IGC Pharma, Inc. 10-K

ITEM 1. BUSINESS Overview IGC is a Maryland corporation established in 2005 with a fiscal year ending on March 31, spanning a 52- or 53-week period. Please refer to Note 1, “Nature of Operations” and Item 8 of this Annual Report on Form 10-K, for further information on business segments. Our mission is to improve the lives of individuals affected by Alzheimer’s disease by addressing both its symptoms and the disease. Our near-term focus is on advancing IGC-AD1, our lead drug candidate currently in Phase 2 clinical trials targeting agitation in Alzheimer’s patients. We are also investing in our early-stage pipeline of investigational therapies and exploring Artificial Intelligence (AI) powered models designed to identify early markers of Alzheimer’s. We believe that combining scientific innovation with operational execution, including leveraging our internal contract research organization, positions us to efficiently advance our pipeline toward commercialization, although there can be no assurance thereof. Our long-term strategy is to build a portfolio of differentiated therapies that not only address symptomatic needs but also target disease-modifying mechanisms, thereby creating sustainable value for patients, caregivers, and shareholders. Our lead investigational drug, IGC-AD1, has progressed through preclinical evaluations and a successful Phase 1 safety trial, and is currently being evaluated in a multicenter, randomized, double-blind, placebo-controlled Phase 2 clinical trial, officially named “CALMA” (Calming Agitation in Alzheimer’s). Interim data from this trial have demonstrated encouraging signs of efficacy, with patients receiving IGC-AD1 experiencing a statistically significant reduction in agitation compared to placebo within the first 2-6 weeks of treatment. This reduction in agitation is particularly notable as it could, although there can be no assurance, significantly improve patient care and represents a potential breakthrough in managing Alzheimer’s-related agitation. In addition, IGC-AD1, Phase 2 clinical trial interim data also demonstrate a clinical and statistically significant reduction in sleep disturbances among Alzheimer’s patients receiving the active medication compared to placebo. During fiscal 2025, the Company reassessed its reportable segment structure in connection with its strategic realignment toward Life Sciences. As a result, management determined that the Company operates as a single reportable segment, focused on the vision to make the world free from Alzheimer’s. Historically, the Company reported two operating segments: Life Sciences and Infrastructure. While the Infrastructure segment generated revenues in fiscal 2024, it did not generate any revenues in fiscal 2025 and is no longer actively managed or evaluated as a discrete operating segment by the Company’s Chief Operating Decision Maker. For more information, please refer to “Note 18 – Segment Information”. Our Drug Development Pipeline IGC Pharma is on a mission to transform Alzheimer’s treatment. We are building a robust pipeline of drug candidates, each targeting different aspects of the disease. Our product candidate pipeline and anticipated milestones include the followings: - Asset Target Indication Mechanism of Action Development Stage Key Milestones IGC- AD1 Agitation in Alzheimer’s dementia CB1 receptor partial agonist; reduces neuroinflammation and restores neurotransmitter balance Phase 2 clinical trial (CALMA study) Interim Phase 2 data analysis suggests cognitive improvements in the active treatment group versus the placebo group. TGR-63 Early to moderate Alzheimer’s disease Disrupts amyloid-beta (Aβ) plaque formation; crosses blood-brain barrier Preclinical Demonstrated favorable safety profile; advancing towards clinical trials LMP Alzheimer’s disease Targets neuroinflammation, neurotransmitter imbalance, and inflammasome-3 Preclinical Bioequivalence to IGC-AD1 anticipated in 2025 IGC-M3 Early-stage Alzheimer’s disease Inhibits Aβ plaque aggregation Preclinical Toxicology studies planned for mid-2025 IGC-1C Alzheimer’s disease and metabolic disorders Targets tau protein phase separation; potential GLP-1 receptor agonist Preclinical Exhibits strong binding affinity to tau protein; potential for weight loss applications IGC-1A Metabolic disorders (e.g., type 2 diabetes, obesity) Potential GLP-1 and GIP receptor agonist; CB1 receptor inverse agonist Preclinical Identified through AI modeling; toxicology and dosing studies underway 5 Table of Contents This pipeline reflects IGC Pharma’s strategic focus on addressing neurodegenerative diseases, particularly Alzheimer’s, through innovative mechanisms targeting key pathological features like amyloid plaques and tau protein aggregation. Additionally, the expansion into metabolic disorders showcases the versatility of our drug discovery platform, leveraging AI to identify promising therapeutic candidates. The Company is also attempting to harness the power of AI to develop early detection models, optimize clinical trials, and explore new applications for our drugs. Additionally, our 31 patent filings, including for IGC-AD1, demonstrate our commitment to innovation and protecting our intellectual property. Artificial Intelligence (AI)/Machine Learning (ML) In our pursuit of innovation, we leverage AI and ML. AI refers to the development of intelligent systems that can learn and act autonomously. ML is a branch of AI that allows computers to learn from data without the need for explicit programming. This technology plays a role in our efforts and could allow companies of our size to do what previously was the domain of much larger pharmaceutical companies. For instance, we are utilizing ML by training transformers, a powerful neural network architecture, to analyze vast datasets from our Phase 1 and unblinded Phase 2 interim clinical trial to identify patterns and optimize the clinical trial protocol for a potential Phase 3 trial. The AI model, for example, has the potential to tell us if a particular neuropsychiatric scale that we used in Phase 1 and Phase 2 added valuable information to the trial, and if it did not, we could remove that scale from a future Phase 3 trial, thus saving money and time in the overall trial management. In the long term, with more data, the trained AI model could allow us to consider incoming patient signatures, such as scans, symptoms, patient history, among others, and predict outcomes for our drug, including adverse effects, thus personalizing the delivery of IGC-AD1, of which there can be no assurance. Currently, the AI team is working on developing a Multimodal Interpretable Transformer for Alzheimer’s Disease (MINT-AD). This tool aims to support clinicians in real-world decision-making towards reducing Alzheimer’s false negatives and delayed diagnosis. We are developing MINT-AD for three aims/phases: risk stratification for AD, cognitive decline prediction 2-5 years in advance, and deployment as a physician’s tool. We have collected and started harmonizing a group of 32 worldwide databases that include longitudinal aging data, clinical and neuroimaging, and omics data. The databases represent participants from various countries, with a large representation from North, Central, and South America, and Asia. A detailed map of the databases is shown in Fig. 1. For the first phase, we are pretraining and finetuning state-of-the-art Large Language Models (LLMs) to extract intricate patterns in the data that uncover groups of interacting risk factors for early detection. Our first efforts have focused on the longitudinal data due to its compatibility and ease of use in LLMs. To input the data into language models, we are building prompts in two formats: semi-structured prompts made up by the original variable names and their values, and descriptive prompts made up by tailored text for each database. Also, we are implementing masked attention strategies to help the model focus on the data that is available for each database. By leveraging LLMs, we aim to enhance interpretability, generalizability, and clinical usability. Regarding interpretability, we have tested adversarial attack approaches that can help understand the decision-making of the model and expose wanted and unwanted behaviors in early stages. Additionally, to define a training target, we have extracted cognitive scales so that the model identifies which risk factors impact the patient the most. Some of the scales we have found across databases include the Mini-Mental State Examination (MMSE), the Community Screening Interview for Dementia (CSI-D), and the Montreal Cognitive Assessment (MoCA). We are also working on incorporating clinical and imaging data, including MRI and PET scans, and varied omics data, such as RNA sequencing, whole genome sequencing, and DNA methylations. Each group of data types will be developed in modules and then integrated through a Mixture-of-Experts (MoE) architecture. Fig. 2 shows a general overview of our approach with MoE. Our next steps will focus on finishing the harmonization process and incorporating the remaining databases. Once we have various modules, we plan to train their ensemble in the MoE and test gating strategies to properly direct the input to the most appropriate expert. So far, the first phase is focused on the current cognitive state and the factors that have the most significant impact on that state. In the second phase, we want to focus on understanding how cognitive abilities evolve over time and how modifiable risk factors lead to a positive or negative cognitive trajectory. For this task, we will include datapoints throughout time, focusing on the importance of temporality and causality in the data. Also, we can leverage strategies like chain-of-thought (CoT) in the transformer-based models from the previous phase to train the models to understand how the reasoning behind a risk factor leads to the cognitive outcome. This strategy will be implemented with help from experts that can provide examples of the analysis process on a case-by-case basis. 