JUPITER NEUROSCIENCES, INC. 10-K

ITEM 1. BUSINESS This Business section, along with other sections of this Annual Report on Form 10-K, includes statistical and other industry and market data that we obtained from industry publications and research, surveys and studies conducted by third parties. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information. While we believe that these industry publications and third-party research, surveys and studies are reliable, we have not independently verified such data and we do not make any representation as to the accuracy of the information. Unless the context otherwise requires, “JNS,” “we,” “us,” “our,” or the “Company” refers to Jupiter Neurosciences, Inc., a Delaware corporation. Overview Jupiter Neurosciences, Inc. (the “Company,” “we” or “us”) is a clinical stage research and development company. We have developed a unique resveratrol platform product primarily targeting treatment of neuro-inflammation. Our platform product, JOTROL, an enhanced oral formulation of resveratrol, has many potential indications of use for rare diseases. In the larger disease areas, we are primarily targeting Parkinson’s Disease and Mild Cognitive Impairment/early Alzheimer’s disease. In December 2024, we received gross proceeds of $11 million in a registered public offering (“Public Offering”) of 2,750,000 shares of our common stock, par value $0.0001 per share (“common stock”) at a price of $4.00 per share for gross proceeds of $11 million before deducing underwriting discounts and other related expenses. In connection with the Public Offering, the Company’s common stock was registered under Section 12(b) of the Exchange Act and began trading on The Nasdaq Capital Market under the symbol “JUNS.” The Company was incorporated in January 2016 under Delaware law under the name of Jupiter Orphan Therapeutics, Inc. On August 30, 2021, the Company filed a Certificate of Amendment with the State of Delaware to change its name to Jupiter Neurosciences, Inc. Business Overview The Company’s platform product, JOTROL, is an enhanced orally administered resveratrol formulation designed and intended to deliver therapeutically relevant, safe levels of resveratrol. This platform has many potential indications of use for rare diseases, which include Mucopolysaccharidoses Type 1, Friedreich’s ataxia and MELAS. In the larger disease areas, we are primarily targeting Parkinson’s Disease and Mild Cognitive Impairment/early Alzheimer’s disease. Currently available resveratrol products are associated with severe gastrointestinal (GI) side effects at the dose levels we believe are needed for therapeutic effect. Our belief, that a high dose of resveratrol is needed for therapeutic effects, is based on available scientific literature, preclinical trial results conducted in mice and rats, and previously conducted human trials with resveratrol. We believe that JOTROL, based on the results from our Phase I clinical trial conducted at the University of Miami and completed in 2021 (“Miami Clinical Trial”), has the potential to deliver a therapeutically effective dose of resveratrol in the blood stream without causing any severe side effects. Based on our own preclinical studies we believe that resveratrol has the ability to cross the blood-brain barrier. In studies conducted in Friedreich’s ataxia (FA) and Alzheimer’s disease (AD) patients, JOTROL resulted in positive effects on oxidative stress, inflammation, and mitochondrial function. The present primary target for the Company is treatment of Parkinson’s Disease (PD). The Company completed preclinical activities in a validated mouse model of Parkinson’s Disease (PD) at the University of Miami in 2021. See our “Clinical Studies”. The model of Parkinson’s Disease that was used in this clinical trial mimics many aspects of the disease utilizing a unilateral injection of a neurotoxin precursor that elicits nigral cell loss, striatal dopamine loss and behavior deficits similar to physiological characteristics of human disease. We believe that results from this clinical trial indicate that Parkinson’s Disease might be the best target for treatment and financial opportunity among the multiple indications where JOTROL might play a role. The Company is now in process to start its first Phase II trial in a patient population. This will be a Phase IIa study conducted with the assistance of Zina Biopharmaceuticals that is led by Dr. Charbel Moussa, MBBS,Ph.D. The study is expected to start in the third quarter of 2025 and have results available approximately 12 months thereafter. The trial design and outcomes are further described in this section, see JNS115. 1 We are also targeting the treatment of MCI/early Alzheimer’s Disease. We received funding of $2.2 million from the National Institute of Aging (“NIA”) in in 2020 and 2022 from a grant application for a Phase 1 study for Mild Cognitive Impairment/ Alzheimer’. In the NIA scientific review summary statement of our Phase I study application, it is stated that the NIA is looking forward to a Phase II study with an enhanced resveratrol product, based on the earlier study results from the well published Turner et al. Alzheimer’s study. We presently have a pending grant application, $16.5 Million, for a Phase II trial in MCI/early Alzheimer’s Disease with the NIA. This is an application for a 3-year Phase II trial that is expected to be completed with approximately 100 patients that have Mild Cognitive Impairment. The award will be decided in May 2025. There is no guarantee that the application will be approved, and the trial will be put on hold if an approval is not rewarded to the Company. A draft of the final study design is not yet determined but a draft synopsis is described in “Item 1. Business - “ of this Annual Report on Form 10-K. We have over the past three years received a strong interest in JOTROL from various Asian organizations. We believe that this interest has been triggered, in part, because resveratrol is becoming commonly used in Asian herbal medicines as a therapeutic strategy as described in available scientific literature published by PubMed Central: PMCID: PMC7498443 (September 2020); (ii) Hong Kong’s and China’s recent approval of the patent for JOTROL; (iii) China releasing a list of approximately 120 rare disease indications issued jointly by five national bodies, including the National Health Commission, Ministry of Science and Technology, Ministry of Industry and Information Technology, State Drug Administration, and State Administration of Traditional Chinese Medicine (May 2018), that we believe JOTROL can be applicable as a treatment for MPS-1 and MELAS in this population; (iv) recent publications regarding JOTROL in the Journal of Alzheimer’s Disease and AAPS Open (Journal of Alzheimer’s Disease 86 (2022) 173–190 February 2022; Kemper et al. AAPS Open June 2022); and (v) the projected increase of the TCM market due to several factors which of one is reformulation of existing compounds. We have recently entered into service agreements in the areas of Business Development, CMC (Chemistry, Manufacturing, and Controls), regulatory affairs and clinical trial management. These agreements are with companies that, we believe, have the knowledge and network in the South-East Asian market to accelerate steps that is needed to have a product that can have treatment value in the territory. The agreements are further described in the section “Activities in Asia”. In March 2025, the Company announced that it had entered into a partnership with Aquanova