Kadimastem's Executive Chairman & President, commented, "We are pleased to announce our merger with NLS and believe that the exposure of the combined company's assets to the U.S. capital markets through our new Nasdaq listing will enable us to develop our portfolio and increase Kadimastem shareholder value. We remain focused on initiating our Phase IIa multi-site clinical trial of AstroRx®, a product candidate for the potential treatment of ALS, which is planned to be initiated following the closing of the merger, and jointly progressing our diabetes program IsletRx with our U.S. based partner to a pre-investigational new drug (IND) submission with the U.S. Food and Drug Administration in the first quarter of 2025."

Professor Michel Revel, Kadimastem's Chief Scientific Officer ("CSO"), said, "I'm excited about this merger because the combined company presents a significant opportunity to progress our portfolio and product candidates into and through clinical trials. As the inventor of Rebif® (interferon beta-1a) and having had the experience of taking it from the lab to a blockbuster product on the market, I also see a tremendous opportunity for Kadimastem to further develop our product candidates for ALS and diabetes. Together with the assets from NLS, we believe that we will be well-positioned to promote and expand these promising treatments."

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®, Kadimastem‘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 Kadimastem‘s treatment for diabetes. IsletRx is comprised of functional pancreatic islet cells producing and releasing insulin and glucagon. IsletRx is intended to treat and potentially cure patients with insulin-dependent diabetes.

Kadimastem was founded by Professor Michel Revel, CSO of Kadimastem, who is 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's ordinary shares are listed on the Tel Aviv Stock Exchange.

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‍Hello Everyone,

We have a past winner back on our radar for tomorrow's session.

This one exploded double digits the last time we took a look at it.

Since the last time we looked at it the company completed a 1-40 reverse split, wiping the float down to a mere fraction of what it was.

Pull up NLSP right away.

NLSP is a clinical-stage pharmaceutical company focused on the discovery and development of innovative therapies for patients with rare and complex central nervous system, or CNS, disorders, who have unmet medical needs.

The global ADHD market is expected to reach over US$ 70 billion by 2032 growing significantly in the coming years, fueled by rising diagnosis rates and demand for innovative treatments. And amid this growing need, NLSP is making impressive progress with a promising drug that targets not only ADHD but also closely linked sleep-wake disorders.

Their lead candidate is Mazindol ER. This one is Phase 3-ready for ADHD as well as for narcolepsy, also targeting excessive daytime sleepiness—a major unmet need in worldwide that is projected to grow at nearly 10% annually.

With a proven safety profile from prior use as an appetite suppressant, Mazindol ER has the potential to move efficiently through the regulatory pipeline. NLSP has also positioned itself with a clean balance sheet, recently regaining full Nasdaq compliance and clearing all debt while raising $3.2M and with a 12-month cash runway and a binding term sheet to merge with Kadimastema larger company that has an executive team with experience taking products from the lab to the market.

CNS disorders are a diverse group of conditions that include neurological, psychiatric, and substance abuse disorders. Their discovery platform currently focuses on single molecules that function through multiple mechanisms designed to target the complexity of the CNS disease state. They believe that this approach may potentially offer new treatment options for patients, including those who are refractory to currently available treatments. Their current focus is in the therapeutic areas of rare hypersomnia disorders (conditions characterized by excessive daytime sleepiness, or EDS, such as narcolepsy) and complex neurodevelopmental disorders. Their drug development pipeline features our lead product candidate, Quilience®, for the treatment of EDS and cataplexy associated with narcolepsy, and our follow-on drug candidate Nolazol®, for the treatment of ADHD.

