IGC Pharma announced that one of the active pharmaceutical ingredients in its investigational Alzheimer's disease drug IGC-AD1 has successfully passed critical genetic toxicology testing, confirming its safety profile. The company presented these findings at the 2025 Genetic Toxicology Association Annual Meeting held in Delaware on May 8, 2025.
The scientific poster, titled "Genetic Toxicity Evaluation of Melatonin in the Bacterial Reverse Mutation Assay," showcased non-clinical data demonstrating that melatonin, one of the two APIs in IGC-AD1, does not alter or mutate genes—a key FDA safety requirement for drugs intended for human consumption.
"This is an important milestone, as we prepare the drug for larger trials and eventual commercialization," said Ram Mukunda, CEO of IGC Pharma. The genetic toxicology data represents a significant advancement in the company's development program for IGC-AD1, which is being investigated for the treatment of agitation in Alzheimer's disease.
Comprehensive Safety Testing Methodology
The GLP-compliant study was conducted by an independent laboratory in Canada using the Bacterial Reverse Mutation Test, commonly known as the Ames test. This test is part of a broader genetic toxicology battery required by regulatory authorities to assess mutagenic potential.
Following OECD Guideline 471 and ICH S2(R1) recommendations, researchers evaluated multiple bacterial strains including Salmonella typhimurium (TA1535, TA1537, TA98, TA100) and Escherichia coli WP2 trp uvrA. Testing was performed both with and without an exogenous mammalian metabolic activation system (±S9), providing a comprehensive assessment of potential mutagenicity.
Conclusive Safety Results
The study examined melatonin at concentrations ranging from 1.6 to 5000 μg/plate and found no evidence of mutagenicity at any dose level. Across all bacterial strains and experimental conditions, Fold Response values remained below 2—the established threshold for mutagenic activity.
Further validating these findings, revertant colony counts remained within the range of negative controls and substantially lower than positive controls. Statistical analysis using Dunnett's test showed no significant dose-related increases (p > 0.05), reinforcing the conclusion that the API does not induce gene mutations under the tested conditions.
Advancing Alzheimer's Treatment
IGC-AD1 is currently in a Phase 2 clinical trial (CALMA) evaluating its efficacy for agitation in Alzheimer's dementia. The drug combines melatonin with a cannabinoid-based therapy, representing a novel approach to addressing behavioral symptoms associated with Alzheimer's disease.
Agitation affects a significant percentage of Alzheimer's patients and presents a substantial challenge for caregivers and healthcare providers. Current treatment options are limited and often carry significant side effects, highlighting the need for safer and more effective therapies.
IGC Pharma's Broader Pipeline
Beyond IGC-AD1, the company is developing several other candidates targeting neurodegenerative conditions. Their pipeline includes TGR-63, which targets amyloid plaques—a hallmark pathological feature of Alzheimer's disease—as well as early-stage programs focused on neurodegeneration, tau proteins, and metabolic dysfunctions.
IGC Pharma is leveraging artificial intelligence to accelerate drug discovery, optimize clinical trials, and enhance patient targeting. With 30 patent filings to date, the company demonstrates a strong commitment to innovation in the neurodegenerative disease space.
Regulatory Context and Future Directions
The successful completion of genetic toxicology testing represents a critical step in the regulatory pathway for IGC-AD1. The FDA requires comprehensive safety data, including genetic toxicology studies, before allowing drugs to proceed to larger clinical trials and eventual market approval.
With this safety milestone achieved, IGC Pharma appears positioned to advance IGC-AD1 through its clinical development program. The company's focus on both safety and efficacy aligns with the increasing regulatory scrutiny applied to novel therapeutics, particularly those targeting vulnerable populations such as Alzheimer's patients.
As the global burden of Alzheimer's disease continues to grow, with more than 55 million people affected worldwide and numbers projected to triple by 2050, the development of new treatment options remains a critical public health priority. IGC Pharma's progress with IGC-AD1 represents a potentially meaningful contribution to addressing this unmet medical need.