AG to develop a series of nutritional products targeting longevity, aging and Healthspan. The first three products, which will focus on the concept of “Beauty from Within”, are slated to hit the market in the third quarter of 2025 through a Direct-to-Consumer model. The Company will form a wholly-owned subsidiary to focus on the consumer market, and will market its products on a to-be-developed website targeting the US market, along with social media marketing. Internationally, the Company is focusing on partners who can market and accelerate sales, with an initial focus on the Asian region. Resveratrol Resveratrol has been studied for over 50 years by academic institutions as well as by small and large pharmaceutical companies. The multi-functional mechanisms of resveratrol are well documented in over 14,000 scientific publications. Several of these publications, including a summary paper by AY Berman et al, published in Precision Oncology 2017, point to the issue of the poor bioavailability that has stopped medical utilization of regular resveratrol and never received regulatory approval for any indication. We believe the Phase I study we have conducted indicates that we have resolved the poor bioavailability issue with JOTROL™. 2 Based upon available scientific literature, it appears that resveratrol is an activator of SIRT1, one of the mammalian forms of the sirtuin family of proteins. SIRT1 deacetylates histones and nonhistone proteins including transcription factors. The SIRT1-regulated pathway affects metabolism, stress resistance, cell survival, cellular senescence, inflammation/immune function, endothelial functions, and circadian rhythms. Resveratrol has been documented in scientific literature to activate SIRT1, NrF2, NLR3P inflammasomes and have an epigenetic mechanism and therefore is predicted to benefit diseases affected by abnormal metabolic control, inflammation, and cell cycle defects. Nonetheless, resveratrol application is a major challenge for the pharmaceutical industry, due to its poor solubility and bioavailability, as well as adverse effects, such as severe gastro-intestinal side effects when taken at effective dose levels (over 2,000 mg daily). Resveratrol has never before been developed with all the necessary steps to achieve an approval as a pharmaceutical product since the existing natural supplements cannot provide high enough levels of resveratrol in blood plasma to be able to provide a therapeutically effective dose without generating severe gastro-intestinal side effects. This means that we need to take JOTROL through the full regulatory NDA (New Drug Application) requirement to obtain a prescription marketing approval in the USA. JOTROL JOTROL was developed together with our technology partner Aquanova AG, Darmstadt, Germany. JOTROL™ is formulated with a unique patented micellar technology that is projected to increase the bioavailability profile of resveratrol. Manufacturing technology transfers were completed in 2017 and manufacturing procedures and clinical trial supply manufacturing has been completed at Catalent Pharmaceutical Services, Inc., St Petersburg, Florida. Catalent is also in process to manufacture the clinical trial supplies for our Phase IIa trial in Parkinson’s Disease. JOTROL is a micellar non-aqueous solution of resveratrol delivered in a softgel capsule. Each capsule includes 100mg of resveratrol. Pre-clinical trials in mice and rats were conducted comparing JOTROL to micronized resveratrol, labeled to have the highest bioavailability in the nutritional market, to demonstrate that we could achieve a significantly higher bioavailability. Summary details of these studies are included in “Item 1. Business” of this Annual Report on Form 10-K. A Phase I dose finding pharmacokinetic (“PK”) study in healthy volunteers was completed during the first half of 2021. The study results met our targeted goals. The results from this study will be used as a cross-reference for all indications where JOTROL will be used in Phase II and Phase III clinical trials. The Phase I results and the FDA guidance of cross-referencing is further described in “Item 1. Business” of this Annual Report on Form 10-K. The Company has not discussed the use of cross-referencing in this manner with the FDA or other comparable regulatory authorities. JOTROL Intellectual Property and License Agreement We hold an exclusive global license from Aquanova AG for micellar technologies to develop, manufacture, and sell JOTROL Our CSO, Marshall Hayward, and Aquanova’s lead scientist, Darius Benham, invented JOTROL. The patent is co-owned by Aquanova AG and us, with the application assigned to Aquanova AG. Filed in Germany on January 29, 2017, the patent (PCT/EP2017/O51659) expires in 2036 and is granted in the USA, Japan, China, Hong Kong, and specific European countries. The patent covers a solubilization product with resveratrol, polysorbate 80 and 20, MCT, and tocopherols for pharmaceutical use. It includes claims on formulation specifics, micelle size, turbidity, and treatment applications for diseases like Alzheimer’s and diabetes. The product is available in various capsule forms and is administered orally. Our license agreement with Aquanova AG is vital, as JOTROL is our primary product. Losing this agreement would delay our plans and force us to seek similar licenses, adversely affecting our business. The agreement grants us worldwide exclusivity to utilize granted and pending patents. Effective from September 15, 2016, it lasts until patent expiration or ten years after the first commercial sale. We paid an upfront fee of $20,000 and an annual license fee of $75,000 until the first product approval. Milestone payments of $200,000 are due per territory upon regulatory approval, with royalties set at 5% of net sales. There is an option to pay $3 million for reduced royalties of 1.25%. Termination can occur due to material breach or insolvency, with specific provisions for retaining licenses. Recent amendments include a Debt Forgiveness and Exchange Agreement on December 1, 2021, where $225,000 of debt was forgiven in exchange for $125,000 cash, a $100,000 promissory note, and stock options. As of December 31, 2024, $75,000 in accrued license fees are recorded in accounts payable. 3 Product Pipeline The Company’s product pipeline is built arounds proprietary platform product, JOTROL an enhanced oral formulation of resveratrol. Resveratrol, a natural compound is optimized in JOTROL to deliver therapeutically effective doses safety, aiming to address oxidative stress, inflammation and mitochondrial issues linked to neurological conditions. The Company has designated the different indications with project numbers, JNS101 – JNS115. The same JOTROL product is planned to be used in all indications although the number of capsules might vary and be indication specific. The pipeline chart above shows the indications that we presently are prioritizing. However, JNS101 is an additional indication that we believe will be of interest to perform a clinical trial in at a later stage. The product pipeline represented above assume drawing upon previous preclinical and clinical data conducted by third parties. This data is available either via public domain or under agreements with our key partner which are further described in “Item 1. Business” of this Annual Report on Form 10-K. The Company has not discussed with the FDA its ability to rely on and reference data from previous third-party trials, such as the Phase II trial in MCI/early Alzheimer’s disease, conducted