8-K: IGC Pharma Reports Positive Interim Phase 2 Results for Alzheimer's Agitation Drug IGC-AD1, Demonstrating Superior Safety and Faster Efficacy Compared to Industry Benchmark

IGC Pharma, Inc. announced positive interim results from its Phase 2 CALMA trial for IGC-AD1, showing significant improvements in agitation and sleep disturbance in Alzheimer's patients with a favorable safety profile, outperforming a comparative industry standard.

Summary

• IGC Pharma, Inc. has released an updated corporate presentation detailing preclinical and clinical study updates for its Alzheimer's drug candidate, IGC-AD1.
• Preclinical studies demonstrated IGC-AD1's potential as a disease-modifying therapy, showing reduction in A40 production and aggregation, decreased Tau and pTau, enhanced mitochondrial function, and improved spatial memory in AD models.
• The drug was found to be non-toxic and non-mutagenic in preclinical in vitro studies and crosses the blood-brain barrier.
• Phase 1 trial results indicated IGC-AD1 was well-tolerated across all three dose levels (once, twice, and three times daily) over 14 days, with no Serious Adverse Events (SAEs), life-threatening AEs, or deaths reported.
• Phase 1 also showed an overall improvement in neuropsychiatric symptoms (NPS) as measured by the NPI-12, with statistically significant reductions in agitation scores (p < 0.05 for each dose group), ranging from 36.36% to 66.66% reduction.
• Interim results from the ongoing Phase 2 CALMA trial for agitation in Alzheimer's disease showed a clinical and statistically significant improvement in agitation at Week 6 (LS mean difference -10.46, p = 0.042, Cohen's d = 0.79).
• At Week 2 of the Phase 2 trial, a strong trend towards improvement in agitation was observed (LS mean difference -12.19, p = 0.071, Cohen's d = 0.79).
• IGC-AD1 also led to clinically and statistically significant improvements in sleep disturbance in Phase 2, with reductions of 71% at Week 2 (p=0.012) and 78% at Week 6 (p=0.02).
• The company holds 31 patent applications in process and 12 granted patents related to its intellectual property, including for IGC-AD1.

Sentiment

Score: 8

Explanation: The document presents highly positive preclinical and clinical (Phase 1 and interim Phase 2) results for IGC-AD1, particularly regarding its safety profile and efficacy in reducing agitation in Alzheimer's patients. The comparative data against Brexpiprazole, despite the 'not a direct comparison' caveat, strongly suggests a superior profile. The strong intellectual property also adds to the positive sentiment.

Positives

• IGC-AD1 demonstrated a favorable safety profile in Phase 1, with no Serious Adverse Events (SAEs), life-threatening AEs, or deaths reported.
• Phase 1 results showed statistically significant reductions in agitation symptoms across all dose groups (p < 0.05).
• Interim Phase 2 results indicate a clinical and statistically significant improvement in agitation at Week 6 (p = 0.042, Cohen's d = 0.79).
• IGC-AD1 showed clinically and statistically significant improvements in sleep disturbance in Phase 2, with reductions of 71% at Week 2 (p=0.012) and 78% at Week 6 (p=0.02).
• Preclinical data supports IGC-AD1's disease-modifying potential by reducing amyloid and tau pathology, enhancing mitochondrial function, and improving spatial memory.
• The drug crosses the blood-brain barrier, indicating direct central nervous system activity.
• IGC-AD1 appears to be faster-acting and demonstrates a larger effect size (Cohen's d = 0.79) compared to Brexpiprazole (Cohen's d = 0.4 at week 12) in treating agitation, based on comparative data.
• The safety profile of IGC-AD1 in Phase 2 interim data (no SAEs, no discontinuations, no deaths) is significantly better than reported for Brexpiprazole (~6% SAEs, 5% discontinuations, 7 deaths).
• The company has a strong intellectual property portfolio with 31 patent applications and 12 granted patents, including for IGC-AD1.

Negatives

• The comparison of IGC-AD1 to Brexpiprazole is explicitly stated as "not a direct comparison," which limits the definitive conclusion of superiority.
• While showing a strong trend, the improvement in agitation at Week 2 in Phase 2 was not statistically significant (p = 0.071).
• The Phase 1 trial identified genotype-dependent variation in IGC-AD1 API half-life, suggesting a potential need for personalized dosing strategies, which could add complexity to future trials.