6 Table of Contents In the last phase, we will deploy the final model with insights from both previous phases to conduct further real-world validation and assess the impact of the model in early detection and cognitive trajectory improvements. Fig. 1: Overview of the database for MINT-AD Fig. 2: MINT-AD architecture using MoE 7 Table of Contents Our Strategy Our goal is to develop product candidates to diagnose and/or treat central nervous system disorders, such as Alzheimer’s disease and neurodegenerative conditions. Key elements of our business strategy to achieve this mission include: ● Advance Differentiated Therapies for High-Need CNS Indications : - Subject to FDA approval and clinical trials, IGC Pharma is advancing IGC-AD1 as a potential treatment for agitation in dementia due to Alzheimer’s disease—an area with limited effective therapies and significant unmet medical need. ● Expand IGC-AD1’s therapeutic potential to treat AD, subject to FDA approval: - Subject to FDA approval, IGC Pharma aims to broaden the clinical application of IGC-AD1 beyond agitation to target core Alzheimer’s disease symptoms, contingent upon regulatory approval and support clinical data. Although there can be no assurance, this expansion could significantly enhance the drug’s value and impact in addressing a major unmet medical need. ● Advance the development of TGR-63 as a potential therapeutic for AD: - IGC Pharma is progressing TGR-63, a preclinical candidate designed to target amyloid-beta plaque formation, a hallmark of Alzheimer’s pathology. This molecule represents a key component of the Company’s long-term strategy to diversify its Alzheimer’s pipeline and address the disease at its biological core. ● Publish scientific findings in peer-reviewed journals to strengthen clinical credibility and visibility: - IGC Pharma actively disseminates research through peer-reviewed publications to validate its scientific approach, enhance transparency, and support regulatory engagement. This strategy reinforces the Company’s reputation within the medical and investor communities and underpins the advancement of its drug development programs. ● Allocate Capital to Enhance Shareholder Value: - IGC Pharma Inc. is committed to strategically allocating capital to enhance shareholder value by advancing its AD pipeline, optimizing operational efficiency, and maintaining a robust financial position. We believe developing a drug for both symptom and disease-modifying agents has less risk due to the need for expensive multi-year trials. However, there is considerable upside and significant value creation to the extent we obtain a first-in-class advantage, of which there can be no assurance. If we were to obtain a first-in-class advantage, such an advantage could result in significant growth if and when an approved drug such as IGC-AD1 launches. We believe that additional investment in clinical trials, AI, R&D, facilities, marketing, advertising, and the acquisition of complementary products and businesses will be critical to the ongoing growth of the Life Sciences segment. Although there can be no assurance, we believe these investments will fuel the development and delivery of innovative products that drive positive patient and customer experiences. We hope to leverage our R&D and intellectual property to develop ground-breaking, science-based products that are proven effective through clinical trials, subject to FDA approval. Although there can be no assurance, we believe this strategy can improve our existing products and lead to the creation of new products that can provide treatment options for multiple conditions, symptoms, and side effects. 8 Table of Contents Core business competencies and advantages Our core competencies include: ● a network of doctors, scientists with Ph.D. degrees, and intellectual property legal experts with a sophisticated understanding of drug discovery, research, FDA filings, intellectual protection, and product formulation; ● knowledge of various cannabinoid strains, their phytocannabinoids profile, extraction methodology, and impact on various pathways; ● knowledge of plant and cannabinoid-based combination therapies; ● knowledge of research and development in the field; ● approximately thirty-one (31) patent applications out of which our portfolio includes twelve (12) granted patents. For more information, please refer to Item I, “Business” of Part I; ● facilities and a team with experience in manufacturing, marketing, and selling products. These competencies have enabled us to make progress on our business goals, specifically completing the Phase 1 clinical trial of IGC-AD1, which has the potential to positively impact on the lives of millions of patients suffering from the symptoms of Alzheimer’s disease, subject to FDA approval. Background on Alzheimer ’ s Disease (AD) Pathology AD pathology can be divided into two categories: familial or inherited AD and sporadic AD. The histopathology of early-onset familial AD and late-onset sporadic AD is indistinguishable. Both forms of AD are characterized by extracellular amyloid-β (Aβ) plaques and intracellular tau-containing neurofibrillary tangles (Gӧtz, et al., 2011). Simplistically, in normal brain functioning, a large protein called Amyloid Precursor Protein (APP) is cleaved into smaller fragments called Aβ proteins. In a normal brain, these are subsequently broken down further and cleared. However, in AD brains, these Aβ proteins are not broken down and cleared; they instead stick to one another and deposit as inter-neuronal sticky plaque—that is, they deposit as plaque between neurons. In the brain, within a neuron, tau (τ) is a key protein that holds together the transport scaffold. As an analogy, it is the brick-and-mortar of the highway over which nutrients are transported within a neuron. In an AD brain, tau breaks down due to a process called hyperphosphorylation and is unable to hold the transport highway. The breakdown results in neurofibrillary tangles (NFTs) and eventually leads to neuronal death. The misfolded structure of Aβ proteins, along with NFTs, generates a characteristic tendency for their aggregation (Chiti & Dobson, 2006) around damaged or dead neurons and within cerebral vasculature in the brain. It manifests in memory loss followed by progressive dementia. It has long been believed that Aβ1–40 (Aβ40) and Aβ1–42 (Aβ42) aggregates are the constituents of the insoluble plaques that are characteristic of AD. This disease is also associated with neuroinflammation, excitotoxicity, and oxidative stress (Campbell & Gowran, 2007; Rich, et al., 1995). However, the continuous aggregation of Aβ proteins along with hyperphosphorylation of tau protein inside the cell, causing NFT formation, are generally accepted as the major etiological factors of the neuronal cell death associated with the progression of Alzheimer’s disease (Octave, 1995; Reitz, et al., 2011; Pillay, et al., 2004). The two hallmarks of Alzheimer’s are shown in Figure 3. Figure 3: Hallmarks of Alzheimer ’ s ● Extracellular Plaque: β-amyloid (Aβ) ● Tau Neurofibrillary Tangles (NTFs). Causes loss of neurons & critical neuronal connections. Also linked to Alzheimer’s: ● Metabolism disruption ● Mitochondrial dysfunction ● Neuroinflammation 9 Table of Contents Alzheimer’s affects not only cognition but also mood and behavior, changes which increase in intensity as the disease progresses. Approximately 6.9 million Americans aged 65 and older are living with Alzheimer’s dementia, according to the Alzheimer’s Association’s 2024 Facts and Figures report. In 2025, it is estimated that 7.2 million Americans aged 65 and older have Alzheimer’s dementia, reflecting the growing aging population. Alzheimer’s is the most common cause of dementia, accounting for an estimated 60% to 80% of cases. Most individuals also have the brain changes of one or more other causes of dementia. This is called mixed pathologies, and if recognized during life it is called mixed dementia. There are various symptoms associated with this medical condition, such as screaming, pacing, biting, disrobing, excessive motor movements, physical aggression, and verbal aggression, among others. These behaviors make up clinical agitation in dementia due to Alzheimer’s disease and it they make it very difficult for caregivers to manage their loved ones. Agitation is associated with increased hospitalization and accelerated cognitive decline. Symptoms of AD depend on the stage of the disease: preclinical, mild, moderate, or severe. NPS, such as agitation, apathy, delusions, hallucinations, and sleep impairment, are common accompaniments of dementia. Loss of functionality, including progressive difficulty in performing instrumental and basic activities of daily living, is also seen with disease progression (Tang et al., 2019). There is a spectrum of behavioral disorders that can affect patients with AD. These include agitation, anxiety, disturbance of the sleep cycle, depression, inappropriate sexual behavior, disinhibition, and irritability, among others (Lyketsos, et al., 2011). These behavioral disturbances not only affect the patient’s quality of life but also cause extreme emotional distress for the caregivers. These disturbances can become very difficult to manage, so most of the time, combined therapy is used (Matsunaga et al., 2015). This can cause secondary undesirable effects, such as excessive sleepiness, which diminishes the capability of the patient to be active and alert during the day; dizziness, which can increase the risk for falls (Allan, et al., 2005); worsening of cognitive function, which in turn worsens functionality (Paterniti S, et al., 2002); and even death due to cardiovascular complications (Qiu, et. Al., 2006). Background on Agitation in Alzheimer ’ s dementia Agitation is a prevalent neuropsychiatric symptom among individuals with Alzheimer’s disease, characterized by restlessness, aggression, and emotional distress. Studies indicate that up to 80% of individuals with Alzheimer’s experience agitation during the course of the disease. Based on these figures, approximately 5.8 million Americans with Alzheimer’s may experience agitation in 2025. This substantial number underscores the critical need for effective interventions targeting agitation to improve patient quality of life and reduce caregiver burden. Agitation is a behavioral syndrome characterized by increased, often undirected, motor activity, restlessness, aggressiveness, and emotional distress. While there can be no guarantee, we expect the Phase 2 trial to take between 12 and 18 months to complete, barring a variety of unknown factors. We are currently