Announcement • Apr 26
Insilico Medicine Nominates First Preclinical Candidate in the UAE
Insilico Medicine nominated ISM0387, the first UAE-based preclinical candidate, jointly announced with the Emirates Drug Establishment (EDE), with the support of local partners including Abu Dhabi Investment Office (ADIO), the Department of Health Abu Dhabi (DoH) and other prominent ecosystem players. ISM0387 is an MTA-cooperative PRMT5 inhibitor with AI-powered novel structure, showing improved in vitro activity and selectivity, enhanced brain penetrant properties, and robust, dose-dependent efficacy in disease models. The discovery process of ISM0387 is local, and it signals that the UAE has evolved into a technology-driven powerhouse with a knowledge-based "Falcon Economy." Based on Chemistry42 and its 40+ models, Insilico's team screened 90 AI-powered novel candidates, considering multiple parameters with a focus on CNS-specific traits, completing the lead discovery phase in just six months. Insilico Medicine, a clinical-stage, generative AI–driven drug discovery company, announced a landmark milestone: the nomination of the UAE's first-ever developmental candidate. Discovered locally by Insilico's UAE team using the company's proprietary Pharma.AI platform, the program completed the early discovery workflow, from molecular design to optimization, within the region. The nomination also represents Insilico's 30th AI-supported preclinical candidate (PCC) to date. In May 2025, Insilico launched an ambitious pilot program in the UAE to prove that generative AI could compress years of traditional research into months. The initiative targeted medium-novelty, genetically validated synthetic-lethality targets for solid tumors. To lead this cycle, Insilico deployed a specialized local team of four—comprising two computational chemists, one medicinal chemist, and one translational biologist—tasked with meeting aggressive benchmarks: target finalization by Third Quarter 2025, hit series generation in under 30 days, and lead optimization in less than 6 months. Insilico has officially nominated ISM0387, an MTA-cooperative PRMT5 inhibitor as the developmental candidate for this program. Featuring a novel structure and exceptional CNS-penetrant abilities, ISM0387 offers a promising new treatment option for patients with Glioblastoma (GBM). The entire development journey, from molecular design, optimization to preclinical nomination, was conducted locally in the UAE. The program reached this critical milestone in under 12 months. The scientific foundation of ISM0387 lies in synthetic lethality, a specific relationship between two genes (known as a synthetic lethal pair) where a mutation or deficiency in either gene alone allows the cell to survive, but the loss of both genes simultaneously is fatal. As a result, the inhibition of Protein Arginine Methyltransferase 5 (PRMT5) enables targeted treatment against cancer cells with deletion of Methylthioadenosine phosphorylase (MTAP), which forms a synthetic lethal pair with PRMT5. In early 2025, Insilico nominated ISM1745, its first MTA-cooperative PRMT5 inhibitor with best-in-class potential, overcoming the selectivity and toxicity issue for the first generation of inhibitors known to shut down PRMT5 in both healthy and cancer cells. More importantly, the nomination of ISM1745 further validates the abilities of Pharma.AI to break complex real-world drug development challenges, and paves the way for MTA-cooperative PRMT5 inhibitors with broader applications in MTAP-deleted cancers, featuring brain-penetrant properties that are particularly suited for treating central nervous system (CNS) diseases, especially glioblastoma (GBM), the most aggressive brain tumor in adults. With a recurrence rate exceeding 70%, GBM takes the lives of over 200,000 patients worldwide each year, and accounts for approximately 48% of all primary malignant brain tumors. MTAP deletion is detected in up to 40–50% of cases, demonstrating potential of PRMT5 inhibition in this field primarily relying on chemotherapy and radiotherapy as standard of care (SOC). Discovered at Insilico's Generative AI and Quantum Computing R&D Center in Abu Dhabi, ISM0387 will potentially expand the "built-in-UAE" innovation to benefit patients all over the globe, demonstrating how HELM enables the translation of advanced research into scalable pharmaceutical innovation and positions Abu Dhabi as an emerging hub for advanced pharmaceutical manufacturing and life sciences exports. The discovery and optimization process for ISM0387 was powered by Chemistry42, Insilico's generative chemistry platform integrated with over 40 generative AI models. More specifically, the team utilized the co-crystal structures of known PRMT5 inhibitors, generating 90 compounds with novel scaffolds with AI, which were subsequently evaluated for a balance between binding affinity, synthetic accessibility, and ADMET properties. To address the specific challenges of Glioblastoma, the AI prioritized CNS-specific engineering, optimizing core parameters such as molecular weight, topological polar surface area (TPSA), hydrogen bond donors, lipophilicity (LogP), and pKa, while simultaneously validating in vitro passive permeability and brain-to-plasma ratios to ensure exceptional blood-brain barrier penetration. The entire lead discovery phase was completed with high efficiency in just six months, identifying four lead compounds with good brain penetration and metabolic stability. In multiple cancer cell lines, ISM0387 demonstrated improved in vitro activity and selectivity, as well as a promising in vitro safety profile. Enhanced blood-brain barrier (BBB) penetration properties were reported across animal species, leading to lower efficacious dose projected in humans, highlighting potential in future clinical development. In orthotopic glioblastoma models, daily administration of ISM0387 at 30 mg/kg robustly suppressed tumor growth over 20 days, in stark contrast to marked tumor progression observed in the vehicle group. With ISM0387 being the 30th PCC nomination, since 2021, Insilico has established a comprehensive portfolio of over 40 assets, with 12 candidates obtaining IND clearance, three reaching Phase II evaluation, among which one Phase IIa clinical trial completed with positive results for the treatment of idiopathic pulmonary fibrosis (IPF). By integrating the technologies of AI and automation, Insilico has demonstrated significant efficiency boost compared to traditional drug discovery methods (often requiring an average of 4.5 years), as announced in the recent key timeline benchmarks for internal programs from 2021 to 2024: the average time to PCC is 12-18 months, with 60-200 molecules synthesized and tested per program.
