Puduri Pharma's PDR-001, the World’s First Peptide-Based Protein Degrader for Parkinson’s Disease, Enters IIT Clinical Trial at Ruijin Hospital

Recently, PDR-001, a novel peptide-based targeted protein degrader independently developed by PRODEGRE (Shanghai) Pharmaceutical Co., Ltd. for the treatment of early-to-mid stage primary Parkinson’s disease, officially commenced its investigator-initiated trial (IIT) at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. At the launch ceremony, Professor Liu Jun, Director of the Department of Neurology; Director Li Dianyou and his team from the Department of Neurosurgery, both at Ruijin Hospital; Academician Wang Yutian, Chairman of PRODEGRE and Director of the Fudan Shangsi Center for Neuroscience; and CEO Tan Shen, along with other senior executives of the company, attended the event and engaged in in-depth discussions.

The current study, titled “A Study on the Safety, Tolerability, and Efficacy of PDR-001 Injection for Stereotactic Bilateral Basal Ganglia Clearance of α-Synuclein,” has successfully completed the enrollment of its first patient. During the meeting, representatives from the project team and PRODEGRE engaged in systematic discussions on multiple key elements, including the drug’s mechanism of action, inclusion and exclusion criteria, trial procedures, surgical approaches, and subject protection, thereby laying a solid foundation for the high-quality advancement of the trial.

Academician Wang Yutian, Chairman of PRODEGRE Pharmaceuticals, Chief Scientist of CNS, and Director of the Fudan Shangsi Center for NeuroscienceIt stated: “There are approximately 25 million Parkinson’s disease patients worldwide, yet no disease-modifying treatments have been approved to date, leaving significant unmet clinical needs. PDR-001 employs an innovative peptide degradation structure that directly targets and clears α-synuclein, the key pathogenic protein in the pathogenesis of Parkinson’s disease, supported by robust efficacy and safety data from non-human primate studies. Furthermore, this pipeline is the first to organically combine protein degraders with adeno-associated virus (AAV) local injection delivery, achieving long-term, high-efficiency expression of degradative peptides in multiple critical brain regions. This approach aims to fundamentally improve the pathological environment, potentially significantly delaying or even halting disease progression, thereby opening up entirely new avenues for etiological treatment of Parkinson’s disease.”

Patient recruitment for the current investigator-initiated trial (IIT) has been successfully launched at Ruijin Hospital. PRODEGRE will engage in comprehensive and close collaboration with the team led by Director Liu Jun of the Department of Neurology at Ruijin Hospital, strictly adhering to the protocol to efficiently advance subject enrollment and ensure the high-quality conduct of the clinical trial. Tan Shen, CEO of PRODEGRE, summarized the kickoff meeting as follows: “It is a great honor to closely integrate our company’s differentiated protein degradation technology and robust scientific foundation in neurodegenerative diseases with Ruijin Hospital’s strong clinical resources, thereby initiating a new therapeutic paradigm that may delay or even halt the progression of Parkinson’s disease. This project not only achieves the company’s first closed loop from differentiated early-stage research to clinical validation but also promotes the clinical translation of Shanghai’s biomedical achievements in neuroscience, enhances Shanghai’s global competitiveness in original brain science therapeutics, and contributes modestly to establishing Shanghai Zhangjiang as a ‘nuclear explosion point’ for pharmaceutical innovation.”

With over ten million Parkinson’s disease patients worldwide, there remains a lack of therapies capable of slowing disease progression. The targeted protein degradation strategy represented by PDR-001 not only offers a novel therapeutic approach for Parkinson’s disease but also provides new avenues for treating a broader range of neurological disorders. Although the road ahead is long, the initiation of this research undoubtedly marks a solid step forward in the company’s pursuit of its ultimate goal: disease-modifying treatment.

PRODEGRE completed its first round of financing in Pudong, Shanghai, in early 2024 and officially commenced operations. As a biotechnology enterprise, PRODEGRE is dedicated to exploring novel mechanisms of protein degradation and innovative drug modalities. The company has established the Prodegre Atlas™ innovative platform for protein degradation and interaction, along with a deeply integrated translational medicine and biological development system. Grounded in fundamental degradation mechanisms and driven by target identification, PRODEGRE focuses on developing differentiated protein degraders for the central nervous system and inflammatory diseases. Currently, PDR-001, the world’s first peptide-based degrader, has entered clinical trials, while additional rationally designed oral molecular glues and novel degraders are being rapidly advanced through R&D.

Xu Jingzhao, Vice President and Chief Financial Officer of PRODEGRE, stated: “The company remains firmly confident in the clinical translation potential and long-term pipeline value of protein degradation technology for neurodegenerative diseases, neuroinflammation, and autoimmune disorders. We are continuously strengthening close communication with industry partners and investors, fully leveraging Shanghai’s comprehensive advantages in R&D, talent, and capital ecosystem to accelerate the development of a globally leading platform for protein degradation and neuroscience translation. Through continuous technological iteration and pipeline expansion, we aim to advance more First-in-class drugs into clinical trials, thereby introducing a powerful growth engine for the company’s future global layout.”

PDR-001 is the world’s first peptide-based degrader to enter human clinical trials. As a first-in-class therapeutic modality, it utilizes a novel, non-CRBN-mediated degron to achieve degradation of pathogenic proteins. It has demonstrated significant efficacy in animal model evaluations and holds promise for providing safe, long-term therapeutic benefits to patients with early-to-mid stage Parkinson’s disease.

Get to the Core: From Supplementation to Clearance, Building a Long-Lasting “Cell Factory”

Traditional Parkinson’s disease medications primarily improve motor symptoms by replenishing dopamine but fail to slow disease progression. In contrast, PDR-001 is designed to target the pathological core—abnormally aggregated α-synuclein. By employing local injection of an AAV vector carrying specific peptide sequences, infected cells are transformed into “cell factories” that continuously express the peptides, thereby overcoming the short half-life associated with peptide-based therapeutics and enabling sustained expression following a single administration. The locally injected dose is 1–2 orders of magnitude lower than that required for systemic delivery, significantly reducing the risks of AAV-related hepatotoxicity and immunogenicity.

Innovative Mechanism: Differentiated Three-Stage Peptide Degradation Modality Expands the Druggable Space of Protein Degraders

What sets peptide degraders apart is their rational, three-part design strategy. The TAT cell-penetrating domain enables peptides to efficiently cross the blood–brain barrier and cell membranes, while the targeting peptide region achieves highly specific recognition of the target. More critically, the degradation domain can be designed directly as a Degron signal peptide based on the N-end rule pathway or C-end rule pathway, thereby overcoming the current heavy reliance of protein degraders on CRBN and greatly expanding the potential target space for degraders.