developing IGC-AD1 for the treatment of Agitation in Alzheimer’s dementia (AAD). There is only one FDA-approved pharmacological treatment for the indication of AAD. The National Institute on Aging (NIA) at the National Institutes of Health (NIH) defines AD as an irreversible, progressive brain disorder that destroys memory and thinking skills. AD is a progressive neurodegenerative disorder that manifests initially as forgetfulness, advancing to severe cognitive impairment and memory loss. Emotional distress, aggressive behaviors, disruptive irritability, and disinhibition characterize agitation. Agitation in Alzheimer’s dementia has been associated with increased caregiver burden, decreased functioning, earlier nursing home placement, and death. The NIA categorizes Alzheimer’s in three stages- mild, moderate, and severe (NIA, 2019). Symptoms of mild Alzheimer’s can include wandering (getting lost, not remembering the way home), trouble handling money and paying bills, repeating questions, and personality or behavior changes. As the disease progresses to moderate, there is damage to the areas of the brain that control language, reasoning, sensory processing, and conscious thought. Patients can have difficulty with multi-step tasks such as getting dressed. Behavioral problems, including hallucinations, delusions, paranoia, and impulsive behavior, can also increase. When severe Alzheimer’s sets in, plaques and tangles spread throughout the patient’s brain, and the brain shrinks significantly. People with severe Alzheimer’s are completely dependent on others for care. They cannot communicate, and near the end of their life, they may be largely bedridden as the body shuts down (NIA, 2021). Patients with AD are currently treated with various medications, including antipsychotics, which have been considered the mainstay of treatment. These treatments, however, are limited by safety concerns. Typical antipsychotics prescribed for agitation, aggression, or insomnia are associated with functional decline in patients with AD, while studies indicate that atypical antipsychotics may be associated with increased rates of cerebrovascular events and death in patients with dementia. Currently, there are limited options to help Alzheimer’s patients with agitation or relief the burden placed on their caregivers (Cheng, 2017). Currently, IGC-AD1 is in a Phase 2 clinical trial, and on March 20, 2024, and on November 14, 2024, IGC announced the “Positive Interim Results for IGC-AD1 in Reducing Alzheimer’s agitation” and “Additional Phase 2 Interim Results Highlighting Cognitive Benefits of IGC-AD1 for Alzheimer’s Treatment”, respectively. The interim data validates IGC-AD1’s potential as a transformative therapeutic option with a large market opportunity in Alzheimer’s disease management, although there can be no assurance. 10 Table of Contents IGC-AD1 as a Treatment for Agitation in Alzheimer ’ s Dementia Approximately 6.9 million Americans aged 65 and older are living with Alzheimer’s dementia, according to the Alzheimer’s Association’s 2024 Facts and Figures report. AAD is associated with an accelerated cognitive decline, increased caregiver burden, increased hospitalization, and increased need for medication, all significantly diminishing the quality of life for patients. Current therapies carry black box warnings, indicative of serious adverse reactions that may lead to death or serious injury. IGC-AD1 is designed to target AAD’s underlying causes and address the unmet need for safe and effective therapy. As illustrated in Figure 2, neuroinflammation, neurotransmitter imbalance, and CB1 receptor dysfunctions are all associated with AAD (Yasuno et al., 2023; Manuel et al., 2014). In addition, upregulation of inflammasome-3 has been shown to lead to neuroinflammation, consequently leading to aggressive behavior (Yu et al., 2023). IGC-AD1’s formulation combines a CB1 receptor partial agonist with anti-neuroinflammatory properties that help balance neurotransmitter imbalance and an inflammasome inhibitor that targets the upregulation of inflammasome-3. The 146-patient IGC-AD1 Phase 2 trial, for which these interim results are presented, continues to enroll in the U.S. and Canada. As the interim results are based on a small number of patients (n=26), there is no guarantee that the positive interim results will hold up as more patients are enrolled in the trial. Learn more and find information about recruitment centers at https://clinicaltrials.gov/study/NCT05543681. Figure 4: Damaged and Healthy Neurons IGC-AD1 Clinical Trial Data To the best of our knowledge, the Company’s Phase 2 clinical trial of IGC-AD1 is the first human clinical trial using low doses of THC, in combination with another molecule, to treat symptoms of dementia in Alzheimer’s patients. THC is a naturally occurring cannabinoid produced by the cannabis plant. It is known for being a psychoactive substance that can impact mental processes in a positive or negative way, depending on the dosage. THC is biphasic, meaning that low and high doses of the substance may affect mental and physiological processes in substantially different ways. For example, in some patients, low doses may relieve a symptom, whereas high doses may amplify a symptom. IGC’s trial is based on low dosing and controlled trials on patients suffering from Alzheimer’s disease. We conducted a double-blind, single-site, randomized, three-cohort, multiple-ascending dose (MAD) clinical trial (FDA IND Number: 146069, NCT04749563) using the investigational new drug (IND) IGC-AD1. In this trial, we looked at safety, tolerability, neuropsychiatric symptoms, and pharmacokinetics, among others. The trial concluded that all three dosing levels (once a day, twice a day, and twice a day) were safe, with no serious or life-threatening events or deaths reported. On December 1, 2021, IGC submitted the Clinical/Statistical Report (CSR) to the FDA on its Phase 1 trial titled “A Phase I Randomized Placebo-Controlled MAD Study to Evaluate Safety and Tolerability of IGC-AD1 in Subjects with Dementia Due to Alzheimer’s Disease.” The already disclosed data is presented here for a better understanding of the safety profile of IGC-AD1. The data presented here is not exhaustive and represents a small portion of the data submitted to the FDA. 11 Table of Contents Phase 1 Primary Endpoint: Safety & Tolerability Safety and tolerability (S&T) were assessed by recording both solicited and non-solicited Adverse Events (AEs). The solicited AEs, assessed daily, were somnolence, falls, dizziness, asthenia, suicidal ideation, hypertension, psychiatric symptoms, and paradoxical nausea. All AEs were graded as mild, moderate, severe, life-threatening, and serious (SAE). In the phase 1 trial, a) there were no SAEs, b) no life-threatening AEs, and c) no deaths. Phase 1 Secondary Endpoints: Neuropsychiatric Inventory (NPI) Neuropsychiatric Symptoms (NPS) such as agitation/aggression, depression, anxiety, elation/euphoria, apathy, disinhibition, irritability, delusions, hallucinations, aberrant motor behavior, sleep disorders, and appetite/eating disorders are prevalent in patients who have AD (Phan et al., 2019). NPS in Alzheimer’s is a significant burden on patients and caregivers, and at some point in the progression of Alzheimer’s disease, more than 97% of patients suffer from at least one symptom. The Neuropsychiatric Inventory (NPI) is a scale that measures the severity of each symptom and establishes both individual symptom scores as well as an overall NPI score. Separately, the NPI also scores caregiver distress (NPI-D). The NPI is used by about 50% of neurologists to assess and treat Alzheimer’s patients (Fernandez et al., 2010). In the Phase 1 trial conducted on patients with AD, we measured changes in NPS as assessed by the NPI as well as caregiver distress as assessed by the NPI-D. In the Phase 1 trial (N=10), seven received the active medication, and at baseline, they had agitation scores between two and twelve. The three Cohorts shown in Table 1 received the medication once a day (qd), twice a day (bid), and three times a day (tid). We measured and analyzed the change in the mean NPI score for agitation between Day 1 and Day 10 and between Day 1 and Day 15 for all three cohorts. ● As shown in the Table 1, our analysis shows Cohort 2 (bid) had the largest absolute change in the mean agitation score between Day one and Day ten (53% drop, p=.085) as well as between Day 1 and Day 15 (67% drop, p=.05). Table 1: NPI (Agitation) analysis for each of the three cohorts Domain Cohort 1 (n=7) qd Cohort 2 (n=6) bid Cohort 3 (n=5) tid NPI (Agitation) Baseline Day Day Baseline Day Day Baseline Day Day Day 0 10 15 Day 0 10 15 Day 0 10 15 Mean Score 4.7 3.3 3 4.3 2.1 1.5 4.2 3.2 1.4 Mean Change - 1.4 1.7 - 2.2 2.8 - 1 2.8 Mean Change% - 37% 48% - 53% 67% - 23% 67% p-values - 0.058 0.045 - 0.085 0.05 - 0.29 0.045 According to the NPI, a reduction of 4 points or 30% in the score is considered clinically meaningful (Cummings et al., 1994). In addition, we used a paired 2-tailed t-test with 9 degrees of freedom to assess the statistical significance of the decrease in the overall NPI agitation domain. As seen in Table 1, the NPI score for Agitation in Cohort 2 at day 15 shows a reduction of 67% ( p = .05). Based on this study the dosing of twice a day or bid was selected for the Phase 2 trial. IGC-AD1 Phase 2 Clinical Trial Update IGC Pharma launched a Phase 2 trial with a protocol titled “A Phase 2, Multi-Center, Double-Blind, Randomized, Placebo-controlled, trial of the safety and efficacy of IGC-AD1 on agitation in participants with dementia due to Alzheimer’s disease” (clinicaltrials.gov, Identifier: CT05543681). The trial treatment duration is 6 weeks, with the intervention, IGC-AD1 or placebo, administered twice a day. The study is powered to include 146 Alzheimer’s patients; as a superiority trial with parallel groups, half of the participants will receive a placebo, and the other half will receive IGC-AD1. The primary and secondary endpoints are the mean change in agitation scores from baseline, compared to placebo, as assessed by the Cohen-Mansfield Agitation Inventory (CMAI) in Alzheimer’s patients after 6 weeks of treatment and the mean change in CMAI scores after 2 weeks of treatment, respectively. Agitation is rated at the trial site, at baseline, week 2, and week 6, by a trained practitioner using the CMAI, a scale designed and widely used to measure agitation in Alzheimer’s dementia (AAD) in clinical trials. The IGC-AD1 Phase 2 is an ongoing clinical trial that continues to enroll. IGC-AD1 is an oral liquid formulation administered twice daily (bid) for six weeks with no placebo run-in and titration to full dose over two days. To date over 1,000 oral doses have been administered, with no dose-limiting adverse events observed, highlighting the safety profile of IGC-AD1. The Investigational product targets different pathways implicated in AAD, including CB1 receptor dysfunction, neuroinflammation and neurotransmitter imbalance. The investigational drug contains THC, the principal psychoactive cannabinoid found in Cannabis, as one of two active pharmaceutical agents. 