Risks

• Clinical trial outcomes may differ from projections.
• Challenges in patient recruitment timelines.
• Variability in clinical site performance.
• Management's ability to recruit sites, patients, and monitor clinical trials.
• Uncertainty regarding regulatory approvals.
• Competition from other drug developers.
• Availability of funding for ongoing and future trials.
• Challenges in intellectual property protection.

Future Outlook

IGC Pharma strategically prioritized a Phase 2 trial targeting agitation in Alzheimer's dementia based on strong clinical signals and urgent unmet clinical need, while disease modification remains a long-term objective. The company expects to complete the Phase 2 trial targeting 146 participants. Future trials may incorporate personalized dosing strategies based on CYP2C9 genotype to optimize safety and efficacy.

Management Comments

• IGC Pharma, Inc. (IGC or the Company) made available on its website an updated corporate presentation titled Clinical Study Update, dated June 17, 2025. The Company expects to use this presentation at upcoming conferences, business events, and in meetings with analysts, investors, and other stakeholders.
• Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized. IGC PHARMA, INC. Dated: June 17, 2025 By: /s/ Claudia Grimaldi Name: Claudia Grimaldi Title: Principal Financial Officer and Vice President

Industry Context

The Alzheimer's disease market is characterized by a high unmet medical need, particularly for symptoms like agitation which significantly impact patients and caregivers. IGC-AD1's focus on agitation, supported by positive interim Phase 2 data, positions it to address a critical symptomatic aspect of AD. The comparative data against Brexpiprazole, a recently approved drug for AD agitation, suggests IGC-AD1 could offer a potentially safer and faster-acting alternative, which would be a significant advancement in the competitive landscape of Alzheimer's therapeutics.

Comparison to Industry Standards

• IGC-AD1's Phase 2 interim results show a Cohen's d effect size of 0.79 for agitation reduction, which is notably higher than Brexpiprazole's reported Cohen's d of 0.4 at Week 12.
• IGC-AD1 demonstrated an effect on agitation as early as Week 2 (p=0.071) and statistically significant improvement by Week 6 (p=0.042), suggesting a faster onset of action compared to Brexpiprazole, which showed limited effect at Week 2 and started showing effect at Week 6.
• In terms of safety, IGC-AD1's interim Phase 2 data reported no Serious Adverse Events (SAEs), no Adverse Events (AEs) leading to discontinuation, and no deaths up to 6 weeks. This contrasts sharply with reported data for Brexpiprazole, which had approximately 6% participants with SAEs, 5% with AEs leading to discontinuation, and 7 deaths (6 in active group, 1 in placebo).
• The comparison is explicitly stated as "not a direct comparison" as it's based on published results of Brexpiprazole (NCT01922258) versus IGC-AD1's ongoing trial (NCT05543681).

Stakeholder Impact

• Shareholders: Positive clinical trial results and a strong safety profile could lead to increased investor confidence and potential share price appreciation.
• Patients: IGC-AD1 offers a potential new treatment option for agitation in Alzheimer's disease, which is a significant unmet medical need, potentially improving quality of life.
• Caregivers: Reduction in patient agitation and improved sleep disturbance could significantly alleviate caregiver burden and distress.
• Employees: Positive clinical progress could enhance company morale and stability.

Next Steps

• Completion of the Phase 2 CALMA trial, targeting 146 participants.
• Potential implementation of personalized dosing strategies in future trials based on CYP2C9 genotype.
• Continued pursuit of disease modification as a long-term objective for IGC-AD1.
• Presentation of the updated corporate presentation at upcoming conferences, business events, and in meetings with analysts, investors, and other stakeholders.

Key Dates

Recommendation

Keywords

Alzheimer's Disease, Agitation, Dementia, IGC-AD1, Clinical Trial, Phase 1, Phase 2, Neuropsychiatric Symptoms, Drug Development, Biotechnology, Pharmaceuticals, SEC Filing, 8-K, Neurodegeneration, Cognitive Impairment, Sleep Disturbance, Amyloid, Tau, Mitochondrial Function, Intellectual Property