Periodic Reporting for period 1 - DOWN-AUTONOMY (LCTB-21: A DYRK1A protein kinase inhibitor for treatment of cognitive decline in Down Syndrome.)
Période du rapport: 2022-06-01 au 2023-11-30
Overactivity of the DYRK1A protein kinase is involved in cognitive impairments associated with Down Syndrome and Alzheimer’s Disease. Around 150,000 children with Down Syndrome live in Western countries. All of them experience a delay in their learning times from birth, and are generally unable to attend school around the age of 12. As a number of their comorbidities can now be cured, people with Down Syndrome live longer and start developing an Alzheimer’s Disease neuropathology at 40. The current standard of care consists in an early intervention program involving various therapists but no treatment is available to improve children with Down Syndrome’s ability to consolidate acquired information and their quality of life in general.
Perha Pharmaceuticals has identified, characterised and optimised families of small molecules inhibiting DYRK1A overactivity. The selected drug candidate, Leucettinib-21, corrects cognitive impairments observed in animal models of Down Syndrome and Alzheimer’s Disease. The DOWN AUTONOMY project aims at developing Leucettinib-21 until proof-of-concept in children with Down Syndrome, i.e. until completion of a successful phase 2a clinical trial.
Perha Pharmaceuticals has identified, characterised and optimised families of small molecules inhibiting DYRK1A overactivity. The selected drug candidate, Leucettinib-21, corrects cognitive impairments observed in animal models of Down Syndrome and Alzheimer’s Disease. The DOWN AUTONOMY project aims at developing Leucettinib-21 until proof-of-concept in children with Down Syndrome, i.e. until completion of a successful phase 2a clinical trial.
The first milestone of the DOWN AUTONOMY project has been achieved: completing preclinical regulatory toxicology studies in animals and being entitled by the French health authorities to assess Leucettinib-21’s safety profile in man during a phase 1 clinical trial. The next and final milestones of the project consist in completing the phase 1 clinical trial (safety), and then the phase 2a one (efficacy). In parallel, the main targets and selectivity of Leucettinib-21 have been extensively characterized. Target engagement has been demonstrated in various cellular models as well as in an animal model of Down syndrome (Ts65Dn). Efficacy at correcting memory/learning disorders has been demonstrated in a few animal models. The physico-chemical and pharmacological properties of Leucettinib-21 have been extensively studied. Results have been published in three J. Med. Chem. articles.
Perha Pharmaceuticals needs to raise series A funds to co-finance preparation and conduct of the phase 2a clinical trial. In terms of research, the company aims at building affinity chromatography reagents with immobilized Leucettinib-21, deciphering the molecular and cellular mechanisms of action of the drug candidate at the synapse level and expanding the proof-of-concept with various animal models of Down syndrome, Alzheimer’s disease and aging.