12 Table of Contents Pre-Specified Interim Results An experienced third party conducted a protocol pre-specified interim analysis, mean changes from baseline were analyzed using a mixed-effects model for repeated measures (MMRM). Findings showed that patients taking IGC-AD1, on average, experienced a significant reduction in agitation scores compared to those on placebo, and the positive effects were observed as early as week two of the trial. Interim results will be discussed in the following sections. IGC-AD1 Trial Interim Primary and Secondary Endpoints Results The primary objective is to assess the efficacy of IGC-AD1 in AAD after six weeks of treatment using the CMAI scale. The secondary objective is to assess IGC-AD1 efficacy and early response in AAD using also the CMAI scale, after 2 weeks of treatment. Based on the CMAI interim results shown in Table 2 below, IGC-AD1 demonstrated a clinical and statistically significant agitation reduction compared to placebo in patients with AD, indicating strong therapeutic potential and meeting the primary endpoint. The CMAI least-squared (LS) mean difference at week 6 was -10.46 (95% CI: -20.53 to -0.40) with a Cohen’s d effect size of 0.79 (p= .042), indicating a large and significant IGC-AD1 effect over placebo. Cohen’s d is a standardized statistical effect size that describes the magnitude of the difference between two groups, taking into account the variability in outcomes. Based on the interim results, the secondary endpoint was also met; the data demonstrates a clinically significant reduction, approaching statistical significance, in agitation in Alzheimer’s at week two compared to placebo. CMAI LS mean difference at week 2, assessing early response, was -12.19 with an ES of 0.79 (p= .071). The ES, similarly, to the primary endpoint, indicates a large magnitude of difference between the active and placebo groups . Table 2:- Interim CMAI Results for Week 2 and Week 6 Week 2 Week 6 (EOT) Scale LS Mean Change (95% CI) p value Cohen’s d LS Mean Change (95% CI) p value Cohen’s d CMAI -12.19 (-25.52, 1.14) .071 0.79 -10.46 (-20.53, -0.4) .042 0.79 IGC-AD1 Clinical Trial Interim Data Demonstrates Significant Reduction in Sleep Disturbances As part of an interim analysis, the Company observed statistically and clinically significant reductions in sleep disturbances, as measured by the Neuropsychiatric Inventory (NPI-12) Sleep Subscale. At week 2, patients receiving the active medication experienced a 71% reduction in sleep disturbance (p = 0.012), which improved further to 78% at week 6 (p = 0.02), compared to placebo. These findings suggest that IGC-AD1 may reduce the frequency and/or severity of nighttime behavioral disturbances, an underrecognized but impactful symptom affecting up to 44% of individuals with AD. Figure 5: - Shows the clinically and statistically significant decrease in the frequency and/or severity of sleep disturbances (B) for the active group versus the placebo group (A) as measured by the NPI Sleep Subscale. Sleep disturbances are known to exacerbate cognitive and behavioral symptoms in AD and are a common contributor to caregiver distress and early institutionalization. The ability to improve sleep quality represents an important potential therapeutic benefit, as enhanced sleep has been linked to reduced amyloid-beta accumulation and slower disease progression in preclinical studies. 13 Table of Contents Beyond its implications in Alzheimer’s care, sleep disorders affect over 30 million Americans and are associated with increased risk for cognitive decline and cardiovascular disease. If the sleep-related benefits of IGC-AD1 are confirmed in larger clinical trials, the candidate may address a significant unmet need within the broader global sleep aid market, which is projected to exceed $100 billion by 2030. Previously reported data from the ongoing Phase 2 trial also demonstrated notable reductions in agitation, further supporting IGC-AD1’s potential as a multi-targeted therapy for managing neuropsychiatric symptoms in AD. The Company anticipates additional data readouts from the CALMA trial in late 2025, including further analysis of sleep-related outcomes. In parallel, IGC Pharma plans to initiate future studies evaluating IGC-AD1 as a disease-modifying therapy, reflecting the Company’s strategic commitment to advancing innovative, mechanism-driven treatments for central nervous system disorders. Existing Treatments for Agitation in Alzheimer ’ s Dementia In May 2023, the U.S. Food and Drug Administration (FDA) approved the first medication for the treatment of AAD, Brexpiprazole, an atypical antipsychotic, with a boxed warning. This approval followed a significantly larger 12-week Phase 3 trial, which showed a CMAI LS mean difference from baseline at week 12, between active treatment and placebo of -5.32 with a Cohen’s d effect size of 0.35, and a p-value of 0.003 (Lee et al., 2023). Regulatory Environment for IGC-AD1 IGC-AD1 is currently made from federally legal hemp In addition, IGC-AD1 contains the federally legal amount of THC as defined in the 2018 Farm Bill. Therefore, IGC-AD1 is federally legal based on the amount of THC in the formulation and the origin of the THC. The Company grew hemp under a license in the state of Arizona. Manufacturing IGC-AD1 from hemp is an extremely inefficient process requiring vast amounts of hemp to manufacture the investigational medication. The regulatory landscape appears to be changing in that the U.S. government is seeking to reschedule THC from Schedule 1 to Schedule 3. The Company use hemp to manufacture IGC-AD1 , which is egal. The Company has received permission from the regulators to conduct the IGC-AD1 Phase 2 trial in the U.S., Canada, and Colombia. TGR-63 and Alzheimer ’ s disease TGR-63 was licensed from the Jawaharlal Nehru Centre for Advanced Scientific Research in India and developed by Prof. T Govindaraju, who designed several naphthalene monoimide compounds and compared their capacity to inhibit Aβ aggregation, their cytotoxicity, and their neuronal rescue capacity, in which TGR-63 excelled. Researchers at the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), in India, conducted approximately 10 years of research on Naphthalene Monoimide (NMI) compounds and the activity of NMI compounds on neurotoxicity associated with AD. 14 Table of Contents In Alzheimer’s patients, neurotoxicity is linked to beta-amyloid (Aβ) plaques and Neuro Fibrillary Tangles (NFT). JNCASR’s research based on Alzheimer’s cell lines identified one lead NMI molecule, TGR-63, from a family of NMI molecules with the potential to reduce amyloid beta (Aβ) plaques. Further, they demonstrated that the molecule reduces cognitive decline in a transgenic mouse model of Alzheimer’s. Their results were published in Advanced Therapeutics under the title “Naphthalene Monoimide Derivative Ameliorates Amyloid Burden and Cognitive Decline in a Transgenic Mouse Model of Alzheimer’s Disease” on January 28, 2021. Pursuant to the signed agreement dated March 28, 2022, IGC Pharma (through Hamsa Biopharma India Pvt. Ltd.) acquired exclusive intellectual property rights to the molecule, which it intends to pursue as a potential new drug candidate, subject to further study, research, and development. IGC Pharma is conducting human trials with IGC-AD1, which is currently being tested as a symptom-modifying agent in Alzheimer’s dementia. TGR-63, on the other hand, could act as a potential disease-modifying agent to expand the Company’s pursuit of a drug that can treat AD. Figures 6 and 7: - Show the destabilization of Aβ plaques and Aβ42 peptide with the help of TGR-63. Computational Studies: A Plausible Mode of Action Figure 6: In silico analysis demonstrated that TGR-63 molecular design enables it to interact with amyloid aggregates, disrupting various types of bonds. This destabilizes plaque’s structure, facilitating their breakdown. (*Adv. Therap. 2021, 4 2000225) . Figure 7: TGR-63 also shows high affinity for the Aß42 peptide, compromising its tertiary structure and promoting the formation of globular non-toxic structures that can be metabolized. (*Adv. Therap. 2021, 4 2000225) . Pre-clinical studies of TGR-63 TGR-63 is a patent-pending molecule designed to disrupt the structure of the amyloid beta (Aβ) plaque, one of the key hallmarks of AD, associated with neuronal toxicity and cognitive decline. TGR-63 targets plaques by inhibiting the aggregation of Aβ42 peptides and destabilizing their tertiary structure. Specifically, the pre-clinical research on TGR-63 showed the following: Impact on plaque levels: Studies in PC12 and SHSY5Y cell lines grown in an AD-like environment have showed TGR-63’s ability in decreasing Aβ plaque levels, leading to an increase in 26% neuron viability (neuronal rescue). TGR-63’s potential as a treatment for AD was further evaluated in a genetically modified mouse model mimicking Alzheimer’s amyloid pathology. In that assay, the group treated with TGR-63, compared to the vehicle-treated group, showed a 78% and 85% reduction in the cortical and hippocampal amyloid load, respectively, demonstrating its potential to alleviate amyloid burden. Figure 5 shows the reduction of the amyloid burden by TGR-63 in the APP/PS1 AD mouse model. 