emugrobart (RG6237) / Roche - LARVOL DELTA

Notice Regarding Discontinuation of Development of GYM329 (Emugrobart) in Spinal Muscular Atrophy (SMA) and Facioscapulohumeral Muscular Dystrophy (FSHD) (Chugai Press Release) - "This decision follows a rigorous assessment of data from the Phase II/III MANATEE study (Part 1) in SMA and the Phase II MANOEUVRE study in FSHD. While emugrobart showed a favorable safety profile and target engagement by reducing mature myostatin, it did not translate into the intended functional outcomes. Specifically, muscle growth and exploratory functional efficacy were neither consistent nor robust enough across study participants to provide sufficient confidence for Phase III development in SMA and FSHD."

Discontinued • Muscular Atrophy

A Study to Evaluate the Effect of RO7204239 on Insulin Sensitivity and Muscle Composition in Participants With Type 2 Diabetes Mellitus (T2DM) and Overweight or Obesity (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Hoffmann-La Roche

Trial initiation date • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Roche-owned Japanese drugmaker Chugai Pharmaceutical expects to seek approval as early as 2028 for a new obesity drug designed to prevent excess body weight from returning after treatment… (Nikkei) - "The drug candidate, GYM329, is now in clinical trials sponsored by Chugai and Swiss parent Roche....The drug is expected to be used alongside existing GLP-1 obesity medications, which mimic hormone effects to promote weight loss. In the clinical trials, changes in weight and muscle mass are being monitored and compared against patients using only existing medication."

Approval • Obesity

Advancing treatment of spinal muscular atrophy through inhibition of the myostatin signaling pathway. (PubMed, Expert Rev Neurother) - "Treatments that inhibit myostatin signaling represent a potential complementary pathway for direct muscle enhancement. In the evolving SMA treatment landscape, understanding how muscle-targeted treatment can be incorporated into clinical practice will facilitate individualized treatment decisions and identify outcomes that best encapsulate maintenance or improvement of motor function across the phenotypic spectrum of SMA."

Journal • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

GYMINDA: A Study to Assess Efficacy, Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of RO7204239 in Combination With Tirzepatide in Participants With Obesity or Overweight With At Least One Weight-related Comorbidity (clinicaltrials.gov) - P2 | N=285 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

MANOEUVRE: A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Nov 2026 ➔ May 2025

Trial primary completion date • Muscular Dystrophy

A Study to Evaluate the Effect of RO7204239 on Insulin Sensitivity and Muscle Composition in Participants With Type 2 Diabetes Mellitus (T2DM) and Overweight or Obesity (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2026 ➔ Mar 2027

Enrollment open • Trial completion date • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

A Study to Evaluate the Effect of RO7204239 on Insulin Sensitivity and Muscle Composition in Participants With Type 2 Diabetes Mellitus (T2DM) and Overweight or Obesity (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P1 trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

GYMINDA: A Study to Assess Efficacy, Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of RO7204239 in Combination With Tirzepatide in Participants With Obesity or Overweight With At Least One Weight-related Comorbidity (clinicaltrials.gov) - P2 | N=234 | Recruiting | Sponsor: Hoffmann-La Roche

New P2 trial • Genetic Disorders • Obesity

MANOEUVRE: A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: May 2025 ➔ Nov 2026

Trial primary completion date • Muscular Dystrophy

MANATEE: A Study to Investigate the Safety and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Participants With Spinal Muscular Atrophy (clinicaltrials.gov) - P2/3 | N=259 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Mar 2028 ➔ Feb 2029

Trial primary completion date • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

MANATEE: A Study to Investigate the Safety and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Participants With Spinal Muscular Atrophy (clinicaltrials.gov) - P2/3 | N=259 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

MANATEE: A Study to Investigate the Safety and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Participants With Spinal Muscular Atrophy (clinicaltrials.gov) - P2/3 | N=259 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2026 ➔ Mar 2029 | Trial primary completion date: Jun 2026 ➔ Mar 2028

Trial completion date • Trial primary completion date • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

MANATEE: A Study to Investigate the Safety and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Participants With Spinal Muscular Atrophy (clinicaltrials.gov) - P2/3 | N=259 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

MANOEUVRE: A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Oct 2026 | Trial primary completion date: Jun 2024 ➔ May 2025

Enrollment closed • Trial completion date • Trial primary completion date • Muscular Dystrophy

MANATEE: GYM329 (RO7204239) in combination with Risdiplam treatment in ambulant children with spinal muscular atrophy (SMA) (WMS 2023) - No abstract available

Clinical • Combination therapy • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Preclinical in vitro evaluation of immune suppression induced by GYM329, Fc-engineered sweeping antibody. (PubMed, J Toxicol Sci) - "The result of the present study demonstrated that Fc-engineered Abs with similar binding affinity to FcγRIIb had different effects. Thus, it is important to also investigate FcγR-mediated immune functions other than binding to fully understand the biological effects of Fc-engineered Abs."

Journal • Preclinical

MANOEUVRE Study Design: A Study of GYM329 (RO7204239) in Patients with Facioscapulohumeral Muscular Dystrophy (FSHD) (AAN 2023) - P2 | "The MANOEUVRE study design will be presented. Conclusions This study will provide valuable information about the PD, safety, PK and efficacy of GYM329 treatment in patients with FSHD."

Clinical • Muscular Atrophy • Muscular Dystrophy

A Study to Investigate the Safety and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Participants With Spinal Muscular Atrophy (clinicaltrials.gov) - P2/3 | N=259 | Recruiting | Sponsor: Hoffmann-La Roche | N=180 ➔ 259 | Trial completion date: Dec 2026 ➔ Jun 2026 | Trial primary completion date: Dec 2026 ➔ Jun 2026

Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

A Clinical Pharmacology Study to Evaluate the Effect of GYM329 on Disuse Muscle Atrophy in Healthy Volunteer (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Chugai Pharmaceutical | Active, not recruiting ➔ Completed

Trial completion • Muscular Atrophy

A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Muscular Dystrophy

Manoeuvre study design: A study of GYM329 (RO7204239) in patients with facioscapulohumeral muscular dystrophy (FSHD) (WMS 2022) - "The Manoeuvre study design will be presented. This study will provide valuable information about the PD, safety, PK and efficacy of GYM329 treatment in patients with FSHD."

Clinical • Muscular Atrophy • Muscular Dystrophy

A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy (clinicaltrials.gov) - P2 | N=48 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P2 trial • Muscular Dystrophy

A Study to Evaluate the Pharmacodynamics, Safety, Tolerability, Pharmacokinetics, and Efficacy of RO7204239 Compared with Placebo in Participants with Facioscapulohumeral Muscular Dystrophy (clinicaltrialsregister.eu) - P2 | N=48 | Ongoing | Sponsor: F.Hoffmann-La Roche Ltd

New P2 trial • Muscular Atrophy • Muscular Dystrophy • Musculoskeletal Diseases

MANATEE: GYM329 (RO7204239) in Combination with Risdiplam Treatment in Ambulant Children with Spinal Muscular Atrophy (ICNMD 2022) - No abstract available

Clinical • Combination therapy • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases