DP Technology Announces Development Candidate, a CNS Penetrable Lp-PLA2 Inhibitor for Alzheimer’s Disease

BEIJING, July 8, 2024 /PRNewswire/ — DP Technology, a company focused on the “AI for Science” paradigm, today announced the nomination of DPT0416, a novel CNS-penetrable small molecule targeting Lp-PLA2, as a preclinical candidate for the treatment of Alzheimer’s disease (AD).

Alzheimer’s disease is the most common cause of dementia (60–70%), affecting approximately 57 million people worldwide. Neurovascular dysfunction is an early and prominent event in the development of Alzheimer’s disease, independent of classical amyloid pathology. Lp-PLA2 is a phospholipase secreted primarily by inflammatory cells, including peripheral macrophages and CNS microglia. It hydrolyzes oxidized phospholipids typically present on low-density lipoproteins (LDL), producing lysophosphatidylcholine (lysoPC) and other potent pro-inflammatory factors. LysoPC is a key inflammatory mediator in vascular endothelial cells, leading to vascular pathology, including vascular leakage and BBB damage. Lp-PLA2 inhibition by Rilapladib significantly slowed Alzheimer’s disease progression and repaired BBB lesions in a phase IIa trial.

DPT0416 is a novel CNS-penetrant Lp-PLA2 inhibitor with higher potency, better ADME and physicochemical properties than Rilapladib. In animal models, DPT0416 has shown improved BBB integrity and reduced brain inflammation. IND-enabling studies are ongoing.

“Alzheimer’s disease is imposing increasing burdens on the world. The approval of three anti-amyloid β (Aβ) antibodies marks a turning point in the fight against Alzheimer’s disease, but the modest clinical efficacy and side effects highlight the complexity of Alzheimer’s disease and call for more innovative and effective interventions. Future treatment of Alzheimer’s disease should address multiple aspects of the disease, including antioxidants, anti-inflammatory, and improving brain resilience, among others,” said Xiaomin ZhangHead of Drug Discovery at DP Technology. “Targeting Lp-PLA2 is a novel therapy that addresses multiple factors beyond amyloid. Given the positive clinical results of rilapladib, the best-in-class molecule DPT0416 is expected to provide further benefits to patients with AD and dementia.”

“DP Technology is revolutionizing the landscape of AI for science by integrating “AI + Simulation + Experiments” into our processes to address important medical needs,” said Weijie SunFounder and CEO of DP Technology“The successful identification of DPT0416 highlights the power of our RiDYMO® platform, particularly the contributions of the Uni-FEP and Uni-QSAR modules in improving molecular interactions, drug-like characteristics and BBB penetration. These real-world applications of our cutting-edge algorithms represent an important step forward in our vision for the future. We look forward to partnering with trusted collaborators to advance this initiative to the next critical milestone.”

RiDYMO® drug design platform integrates various AI and physics algorithms, dedicated to drug development for “non-drug” targets and “first-in-class” molecules. As one of its core algorithms, Reinforced Dynamics (RiD) has a significant advantage in the sampling efficiency of molecular dynamics simulation. By fully exploiting the high-dimensional representation capabilities of neural networks, RiD can effectively capture dynamic conformational changes in complex biomolecular systems.

The RiDYMO® platform is dedicated to studying the dynamics of biological systems and revealing cryptic binding sites, encompassing a range of complex systems including protein-protein interactions (PPIs), intrinsically disordered proteins (IDPs), membrane proteins, RNA and others. Its effectiveness has been confirmed by validation on complex targets including c-Myc protein, c-Myc RNA, GPX4 protein, Kv1.3 protein and others.

About DP Technology

DP Technology, a company focused on the new “AI for science” paradigm, dedicated to the application of artificial intelligence algorithms and molecular simulation to solve important scientific problems by combining advanced computational methods.

Leveraging DP Technology’s RiDYMO® dynamics-based drug design platform, we have established a leading drug discovery platform. The team has established external collaborations and built a robust internal pipeline, focusing on three areas: central nervous system, oncology and autoimmune diseases.

For collaboration and further information please contact Dr. Xiaomin Zhang ((protected email)).

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(5) Diab. Vasc. Say. Res. 14, 200-213 (2017).

SOURCE DP Technology