15 Table of Contents Figure 8: Reduction of the amyloid burden by TGR-63 in the APP/PS1 AD phenotypic mice model. A) Visualization of amyloid plaques in the half hemisphere: Confocal microscopy images of coronal section of WT, AD mice, and TGR-63 treated AD mice brain. B) Reduction of cortical and hippocampal amyloid burden by TGR-63 treatment: Higher magnification images of vehicle and TGR-63 treated mice (WT and AD) brain sections to visualize and compare the Aβ plaques deposition in the cortex and hippocampus areas. C, D) Quantification of Aβ plaques: The amount of Aβ plaques (%area) deposited in different regions (cortex and hippocampus) of vehicle and TGR63 treated mice (WT and AD) brain was analyzed. Data represent mean ± SEM, number of mice = 3 per group (* p < 0.05). Scale bar: 20 µm. (*Adv. Therap. 2021, 4 2000225) . Behavioral Impact: During the investigation, two groups of APP/PS1 mice undertook an Open-Field (OF) test, a behavioral assessment designed to measure aberrant behavior, stress and coping responses, and emotional state, among others, in rodent models. The mice in the APP/PS1 group that received TGR-63 treatment showed a 43% reduction in their overall movement within the test area (p<.0001), a 59% reduction in movement within the central zone of the test area (p<.01), and a 55% reduction in entries to the center zone compared to the untreated group (p<.05). These are shown in Figure 6. The results from these multiple tests indicate that TGR-63 treatment helped to improve in their anxious-like and aggressive-like behaviors compared to the group that did not receive the treatment, normalizing emotional and behavioral responses in the mouse model, reinforcing its potential as a promising treatment. Figure 9 Behavioral Tests 16 Table of Contents Impact on memory : The cognitive impact of TGR-63 was assessed using two renowned behavioral tests, the Novel Object Recognition (NOR) Test and the Morris Water Maze (MWM), conducted on APP/PS1 genetically modified Alzheimer’s mice. During the NOI Test, mice were familiarized with two identical objects, followed by exploration of both novel and familiar objects after 24 and 48 hours, to establish the discrimination index (DI). AD mice displayed a significantly lower DI (-3, p<0.0001, 24h; -7, p<0.0001, 48h) compared to wild-type (WT) mice (+49, 24h; +43 48h), indicating impaired long-term memory formation, while AD mice treated with TGR-63 exhibited an improved DI (+50, p<0.0001; +38, p<0.001), indicative of healthy long term memory formation and successful memory retrieval. In the MWM test, the time to reach a platform hidden in a pool for four training days showed a remarkable improvement for the TGR-63 treated AD model compared to the AD-vehicle group, indicating enhanced spatial memory, as demonstrated by a significant reduction (~60% reduction; p < 0.05) in the time required by the TGR-63 treated AD mice to locate the hidden platform, exhibiting a similar behavior to healthy mice. The results of the novel recognition test and the MWM are shown in Figures 7 and 8 respectively. Figure 10: In the Novel Object Recognition test, mice treated with TGR-63 showed increased exploration of a new object over a familiar one, indicating enhanced learning capacity. (*Adv. Therap. 2021, 4 2000225) . Figure 11: During the Morris Water Maze test, mice treated with TGR-63 exhibited improved spatial memory, with decreased latency in finding the target compared to the untreated group. ( *Adv. Therap. 2021, 4 2000225). Contract Research Organization (CRO) and Clinical Trial Software The IGC-Pharma Electronic Data Capture system (IGC-EDC) is a secure and user-friendly data management software designed to collect clinical trial data in electronic format. The software incorporates rigorous security measures that help IGC to protect data and ensure compliance with regulatory requirements and industry standards. This format is designed for our clinical trials, especially our Phase 2 trial. The EDC system is designed to store and organize handwritten source documents, including medical history, concomitant medications, laboratory results, neuropsychiatric scale scores, adverse events, vital signs, safety calls, and demographics, among others. The system allows users to generate data reports that will be used for data analysis and generate computational models to simulate the effects of our investigational drug IGC-AD1 on participants’ outcomes. At IGC Pharma, we recognize the significance of operational excellence and cost management in clinical trials. One major cost driver in conducting trials is the expense associated with engaging CROs. These costs can significantly impact the overall budget of a trial. To address this challenge and optimize trial costs, we have established an internal CRO, including proprietary software, that we believe sets us apart from the traditional approach of outsourcing. We believe this strategic move should enable us to reduce the costs associated with clinical trials compared to relying on external CROs, although there can be no assurance. Intellectual Property IGC Pharma, is committed to building a strong and defensible intellectual property (IP) portfolio that supports our strategic focus on neurodegenerative diseases and related therapeutic areas. Our IP strategy is centered on securing exclusive rights to proprietary technologies, inventions, and product candidates through the development, acquisition, and licensing of patents and related protections both in the United States and internationally. We actively seek to protect our innovations by filing patent applications that cover novel methods, compositions, and uses associated with our investigational drug candidates, formulations, and related technologies. Our patent strategy is designed to cover key elements of our research and development efforts, particularly in the fields of AD, epilepsy, pain management, and other central nervous system (CNS) disorders. In addition to patent protection, we intend to leverage data exclusivity, market exclusivity, and patent term extensions, where applicable, to maximize the commercial potential and lifecycle of our assets, although there can be no assurance thereof. 17 Table of Contents Our commercial success depends in part on our ability to: ● Obtain and maintain strong patent and proprietary protection; ● Protect our trade secrets and proprietary know-how; ● Secure necessary licenses for third-party intellectual property; ● Enforce our rights against infringement; and ● Operate without infringing valid, enforceable third-party patents. We aim to commercialize our intellectual property through multiple channels: 1. Pharmaceutical products are subject to U.S. Food and Drug Administration (FDA) approval. Our lead candidate, IGC-AD1, is currently in a Phase 2 clinical trial for treating agitation in AD. We are also developing TGR-63, a pre-clinical candidate with potential disease-modifying effects in Alzheimer’s. 2. Branded wellness and lifestyle products, offered through retail and online distribution channels, in compliance with applicable federal, state, and local laws. 3. Partnerships and licensing agreements with third parties to accelerate product development and market entry. We hold exclusive rights to all patents filed with the U.S. Patent and Trademark Office (USPTO). In Fiscal 2017, we acquired exclusive rights to data and a patent application from the University of South Florida (USF), and following Fiscal 2022, we acquired similar exclusive rights from the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR). While patent registration is a key component of our business strategy, we cannot guarantee that all provisional or non-final patent applications will result in granted patents. Please refer to Item 1A. Risk Factors – “We may not successfully register the provisional patents with the USPTO.” As of March 31, 2025, our intellectual property portfolio comprised twelve (12) issued patents and thirty-one (31) pending patent applications across the United States and international jurisdictions. Of the twelve issued patents, four (4) patents are licensed from third parties. These patents and applications cover compositions, methods of treatment, and formulations relevant to our core therapeutic areas, including AD, epilepsy, pain, and other neurodegenerative and central nervous system disorders. Table 3 below provides the status of our patent filings: Table 3 Patent Filings & Status TARGET DESCRIPTION PATENT PENDING GRANTED PATENTS US FOREIGN Alzheimer’s Disease (IGC-AD1) Method & Composition for Treating CNS Disorders 12 - 1 Alzheimer’s Disease (IGC-AD1) Method & Composition for Treating CNS Disorders 1 2 - Alzheimer’s Disease (TGR-63) Naphthalene Monoimide Derivatives with the ability to impact Aβ protein build-up 6 - - Alzheimer’s Disease (IGC-1C) Naphthalene Monoimide Derivatives with the ability to impact Tau aggregation and neurofibrillary tangle formation 5 - - Alzheimer’s Disease (IGC-M3) Naphthalene Monoimide Derivatives with the ability to impact Aβ plaque buildup and neurofibrillary tangle formation 4 - - Cancer (Naphthalene Diimdes) Naphthalene Diimide Derivatives with the ability to self-assemble molecular interactions for biological and nonbiological systems - 1 1 Alzheimer’s Disease (IGC-LMP) Composition, Synthesis, & Medical use of Hybrid Cannabinoid 1 - - Epilepsy Composition & Method for Treating Seizures in humans & cats/dogs - 2 - Eating Disorders Cannabis formulation with Cyproheptadine for treating Cachexia & Eating Disorders - 1 - Stuttering & Tourette Syndrome Cannabinoid-Based formulation for Treating Stuttering & Symptoms of Tourette Syndrome 1 - - Pain Cannabinoid-Based Formulation combined with Cobalamin and method for Pain Management 1 2 2 TOTAL 31 8 4 18 Table of Contents Patent Term Extension After NDA approval, owners of relevant drug patents may apply for up to a five-year patent extension. The allowable patent term extension is calculated as half of the drug’s testing phase — the time between IND submission and NDA submission — and all of the review phase — the time between NDA submission and approval up to a maximum of five years. The time can be shortened if the FDA determines that the applicant did not pursue approval with due diligence. The total patent term after the extension may not exceed 14 years. For patents that might expire during the application phase, the patent owner may request an interim patent extension. An interim patent extension increases the patent term by one year and may be renewed up to four times. For each interim patent extension granted, the post-approval patent extension is reduced by one year. The director