ABBV-1088 / AbbVie - LARVOL DELTA

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