DP Tech Nominates CNS Penetrable Lp-PLA2 Inhibitor for Alzheimer's

DP Technology, a company focused on utilizing artificial intelligence (AI) for scientific advancements, has announced the nomination of a new preclinical candidate, DPT0416. This novel small molecule, which can penetrate the central nervous system (CNS), targets Lp-PLA2 and is intended for the treatment of Alzheimer's disease (AD). Alzheimer's disease, the leading cause of dementia, impacts around 57 million people globally. Neurovascular dysfunction, rather than just amyloid pathology, is a significant early event in the development of AD. Lp-PLA2, a phospholipase secreted by inflammatory cells such as macrophages and microglia, plays a key role in this process. It hydrolyzes oxidized phospholipids on low-density lipoprotein (LDL), resulting in the production of lysophosphatidylcholine (lysoPC) and other proinflammatory factors. LysoPC, in turn, is an important inflammatory mediator in vascular endothelial cells, leading to issues like vessel leakage and blood-brain barrier (BBB) damage.

Previous studies have shown that the inhibition of Lp-PLA2 by Rilapladib can significantly slow the progression of AD and repair BBB damage, as evidenced in a Phase IIa clinical trial. DPT0416, a next-generation Lp-PLA2 inhibitor developed by DP Technology, has demonstrated higher potency and better absorption, distribution, metabolism, and excretion (ADME) and physicochemical properties compared to Rilapladib. In animal studies, DPT0416 has shown improvements in BBB integrity and a reduction in brain inflammation. The drug is currently undergoing IND-enabling studies.

Xiaomin Zhang, Head of Drug Discovery at DP Technology, emphasized the growing global burden of Alzheimer's disease and the need for novel treatments that go beyond targeting amyloid pathology. Zhang pointed out that although recent approvals of anti-amyloid β antibodies are significant, their modest clinical efficacy and side effects underline the complexity of AD. Future treatments should address multiple aspects of the disease including antioxidants, anti-inflammatory measures, and enhancing brain resilience. He further stated that targeting Lp-PLA2 offers a promising new therapeutic approach, building on the positive clinical outcomes seen with rilapladib and aiming to provide even greater benefits to patients with AD and other forms of dementia.

Weijie Sun, Founder and CEO of DP Technology, highlighted the innovative approach of integrating AI, simulation, and experimental methods to meet significant medical needs. He noted that the successful identification of DPT0416 underscores the capabilities of the company’s RiDYMO® platform, particularly its Uni-FEP and Uni-QSAR modules, in enhancing molecular interactions, drug-like properties, and BBB penetration. Sun expressed optimism about forming partnerships to advance this initiative further.

The RiDYMO® drug design platform combines multiple AI and physical algorithms, aiming to develop drugs for challenging targets and creating best-in-class molecules. One of its core algorithms, Reinforced Dynamics (RiD), excels in efficiently sampling molecular dynamics. By leveraging neural networks' high-dimensional representation capabilities, RiD captures dynamic conformational changes in complex biomolecular systems. The platform is focused on studying biological system dynamics and identifying cryptic binding sites, with applications in protein-protein interactions (PPIs), intrinsically disordered proteins (IDPs), membrane proteins, RNA, and other challenging systems. Its effectiveness has been validated on difficult targets, including the c-Myc protein, c-Myc RNA, GPX4 protein, and Kv1.3 protein.

DP Technology leverages its AI-driven approaches to tackle significant scientific challenges, particularly in CNS disorders, oncology, and autoimmune diseases. With a robust internal pipeline and strong external collaborations, the company is positioned at the forefront of scientific innovation.