COMPANY HIGHLIGHTS

Mazindol ER has successfully completed a Phase 2 trial, including OLE, for narcolepsy treatment: projected to be $4.5B annual market by 2027**
Orphan Drug Designation (ODD) granted in the US and Europe
AMAZE phase 3 program starting in July 2023, secured funding for current projects and existing operations through 2025. Development of Mazindol ER is in the spotlight for progression purposes, particularly for the treatment of EDS and cataplexy in adult patients who suffer from narcolepsy
Named Patient Program for patients suffering from idiopathic hypersomnia launched in target markets across Europe
Key Executive Leadership roles filled
Pipeline progressed and expanded with long-dated IP protections in major markets
Over 100 patents in over 140 countries including technology and application for a variety of diseases such as ADHD, Cancer Fatigue, Parkinson’s and more. Not to mention that several products are nearing the end of Phase 2 and approaching NDA filing
POLARIS: Mazindol ER Phase 2 Program in Narcolepsy, consisted of two US clinicaltrials approved by the FDA, met its primary endpoint with high statistical significance and demonstrated a favorable safety and tolerability profile. These results were promising, i.e, Sustained EDS and cataplexy improvements at all time points. OLE conclusions: 6-month OLD, displayed good subject participation (87%) and retention (11.5%)
Partnership with Université de Lausanne (UNIL) (preclinical projects), University of Berne (narcolepsy reserach), Swiss Narcoslpsy Network (narcolepsy reserach) ( (BVF Partners L.P (financial partnership)
Partnerships with Patient advocacy groups including Narcolepsy Network, The Narcolepsy Foundation, The Sleep Consortium, Hypersomnia Foundation, and Wake Up Narcolepsy

PIPELINE

Lead Asset: Mazindol ER

Mazindol ER is a patented and proprietary formulation of the active compound mazindol, and are designed for once-daily dosing. Mazindol has a well-established safety record from its long history of clinical use in the United States and in Europe when the drug was approved in an immediate release formulation for the management of obesity. Mazindol was marketed for nearly 30 years under the trade name Sanorex® before being voluntarily withdrawn from the market, and the drug is no longer available nor marketed in these regions. During its time on the market, mazindol was also widely used off-label and prescribed under compassionate use for the treatment of narcolepsy for several decades. Use in these compassionate use programs has yielded evidence of positive efficacy in patents suffering from the symptoms of narcolepsy including patients that were refractory to approved treatments for the disorder. Additionally, these same programs, a retrospective analysis of investigator sponsored studies, and NLS’s own trial evaluating Mazindol ER in patients with ADHD provide evidence of the drug’s favorable safety profile at doses that yielded efficacy signals.

We believe that our lead product candidate, Mazindol ER, offers a differentiated profile with clincally meaningful advantages over current treatment options for narcolepsy for the following reasons:

Mechanism of action

If approved, Mazindol ER would be the only partial orexin 2 receptor agonist as well as the only triple monoamine reuptake inhibitor approved by the FDA for the treatment of narcolepsy. Narcolepsy is caused by a profound loss of orexin producing neurons. A partial orexin 2 receptor agonist may help to replace missing endogenous orexin peptide, addressing the underlying cause of the disease. In addition, the drug’s action as a triple monoamine reuptake inhibitor can further reduce disease specific symptoms, offering patients a treatment option that may address the two primary symptoms of narcolepsy – excessive daytime sleepiness (EDS) and cataplexy attacks – in a convenient once-daily oral tablet.

Low potential for abuse, misuse, and diversion.

Mazindol is currently classified by the DEA as a Schedule IV controlled substance . The DEA defines Schedule IV controlled substances as those “with a low potential for abuse and a low risk of dependence”. Unlike Xyrem® (sodium oxybate), the top-selling treatment for narcolepsy in the United States deemed to have a high potential for abuse/misuse (Schedule III), mazindol was never required by the FDA to have a risk evaluation and mitigation strategy (REMS) program in place to manage known or potential serious risks associated with its use.

Quilience® has potential to be administered as a monotherapy.

Narcolepsy is a difficult disorder to manage and even with available treatments, the majority of narcolepsy patients often require multiple medications to treat their symptoms. According to the current treatment guidelines (initially published in 2007) of the American Academy of Sleep Medicine, or AASM, medications for narcolepsy, at best, provide only moderate improvement in narcolepsy symptoms, and their respective side effects may limit their use. The AASM specifically highlights that future investigations should be directed toward more effective and better tolerated therapies for treatment. The Voice of the Patient report from the FDA’s patient-focused drug development initiative, published in 2014, concluded that, based on the overall benefit-risk assessment of current medications, there is a continued need for additional effective and tolerable treatment options for patients with narcolepsy. A retrospective analysis (Nittur et.al, Sleep Med. 2013 Jan;14(1):30-6) showed that mazindol has a long-term, favorable benefit/risk ratio in 60% of drug-resistant patients with hypersomnia, including a clear benefit on the two primary symptoms of narcolepsy–EDS and cataplexy.