by Georgetown University. Our top priorities are advancing our clinical studies for JNS115 for Parkinson’s Disease and JNS 1 08 for MCI/early Alzheimer’s Disease. We have started the work with the JNS115 Phase IIa trial and estimate that first dosing of a patients will occur in Q3 of 2025. If we receive funding from the NHI, we will start our clinical trial for MCI/Early Alzheimer’s Disease later this year. We have not set any timeline for starting clinical trials for rare diseases. We may work with other strategic partners on these clinical trials. JNS115 Parkinson’s Disease We will be utilizing JOTROL in our application for investigating a treatment for Parkinson’s Disease (PD). People are usually more familiar with the motor symptoms of Parkinson’s disease (PD), which are noticeable and used by doctors for diagnosis. The three cardinal motor symptoms are stiffness (rigidity), slowness (bradykinesia), and resting tremors. Stiffness involves muscle rigidity detected during examination, while slowness refers to decreased spontaneous and voluntary movement, such as slower walking or reduced facial expression. Resting tremor is an involuntary shaking that occurs when a limb is relaxed and disappears during movement. Non-motor symptoms, often called the “invisible” symptoms, can affect almost every body system and vary in severity. These symptoms can significantly impact quality of life and include autonomic dysfunctions like constipation, low blood pressure, sexual problems, sweating issues, and urinary problems. While available therapies can treat some symptoms, there is an urgent need for better treatments to improve quality of life and slow disease progression. Approved medications for motor symptoms include dopamine replacement therapy (levodopa/carbidopa), adenosine receptor antagonists, amantadine, anticholinergic medications, COMT inhibitors, decarboxylase inhibitors, dopamine agonists, and MAO-B inhibitors. Researchers are increasingly recognizing the debilitating nature of non-motor symptoms and are working on new therapies, while doctors manage these symptoms with current treatments. 4 Upcoming Phase 2a study in Parkinson’s Disease patients The Company has engaged Zina Biopharmaceuticals to assist with study design, FDA communications including IND and manage the execution of the trial. Catalent has been engaged to manufacture the JOTROL clinical trial supplies. The preliminary study design is described below and is subject to final IND approval by the FDA. The Company expects to start the clinical trial in the third quarter of 2025 and have the first study results available within 12 months thereafter. We are sponsoring a Phase 2a clinical trial to evaluate the safety, tolerability, and pharmacokinetics of Resveratrol (JOTROLTM) in individuals with Parkinson’s Disease. This multicenter, randomized, double-blind, placebo-controlled study involves approximately 30 participants across three centers in the US. Participants are randomly assigned to one of three groups to receive either a placebo or JOTROL at doses of 200mg or 400mg daily for three months. The study aims to explore JOTROL’s potential to improve energy metabolism in Parkinson’s Disease. An optional biomarker sub-study will assess cerebrospinal fluid, requiring additional consent. Each participant will be involved for 4-5 months, with the entire study lasting two years. First readout of results are expected within 12 months of first dosing. JNS108 Mild Cognitive Impairment/early Alzheimer’s Disease We will be utilizing JOTROL in our applications for investigating treatment of various segments of Alzheimer’s disease of which MCI/early AD is the initial target. If any NIA grant application is successful, we will have the funding to conduct a Phase II trial in MCI/early Alzheimer’s Disease. Our failure to obtain such a grant will most likely result in delays of this project and the need to raise additional capital. Early-stage Alzheimer’s (mild) Later stages of Alzheimer’s are very difficult to reverse and therefore it is important to start treatment of Alzheimer’s in the earliest possible stage so the individuals can continue living normal lives and maintain their independence. In the early stage of Alzheimer’s, a person may function independently. He or she may still drive, work and be participate in social activities. Despite this, the person may feel as if he or she is having memory lapses, such as forgetting familiar words or the location of everyday objects. Symptoms may not be widely apparent at this stage, but family and close friends may take notice and a doctor would be able to identify symptoms using certain diagnostic tools. Common difficulties include finding the right word or name, remembering names when meeting new people, and performing tasks in social or work settings. People may also forget material they just read, lose or misplace valuable objects, and experience increased trouble with planning or organizing. This is the Alzheimer’s disease patient category that we will include in our proposed Phase II clinical trial with the final objective of showing that JOTROL has the potential of slowing and/or possibly stopping the progression of this disease. The effect of JOTROL treatment, in the Phase II trial, will primarily be measured through several biomarkers. Economic burden of Alzheimer’s disease on society in USA is generating a very large opportunity According to Alzheimer’s Association’s 2020 annual report Alzheimer’s disease has impacted 5.7 million Americans and that it costs the US $277 billion each year, excluding the cost of “unpaid time and effort of the people, mostly women, who are caring for spouses, parents, siblings, and friends with dementia.” The Association explained, “In 2017, 16 million Americans provided an estimated 18.4 billion hours of unpaid care in the form of physical, emotional and financial support – a contribution to the nation valued at $232.1 billion.” Any product that delays the onset of severe Alzheimer’s disease should represent a significant savings to society. 5 JNS108 Phase II Clinical Trial for MCI/early Alzheimer’s Disease National Institute on Aging (“NIA”) financed our Phase I study with $1.76 million through grant 1R44AG067907-01A1. Since there were unanticipated higher costs, mostly due to Covid-19 related additional procedures during the Phase I trial, a supplemental grant of $233,281 was submitted to the NIA in December of 2021. We were awarded the supplemental grant on April 7, 2022. In April 2021, we submitted our first grant application to the NIA for full funding of a Phase II trial in Mild Cognitive Impairment (MCI) and early Alzheimer’s disease. The Phase II trial was designed to focus on 3 areas: 1) safety and tolerability; 2) pharmacokinetics and pharmacodynamics, measuring of responses from 2 different doses vs. placebo; and, 3) measuring of effect on multiple biomarkers related to the disease. The application was not accepted, but we were encouraged by the NIA to refine our application and submit again. We have since submitted 3 grant applications, with budgets of $20 million or higher, to the NIA for full funding of such Phase II trial but none of those applications were successful. The NIA scientific review of our Alzheimer’s Phase II trial grant application shows a total score of 47 which is our best score so far. A score of 40 or below is necessary for being considered for funding. After discussions with the NIA, we have decided to apply, in September of 2024, for a much smaller grant, $2.5 million, for a Proof of Concept