fosigotifator (ABBV-CLS-7262) / AbbVie, Calico Life Sciences - LARVOL DELTA

UPDATED: AbbVie to end Calico collab after 11-year run, plans layoffs: Stat (FierceBiotech) - "The changes come as North Chicago-based AbbVie pivots away from small molecules in favor of injectables and genetic medicines, according to the email cited by Stat...Central to the partnership was fosigotifator, an amyotrophic lateral sclerosis asset designed to target eIF2B....Additionally, the pair were working on an investigational monoclonal antibody dubbed ABBV-CLS-628."

Commercial • Amyotrophic Lateral Sclerosis • Major Depressive Disorder • Polycystic Kidney Disease

A Study to Assess Adverse Events of Fosigotifator (ABBV-CLS-7262) in Adults With Major Depressive Disorder (clinicaltrials.gov) - P1 | N=20 | Terminated | Sponsor: AbbVie | Active, not recruiting ➔ Terminated; Company Decision

Adverse events • Trial termination • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology. (PubMed, Genes (Basel)) - "The 2025 failures of DNL343 and ABBV-CLS-7262 in ALS trials underscore the need for precision medicine approaches that account for context-dependent ISR functions, temporal dynamics, and disease-specific mechanisms."

Journal • Review • CNS Disorders • Metabolic Disorders

A Phase 1 Study to Investigate the Safety and Pharmacokinetics of Fosigotifator in Patients With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P1 | N=31 | Terminated | Sponsor: AbbVie | Trial completion date: Nov 2025 ➔ Jul 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2025 ➔ Jul 2025; Company Decision

Trial completion date • Trial primary completion date • Trial termination • Amyotrophic Lateral Sclerosis • CNS Disorders

A Study to Assess Adverse Events of Fosigotifator (ABBV-CLS-7262) in Adults With Major Depressive Disorder (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting | N=106 ➔ 20 | Trial completion date: Nov 2026 ➔ Sep 2025 | Trial primary completion date: Nov 2026 ➔ Sep 2025

Adverse events • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

An atypical initial revelation of CACH-vanishing white matter syndrome miming herpetic encephalitis in a 6-year-old child: Case report and brief review. (PubMed, Radiol Case Rep) - "MRI is a fundamental diagnostic test with good sensitivity for establishing the diagnosis because of a very good correlation between MRI aspects and mutations in the EIF2B1-5 genes. Guanabenz and Fosigotifatorsont represent 2 promising molecules for improving quality of life and prognosis in this population."

Journal • Ataxia • CNS Disorders • Genetic Disorders • Infectious Disease • Movement Disorders • EIF2B4

Food Effect Study of Fosigotifator, an eIF2B Activator being developed as a Potential Treatment for Amyotrophic Lateral Sclerosis, Vanishing White Matter Disease, and Major Depressive Disorder (AAN 2025) - P1/2, P2/3 | "Fosigotifator may be administered without regard to food and may be administered with various soft foods such as applesauce, yogurt, cream cheese, and strawberry jam."

Amyotrophic Lateral Sclerosis • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry • EIF2B4

HEALEY ALS Platform Trial - Regimen F ABBV-CLS-7262 (clinicaltrials.gov) - P2/3 | N=310 | Completed | Sponsor: Merit E. Cudkowicz, MD | Enrolling by invitation ➔ Completed

Trial completion • Amyotrophic Lateral Sclerosis • CNS Disorders

An Open-Label Exploratory Study of Fosigotifator in Participants With Vanishing White Matter Disease (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: AbbVie | N=38 ➔ 50 | Trial completion date: Dec 2027 ➔ Nov 2029

Enrollment change • Trial completion date • CNS Disorders • Pediatrics • EIF2B4

A Study to Assess Adverse Events of Fosigotifator (ABBV-CLS-7262) in Adults With Major Depressive Disorder (clinicaltrials.gov) - P1 | N=106 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