Mazindol ER is being developed as a once-daily oral tablet administered in the morning upon wakening.

Patients have identified a need for treatment options that are easier to take, dosed less frequently, do not disrupt nighttime sleeping, and provide full day coverage of symptoms. We believe that once-daily dosing with Mazindol ER may address this need and may help improve patient compliance and adherence with treatment. Mazindol ER utilizes our patented and proprietary extended-release (ER) formulation and is being designed to optimize its pharmacokinetic and pharmacodynamic properties with a rapid onset of action and prolonged controlled therapeutic effect, allowing for a daily oral dose that effectively provides consistent and long-acting symptom control to uniquely meet the needs of patients.

Relationship Between Narcolepsy and ADHD

Narcolepsy and psychiatric disorders have a significant but under-recognized relationship in which the two may coexist. However, narcolepsy is frequently misdiagnosed initially as a psychiatric condition, contributing to protracted times for accurate diagnosis and treatment. Narcolepsy is a disabling neurological condition that carries a high risk for the development of social and occupational dysfunction. Deterioration in function associated with narcolepsy may lead to the secondary development of psychiatric symptoms and inversely, the development of psychiatric symptoms can lead to a deterioration in function and quality of life. The overlap in treatments may further enhance the difficulty to distinguish between diagnoses.

ADHD is the most common neurobehavioral disorder characterized by symptoms of inattention, impulsivity and hyperactivity with an estimated prevalence rate of approximately 4-12% worldwide, as reported by the paper, “Understanding Attention Deficit/Hyperactivity Disorder From Childhood to Adulthood,” by Drs. Timothy E. Wilens and Thomas J. Spencer.

On the surface, ADHD may appear to be the opposite of narcolepsy; however, there may actually be significant clinical similarities between the two disorders. Cumulative data on sleep problems in children and adolescents with ADHD have shown that children with ADHD have had a higher rate of restless sleep, impaired sleep, and daytime sleepiness than children without ADHD. However, it is unclear whether EDS in ADHD is due to nocturnal sleep disturbances or primary vigilance disorders because shorter sleep onset latency is assessed in ADHD patients by the Multiple Sleep Latency Test, rather than in the control group irrespective of the presence/absence of sleep disturbances.

Alternatively, problems with sleep may represent an intrinsic component of ADHD. The presence of ADHD symptoms in children and adolescents with narcolepsy has been found to be about two-fold higher than in the general control population. Adults with narcolepsy have been found to have a much greater likelihood of having a diagnosis of ADHD in childhood compared to the general control population. Hyperactivity seen in ADHD may, in fact, be a compensatory response for individuals who are under-aroused or sleepy, and ADHD symptoms contribute to poor quality of life and increased frequency of depressive symptoms, similar to narcolepsy. To the best of our knowledge, almost all of the treatments used in ADHD have mechanistic overlap with treatments used in narcolepsy for EDS, and researchers suggest that the symptoms of EDS, fatigue, and sleep fragmentation may be the cause for ADHD symptoms, which is consistent with similar findings in other hypersomnia disorders.

AstroRx, the medical product for ALS treatment that is being researched by Kadimastem, the company NLSP has signed a binding merger agreement with, was granted Orphan drug status by the FDA. This status grants the company that manufactures the drug marketing exclusivity for 7 years from the date of receipt of marketing approval of the drug. The recognition of orphan drug status also enables accelerated examination and response paths from the FDA and other regulatory authorities.
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Additionally, Kadimastem is focused on the generation and manufacturing of pancreatic insulin secreting islets (IsletRx) from embryonic stem cells for the treatment of insulin dependent diabetes such as Type 1 Diabetes. This program is in pre-clinical phase and they are moving fast down the regulatory path to start human trials. The number of patients with diabetes was estimated to be over 366 million worldwide in 2011 and is projected to be more than 552 million in 2030. The American Diabetes Association (ADA) estimated the total annual costs of diabetes to be US$223.5 billion (in the US alone). The global cost is estimated to be US$465 billion annually and will grow to about US$510 billion by 2030.

