Slide 1: Long-term Sustained Improvement of Neurological Symptoms in Wilson Disease Patients on Tiomolybdate Choline
Long-term Sustained Improvement of Neurological Symptoms in Wilson Disease Patients on Tiomolybdate Choline Dr. Matthew Lorincz, MD PhD University of Michigan, Ann Arbor
Slide 2: Disclosures
Disclosures • Travel expenses to attend and present at ANA 2025 were paid for by Monopar Therapeutics • No additional conflicts of interest to disclose
Slide 3: Wilson Disease
Wilson Disease Wilson disease (WD) is a genetic disorder of impaired copper (Cu) transport Cu accumulation ATP7B Cu accumulates in the liver and brain, causing hepatic damage and Parkinson-like symptoms Impaired Cu excretion Healthy Wilson disease
Slide 4: Unmet Need
Unmet Need Current standard of care (SoC) therapies have numerous limitations: ▪ May cause paradoxical neurological worsening (up to 30%)1 ▪ Complex, multiple-per-day dosing results in poor adherence (up to 50%)2 ▪ Risk of severe side effects (up to 31%)3 ▪ Slow onset of action4 1. Ala A et al. Lanc
Slide 5: Tiomolybdate Choline (ALXN1840)
Tiomolybdate Choline (ALXN1840) ALXN1840 is an investigational, once- Tripartite Complex daily, oral small molecule that binds Cu with high affinity1 Cu ALXN Cu TMC 1840 ALXN1840 forms a tripartite complex with ALXN 1840 Cu and albumin, mobilizing and sequestering toxic Cu2,3 1. Smirnova J et al. Sc
Slide 6: Unified Wilson Disease Rating Scale (UWDRS)
Unified Wilson Disease Rating Scale (UWDRS) UWDRS is a validated tool for assessment of neurological symptoms in WD patients1-3 Significant overlap with the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) UWDRS MDS-UPDRS Wilson disease Parkinson’s disease 13 25 28 Other Similar Other Questions
Slide 7: ALXN1840 Prevents Toxic Copper Build-up in the Liver and Brain
ALXN1840 Prevents Toxic Copper Build-up in the Liver and Brain Liver Brain Human Human In vitro Human Blood-brain barrier Before treatment Before treatment (median) After treatment After treatment (median) Figures adapted from Kirk FT et al. J Hepatol. 2024;80(4):586-595; Borchard S et al. Life Sci
Slide 8: Sustained Neurologic Improvement Over Years
Sustained Neurologic Improvement Over 6 Years UWDRS Part II (Patient-reported) UWDRS Part III (Physician-assessed) Least squares mean (LSM) ± standard error – Ph2 & Ph3 Least squares mean (LSM) ± standard error – Ph2 & Ph3 * p-value < 0.05 vs. baseline * p-value < 0.05 vs. baseline 0 Baseline 1 Base
Slide 9: Neurological Benefit Reproduced Across Independent Studies
Neurological Benefit Reproduced Across Independent Studies UWDRS Minimum Clinically Important Difference (MCID) • Previous studies have reported a Part II MCID of 1 pt1,2 and a Part III MCID of 4 - 6.9 pts1-3 • Calculated UWDRS Part III MCID from Ph2 & Ph3 (n=255) – Part II: 1.84 pts; Part III: 4.69
Slide 10: Patients Further Improve After Crossover from SoC to ALXN1840
Patients Further Improve After Crossover from SoC to ALXN1840 UWDRS Part III MCID responder rate – Ph3 40% SoC-Crossover patients (n=56) All changes vs. Wk 0 (baseline) Improved† 20% 0% 31% 42% SoC Crossover SoC to ALXN1840 Worsened 10% @ Week 48 14% 5% 0% Week 48 Final crossover visit Median: 120 w
Slide 11: Neurologic Benefit Increases Over Time
Neurologic Benefit Increases Over Time UWDRS Part II (Patient-reported) UWDRS Part III (Physician-assessed) MCID responder rate (1.84 pts) – Ph2 & Ph3 MCID responder rate (4.69 pts) – Ph2 & Ph3 100% 100% Responder rate (95% CI) Responder rate (95% CI) 75% 75% 50% 50% 25% 25% 0% 0% 77 70 54 36 20 9 9
Slide 12: Sustained Improvement in Psychiatric Symptoms
Sustained Improvement in Psychiatric Symptoms Brief Psychiatric Rating Scale (BPRS) (Clinician-assessed) Least squares mean (LSM) ± standard error – Ph3 0 Baseline LSM Change from Baseline * p-value < 0.05 vs. baseline -1 * * * * -2 ALXN1840 -3 169 152 147 125 131 135 114 0 24 48 72 96 120 144 Study
Slide 13: ALXN1840 Has a Favorable Safety Profile
ALXN1840 Has a Favorable Safety Profile Long-term Safety Serious Adverse Events (SAEs) on ALXN1840 Number of patients 266 Median time on treatment (years) 2.58 Total patient-years (PYs) 645.6 Patients with any drug-related SAE 13 (4.9%) Neurologic 2 (0.8%) Psychiatric 1 (0.4%) No deaths occurred tha
Slide 14: Questions?
Questions?