taldefgrobep alfa (BHV-2000) / Roche, BMS, Biohaven - LARVOL DELTA

Biohaven Reports First Quarter 2025 Financial Results and Recent Business Developments (PRNewswire) - "Expected Upcoming Milestones:...(i) Myostatin (Taldefgrobep alfa): FDA interaction to discuss Spinal Muscular Atrophy ('SMA') registrational path planned in 1H 2025. Initiate taldefgrobep Phase 2 study in obesity in 1H 2025; (ii) TRPM3 Antagonist (BHV-2100): Expect data from proof-of-concept trial with BHV-2100 in acute migraine in 1H 2025."

FDA event • New P2 trial • P2 data • Migraine • Muscular Atrophy • Obesity • Pain

Biohaven Reports Recent Business Developments and Fourth Quarter and Full Year 2024 Financial Results (PRNewswire) - "Glutamate Modulator (Troriluzole)...Topline data from two Phase 3 OCD trials in 1H 2025 and 2H 2025, respectively. Myostatin (Taldefgrobep alfa): Expect FDA meeting to discuss SMA registrational path in 1H 2025. Initiate taldefgrobep Phase 2 study in obesity in 1H 2025. Continue advancing enrollment in proof of concept trial with BHV-2100 in acute migraine; data from the laser-evoked potential study expected in 1H 2025...Initiate BHV-8000 Phase 2/3 study in Parkinson's disease in 1H 2025."

FDA event • New P2 trial • New P2/3 trial • P2 data • P3 data • Migraine • Muscular Atrophy • Obesity • Obsessive-Compulsive Disorder • Parkinson's Disease

Taldefgrobep Alfa Improved Body Composition as Mono or in Combination With Semaglutide in DIO Model (OBESITY WEEK 2024) - "Taldefgrobep, as monotherapy or in combination with a GLP-1R agonist, demonstrated a significant reduction in adipose tissue while increasing lean mass despite GLP1 induced muscle loss supporting the continued development in individuals living with overweight and obesity."

Combination therapy • Genetic Disorders • Obesity

Taldefgrobep Alfa Reduces Lipids and Increases Mitochondrial Content in Adipocytes (OBESITY WEEK 2024) - "Taldefgrobep/myostatin complexes directly affect activin II receptor signaling cascades in adipose tissue to reduce fat storage. SMAD signaling negatively regulates lipolysis in adipose tissue and pharmacological inhibition potentiates lipolysis, leading to reduced adipocyte size. Recently, antibodies against the adipose-specific activin-like kinase 7 were shown to significantly reduce adipose tissue and increase insulin sensitivity."

Genetic Disorders • Obesity

Taldefgrobep Alfa and the Phase 3 RESILIENT Trial in Spinal Muscular Atrophy. (PubMed, Int J Mol Sci) - P3 | "Given a robust scientific and clinical rationale and the favorable safety profile of taldefgrobep in patients with neuromuscular disease, the RESILIENT phase 3, randomized, placebo-controlled trial is investigating taldefgrobep as an adjunct to SMN upregulators in SMA (NCT05337553). This manuscript reviews the role of myostatin in muscle, explores the preclinical and clinical development of taldefgrobep and introduces the phase 3 RESILIENT trial of taldefgrobep in SMA."

Journal • P3 data • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • TGFB1

Taldefgrobep Alfa Improves Body Composition as Monotherapy and in Combination with Semaglutide in a DIO Mouse Model (ADA 2024) - "This study supports the development of taldefgrobep as a monotherapy or combination with GLP-1R agonists to reduce fat and maintain lean mass in individuals living with overweight and obesity."

Combination therapy • Late-breaking abstract • Monotherapy • Preclinical • Metabolic Disorders • Obesity

Stride Velocity 95th Centile Detects Decline in Ambulatory Function Over Shorter Intervals than the 6-Minute Walk Test or North Star Ambulatory Assessment in Duchenne Muscular Dystrophy. (PubMed, J Neuromuscul Dis) - "SV95C was a secondary endpoint in a subset (n = 47) of participants in the SPITFIRE/WN40227 trial of taldefgrobep alfa, which was discontinued due to lack of clinical benefit...Overall, SV95C demonstrated sensitivity to ambulatory decline over short intervals, low variability, and correlation with established COAs. Although the negative trial precluded demonstration of SV95C's sensitivity to drug effect, these findings support the continued use of SV95C in DMD clinical trials."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

The Phase 3 RESILIENT Study: Taldefgrobep Alfa in Spinal Muscular Atrophy (AAN 2024) - P3 | "This phase 3 study aims to investigate the efficacy and safety of taldefgropeb as an adjunctive treatment with SMN upregulators in particpants with SMA."