NLS Pharmaceutics and Kadimastem Announce Binding Term Sheet to Merge

The proposed transaction will create a Nasdaq-traded, biotechnology company with product candidates in advanced stages of clinical development and focused on advancing Kadimastem's allogeneic cell therapy platform

Each of Kadimastem and NLS Pharmaceutics has received commitments of support for the transaction from shareholders representing more than 40% of their respective outstanding shares

ZURICH, SWITZERLAND and NESS ZIONA, ISRAEL / ACCESSWIRE / July 29, 2024 / NLS Pharmaceutics Ltd. (NASDAQ:NLSP) ("NLS"), a biopharmaceutical company. and Kadimastem Ltd ("KDST.TA", "Kadimastem"), a clinical-stage cell therapy company developing and manufacturing "off-the-shelf" allogeneic cell products for the treatment of neurodegenerative diseases and potential cure of diabetes, announced today that they have entered into a binding term sheet for a transaction under which Kadimastem is anticipated to become a wholly owned subsidiary of NLS, and Kadimastem's shareholders will acquire an 85% interest in NLS (the "Transaction"). Upon completion of the Transaction, which is subject to, among other things, approval by NLS and Kadimastem stockholders, the combined company is expected to operate under the name Kadimastem and be traded on the Nasdaq Capital Market. Under the proposed terms, existing Kadimastem shareholders will hold 85% of the issued and outstanding shares of the merged company and the existing shareholders of NLS will hold the remaining 15% of the issued and outstanding shares of NLS.

About the Proposed Transaction

The proposed Transaction will be affected through a reverse triangular structure in which Kadimastem will become a wholly owned subsidiary of NLS. In consideration, NLS will issue its shares to the Kadimastem shareholders who, after completing the Transaction, will hold 85% of the issued and outstanding shares of NLS, and the existing shareholders of NLS will hold the remaining 15% of NLS.

The Transaction is subject to approval by Nasdaq and is structured so that NLS will remain an SEC reporting company whose shares are listed on the Nasdaq Capital Market. All but one of the NLS officers and directors is expected to resign from their positions at NLS.

Following the Transaction, the parties expect to continue developing NLS's promising, first-in class Dual Orexin Agonist platform ("DOXA") within the merged company. The remaining NLS assets are expected to be divested subject to a contingent value rights ("CVR") agreement, the proceeds of which will be distributed entirely to the current shareholders of NLS.

At the closing of the Transaction, Kadimastem will be required to have $3.5 million of cash on hand and NLS will be required to have $0.6 million of cash on hand.

The binding term sheet has been approved by the boards of directors of both companies. The definitive agreement will include customary closing conditions, including certain regulatory approvals, and approval from the shareholders of both NLS and Kadimastem Each of Kadimastem and NLS has received commitments of support for the Transaction from shareholders representing more than 40% of its outstanding shares.

In addition, as a condition to the consummation of the Transaction, the liabilities of NLS to its vendors and insiders will be settled and removed from its balance sheet.

The definitive agreement is expected to be executed in September 2024. The Transaction is expected to close before December 31, 2024.

‟We are pleased to be working together with Kadimastem as our pipelines hold significant synergies, especially in the area of diabetes which is often associated with sleep-wake dysregulation manifesting as insomnia, excessive daytime sleepiness and altered sleep architecture,″ said Alex Zwyer, Chief Executive Officer of NLS. ‟The merger with Kadimastem reflects the continued commitment of our management team and board of directors to deliver long-term value to our stockholders. In particular, NLS shareholders will have the opportunity to benefit from the equity of the merged company and, through the contingent value rights agreement, from the value of our legacy assets, including Mazindol.″

Professor Michel Revel, Kadimastem's CSO said, "I'm thrilled about this merger, and believe the combined company presents a great opportunity to enhance our portfolio and product candidates. In the past, I had the privilege of working on a medicine for multiple sclerosis, Rebif®, taking it from the lab to the market and transforming it into a blockbuster product. Similarly, I see tremendous potential here to develop our AstroRx® product candidate for ALS patients, as well as advancing our diabetes product IsletRx. Together with the assets from NLS. The completion of the Transaction is expected to promote and expand the development of Kadimastem's groundbreaking technological platform."

Ronen Twito, Kadimastem's Executive Chairman and President, commented, "The merger with NLS will enhance our visibility to the market as a Nasdaq listed company and strengthen our portfolio with the addition of DOXA. Moreover, as previously reported, our AstroRx® product candidate for Amyotrophic Lateral Sclerosis, also known as ALS, treatment received FDA approval for a Phase IIa multi-site clinical trial in the U.S.In addition, our joint development of a diabetes product with iTolerance, a U.S.-based company, proceeding towards pre-Investigational New Drug submission to the FDA. We believe that the exposure of the merged company to the U.S. capital markets will enable us to develop the company's clinical assets and increase shareholder value."