study focusing on JOTROL’s effect on validated biomarkers. The final study design is not yet determined but a draft synopsis is described below. There is however no guarantee that we will ever receive NIA grant funding for this project. A delay or rejection of this funding will cause a delay in this program and most likely requiring additional financing. The proposed Phase II trial is utilizing published information from the earlier Turner et al Phase II trial, completed in 2015 with 119 patients with early Alzheimer’s disease who were treated with 4 different doses of resveratrol. The study was conducted by Professor Raymond Turner, MD. at Georgetown University, a member of our Scientific Advisory Board, as the Principal Investigator. Dr. Turner is the Principal Investigator of our proposed Phase II trial. The study tried 500mg, 1000mg, 1500mg and 2000mg daily doses with each dose taken by the patients over 13 weeks. Only the highest dose of 2000mg (2 X 1g per day) showed positive results on biomarkers which lead to the conclusion that this study was most likely underdosed for achieving the best therapeutic effect. PK analysis showed that the average C-Max of resveratrol in the blood on the highest dose was 181 ng/ml, which is far from the target of 300ng/ml that we believe is needed for reaching therapeutic effect. Based on the recent Scientific Review received from NIA. Our team of scientists in the Alzheimer’s field, Professors Raymond Turner, MD, Ph.D. and Charbel Moussa, Ph.D. from Georgetown University, Rudolph Tanzi, Ph.D. Harvard and Li-Huei Tsai, Ph.D. MIT are assisting in designing our POC study to address and explore several biomarkers and areas where the trial results can guide us to a follow-on Phase II trial, if approved to do so by the FDA, that might generate meaningful outcomes for MCI/early AD patients. The Company has not discussed its ability to rely on and reference the Phase II trial conducted by Georgetown with the FDA nor has it discussed the design of the planned POC study in MCI patients with the FDA. Proposed JOTROL MCI Phase II Study STUDY SYNOPSIS Title: A phase II, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of JOTROL (micellar resveratrol solubilisation formulation) in early Alzheimer’s Disease (AD) patients Study Description: This study seeks to assess the safety and efficacy of JOTROL (resveratrol) in patients with MCI/early AD. Approximately 105 patients will be enrolled at study centers across the United States. Patients will be randomized into one of two active treatment arms to receive JOTROL 200 mg BID or JOTROL 500 mg BID or to a placebo group. We hypothesize that JOTROL will be safe and tolerable in individuals with MCI/early AD. Objectives: To determine the safety and efficacy of JOTROL (200 mg resveratrol BID and 500 mg resveratrol BID) for neuroinflammation and biomarkers of MCI/early AD. ● Primary Objective: ○ To assess safety and tolerability of JOTROL in AD-MCI patients by monitoring adverse events (AEs) and serious adverse events (SAEs) and assessing their relationship to the study drug. Tolerability will be measured by subjects’ ability to remain on treatment. Overall tolerability of the drug will be defined as fewer than 25% discontinuations due to drug-related AEs and SAEs ○ A first efficacy indicator will be stabilization of Abeta 40/42. ● Secondary Objectives: ● To assess population pharmacokinetics (Population PK) in the ITT population 6 ● To measure the effect of JOTROL on biochemical markers for AD, neurodegeneration, vascular damage, metabolic effects, and neuroinflammation ● To determine the effects of JOTROL on whole-brain and regional brain atrophy ● To measure the effects of JOTROL on functional MRI measures ● To assess cognitive effects of JOTROL ● To examine the influence of Apolipoprotein E genotyping on both biomarker and cognitive endpoints Endpoints: Primary Endpoint: ● Assessment of safety/tolerability by monitoring AEs and SAEs, assessing their potential relationship to the study drug and Abeta 40/42. Secondary Endpoints: ● Levels of AD relevant biomarkers ● Volumetric MRI and Cortical Disarray Measurement ● Additional experimental biomarkers as stated in protocol, such as those for neuroinflammation Study Population: Approximately 105 male or female subjects between 55 and 85 years of age with a diagnosis of MCI/early AD will be enrolled. MCI/early AD patients should be amyloid positive with an AD/MCI clinical diagnosis. Phase: Phase II Description of Sites/Facilities Enrolling Participants: Approximately 8 study centers in the USA. Study sites will be determined by competitive selection of interested and eligible ADCS sites - with experienced study coordinators, raters, and site PIs Description of Study Intervention: Subjects will be randomized 1:1:1 to receive 500 mg bid (1g/day) resveratrol as JOTROL; or 200 mg bid (400mg/day) resveratrol as JOTROL; or placebo. Participant Duration: Treatment phase will be 6 months with a one month follow up safety visit and safety monitoring over a 6 month period to ensure that patients have no long lasting treatment related effects. Rare Orphan Diseases JNS101 Friedreich’s ataxia direct to Phase II JNS101 is a project utilizing JOTROL, specifically designed to treat Friedreich’s Ataxia. Friedreich’s Ataxia (FA) is a rare inherited disease that causes damage to the nervous system as well as mobility dysfunctions. FA usually begins in childhood and leads to impaired muscle coordination (ataxia) which worsens over time. It is caused by a defect (mutation) in a gene labeled FXN. Friedreich’s ataxia is recessive, meaning it only occurs in someone who inherits two defective copies of the gene, one from each parent. Although rare, FA is the most common form of hereditary ataxia, affecting about 1 in 50,000 people in the United States. EU5 (5 largest European countries) alone has approximately the same amount of FA patients as there are in USA. In 2014 Murdoch Children’s Research Institute (MCRI) conducted a clinical trial in 27 human subjects where 24 completed the study, resulting in that a high daily dose (5 grams) of nutritional grade trans-resveratrol had statistically different positive results, see p-values for 5 g daily dosing in the table below, on established Friedreich’s Ataxia measurements. Key markers, such as FARS Score and measurements of hearing and speech parameters were included in these positive results. The results indicate that an effective dose of resveratrol is expected to be a meaningful treatment for patients with Friedreich’s Ataxia. The data from the MCRI study was used in pre-IND meetings with the FDA discussing our Phase II study and was also referenced in our application for orphan drug designation (ODD). The ODD, request #17-5978, was granted to us by the FDA on August 16, 2017. The MCRI study is widely published, Eppie M. Yiu et al., and below is a summary table of the results including the demonstrated issue with gastro-intestinal side effects at a higher dose. The p-value (or probability value) is used to determine if the outcome of an experiment is statistically significant. A low p-value means that there is a very low likelihood that this outcome was a result of luck or is a random occurrence. A high p-value means that assuming the null hypothesis is true, this outcome was very likely. Generally, a p value less than 0.05 (or 5% odds of the event being random) is regarded as statistically significant. The lower the P value, the less chance that the comparison is a random outcome. The FDA follows these accepted measures