Leuven Belgium, 03 May 2022: reMYND NV, a clinical stage company tackling neurodegeneration, today announces that its lead Alzheimer program ReS19-T has successfully completed its Phase 1 study. Topline data has demonstrated excellent brain exposure and strong safety profile. These results support the next phase of clinical development, a Phase 2a proof-of-mechanism study slated for initiation soon.
The Phase 1 study investigated RES19-T in 77 healthy volunteers, with doses up to 2 × 700 mg/day for seven days. Cerebrospinal fluid (CSF) exposure in elderly volunteers was well above the anticipated therapeutic levels, dose-linear, stable over 24 hours, and with less than 12% variation between subjects and genders.
Based on this data, reMYND will accelerate the clinical trial application for its Phase 2a proof-of-mechanism study with leading centers in the Netherlands and Spain. The study will cover placebo, low-dose and high-dose, with the low dose already providing sustained brain concentrations throughout the day, above what would be therapeutically required. The Phase 2a results are expected by mid-2023.
reMYND’s ReS19-T program is a first-in-class small molecule with the potential to combine disease modification and fast restoration of synaptic plasticity by addressing the disease at its root.
“I have been following the reMYND program now for several years, and every test so far confirms their hypothesis. This is exactly the type of program the Alzheimer’s field needs: a novel approach, based on a sound scientific rationale to potentially restore symptoms and modify the disease in sporadic Alzheimer’s. The pre-clinical data and Phase 1 data could not look better. There are good reasons to believe that this compound could address the issue as to why previous Alzheimer treatments have failed. But in the end, the real proof will only be in the Phase 2a results, which I look forward to seeing by mid-2023.” commented Prof. Henrik Zetterberg, the leading AD biomarker expert and a member of reMYND’s Clinical Advisory Board.
“I have been pleased to see the growing enthusiasm of leading opinion leaders and clinicians to start administering our investigational treatment for the first time to their patients, after having rowed upstream for so many years,” commented Koen De Witte, Managing Director of reMYND, adding: “Knowing our extensive pre-clinical efficacy data when we entered clinical development, we considered the major hurdles to demonstrating clinical efficacy were off-target side effects and insufficient brain exposure, which now have been overcome by the compound being safely delivered into the brain.”
Alzheimer patient needs
Alzheimer's disease is not about memory loss in itself, but about losing the capacity to form new memories to continue a normal social life. That memory formation capacity is most closely linked to loss of synaptic plasticity.
Calcium dyshomeostasis has been known for decades to be a fast and pivotal process in AD linking the loss of synaptic plasticity and neuronal loss with amyloid, Tau and all other AD risk factors. This has been quite widely accepted for decades and has been recently indirectly confirmed in human by calcineurin inhibitors preventing AD onset in patients who underwent organ transplants. So far however, the caution for widespread use of calcium modulators has been regarding potential safety concerns when interfering with such a central process.
About reMYND’s ReS19-T Alzheimer’s program
ReS19-T is reMYND’s most advanced program, an investigational compound for the treatment of Alzheimer’s, with the potential to combine disease modification and fast restoration of synaptic plasticity by addressing the disease at its root. Through a novel and proprietary target, ReS19-T restores robustly elevated pathological cytosolic calcium levels safely to physiological levels, but not below – hence ReS19-T selectively impacts diseased cells and has no effect on healthy cells, underpinning its compelling safety profile. Genome-wide expression profiling in the hippocampus of AD patients has identified ReS19-T’s novel target as one of the 12 most relevant Alzheimer genes.
In pre-clinical models, ReS19-T almost fully restores synaptic plasticity after 7 days of oral treatment in mouse models with severe cognitive deficits induced by aβ, Tau and aβxTau risk factors, and fully restores in-vivo pharmaco-EEG and cognition. ReS19-T reduces CSF Tau and inflammation by more than 50%, and prevents the formation of aBeta plaques, without any impact on healthy animals.
The Phase I study has been conducted by Prof. Wolzt at the Medical University of Vienna in Austria.
reMYND is a clinical stage company developing novel treatments for Alzheimer’s, Huntington’s, epilepsy, ALS and other neurodegenerative diseases caused by neuronal dysfunction. It is backed by a proprietary drug discovery platform, which enables the identification of novel mechanisms-of-action, targets and first-in-class small molecules.
reMYND’s most advanced program is ReS19-T, an investigational compound for the treatment of Alzheimer’s and ready to start Phase 2a. Similarly, reMYND’s Huntington program fully restores cortico-striatal transmission and regenerates the mouse brain in the standard Huntington knock-in mice. This program is 12-18 months pre-IND.
In addition, reMYND has a dedicated Contract Research Organization (CRO), which focuses on CNS disorders. The team helps clients to assess the pharmacokinetics, pharmacodynamics and efficacy of their experimental treatments in reMYND’s proprietary animal models. The CRO has a global client base, including the US, Europe and Japan.
reMYND was founded in 2002 as a spin-off from the University of Leuven, and has been substantially supported by grants from VLAIO/IWT (Flanders, Belgium). Find out more at https://www.remynd.com.