About Kadimastem

Kadimastem is a clinical stage cell therapy company whose shares are listed on the Tel Aviv Stock Exchange "KDST.TA". Kadimastem is 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®, Kadimastem‘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

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MANAGEMENT TEAM

AlexZwyer, MBA

Chief Executive Officer & Co-Founder

A co-founder of the company with extensive operational, C-level pharmaceutical experience as well as a serial entrepreneur and strong leader with a proven track-record.

Alex Zwyer has served as our Chief Executive Officer and as a Director since our incorporation in August 2015. Mr. Zwyer has over 25 years of international business experience of which more than 10 years as a C-level executive in the pharma/biotech field. In 2007, prior to, and until founding NLS in 2015, Mr. Zwyer founded a startup in the high-end luxury food sector, and served as its chief executive officer until 2015 when he successfully sold the company. From 1991 and until 2007, Mr. Zwyer served in various positions with Viforpharma AG (SWX: VIFN) (then known as Vifor (International) Inc.), most notably serving as Executive Vice President (chief operating officer), leading the company’s global regulatory affairs, medical affairs, sales and marketing as well as business development teams. Mr. Zwyer speaks seven languages fluently. Mr. Zwyer holds a B.B.A. in business administration from Oekral, Zurich, Switzerland and an executive M.B.A. from GSBA/Lorange Institute of Business, Zurich, Switzerland and an M.B.A. from University at Albany SUNY.

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GeorgeApostol, MD MS

CMO & Global Head R&D

Dr. Apostol’s career spans more than 20 years in pharma industry and consists of a broad drug development expertise across early, middle and late phases of development at the global R&D organizations of Eli Lilly, Pfizer, Abbott, Novartis, Shire and Endo.

His main areas of capability include orphan diseases in CNS, in particular Fragile X Syndrome, Alagille Syndrome, but also ADHD, anxiety, depression, migraine, Parkinson’s and schizophrenia. He has built multiple drug development teams both in the US and Europe, several receiving distinguished corporate R&D awards and achieving multiple regulatory approvals in US, EU and Japan. He holds a MD degree from the Carol Davila Medical School in Romania and a MS in Clinical Research from University of Minnesota.

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EricKonofal, MD, PhD

Chief Scientific Officer and Co-Founder

A co-founder of the company with a deep knowledge and experience in clinical and scientific research. He is also a drug-hunter & pipeline developer for sleep disorders as ADHD.

Dr. Konofal is a primary clinical and international scientific researcher, and is an accomplished drug hunter and drug pipeline developer. He is a senior medical consultant for the Pediatric Sleep Disorders Center at Robert-Debre University of Paris (APHP). Dr. Konofal served as Principal Clinical Investigator at the Clinical Pharmacology & Pharmacogenetic Department at Robert-Debre University of Paris. His research has focused on brain- and iron-dopamine interactions in subjects with neurological sleep disorders (RLS, PLMS), and ADHD. Additionally, Dr. Konofal served as a consultant at the sleep disorder center of Pitié-Salpêtrière University Hospital Group (APHP), specializing in ADHD, RLS, PLMS and CDH. He initiated previous studies based on iron and its role in the pathophysiology of ADHD, and has conducted extensive research on the relationship between the brain and iron.

He launched a clinical trial on the efficacy of mazindol in children with ADHD (clinicaltrials.gov identifier: NCT00508677) and obtained the U.S. patent for mazindol in the treatment of ADHD. Dr. Konofal wrote the scientific rationale for Nolazol® and discovered the pharmacological profile of mazindol and its orexin-2 receptor binding properties. He has authored over 70 peer-reviewed publications in the area of sleep disorders and other CNS diseases.

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ElenaThyen-Pighin

Chief Financial Officer

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Ms. Thyen-Pighin holds extensive experience in leadership and management functions as both head of finance and human resources across a number of industries. Based in Switzerland, Ms. Thyen-Pighin has a successful track record, most notably in accounting for both private and publicly listed enterprises.

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