Foresee's Oral ALDH2 Activator Mirivadelgat Selected for Parkinson's Disease Platform Trial
核心洞察
Foresee Pharmaceuticals (搜索)' oral ALDH2 (搜索) activator mirivadelgat has been selected for the SLEIPNIR Phase 2a platform trial in Parkinson's disease (搜索), in collaboration with Haukeland University Hospital (搜索) in Bergen, Norway.
The biomarker-driven trial will assess central nervous system penetration, target engagement, and safety of mirivadelgat in 40 participants randomized 3:1 to drug or placebo over 12 weeks.
Mirivadelgat is designed to boost ALDH2 (搜索) enzyme activity to clear toxic aldehydes from the brain, potentially slowing nerve cell loss in Parkinson's and other neurodegenerative diseases.
Foresee Pharmaceuticals (搜索) announced today that its oral ALDH2 (搜索) activator, mirivadelgat, has been selected to enter clinical testing in Parkinson's disease (搜索) through the SLEIPNIR Phase 2a platform trial, in collaboration with Haukeland University Hospital (搜索) in Bergen, Norway. The trial is funded by Cure Parkinson's (搜索), a UK-based charity dedicated to developing a cure for Parkinson's disease.
Professor Charalampos Tzoulis, MD, PhD, Chief Investigator of the SLEIPNIR Platform and Director of the Neuro-SysMed Center of Excellence for Clinical Neurological Research and the Innovation Center for Neuroresilience (ICoN) at Haukeland University Hospital (搜索) and the University of Bergen, stated: "Foresee's oral ALDH2 (搜索) activator, mirivadelgat, was selected through a highly competitive and scientifically rigorous process as one of several therapies to be included in SLEIPNIR. This platform is specifically designed to assess central nervous system penetration and biological target engagement in patients with Parkinson's disease (搜索). This information will be indispensable in allowing us to prioritize treatments for further development."
Mechanism of Action and Rationale
Research suggests that toxic compounds called aldehydes accumulate inside brain cells, playing a critical role in Parkinson's disease (搜索) pathogenesis. Over time, these aldehydes cause proteins to clump together and contribute to the loss of nerve cells. Mirivadelgat is designed to increase the activity of ALDH2 (搜索), a mitochondrial enzyme that directly clears these harmful compounds from the brain. By supporting this natural defense system, mirivadelgat accelerates detoxification and could potentially slow the ongoing loss of nerve cells in neurodegenerative diseases such as Parkinson's disease.
Dr. Wenjin Yang, CSO at Foresee, noted: "The role of ALDH2 (搜索) in the pathophysiology of PD and other neurological diseases is quite compelling when looking at the current body of data. We are confident the results from this study will provide a strong foundation for further development in PD and other CNS diseases as this study will provide data related to CNS penetration and target/biomarker engagement of mirivadelgat."
SLEIPNIR Platform Trial Design
SLEIPNIR is a biomarker-driven Phase 2a multi-arm platform trial designed to assess whether candidate disease-modifying therapies for Parkinson's disease (搜索) reach the brain and interact with their intended biological targets. Rather than testing each treatment in a separate stand-alone study, SLEIPNIR evaluates several investigational therapies in parallel using a shared platform design, enabling more efficient assessment of brain penetration, target engagement, and mechanistic biomarker effects.
Within the mirivadelgat cohort, 40 eligible participants with Parkinson's disease (搜索) will be randomized 3:1 to receive either mirivadelgat once daily or matching placebo, in addition to standard dopaminergic treatment. The placebo participants from the mirivadelgat cohort will contribute to a pooled placebo group shared across concurrent SLEIPNIR treatment arms, resulting in an effective comparison of 30 participants receiving mirivadelgat versus 30 participants receiving placebo across the platform. Participants will receive study treatment for 12 weeks, followed by a two-week post-treatment safety follow-up. The primary assessment will take place at the end of the 12-week treatment period, with the week-14 visit used to evaluate safety after treatment discontinuation.
Dr. Simon Kverneng, MD, PhD, a neurology resident and experienced clinical researcher in Professor Tzoulis' group, serves as the Principal Investigator of SLEIPNIR.
Market Context and Unmet Need
The Parkinson's disease (搜索) treatment market is projected to expand from $2.2 billion in 2023 to $3.6 billion in 2032 across the US, Japan, and five major European markets, representing a compound annual growth rate of 5.47%. The market is mainly comprised of levodopa-based therapies, COMT inhibitors, MAO-B inhibitors, and dopamine agonists, many of which are approved for patients with "off" episodes resulting from long-term levodopa use.
People in the early stages of Parkinson's disease (搜索) (Stages 1–3) make up approximately 60% of those receiving treatment, contributing significant revenue to the market. Despite this, the PD drug market remains highly genericized in the US and Europe, with limited new approved therapies featuring novel mechanisms. While several new therapies are expected to enter the market, most focus on improved delivery and reformulation of existing mechanistic classes. Apart from a few targeted therapies such as alpha-synuclein antibodies currently in development, there remains a high unmet need for first-in-class oral therapies with disease-modifying potential.
Broader Development Context
Dr. Ben Chien, Chief Executive Officer of Foresee, commented: "This is a significant opportunity to provide further validation of mirivadelgat/ALDH2 (搜索) activation as a potential treatment approach for Parkinson's, and potentially other CNS diseases. We are grateful to the SLEIPNIR team, potential participants in the study and Cure Parkinson's (搜索) for their support."
Mirivadelgat (FP-045) is a highly selective oral small molecule allosteric activator of ALDH2 (搜索). Foresee is also developing the compound in a Phase 2 WINDWARD study in pulmonary hypertension-interstitial lung disease (搜索) (PH-ILD) patients, initiated in the second quarter of 2025. The SLEIPNIR trial is embedded within a translational trial infrastructure developed under the Innovation Center for Neuroresilience (ICoN) and is additionally funded by the Research Council of Norway, Western Norway Regional Health Authority, Norwegian Parkinson's Research Fund, and the Norwegian Parkinson's Association.