leucettinib-21 (LCTB-21) / Perha Pharma - LARVOL DELTA

Leucettinib-21 decreases dosage effects of DYRK1A in human trisomy 21 iPSC-derived neural cells. (PubMed, bioRxiv) - "We show for the first time that Leucettinib-21 reduces DYRK1A activity in a relevant human disease model, supporting future human trials. We show for the first time that Leucettinib-21, a pharmacological inhibitor of DYRK1A, decreases DYRK1A activity in a human iPSC-derived neural cell culture model of Down syndrome."

Journal • Alzheimer's Disease • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Movement Disorders • Parkinson's Disease • DYRK1A

LEUCETTA: Leucettinib-21 First-in-Human Phase 1 in Healthy Volunteers and Subjects With Down Syndrome and Alzheimer's Disease (clinicaltrials.gov) - P1 | N=164 | Recruiting | Sponsor: Perha Pharmaceuticals | N=120 ➔ 164 | Trial completion date: Jul 2025 ➔ Jun 2026 | Trial primary completion date: Jul 2025 ➔ Jun 2026

Enrollment change • First-in-human • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Genetic Disorders

Novel Dyrk1a inhibitors impair glioblastoma proliferation and enhance the effectiveness of other cell-cycle-directed therapies (SNO 2025) - " The effects of two DYRK1A inhibitors (Leucettinib-21 and #423) were evaluated against SB28 mouse glioblastoma cells in vitro and in vivo. Dyrk1a inhibition dramatically impairs SB28 cell proliferation with IC50 values in the micromolar range based on CFSE dilution and MTS cell viability assays. Treatment at IC50 concentrations reduces cell migration in a scratch assay and increases nuclear size compared to vehicle-treated controls. Western blot analyses indicate that inhibitor-treated SB28 cells do not undergo apoptosis, suggesting Dyrk1a inhibition has a cytostatic effect."

Brain Cancer • Glioblastoma • Solid Tumor • CXCL10 • IL6

Novel Dyrk1a inhibitors impair glioblastoma proliferation and enhance the effectiveness of other cell-cycle-directed therapies (WFNOS 2025) - " The effects of two DYRK1A inhibitors (Leucettinib-21 and #423) were evaluated against SB28 mouse glioblastoma cells in vitro and in vivo. Dyrk1a inhibition dramatically impairs SB28 cell proliferation with IC50 values in the micromolar range based on CFSE dilution and MTS cell viability assays. Treatment at IC50 concentrations reduces cell migration in a scratch assay and increases nuclear size compared to vehicle-treated controls. Western blot analyses indicate that inhibitor-treated SB28 cells do not undergo apoptosis, suggesting Dyrk1a inhibition has a cytostatic effect."

Brain Cancer • Glioblastoma • Glioma • Solid Tumor • CXCL10 • IL6

LEUCETTA: Leucettinib-21 First-in-Human Phase 1 in Healthy Volunteers and Subjects With Down Syndrome and Alzheimer's Disease (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Perha Pharmaceuticals | Trial completion date: Aug 2024 ➔ Jul 2025 | Trial primary completion date: Aug 2024 ➔ Jul 2025

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Genetic Disorders

Phase 1 clinical trial of Leucettinib-21, a DYRK1A kinase inhibitor aiming at the correction of cognitive disorders in Alzheimer's disease and Down syndrome (CTAD 2024) - No abstract available

Clinical • P1 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Genetic Disorders

Leucettinib-21, a DYRK1A Kinase Inhibitor as Clinical Drug Candidate for Alzheimer's Disease and Down Syndrome. (PubMed, J Alzheimers Dis) - "Leucettinib-21 is now undergoing a phase 1 clinical trial (120 participants, including 12 adults with DS and 12 patients with AD). The therapeutic potential of DYRK1A inhibitors in AD and DS is presented."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Genetic Disorders • DYRK1A

LEUCETTA: Leucettinib-21 First-in-Human Phase 1 in Healthy Volunteers and Subjects With Down Syndrome and Alzheimer's Disease (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Perha Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Genetic Disorders

CHEMICAL, BIOCHEMICAL, CELLULAR, AND PHYSIOLOGICAL CHARACTERIZATION OF LEUCETTINIB-21, A DOWN SYNDROME AND ALZHEIMER'S DISEASE DRUG CANDIDATE (ADPD 2024) - "Leucettinib-21 is entering safety/tolerance phase 1 clinical trials in Q4-2023."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Genetic Disorders • CCND1 • DYRK1A

PHASE 1 CLINICAL STUDY OF LEUCETTINIB-21, A DYRK1A KINASE INHIBITOR DRUG AIMING AT THE CORRECTION OF COGNITIVE DISORDERS (ADPD 2024) - "The first results of this phase 1 clinical study will be presented. The study should be completed by Q4-2024, hopefully opening the door to phase 2a studies to evaluate the ability of Leucettinib-21 to correct cognitive disorders in children with DS and patients with early AD."

Clinical • P1 data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Genetic Disorders