of statistical probability in the evaluation of significant results in preclinical experimental outcomes and for clinical trials. In general, if a primary endpoint in a Phase III/Pivotal trial gets a p-value below 0.05 there is a good possibility, unless there are simultaneous safety issues, that a product may receive approval from the FDA. 7 The below graph representing results of two different doses of resveratrol in the same patient population. Comparisons are made from the patients’ baseline and was not placebo controlled. There is a clear difference between the 1gram daily dosing vs the 5 gram daily dosing in p-values in all areas measured. There is also a clear difference in adverse events, primarily GI related between the 2 doses. This clearly demonstrates that the significantly higher dose is effective while the lower dose is not. However, it also shows that the high dose of the regular resveratrol administered cause unacceptable high gastro-intestinal side effects. Therefore, we believe that our JOTROL product in a Phase II/II trial will replicate the positive outcomes without any severe gastro-intestinal side effects. JNS102 Phase II trial for Mucopolysaccharidosis Type 1 (MPS I) JNS102 is utilizing JOTROL for the treatment of Lysosomal Storage disease areas whereas MPS Type I is the first target. MPS I is divided into three subtypes based on severity of symptoms. All three types result from an absence of, or insufficient levels of, the enzyme alpha-L-iduronidase. Children who have parents with MPS I will carry the defective gene. MPS I patients are presently treated with an Enzyme Replacement Therapy (ERT) named Aldurazyme. This requires a weekly infusion of 4 hours per event and cost over $500,000 per year per patient. The ERT is effective in significantly prolonging life however since the ERT does not penetrate the Blood Brain Barrier, Ears, Eyes and Joints, it leaves the patients with a gradually worsening quality of life including loss of hearing, blindness and severe arthritis. JNS102 is targeting the specific areas that ERT cannot treat, with JOTROL™ treatment. JNS102 Phase II Clinical Trial 1. Preclinical studies conducted at University of Miami in MPS I mice results showed that a high dose of resveratrol increased the alpha-L-iduronidase which is the critical enzyme that is too low in these patients. 2. IND application for Phase I study was approved by the FDA and the clinical trial is completed. Results documented in the section JOTROL Phase I Pharmacokinetic (“PK”) and Safety Study . 3. Final study details and start to be determined by consultation with the FDA and supportive additional financing. 8 4. Primary endpoint: Safety, tolerability and PK/PD values 5. Secondary endpoints to include (subject to FDA acceptance) i. Improvement in 6-minute walk distance ii. Forced vital capacity iii. Biomarkers, such as alpha-L-iduronidase levels iv. MPS I validated pain survey JNS107 Phase II trial for MELAS Syndrome JNS107 is utilizing JOTROL as the product to treat MELAS Syndrome. MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes) syndrome is a rare disorder that begins in childhood, usually between two and fifteen years of age, and mostly affects the nervous system and muscles. The most common early symptoms are seizures, recurrent headaches, loss of appetite, and recurrent vomiting. Stroke-like episodes with temporary muscle weakness on one side of the body (hemiparesis) may also occur and this can lead to altered consciousness, vision and hearing loss, loss of motor skills, and intellectual disability. MELAS is caused by mutations in mitochondrial DNA. Pre-clinical trials performed with mice at University of Miami showed that JOTROL™ increased mitochondrial biogenesis in the liver with 70% and in the brain with 30%, which is expected to lead to an increase in the mitochondria levels in MELAS patients and thereby show positive patient outcomes. Symptoms of MELAS syndrome usually begin between the ages of two and fifteen years, but delayed onset cases have also been reported in people aged fifteen to forty years and older. In approximately 75 percent of cases, onset of the disorder occurs before the age of 20 years. Symptoms and physical findings associated with MELAS syndrome vary greatly among affected individuals. The distinguishing feature in MELAS syndrome is the recurrence of stroke-like episodes. It is currently thought that the deficiency of a compound called nitric oxide in the small blood vessels of the brain may be responsible for the stroke-like episodes. Short stature and hearing loss may be present and fatigue and difficulty tolerating exercise may be early symptoms. MELAS syndrome is a rare disorder that affects males and females in equal numbers. Although rare, MELAS syndrome is probably the most common type of mitochondrial myopathy caused by mutations in mtDNA. Some researchers believe that mitochondrial myopathies may go unrecognized and underdiagnosed in the general population, making it difficult to determine the true frequency of disorders like MELAS syndrome. Opportunity for JNS107 The potential market for JOTROL in the USA includes approximately 80,000 patients. With a projected treatment cost for MELAS syndrome of $75,000 per patient annually, treating 50,000 patients could generate around $3.75 billion per year. Furthermore, successful clinical trial results may extend JOTROL’s applicability to other mitochondrial diseases, potentially expanding its market impact. 9 Competition The following is an overview of JNS’s competitors. Many companies, including the largest pharma companies in the world, are competitors in some of the disease areas for which we are developing treatments for through our various projects. We will compete with both small and large companies in each indication we are pursuing. There are a multiple of companies, both smaller biotech’s as well as large pharmaceutical companies, that are working on solutions for the same indications that we are pursuing. There is no assurance that we will be able to compete with these companies even if our product gets approved in an indication. Parkinson’s Disease Despite the availability of FDA-approved treatments for Parkinson’s Disease, no breakthrough therapies have emerged recently to halt disease progression. The most commonly prescribed treatment is levodopa/carbidopa, which has been used since the late 1960s. Levodopa is absorbed in the intestine and converted to dopamine in the brain, addressing the dopamine deficiency in Parkinson’s patients. Carbidopa prevents premature conversion of levodopa to dopamine outside the brain, reducing side effects like nausea. This combination is available in various forms, including pills, dissolvable tablets, and a gel infused directly into the intestine. Levodopa/carbidopa significantly improves motor symptoms in most patients, especially those with mild symptoms, and remains effective over time. However, as Parkinson’s progresses, dosage adjustments may be necessary. Initial side effects can include nausea and vomiting, which can be mitigated by taking the medication with a small snack or adding extra carbidopa. Other side effects may include drowsiness, low blood pressure, and hallucinations. Despite these challenges, levodopa/carbidopa remains a cornerstone in managing Parkinson’s symptoms. Alzheimer’s Disease Several companies are actively developing treatments for Alzheimer’s disease, each with unique approaches and challenges. Biogen’s Aduhelm, an IV infusion targeting amyloid-beta plaques, has faced reimbursement