A Study to Assess Adverse Events of Fosigotifator (ABBV-CLS-7262) in Adults With Major Depressive Disorder (clinicaltrials.gov) - P1 | N=106 | Not yet recruiting | Sponsor: AbbVie

New P1 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

A Phase 1 Study to Investigate the Safety and Pharmacokinetics of Fosigotifator in Patients With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: AbbVie | Trial primary completion date: Jan 2023 ➔ Nov 2025

Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

An Open-Label Exploratory Study of Fosigotifator in Subjects With Vanishing White Matter Disease (clinicaltrials.gov) - P1/2 | N=38 | Recruiting | Sponsor: AbbVie | N=14 ➔ 38 | Trial completion date: Oct 2026 ➔ Dec 2027 | Trial primary completion date: Oct 2026 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date • CNS Disorders • Pediatrics • EIF2B4

Expanded Access to Fosigotifator (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: AbbVie

New trial • CNS Disorders

Study of [14C] ABBV-CLS-7262 in Healthy Male Volunteers Following Single Oral Dose Administration (clinicaltrials.gov) - P1 | N=7 | Completed | Sponsor: Calico Life Sciences LLC | Active, not recruiting ➔ Completed

Trial completion

A Thorough QT Study of ABBV-CLS-7262 in Healthy Subjects (clinicaltrials.gov) - P1 | N=72 | Completed | Sponsor: Calico Life Sciences LLC | Active, not recruiting ➔ Completed

Trial completion

Study of [14C] ABBV-CLS-7262 in Healthy Male Volunteers Following Single Oral Dose Administration (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: Calico Life Sciences LLC | Recruiting ➔ Active, not recruiting

Enrollment closed

A Thorough QT Study of ABBV-CLS-7262 in Healthy Subjects (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: Calico Life Sciences LLC | Recruiting ➔ Active, not recruiting

Enrollment closed

Study of [14C] ABBV-CLS-7262 in Healthy Male Volunteers Following Single Oral Dose Administration (clinicaltrials.gov) - P1 | N=7 | Recruiting | Sponsor: Calico Life Sciences LLC | Not yet recruiting ➔ Recruiting

Enrollment open

Study of [14C] ABBV-CLS-7262 in Healthy Male Volunteers Following Single Oral Dose Administration (clinicaltrials.gov) - P1 | N=7 | Not yet recruiting | Sponsor: Calico Life Sciences LLC

New P1 trial

HEALEY ALS Platform Trial - Master Protocol (clinicaltrials.gov) - P2/3 | N=1500 | Active, not recruiting | Sponsor: Merit E. Cudkowicz, MD | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyotrophic Lateral Sclerosis • CNS Disorders

Phase 1 Asian PK Study of ABBV-CLS-7262, an eIF2B Activator Being Developed as a Potential Treatment for Amyotrophic Lateral Sclerosis and Vanishing White Matter Disease (AAN 2024) - P1, P1/2, P2/3 | "No meaningful differences in exposures after a single oral dose of ABBV-CLS-7262 in Japanese and Han Chinese vs Western subjects were observed. Dose adjustments are not needed for Asian populations."

P1 data • Amyotrophic Lateral Sclerosis • CNS Disorders • EIF2B4

Development of eIF2B Activator ABBV-CLS-7262 as a Novel Treatment for Vanishing White Matter Disease (AAN 2024) - P1/2 | "ABBV-CLS-7262 is being developed as a potential first-in-class treatment for VWM, supported by preclinical studies and Phase 1 healthy volunteer data. A Phase 1b/2 study in people with VWM has been initiated which may enable future studies."

CNS Disorders • EIF2B4

A Thorough QT Study of ABBV-CLS-7262 in Healthy Subjects (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Calico Life Sciences LLC | Not yet recruiting ➔ Recruiting

Enrollment open

A Thorough QT Study of ABBV-CLS-7262 in Healthy Subjects (clinicaltrials.gov) - P1 | N=72 | Not yet recruiting | Sponsor: Calico Life Sciences LLC

New P1 trial