ABBV-1088 / AbbVie - LARVOL DELTA

UQCRC1 deficiency impairs mitophagy via PINK1-dependent mechanisms in Parkinson's disease. (PubMed, NPJ Parkinsons Dis) - "Treatment with two PINK1 activators, kinetin and MTK458, resulted in similar protective effects in the fly and cell models. Overall, we identified OXPHOS stress led by deficiency of UQCRC1 as an etiology of mitophagy defects in PD and PINK1 as a therapeutic target for UQCRC1-associated PD."

Journal • CNS Disorders • Lewy Body Disease • Movement Disorders • Parkinson's Disease • PINK1 • UQCRC1

Astragaloside IV alleviates D-GAL-induced endothelial cell senescence by promoting mitochondrial autophagy via inhibiting the PINK1/Parkin pathway (PubMed, Nan Fang Yi Ke Da Xue Xue Bao) - "AS-IV alleviates D-GAL-induced endothelial cell senescence by inhibiting the PINK1/Parkin pathway to regulate mitochondrial autophagy."

Journal • CDKN1A • TP53

A Study to Assess Multiple Ascending Dose, Drug-Drug Interaction, and Asian Pharmacokinetic Study of ABBV-1088 (clinicaltrials.gov) - P1 | N=72 | Terminated | Sponsor: AbbVie | Trial completion date: Aug 2026 ➔ Sep 2025 | Suspended ➔ Terminated | Trial primary completion date: Aug 2026 ➔ Sep 2025; Strategic considerations

Trial completion date • Trial primary completion date • Trial termination

PINK1 activation improves outcomes in the UQCRC1 models of Parkinson's disease (MDS Congress 2025) - "When PINK1 activators, kinetin and MTK458, were administered to our UQCRC1 models of PD, we found they can rescue the locomotion defects in flies and the neurite length in SH-SY5Y cell models... We discovered that UQCRC1 is deficient in idiopathic PD. Deficiency of UQCRC1 undermined the PINK1-mdeiated mitophagy. Treatment of PINK1 activators alleviated the defects in the UQCRC1 models of PD, suggesting their potential in PD treatment."

CNS Disorders • Lewy Body Disease • Movement Disorders • Parkinson's Disease • PINK1 • UQCRC1

A Study to Assess Multiple Ascending Dose, Drug-Drug Interaction, and Asian Pharmacokinetic Study of ABBV-1088 (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Assess Multiple Ascending Dose, Drug-Drug Interaction, and Asian Pharmacokinetic Study of ABBV-1088 (clinicaltrials.gov) - P1 | N=72 | Suspended | Sponsor: AbbVie | Trial completion date: Sep 2025 ➔ Aug 2026 | Active, not recruiting ➔ Suspended | Trial primary completion date: Sep 2025 ➔ Aug 2026

Trial completion date • Trial primary completion date • Trial suspension

Putative PINK1/Parkin activators lower the threshold for mitophagy by sensitizing cells to mitochondrial stress. (PubMed, Sci Adv) - "Here, we characterize two mitophagy activators: a novel Parkin activator, FB231, and the reported PINK1 activator MTK458...Our findings support a model whereby weak or "silent" mitochondrial toxins potentiate other mitochondrial stressors, enhancing PINK1/Parkin-mediated mitophagy. These insights highlight important considerations for therapeutic strategies targeting mitophagy activation in Parkinson's disease."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

PINK1 activation by MTK458 ameliorates neurological impairments and pyroptosis after intracerebral hemorrhage in mice. (PubMed, Brain Res) - "It also reversed ICH-induced cortical cell pyroptosis by promoting Parkin/PINK1-mediated mitophagy and inhibiting NLRP3 inflammasome activation, as well as the expression of IL-1β and IL-18. These results suggest that MTK458 effectively reduces neurological impairments, brain edema, and anxiety-related behaviors in mice following ICH, highlighting PINK1 activation as a promising therapeutic strategy for ICH-induced neurological deficits."

Journal • Preclinical • Cerebral Hemorrhage • CNS Disorders • Cognitive Disorders • Hematological Disorders • Psychiatry • IL18 • IL1B • NLRP3 • PTEN

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ABBV-1088 Oral Dose in Healthy Adult Participants. (clinicaltrials.gov) - P1 | N=60 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Trial completion

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ABBV-1088 Oral Dose in Healthy Adult Participants. (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Assess Multiple Ascending Dose, Drug-Drug Interaction, and Asian Pharmacokinetic Study of ABBV-1088 (clinicaltrials.gov) - P1 | N=66 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Assess Multiple Ascending Dose, Drug-Drug Interaction, and Asian Pharmacokinetic Study of ABBV-1088 (clinicaltrials.gov) - P1 | N=66 | Not yet recruiting | Sponsor: AbbVie

New P1 trial

AbbVie Exercises Exclusive Right to Acquire Mitokinin, Further Strengthening Neuroscience Pipeline (PRNewswire) - "AbbVie...announced today that it has exercised its exclusive right and completed the acquisition of Mitokinin, a discovery-stage biotechnology company developing a potentially first-in-class disease-modifying treatment for Parkinson's Disease (PD). Mitokinin's lead compound, a selective PINK1 activator, is designed to address mitochondrial dysfunction that is believed to be a major contributing factor to Parkinson's disease pathogenesis and progression....Under the terms of the agreement, AbbVie will pay Mitokinin shareholders $110 million at closing for the acquisition of Mitokinin. Mitokinin shareholders remain eligible for potential additional payments of up to $545 million upon the achievement of certain development and commercial milestones related to the success of the PINK1 program, plus tiered royalties based on net sales."

M&A • Alzheimer's Disease • CNS Disorders • Huntington's Disease • Parkinson's Disease

SMALL MOLECULE PINK1 ACTIVATORS RESCUE MITOCHONDRIA-ASSOCIATED PATHOLOGY IN IDIOPATHIC PARKINSON'S DISEASE MODELS (ADPD 2023) - "Our data support the clini cal development of PINK1 activators as disease -modifying therapeutics for the treatment of idiopathic PD."

CNS Disorders • Metabolic Disorders • Movement Disorders • Parkinson's Disease • PINK1