of the PTO must determine that approval of the drug covered by the patent for which a patent extension is being sought is likely. Interim patent extensions are not available for a drug for which an NDA has not been submitted. Products and Services in the Life Sciences segment We believe developing a drug for either symptoms or as a disease-modifying agent has less risk due to the need for multi-year trials and FDA approval. However, there is a considerable upside and significant value creation to the extent we obtain a first-to-market advantage, of which there can be no assurance. If we were to obtain a first-to-market advantage, such an advantage could result in significant growth if and when an approved drug launches. We believe that additional investment in clinical trials, research and development (R&D), facilities, marketing, advertising, and acquisition of complementary products and businesses will be critical to the ongoing growth of the Life Sciences segment. These investments will fuel the development and delivery of innovative products that drive positive patient and customer experiences. We hope to leverage our R&D and intellectual property to develop ground-breaking, science-based products that are proven effective through clinical trials, subject to FDA approval. Although there can be no assurance, we believe this strategy can improve our existing products and lead to the creation of new hemp-based products that can provide treatment options for multiple conditions, symptoms, and side effects. Markets and Distribution In Fiscal 2025, our Life Sciences segment is focused on the Phase 2 clinical trial for IGC-AD1 and building a pipeline of other assets. In addition, the Company sells over-the-counter products and formulations made in Vancouver, Washington facilities. Our Life Sciences revenue is less than 1% of the relevant global market, which implies a good opportunity for growth. In Fiscal 2025, our sales and suppliers were concentrated, which represents some risk. Two customers individually accounted for over 10% of total sales. Competition Overview Our industry is highly competitive and subject to rapid and significant technological change. The large size and expanding scope of the CNS markets make them attractive therapeutic areas for biopharmaceutical businesses. Our competitors include well-funded pharmaceutical companies, companies in the food and skincare industries, and companies with experience in providing white labeling and tolling services. While we believe that our employees and consultants, scientific knowledge, technology, and development experience provide us with competitive advantages, we face competition from many different sources. Many of our competitors may have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do. Competition for the Company’s investigational medications, products, and services: We are aware of other companies working to develop therapeutics for the treatment of AAD, including Axsome Therapeutics, Inc., which is working to develop a combination of dextromethorphan and bupropion, and Otsuka and Lundbeck A/S, which recently received approval for Rexulti for this indication. 19 Table of Contents Interim data from our Phase 2 trial of IGC-AD1 for agitation in Alzheimer’s disease show a statistically significant improvement in symptoms compared to placebo over six weeks, as measured by the Cohen-Mansfield Agitation Inventory (CMAI). IGC-AD1 demonstrated a large effect size (Cohen’s d = 0.79) and showed improvement as early as Week 2. For context, Brexpiprazole (Rexulti), the currently approved therapy, reported a moderate effect size (Cohen’s d = 0.4) and showed separation from placebo only by Week 6, based on published trial data, albeit with a significantly larger patient base. In addition to efficacy, IGC-AD1 has shown a favorable safety profile to date. As of the 6-week interim analysis: ● No serious adverse events (SAEs) were reported ● No adverse events (AEs) led to treatment discontinuation ● No deaths occurred in the treatment or placebo arms While cross-trial comparisons must be interpreted with caution due to differences in trial design and patient populations, these early findings suggest that IGC-AD1 may offer faster symptom relief with a potentially improved safety profile compared to the currently approved therapy. The study remains ongoing to further assess efficacy, durability, and long-term safety. Licenses, Technology, and Cybersecurity We have intellectual property attorneys that advise, counsel, and represent the Company regarding the filing of patents or provisional patent applications, copyright applications, and trademark applications; trade secret laws of general applicability; employee confidentiality and invention assignment. Most of our data, including our accounting data, is stored in the cloud, which helps us mitigate the overall risk of losing data. We have a cybersecurity policy in place and are in the process of implementing tighter cybersecurity measures to safeguard against hackers. The Company holds all rights to the patents that have been filed by us with the USPTO. The table below summarizes the nature of the activity, the type of license required and held, and encumbrances in obtaining permits for each location where the Company operated through its subsidiaries in Fiscal 2025: Location Nature of Activity Type of License Required Type of License held Encumbrances in Obtaining Permit U.S. Life Sciences Products and General Management General business Clinical Trials; Good Manufacturing Practices (GMP) certification. FDA approval to run a trial General business licenses; Industrial Alcohol User Permit; FDA approval to run a trial. None. India Infrastructure Contract, Rental of heavy equipment, and land General business license Business registrations with tax authorities in various states in India None. Colombia Life Sciences Products and General Management General business license; Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA) Permits; Fondo Nacional De Estupefacientes (FNE) Permits. General business license; Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA) Permits; Fondo Nacional De Estupefacientes (FNE) Permits. None. Canada Clinical Trials Permit from Health Canada to conduct a trial in Canada. Permit to import IGC-AD1 into Canada. Permit to conduct a trial and to import IGC-AD1 into Canada. None 20 Table of Contents Governmental Regulations In the U.S., we are subject to oversight and regulations, for some or all of our activities, by the following agencies: SEC, state regulators, NYSE, FTC, FINRA, and the FDA. Hemp is cannabis plant. Under the 2018 Farm Bill, Hemp is classified as a cannabis plant that has 0.3% or less THC by dry weight. The 2018 Farm Bill, which was effective January 1, 2019, contains provisions that make industrial hemp, defined as a cannabis plant that has 0.3% of less THC by dry weight, legal. Although hemp is legal at the federal level, most states have created licensing and testing processes for the growing, processing, and sale of hemp and hemp-derived products. For our business, we must apply for licenses in states where we desire to grow and process hemp. For example, in the state of Arizona, where we grew hemp, we were required to apply for licenses and register with the state the geo-location of all our operations, including the land on which hemp was grown and the facilities where hemp would be processed. These regulations are evolving, differ from jurisdiction to jurisdiction, and are subject to change. FDA Approval Process In the U.S., pharmaceutical products are subject to extensive regulation by the FDA. The Federal Food, Drug, and Cosmetic Act, or the FDC Act, and other federal and state statutes and regulations, govern the research, development, testing, manufacturing, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring, and reporting, sampling, and importing and exporting of pharmaceutical products, among other things. Failure to comply with applicable U.S. requirements may subject a company to a variety of administrative or judicial sanctions, such as the imposition of clinical holds, FDA refusal to approve pending New Drug Applications (NDA), warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement, civil penalties, and criminal prosecution. Pharmaceutical product development in the U.S. typically involves pre-clinical laboratory and animal tests and the submission to the FDA of an Investigational New Drug (IND), which must become effective before clinical testing may commence. For commercial approval, the sponsor must submit adequate tests by all methods reasonably applicable to show that the drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling. The sponsor must also submit substantial evidence, generally consisting of adequate, well-controlled clinical trials, to establish that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the proposed labeling. In certain cases, the FDA may determine that a drug is effective based on one clinical study plus confirmatory evidence. Satisfaction of FDA premarket approval requirements typically takes many years, and the actual time required may vary substantially based upon the type, complexity of the product, or disease. Pre-clinical tests include laboratory evaluation of product chemistry, formulation, and toxicity, as well as animal trials to assess the characteristics and potential safety and efficacy of the product. The conduct of the pre-clinical tests must comply with federal regulations and requirements, including the FDA’s good laboratory practices regulations and the U.S. Department of Agriculture’s (USDA’s) regulations implementing the Animal Welfare Act. The results of pre-clinical testing are submitted to the FDA as part of an IND along with other information, including information about product chemistry, manufacturing, and controls, and a proposed clinical trial protocol. Long-term pre-clinical tests, such as animal tests of reproductive toxicity and carcinogenicity, may continue after the IND is submitted. A 30-day waiting period after the submission of each IND is required prior to the commencement of clinical testing in humans. If the FDA has not imposed a clinical hold on the IND or otherwise commented on or questioned the IND within this 30-day period, the clinical trial proposed in the IND may begin. Clinical trials