issues despite FDA approval, leading to low market penetration. Eli Lilly’s donanemab, targeting a modified form of beta amyloid, recently received FDA approval and is priced at $32,000 annually. It has shown promise in early Alzheimer’s patients and is undergoing further trials. Cognition Therapeutics is developing CT1812, an orally dosed molecule in Phase II, supported by significant NIA grants. Anavex Life Sciences is advancing Anavex 2-73, a Phase III candidate from their SIGMACEPTOR™ platform, targeting CNS conditions with genomic precision. Eisai and Biogen’s Leqembi, approved by a panel of experts, is expected to receive traditional FDA approval, potentially expanding Medicare coverage. Priced at $26,000 per year, Leqembi has shown benefits for early-stage Alzheimer’s patients. Despite these advancements, the competitive landscape remains dynamic, with the possibility of other companies emerging with successful treatment Rare Diseases There are several companies that are targeting the same rare diseases as us. Below is a description of a selection of those companies that we see as our closest competitors. However, it is possible that another company, that is not listed below, can potentially have a successful product approved before us and have a more effective treatment. In the MPS-1 space, several companies offer competitive products to Jupiter. Sanofi Genzyme’s Aldurazyme has been the standard enzyme replacement therapy for nearly 20 years. RegenexBio is developing RGX-111, a gene therapy designed to deliver a functional copy of the IDUA gene to the central nervous system. Sigilon Therapeutics, Inc. is working on SIG-005, which uses a genetically modified human cell line to express the IDUA enzyme, with an IND application for Phase I submitted to the FDA. Additionally, Sangamo Therapeutics, Inc. is exploring gene editing products, although no positive results have been published yet. These developments represent significant competition in the treatment of MPS-1. 10 In the treatment of Friedreich’s Ataxia, several products compete with Jupiter’s offerings. Reata Pharmaceuticals’ Omaveloxolone, branded as SKYCLARYS, received approval in 2023 following successful Phase II and pivotal trials. Despite its effectiveness, Jupiter anticipates conducting future studies in Europe and Australia due to market competition in the USA, especially after Biogen’s acquisition of Reata. Minoryx Therapeutics has completed a Phase II trial for MIN-102, a selective PPAR gamma agonist, showing promise in this space. Additionally, Larimar Therapeutics is developing CTI-1601, a recombinant fusion protein intended to deliver human frataxin to mitochondria, currently in Phase I trials. These advancements highlight the competitive landscape in Friedreich’s Ataxia treatment. In the treatment of MELAS, several products present competition to Jupiter’s offerings. Cyclerion Therapeutics is advancing CY643, currently in Phase 1B, which evaluates safety and its impact on mitochondrial dysfunction and cognition. Abliva AB is developing KL1333, which has been granted orphan drug designation in both the United States and Europe. This product has been tested in healthy volunteers and patients, with a registrational Phase 2/3 study initiated in December 2022. These developments underscore the competitive landscape in the search for effective MELAS treatments. Competitive Advantages We believe that we are positioned to outperform competitors for the following reasons: We believe that the focus on a new product based on resveratrol with higher bioavailability, JOTROL, will enable us to utilize the same product for several indications, subject to FDA’s approval. We believe that this enables us to have several opportunities to obtain regulatory approval in case we are able to show efficacy and safety acceptable to regulatory agencies for one or more of our targeted indications. JOTROL is an oral product based on a natural compound. Oral delivery of medications is a physician and patient preferred treatment compared with injections and infusions and we expect that our product will have an attractive and affordable price point for reimbursors and patients. We are building a close relationship with Key Opinion Leaders (KOL’s) and patient organizations to facilitate a better understanding of patient needs and thereby design trials targeting solutions to those needs as long as these targets are acceptable to the FDA. The natural product resveratrol is well studied with over 14,000 scientific publications to date. Published scientific papers, such as AY Berman et al, indicate that a highly bioavailable product generating less GI side effects may have application in a number of indications. Based upon available scientific literature, it appears that resveratrol is an activator of SIRT1, one of the mammalian forms of the sirtuin family of proteins. SIRT1 deacetylates histones and nonhistone proteins including transcription factors. The SIRT1-regulated pathway affects metabolism, stress resistance, cell survival, cellular senescence, inflammation/immune function, endothelial functions, and circadian rhythms. Resveratrol has been documented in scientific literature to activate SIRT1, NrF2, NLR3P inflammasomes and have an epigenetic mechanism and therefore is predicted to benefit diseases affected by abnormal metabolic control, inflammation, and cell cycle defects. Nonetheless, resveratrol application is a major challenge for the pharmaceutical industry, due to its poor solubility and bioavailability, as well as adverse effects, such as severe gastro-intestinal side effects when taken at effective dose levels (over 2,000 mg daily). In this context, studies have proposed that structural changes in the resveratrol molecule, including glycosylation, alkylation, halogenation, hydroxylation, methylation, and prenylation could lead to the development of derivatives with enhanced bioavailability and pharmacological activity. Resveratrol has never been developed with all the necessary steps to achieve an approval as a pharmaceutical product since the existing natural supplements cannot provide high enough levels of resveratrol in blood plasma to be able to provide a therapeutically effective dose without generating severe gastro-intestinal side effects. This means that we need to take JOTROL through the full regulatory NDA (New Drug Application) requirement to obtain a marketing approval. We were able to receive, through a confidential agreement from a major pharmaceutical company, a chronic toxicology study performed with resveratrol, in two different species, that was referenced in our approved Phase I IND application submitted to the FDA. The study was conducted by Charles River Laboratories. 