Parkinson Agent HL192 Successfully Completes Phase 1 First-In-Human Study

Sean Jeong, MD, chief executive officer at HanAll Biopharma

In a new update, investigational HL192 (HanAll Biopharma/Daewoong Pharmaceutical/NurrOn Pharmaceuticals), an agent in development for Parkinson disease (PD), met its primary end point of safety and tolerability in its first-in-human phase 1 study. The companies plan to initiate the next clinical trial in patients with PD to further evaluate the safety of the drug, which targets Nurr1, a master regulator associated with the development and maintenance of dopaminergic neurons.¹

In the phase 1 study, HL192 demonstrated a favorable safety profile among healthy volunteers, with a treatment-emergent adverse event (TEAE) incidence that was similar to that observed in the placebo group. Additionally, all tested dose levels, both in the single-ascending (SAD) and multiple-ascending dose (MAD) cohorts, were well below the pre-determined NOAEL (no observed adverse effect level) concentrations, further confirming the safety and tolerability of the chosen dose levels.

The study, powered by a $1.7 million grant from The Michael J. Fox Foundation for Parkinson’s Research, included 76 healthy participants. Participants in the SAD and food effect arms received HL192 once, while participants in the MAD arm received a single dose once a day for 12 days, with careful monitoring and assessment of safety and tolerability. Overall, the study met its primary end points of safety and tolerability in the 5 different ascending dose groups included, further signifying the progress of this treatment in PD.

"We are extremely pleased to announce the completion of the first-in-human study,” Sean Jeong, MD, chief executive officer at HanAll Biopharma, said in a statement.¹ "Successfully demonstrating the safety and tolerability in healthy volunteers, including older adults, is a key step in our mission to develop a disease-modifying therapy for Parkinson's disease. These findings bring hope to millions of patients and their families who are affected by this challenging condition."

READ MORE: StrivePD: Revolutionizing Parkinson Disease Care Through Data and Personalization

Prior to the phase 1 study, HN192 was tested in animal models, where it demonstrated improvements in behavioral deficits. Leveraging Nurr1’s dual role in developing and maintaining dopaminergic neurons, as well as protecting them from inflammation-induced damage, NurrOn aims to establish Nurr1 as a target for groundbreaking therapeutic development in PD.

In 2015, a proof-of-concept study further validated the potential of targeting Nurr1’s ligand-binding domain as a neuroprotective strategy for PD. In the analysis, researchers identified small molecules AQ and CQ using high-throughput assays, which activated Nurr1 through its LBD and improved motor impairments without causing dyskinesia. These compounds were shown to enhance Nurr1’s dual functions: promoting dopaminergic neuron activity while suppressing microglial activation and neurotoxic cytokine expression. This resulted in significant neuroprotective and neurorestorative effects, further supporting the therapeutic promise of Nurr1 activation.

"The Michael J. Fox Foundation remains steadfast in our commitment to accelerate the development of better treatments for the more than 6 million people living with Parkinson's disease around the world," Katharina Klapper, principal of clinical research at the MJFF, said in a statement.¹ "The successful completion of the study's Phase 1 HL192 (ATH-399A) trial marks a meaningful step forward in advancing today's therapeutic pipeline."

REFERENCES
1. HanAll Biopharma, Daewoong Pharmaceutical and NurrOn Pharmaceuticals Announce Successful Completion of a First-in-Human Study for Potential Disease-Modifying Therapy for Parkinson's Disease. News release. November 25, 2024. Accessed November 25, 2024. https://www.prnewswire.com/news-releases/hanall-biopharma-daewoong-pharmaceutical-and-nurron-pharmaceuticals-announce-successful-completion-of-a-first-in-human-study-for-potential-disease-modifying-therapy-for-parkinsons-disease-302315158.html
2. Kim CH, Han BS, Moon J, et al. Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson’s disease. PNAS Neuroscience. 2015;112(28):8756-8761. Doi:10.1073/pnas.1509742112