involve the administration of an investigational new drug to healthy volunteers or patients under the supervision of a qualified investigator. Clinical trials must be conducted: (i) in compliance with federal regulations; (ii) in compliance with Good Clinical Practice (GCP), an international standard meant to protect the rights and health of patients and to define the roles of clinical trial sponsors, administrators, and monitors; and (iii) under protocols detailing the objectives of the trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. Each protocol involving testing on U.S. patients and subsequent protocol amendments must be submitted to the FDA as part of the IND. The FDA may order the temporary or permanent discontinuation of a clinical trial at any time or impose other sanctions if it believes that the clinical trial either is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial patients. The trial protocol and informed consent information for patients in clinical trials must also be submitted to an institutional review board, or IRB, for approval. An IRB may also require the clinical trial at the site to be halted, either temporarily or permanently, for failure to comply with the IRB’s requirements or may impose other conditions. Clinical trials to support NDAs for marketing approval are typically conducted in three sequential phases, but the phases may overlap. In general, in Phase 1, the initial introduction of the drug into healthy human subjects or patients, the drug is tested to assess metabolism, pharmacokinetics, pharmacological actions, side effects associated with increasing doses, and, if possible, early evidence on effectiveness. Phase 2 usually involves trials in a limited patient population to determine the effectiveness of the drug for a particular indication, dosage tolerance, and optimum dosage and to identify common adverse effects and safety risks. If a compound demonstrates evidence of effectiveness and an acceptable safety profile in Phase 2 evaluations, Phase 3 trials are undertaken to obtain additional information about clinical efficacy and safety in a larger number of patients, typically at geographically dispersed clinical trial sites, to permit the FDA to evaluate the overall benefit-risk relationship of the drug and to provide adequate information for the labeling of the drug. In most cases, the FDA requires two adequate and well-controlled Phase 3 clinical trials to demonstrate the efficacy of the drug. The FDA may, however, determine that a drug is effective based on one clinical study plus confirmatory evidence. Only a small percentage of investigational drugs complete all three phases and obtain marketing approval. In some cases, the FDA may require post-market studies, known as Phase 4 studies, to be conducted as a condition of approval in order to gather additional information on the drug’s effect in various populations and any side effects associated with long-term use. Depending on the risks posed by the drugs, other post-market requirements may be imposed. 21 Table of Contents After completion of the required clinical testing, an NDA is prepared and submitted to the FDA. The FDA approval of the NDA is required before marketing of the product may begin in the U.S. The NDA must include the results of all pre-clinical, clinical, and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture, and controls. The cost of preparing and submitting an NDA is substantial. The FDA has 60 days from its receipt of an NDA to determine whether the application will be accepted for filing based on the agency’s threshold determination that it is sufficiently complete to permit substantive review. Once the submission is accepted for filing, the FDA begins an in-depth review. Under the statute and implementing regulations, the FDA has 180 days (the initial review cycle) from the date of filing to issue either an approval letter or a complete response letter unless the review period is adjusted by mutual agreement between the FDA and the applicant or as a result of the applicant submitting a major amendment. In practice, the performance goals established pursuant to the Prescription Drug User Fee Act have effectively extended the initial review cycle beyond 180 days. The FDA’s current performance goals call for the FDA to complete a review of 90 percent of standard (non-priority) NDAs within 10 months of receipt and within six months for priority NDAs, but two additional months are added to standard and priority NDAs for a new molecular entity (NME). The FDA may also refer applications for novel drug products, or drug products that present difficult questions of safety or efficacy, to an advisory committee, which is typically a panel that includes clinicians and other experts, for review, evaluation, and a recommendation as to whether the application should be approved. The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations. Before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. Additionally, the FDA will inspect the facility or the facilities at which the drug is manufactured. The FDA will not approve the product unless compliance with the current GMP is satisfactory, and the NDA contains data that provides substantial evidence that the drug is safe and effective in the indication studied. After the FDA evaluates the NDA and the manufacturing facilities, it issues either an approval letter or a complete response letter. A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing or information for the FDA to reconsider the application. If, or when, those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue an approval letter. The FDA has committed to reviewing 90 percent of resubmissions within two to six months, depending on the type of information included. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications. As a condition of NDA approval, the FDA may require a risk evaluation and mitigation strategy (REMS) to help ensure that the benefits of the drug outweigh the potential risks. REMS can include medication guides, communication plans for health care professionals, and elements to assure safe use (ETASU). ETASU can include but is not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring, and the use of patient registries. The requirement for a REMS can materially affect the potential market and profitability of the drug. Moreover, product approval may require substantial post-approval testing and surveillance to monitor the drug’s safety or efficacy. Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained, or problems are identified following initial marketing. Expedited Development: Designations such as Breakthrough Therapy Designation (BTD) and Fast Track Designation can speed up the development process by allowing for more frequent communication with the FDA and potentially faster review timelines. This can translate to getting the drug to market quicker. ● Breakthrough Therapy Designation (BTD): This designation is given by the FDA to drugs that have the potential to significantly improve treatment for serious or life-threatening conditions. It allows for more intensive interaction with the FDA during development and can expedite the review process. ● Fast Track Designation: This designation is designed to facilitate the development and expedite the review of drugs that address unmet medical needs. It offers some advantages like more frequent meetings with the FDA and potential for rolling review (reviewing data as it becomes available). Disclosure of Clinical Trial Information Sponsors of clinical trials of certain FDA-regulated products, including prescription drugs, are required to register and disclose certain clinical trial information on a public website maintained by the U.S. National Institutes of Health. Information related to the product, patient population, phase of the investigation, study sites, investigator, and other aspects of the clinical trial is made public as part of the registration. Disclosure of the results of these trials can be delayed for up to two years if the sponsor certifies that it is seeking approval of an unapproved product or that it will file an application for approval of a new indication for an approved product within one year. Competitors may use this publicly available information to gain knowledge regarding the design and progress of our development programs. 22 Table of Contents The Hatch-Waxman Act Orange Book Listing In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent the claims of which cover the applicant’s product. Upon approval of a drug, each of the patents listed in the application for the drug is then published in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book. Drugs listed in the Orange Book can, in turn, be cited by potential generic competitors in support of approval of an abbreviated new drug application (ANDA). An ANDA provides for the marketing of a drug product that has the same active ingredients in the same strengths and dosage form as the listed drug and has been shown through bioequivalence testing to be bioequivalent to the listed drug. Other than the requirement for bioequivalence testing, ANDA applicants are not required to conduct or submit results of pre-clinical or clinical tests to prove the safety or effectiveness of their drug product. Drugs approved in this way are considered to be therapeutically equivalent to the listed drug, are commonly referred to as “generic equivalents” to the listed drug and can often be substituted by pharmacists under prescriptions written for the original listed drug in accordance with state law. The ANDA applicant is required to certify to the FDA concerning any patents listed for the approved product in the FDA’s Orange Book. Specifically, the applicant must certify that: (i) the required patent information has not been filed; (ii) the listed patent has expired; (iii) the listed patent has not expired but will expire on a particular date, and approval is sought after patent expiration; or (iv) the listed patent is invalid or will not be infringed by the new product. The ANDA applicant may also elect to submit a section viii statement, certifying that its proposed ANDA labeling does not contain (or carves out) any language regarding the patented method-of-use rather than certify to a listed method-of-use patent. If the applicant does not challenge the listed