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

An Open-Label Exploratory Study of Fosigotifator in Participants With Vanishing White Matter Disease (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: Calico Life Sciences LLC | Trial completion date: Nov 2029 ➔ Oct 2035

Trial completion date • CNS Disorders • Pediatrics • EIF2B4

Calico Life Sciences Announces Fosigotifator Granted Breakthrough Therapy Designation by the U.S. FDA for the Treatment of Vanishing White Matter Disease (Yahoo Finance)

Breakthrough therapy • CNS Disorders • Genetic Disorders

Discovery of Fosigotifator, a Potent eIF2B Activator with Desired Properties for Human Studies. (PubMed, J Med Chem) - "Potent analogue 9 was identified with significantly improved solubility vs 1 but was still projected to have solubility-limited absorption. A prodrug campaign resulted in the identification of compound 26 (fosigotifator), which exhibited significantly improved solubility and is currently being investigated in the clinic."

Journal • Cardiovascular • ATF4 • EIF2B4

An Open-Label Exploratory Study of Fosigotifator in Participants With Vanishing White Matter Disease (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: Calico Life Sciences LLC | N=16 ➔ 50

Enrollment change • CNS Disorders • Pediatrics • EIF2B4

HEALEY ALS Platform Trial - Master Protocol (clinicaltrials.gov) - P2/3 | N=1500 | Recruiting | Sponsor: Merit E. Cudkowicz, MD | Active, not recruiting ➔ Recruiting | Trial primary completion date: Nov 2027 ➔ Jul 2027

Enrollment open • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Single Patient Investigational Treatment for Cree Leukoencephalopathy (clinicaltrials.gov) - P=N/A | N=1 | Active, not recruiting | Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • CNS Disorders

HEALEY ALS Platform Trial - Master Protocol (clinicaltrials.gov) - P2/3 | N=1500 | Active, not recruiting | Sponsor: Merit E. Cudkowicz, MD | Trial completion date: Apr 2026 ➔ Aug 2028 | Trial primary completion date: Jul 2025 ➔ Nov 2027

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

Single Patient Investigational Treatment for Cree Leukoencephalopathy (clinicaltrials.gov) - P=N/A | N=1 | Enrolling by invitation | Sponsor: Genevieve Bernard

New trial • CNS Disorders

Research Study for Single-Patient Treatment of Cree Leukoencephalopathy/Vanishing White Matter Disease (clinicaltrials.gov) - P1 | N=1 | Active, not recruiting | Sponsor: Genevieve Bernard | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • CNS Disorders

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