11 Possible out-licensing for Asian markets is being considered as it may reduce risk and cost of product development in those markets that requires confirming trials in an Asian population, while generating income through milestones and royalty agreements, see “Asian Business Development Activities” regarding further developments and strategy in the Asian market. Marketing and Commercialization Plan In March 2025, the Company announced that it had entered into a partnership with Aquanova AG to develop a series of nutritional products targeting longevity, aging and Healthspan. The first three products, which will focus on the concept of “Beauty from Within”, are slated to hit the market in the third quarter of 2025 through a Direct-to-Consumer model. The Company will focus on the consumer market, and will market its products on a to-be-developed website targeting the US market, along with social media marketing. Internationally, the Company is focusing on partners who can market and accelerate sales, with an initial focus on the Asian region. In addition, we may also consider out-license JOTROL to one or more companies that has such commercialization capability in place. We may consider at any time a complete exit through any proposed acquisition of our company. In case no acceptable M&A offer is presented we might consider marketing and distributing JOTROL in the USA for the rare disease market only and have companies with large sales organizations distribute our product for the larger indications. All international distributions will most likely be out licensed. The marketing and sales of orphan drugs can be relatively fast and effective. We believe, based on discussions with organizations such as the EveryLife Foundation an approval of a drug for a rare disease is efficiently communicated through social media to Key Opinion Leaders (KOL), patient advocacy groups and directly to patients, which may reduce marketing costs. We are already using information regarding our development progress through KOL’s and the respective patient organizations that exist for each indication. We have also initiated a collaboration with several patient organizations such as the FARA organization, www.curefa.org, the National MPS Society, UMDF, www.umdf.org, and the EveryLife Foundation in USA. We have been approached by several large and mid-size pharmaceutical companies discussing future collaborations once we have more clinical data available. We will try to utilize this interest by out-licensing primarily the Asian territories while waiting to conduct out-licensing in USA and Europe until after Phase II results are obtained. We have participated in several industry trade shows, such as Biotech Showcase, BIO USA, LSX World, World Orphan Congress, World Symposium for LSD, BIO Hong Kong 2023 and many others. We plan to continue to participate in those conferences as well as conferences targeting presentations by publicly traded companies. Operation and Organization We are, and plan to stay, primarily a virtual organization utilizing partnership arrangements for certain functions including but not limited to our R&D, clinical trial work, regulatory affairs and product manufacturing. A core organization is in place and will be expanded handling Strategy, Project Management, Clinical trial Management, Regulatory Affairs, Finance and Business Development. We believe that our core management team structure has proven experience in utilizing outside resources which allows us to efficiently execute several programs simultaneously in what we believe to be a very cost-effective way. Regulatory Approval Our management, Scientific Board of Advisors and business advisors have extensive experience in regulatory affairs and clinical development of product candidates for the treatment of rare diseases, Parkinson’s Disease and Alzheimer’s disease. The overall regulatory approval process for product candidates for the treatment of rare diseases are generally conducted with a smaller number of patients in clinical trials and over a shorter amount of time than more prevalent diseases. There is a documented pathway to get accelerated FDA approval for a rare disease indication if there is no existing treatment for the indication, if a product shows efficacy and has a good safety profile. There is also a possibility of receiving a Priority Review Voucher (PRV) from the FDA upon an approval in pediatric population in a rare disease. One or more of our programs, such as MPS-I, will be targeting pediatric patients. The voucher entitles the bearer to regulatory review in about six months rather than the standard ten months. The Food and Drug Administration (FDA) awards a voucher following approval of a treatment for a neglected disease, rare pediatric disease, or medical countermeasure. Two drugs can receive priority review for each voucher: the drug winning a voucher for a neglected or rare pediatric disease, and the drug using a voucher for another indication. The voucher may be sold. For example, a small company might win a voucher for developing a drug for a neglected disease and sell the voucher to a large company for use on a commercial disease. 12 There are four specific approval pathways applicable for rare disease indication. We will be evaluating and most likely applying for one or more of these when we get closer in the FDA approval process. These include the following pathways for the indications that it is targeting: (1) Priority Review (2) Fast Track (3) Accelerated Approval Pathway and (4) Breakthrough therapy. Priority Review Priority Review was authorized in 1992 by the Prescription Drug User Fee Act (PDUFA) which created the two-tiered FDA drug review system (standard v. priority). This pathway shortens application review from 10 months (standard) to 6 months (priority). The FDA determines if a drug receives a standard or priority review, although sponsors may request a priority review. Priority review is granted if a new drug would result in a significant improvement in safety and effectiveness compared to existing therapies. Fast Track Drugs for the treatment of serious conditions that address an unmet medical need receive an expedited review. The purpose of this pathway is to get important new drugs to patent earlier, for conditions such as Alzheimer’s disease, epilepsy, depression, and multiple sclerosis. Any drug being developed to treat or prevent a condition with no current therapy is prioritized. If there are available therapies, the new drug must: 1. Show superior efficacy; 2. Avoid serious side effects of the available therapy; 3. Decrease clinically significant toxicity of an available therapy; and 4. Address an emerging or anticipated public health need Fast Track designation should come at the time of submission and be requested by the manufacturer, although it can be requested at any time in the approval process. Once in the Fast Track pathway, there are more frequent meetings with the FDA to discuss the development plan and appropriate data needed to support drug approval. Drugs in the Fast Track pathway are also eligible for accelerated approval and priority review if relevant criteria are met. Accelerated Approval Pathway Authorized in 1992 and updated in 2012, this pathway is applied to new therapies that treat serious or life- threatening conditions for which there is an unmet medical need and have a “clinically meaningful” outcome. Drugs that are eligible for this pathway must be reasonably likely to improve a surrogate endpoint if a standard endpoint would require long-term evaluation. If given conditional approval, the sponsor must conduct post-marketing clinical trials to ensure endpoints are met. If the standard endpoints are not met, the FDA can withdraw approval. Breakthrough Therapy This designation is designed to expedite the development and review of drugs that are intended to treat serious conditions and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies on clinically significant endpoints. There is however no guarantee that an accelerated pathway will lead to an accelerated FDA review and that a pediatric approval leads to a PRV. Additionally, there can be no guarantee that the Company can be successful in its plans under any FDA pathway. 