patents, the ANDA application will not be approved until all the listed patents claiming the referenced product have expired. A certification that the new product will not infringe the already approved product’s listed patents or that such patents are invalid is called a Paragraph IV certification. If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months, expiration of the patent, settlement of the lawsuit, or a decision in the infringement case that is favorable to the ANDA applicant. The ANDA application also will not be approved until any applicable non-patent exclusivity listed in the Orange Book for the referenced product has expired. Exclusivity Upon NDA approval of a new chemical entity or NCE, which is a drug that contains no active component that has been approved by the FDA in any other NDA, that drug receives five years of marketing exclusivity, during which time the FDA cannot receive any ANDA or 505(b)(2) application seeking approval of a drug that references a version of the NCE drug. Certain changes to a drug, such as the addition of a new indication to the package insert, are associated with a three-year period of exclusivity during which the FDA cannot approve an ANDA or 505(b)(2) application that includes the change. An ANDA or 505(b)(2) application may be submitted one year before NCE exclusivity expires if a Paragraph IV certification is filed. If there is no listed patent in the Orange Book, there may not be a Paragraph IV certification, and thus, no ANDA or 505(b)(2) application may be filed before the expiration of the exclusivity period. For a botanical drug, the FDA may determine that the active moiety is one or more of the principal components or the complex mixture as a whole. This determination would affect the utility of any five-year exclusivity as well as the ability of any potential generic competitor to demonstrate that it is the same drug as the original botanical drug. Five-year and three-year exclusivities do not preclude FDA approval of a 505(b)(1) application for a duplicate version of the drug during the period of exclusivity, provided that the 505(b)(1) applicant conducts or obtains a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness. 23 Table of Contents Orphan Drug Act Under the Orphan Drug Act, the FDA may grant orphan drug designation to drugs intended to treat a rare disease or condition, generally a disease or condition that affects fewer than 200,000 individuals in the U.S. (or affects more than 200,000 in the U.S. and for which there is no reasonable expectation that the cost of developing and making available in the U.S. a drug for such disease or condition will be recovered from sales in the U.S. of such drug). Orphan drug designation must be requested before submitting an NDA. After the FDA grants orphan drug designation, the generic identity of the drug and its potential orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process. The first NDA applicant to receive FDA approval for a particular active ingredient to treat a particular disease with FDA orphan drug designation is entitled to a seven-year exclusive marketing period in the U.S. for that product for that indication. During the seven-year exclusivity period, the FDA may not approve any other applications to market the same drug for the same disease, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity. If the FDA designates an orphan drug based on a finding of clinical superiority, the FDA must provide a written notification to the sponsor that states the basis for orphan designation, including “any plausible hypothesis” relied upon by the FDA. The FDA must also publish a summary of its clinical superiority findings upon granting orphan drug exclusivity based on clinical superiority. Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same disease or condition or the same drug for a different disease or condition. Among the other benefits of orphan drug designation are tax credits for certain research and a waiver of the NDA application user fee. Special Protocol Assessment A company may reach an agreement with the FDA under the Special Protocol Assessment (SPA), process as to the required design and size of clinical trials intended to form the primary basis of an efficacy claim. According to its performance goals, the FDA is supposed to evaluate the protocol within 45 days of the request to assess whether the proposed trial is adequate, and that evaluation may result in discussions and a request for additional information. A SPA request must be made before the proposed trial begins, and all open issues must be resolved before the trial begins. If a written agreement is reached, it will be documented and made part of the administrative record. Under the FDC Act and FDA guidance implementing the statutory requirement, an SPA is generally binding upon the FDA except in limited circumstances, such as if the FDA identifies a substantial scientific issue essential to determining safety or efficacy after the study begins, public health concerns emerge that were unrecognized at the time of the protocol assessment, the sponsor and the FDA agree to the change in writing, or if the study sponsor fails to follow the protocol that was agreed upon with the FDA. U.S. Coverage and Reimbursement Significant uncertainty exists as to the coverage and reimbursement status of our lead product candidates, such as IGC-AD1 or any other for which we may seek regulatory approval. Sales in the U.S. will depend in part on the availability of adequate financial coverage and reimbursement from third-party payors, which include government health programs such as Medicare, Medicaid, TRICARE, and the Veterans Administration, as well as managed care organizations and private health insurers. Prices at which we or our customers seek reimbursement for our product candidates can be subject to challenge, reduction, or denial by payors. The process for determining whether a payor will provide coverage for a product is typically separate from the process for setting the reimbursement rate that the payor will pay for the product. Third-party payors may limit coverage to specific products on an approved list or formulary, which might not include all the FDA-approved products for a particular indication. Also, third-party payors may refuse to include a branded drug on their formularies or otherwise restrict patient access to a branded drug when a less costly generic equivalent or another alternative is available. Medicare Part D, Medicare’s outpatient prescription drug benefit, contains protections to ensure coverage and reimbursement for oral oncology products, and all Part D prescription drug plans are required to cover substantially all oral anti-cancer agents. However, a payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be available. Private payors often rely on the lead of the governmental payors in rendering coverage and reimbursement determinations. Sales of products such as IGC-AD1 or any other product candidates will, therefore, depend substantially on the extent to which the costs of our products will be paid by third-party payors. Achieving favorable coverage and reimbursement from the Centers for Medicare and Medicaid Services (“CMS”) and/or the Medicare Administrative Contractors is typically a significant gating issue for the successful introduction of a new product. Third-party payors are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy. In order to obtain coverage and reimbursement for any product that might be approved for marketing, we may need to conduct studies in order to demonstrate the medical necessity and cost-effectiveness of any products, which would be in addition to the costs expended to obtain regulatory approvals. Third-party payors may not consider our product candidates to be medically necessary or cost-effective compared to other available therapies, or the rebate percentages required to secure favorable coverage may not yield an adequate margin over cost or may not enable us to maintain price levels sufficient to realize an appropriate return on our investment in drug development. 24 Table of Contents Human Capital Management and Environment, Health, and Safety Human Capital Management We believe that our ability to attract, retain, and develop exceptional talent is critical to our success, particularly in advancing our clinical development programs and scientific research. As of March 31, 2025, our full-time employee headcount worldwide was 70. We foster a culture of collaboration, accountability, and innovation. We comply with all applicable labor, health, and safety laws and support employee well-being through flexible work policies and safe workplace practices. We invest in employee development, offering training and learning opportunities to help our teams grow professionally and contribute to our long-term success. We are committed to providing equal opportunities for all employees. Our compensation and equity programs are designed to retain talent and align with long-term shareholder value.8 Environment, Health, and Safety (EHS) We are committed to health, safety, and environmental compliance in all our operations in the U.S., Colombia and India. While our operations have a limited environmental impact, we promote responsible practices to minimize waste and ensure safety in our research and office environments. Management oversees our EHS practices and updates them as needed to meet regulatory and operational requirements. Available Information The Company’s Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and amendments to reports filed pursuant to Sections 13(a) and 15(d) of the Exchange Act are filed with the Securities and Exchange Commission (the SEC”). The Company is subject to the informational requirements of the Exchange Act and files or furnishes reports, proxy statements, and other information with the SEC. Such reports and other information filed by the Company with the SEC are available free of charge on the Company’s website at www.igcpharma.com when such reports are available on the SEC’s website. The SEC maintains an Internet site that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC at www.sec.gov. The contents of these websites are not incorporated into this filing. Further, the Company’s references to the URLs for these websites are intended to be inactive textual references only.