Platform

reMYND has a proprietary phenotypic screening platform to discover disease-modifying small molecule treatments and their novel target and MoA to counteract the toxicity induced by misfolded proteins, such as Tau for AD or Synuclein for PD. We validate and optimize our leads in our proprietary cellular assays and animal models. In addition, we can identify the corresponding novel drug target and its mode-of-action through a multitude of assays such as three-hybrid screening.

Such phenotypic platform is especially fit to address the need for real breakthroughs by discovering first-in-class medicines, cfr. Swinney et al.

Pipeline overview

reMYND pipeline
Lead Alzheimer program ReS19-T

Alzheimer

Currently 46,8 million people worldwide suffer from dementia, doubling every 20 years. Alzheimer’s disease (AD) is by far the most common dementia in late life with a prevalence of one in nine people with an age of 65 and older and is the 6th leading cause of death.

Pathologically the disease is characterized by the presence of amyloid aBeta plaques and fibrillary Tau tangles.  Symptoms include memory loss and other cognitive tasks which severely disrupt daily life of patients and family members. This cognitive impairment results from synaptic loss, later on followed by neuronal degeneration in specific brain regions. Ca2+ dyshomeostasis is a pivotal process driving the loss of synaptic plasticity with as well aBeta as Tau pathology

Even though current therapeutics sell for 5 billion USD and are forecasted to grow to 11 billion USD by 2021 (CAGR 11%),no treatments are available that stop or even slow down disease progression. Existing therapies are all symptomatic, whereas most ongoing developments for causal remedies aimed to inhibit neuronal degeneration have had mixed results up to now.

reMYND’s lead ReS19-T program restores calcium dyshomeostasis in AD, a process central in the disease cascade leading to neuronal demise and built-up of plaques and tangles. By targeting the disease in its tracks ReS19-T mitigates neuronal loss and pathology but has also an immediate symptomatic benefit on synaptic plasticity, cognition and cerebrospinal biomarkers, allowing for a manageable clinical translatibility.

Currently the program is undergoing IND-enabling tox studies in order to to start clinical studies.

Lead Diabetes program ReS39

Finger prick

The number of patients with diabetes has risen from 108 million in 1980 to 422 million in 2014, making diabetes the largest pandemic to hit our societies in the coming years.

 

Diabetes is a chronic metabolic disorder resulting from a failure to manage glucose levels in the blood appropriately. In Type 2 Diabetes Mellitus (T2DM), a loss of insulin sensitivity keeps increasing the stress on beta-cells in the pancreas, until these cells ultimately degenerate. In Type 1 Diabetes Mellitus (T1DM), beta-cells are directly attacked. The elevated glucose levels make diabetes a major cardiovascular risk factor and cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation.

Current diabetes treatments on the market and in development all treat symptoms only, without addressing fundamentally the underlying beta-cell degeneration which keeps progressing at a steady rate. Hence, the key patient need in diabetes is durability, i.e. how to prevent the increase in dose and addition of multiple therapies. Most diabetes companies have beta-cell health as a core pillar in their R&D strategy, but none have such projects close to clinical development

reMYND’s lead diabetes program ReS39 sustains and even doubles the endogenous insulin production capacity of the pancreas by restoring beta-cell function in as well T1DM as T2DM animal models through mitigating the formation of oxidative stress. Hence, ReS39 provides as well fast symptomatic relief as durability in T2DM. And in T1DM, provided sufficient beta-cells remain to be re-functionalised. Moreover, ReS39 reduces liver weight and its triglyceride content, making it also relevant for NASH.

Currently the program is in preclinical candidate is being profiled.

Epilepsy/Alzheimer’s program ReS3-T

Epilepsy is a prominent co-morbidity in Alzheimer’s and is a reflection of elevated neuronal hyperactivity of diseased neurons. reMYND’s lead ReS3-T program targets a central regulator of neuronal activity to restrain neuronal hyperactivity. As a result ReS3-T treatment counters Tau and Abeta driven toxicity, restores neuronal hyperactivity and is neuroprotective in preclinical models of Alzheimer’s. 

Given the mechanism and its efficacy profile in Alzheimer’s, ReS3-T is expected to counter epileptogenesis and to have neuroprotective activity in epilepsy without the severe side effects of currently existing symptomatic treatments.

Parkinson program ReS9-S

Parkinson’s disease (PD) is the most common motor disorder, typically affecting the aged 65+population, and is caused by degeneration of dopaminergic neurons required for appropriate control of motoric functions. It is expected that the number of patients suffering from Parkinson’s disease will double in the next ten years, reflecting the aging of the population. With the exception of cell transplants and gene therapy programs there have been no breakthroughs in the field since the seventies.

ReS9-S targets alpha-synuclein driven neuronal degeneration, a process which fundamentally underlies dopaminergic degeneration in PD. The program therefore has the potential to delay or, as we observed in our animal models, even stop neuronal cell loss allowing patients to sustain dopaminergic signaling.

Orphan programs

reMYND’s technology platform is amenable to address numerous other, highly debilitating protein-misfolding disorders, such as Huntington’s disease or Amyotrophic Lateral Sclerosis, to discover and develop first-in-class drug candidates. For instance, our Huntington program rescues huntingtin-driven neuronal  toxicity by inhibiting JNK activity and mitigating ER Ca2+ leakage through a novel proprietary target. This program improves neurite outgrowth and arborisation ex-vivo in R6/1 and wild-type neurons at the same level as BDNF, and reduces pJNK levels in wild type mice after acute administration.