13 Research Agreement On July 1, 2022, the Company entered into a research agreement with the University of Miami to conduct a preclinical study to evaluate the effect of JOTROL in Parkinson’s Disease models. The cost of the research agreement activities, to be paid by the Company, is $72,844. The Company owns any intellectual property generated from the research. The agreement is for 1 year from the start date, July 1, 2022. Either the Company or the University of Miami may terminate this agreement upon thirty (30) days written notice for any reason. In the event of such termination, both the Company and the University of Miami shall take all reasonable steps to cancel further costs in connection with this agreement. The Company and the University of Miami will be entitled to reimbursement for costs and non-cancelable obligations incurred prior to effective day of the termination, not to exceed the total amount of the project. Asian Business Development Activities We have recently agreed to service agreements in the areas of CMC (Chemistry, Manufacturing, and Controls), regulatory affairs and clinical trial management with companies with operations in SE Asia. These agreements are with companies that, we believe, have the knowledge and network in the South-East Asian market. The agreements are further described in the section “Other Material Agreements”. In addition, we are in active negotiations with Dominant Treasure Health (“DTH”), a BVI company. DTH has demonstrated to us, through several company introductions, that they have business relationships, either directly or through affiliates, with many South-East Asian pharmaceutical companies as well as companies involved in distribution and sales of TCM, Traditional Chinese Medicine. We are therefore planning to engage DTH in active business development in China, Malaysia and Singapore as soon as we have financing in place for their engagement. DTH has already introduced us to 3 Chinese companies, Beimei Pharma, http://en.beimeiyaoye.com, that specializes in pediatric medications, Sichuan Kelun Pharmaceutical Co., ltd, a publicly traded company that is part of the Kelun Industrial Group, https://www.kelun.com/, and Tianjin Pharmaceuticals, https://en.pharm.com.cn/, that advocates the corporate core values of “Love, Integrity and Power”. TCM products are run in a separate division within Tianjin. The Asian market is very large and hard to penetrate for a small company and we believe that our strategy with these agreements have the possibility to accelerate an out-licensing deal in the South-East Asian territories. However, there are no assurances that this approach will be successful. Our rationale for the strong approach into the South-East Asian market is: Background: Asian countries are not accepting pharmaceutical products to be sold without clinical trial approvals based on trials conducted in an Asian population ● The Company’s strategy is to partner with organizations in the territory that can execute much more efficiently than trying to manage the process from USA. ● We have already received interest for our JOTROL product in the Asian market since resveratrol is listed as a Traditional Chinese Medicine. ● The need for a set up that can service this market is imperative for success. ● Strategic collaboration agreements have been executed to facilitate an expedited execution of an out-licensing agreement with one or more Chinese or other SE Asian pharmaceutical companies. ● The Company is too small, both financially as well as internal manpower, to manage developments in the territory. ● The Company has a history of poor financial status and not being able to fulfill commitments and finalize clinical studies. ● By utilizing equity as service payments, the company believes that it can get projects finalized without any significant cash outflow. ● The service agreements are therefore designed to be a win for both parties, assuming an increase in equity value, in case clinical studies and out-licensing activities will be successful in the territory. 14 Other Material Agreements The agreement with a major pharmaceutical company, restricted by confidentiality, grants us data access to resveratrol toxicology studies through a letter of reference. Executed on May 2, 2017, it can only be terminated due to a material breach. The studies were conducted at Charles River Laboratories, and there are no payments associated with this agreement. Recent Agreements – South-East Asia On June 3, 2024, the Company entered into three service agreements to expand in South-East Asia; a CRO Services Agreement with Optimize Wellness Limited providing clinical trial guidance in China, Malaysia, and Singapore, a Regulatory Services Agreement with Regis Healthcare Group Limited providing regulatory strategy and guidance, and a Product Services Agreement with Longevity Technology Group Limited providing manufacturing guidance. Each of the three service agreements were paid for with an upfront issuance of 1,162,500 shares of common stock, which were registered for resale as part of the initial public offering, and have a term of three years. On December 15, 2024, the Company entered into a Strategic Services Agreement (the “Dominant Treasure Agreement”) with Dominant Treasure Health Company Limited (“Dominant Treasure”). Pursuant to the terms of the Dominant Treasure Agreement, Dominant Treasure agreed to provide certain services to the Company to assist the Company in accelerating the Company’s desire to get its products developed and distributed in the Southeast Asian market. In exchange for Dominant Treasure’s services pursuant to the Dominant Treasure Agreement, the Company agreed to pay Dominant Treasure a one-time payment of $2,300,000. In addition, if Dominant Treasure is involved in generating negotiations and conclusion of a distribution agreement for the Company in the countries of China (including Hong Kong), Singapore and Malaysia, the Company will pay Dominant Treasure a success fee of 5% of any upfront and/or milestone payments to be received by the Company. If such agreement includes a royalty payment to the Company, Dominant Treasure will receive 5% of such royalty payment. The Dominant Treasure Agreement has a term of 36 months and may be terminated at any time upon mutual agreement of the parties. Legal Proceedings From time to time, we are involved in various legal proceedings arising from the normal course of business activities. We are not presently a party to any litigation the outcome of which, we believe, if determined adversely to us, would individually or taken together have a material adverse effect on our business, operating results, cash flows or financial condition. Facilities Our corporate headquarters are located at 1001 North US Hwy 1, Suite 504, Jupiter, Florida 33477, where we lease approximately 1,206 rentable square feet of office space. This lease expires on May 31, 2026. Terms of the office lease provide for a base rent payment of $3,783 per month and a share of the building’s operating expenses, such as taxes and maintenance, of $476 per month. In September 2021, we added an additional office located at 127 Main Street, Boston, Massachusetts 02129 for 120 rentable square feet of office space for our Boston-based employees and scientist to utilize as necessary. We believe that these facilities are adequate for our current and near-term future needs. Employees As of December 31, 2024, we had a total of four full-time employees, two full-time consultants, one part-time consultant, and our six Scientific Advisory Board members. Of these, three were primarily engaged in research or product development and clinical activities. 15