P3 data • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

The Clinical Development of Taldefgrobep Alfa: An Anti-Myostatin Adnectin for the Treatment of Duchenne Muscular Dystrophy. (PubMed, Neurol Ther) - P1, P1/2, P2/3 | "The futility analysis demonstrated that taldefgrobep alfa did not result in functional change for boys with DMD. The program was subsequently terminated in 2019. Overall, there were no safety concerns, and no patients were withdrawn from treatment as a result of treatment-related adverse events or serious adverse events."

Clinical • Journal • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Biohaven Presents Preclinical Data Demonstrating Taldefgrobep alfa Reduces Fat and Improves Lean Mass at The Obesity Society’s Annual Meeting, ObesityWeek (PRNewswire) - "Biohaven Ltd...announced the presentation of preclinical data demonstrating the ability of taldefgrobep alfa to significantly reduce fat mass while increasing lean mass in an obese mouse model....Both sets of data were presented on October 15, 2023 at The Obesity Society's annual ObesityWeek conference held in Dallas, TX....In a mouse model of diet-induced obesity, untreated mice exhibited an increase in fat mass of 31%, while the taldefgrobep-treated mice demonstrated increases in lean mass of 25% from baseline (p≤.0.001; Figure 1) and lost 11% of their baseline fat (p≤.0.001; Figure 2) compared to vehicle (placebo) treated mice. Insulin and leptin levels were consistently lower in taldefgrobep-treated mice compared to untreated. There was no difference in food intake over time across the taldefgrobep and untreated mice....A Phase 2 obesity study with taldefgrobep is planned for 2024."

New P2 trial • Preclinical • Metabolic Disorders • Obesity

RESILIENT: A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy (clinicaltrials.gov) - P3 | N=269 | Active, not recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Biohaven’s Taldefgrobep Alfa Receives EU Orphan Drug Designation for Spinal Muscular Atrophy (PRNewswire) - "Biohaven Ltd...announced today that it received orphan medicinal product designation from the European Commission (EC) for taldefgrobep alfa, a novel anti-myostatin adnectin, for the treatment of spinal muscular atrophy (SMA). Orphan Designation highlights the potential for taldefgrobep to deliver significant benefit for people with SMA and provides regulatory and commercial incentives including a reduction in regulatory fees associated with protocol reviews and scientific advice, along with an additional ten-years of market protection. Biohaven previously received fast track and orphan drug designation from the FDA for taldefgrobep in the treatment of SMA....Biohaven is currently enrolling a Phase 3 clinical trial of taldefgrobep in SMA: A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants with Spinal Muscular Atrophy (RESILIENT) (NCT05337553)."

Enrollment status • European regulatory • Orphan drug • CNS Disorders • Muscular Atrophy • Muscular Dystrophy

Taldefgrobep alfa: preclinical and clinical data supporting the phase 3 RESILIENT study in Spinal Muscular Atrophy (WMS 2023) - No abstract available

Clinical data • P3 data • Preclinical • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

The Phase 3 RESILIENT Study: Taldefgrobep Alfa in Spinal Muscular Atrophy (EAN 2023) - P3 | "This phase 3 study aims to investigate the efficacy and safety of taldefgrobep as an adjunctive treatment with SMN upregulators in patients with SMA."

P3 data • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Taldefgrobep Alfa: Preclinical and Clinical Data Supporting the Phase 3 RESILIENT Study in Spinal Muscular Atrophy (EPNS 2023) - P3 | "Preclinical data suggest a potential benefit from taldefgrobep combined with SMN upregulation in SMA treatment. In addition to robust safety data from clinical studies, these preclinical results support conducting the global, prospective, randomized, double-blind, placebo-controlled phase 3 RESILIENT study (NCT05337553). The study is now enrolling ambulatory and non-ambulatory patients with SMA who are receiving SMN-upregulating therapies, with the aim of evaluating the efficacy and safety of taldefgrobep in this population."

Clinical data • P3 data • Preclinical • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Biohaven's Taldefgrobep Alfa Receives FDA Fast Track Designation for Spinal Muscular Atrophy (PRNewswire) - "Biohaven...announced today that it received Fast Track designation from the U.S. Food and Drug Administration (FDA) for taldefgrobep alfa, a novel anti-myostatin adnectin, for the treatment of spinal muscular atrophy (SMA). Fast Track designation enables important new drugs to reach patients earlier by facilitating more frequent communications with the FDA and expeditious review of a drug which treats a serious condition and fills an unmet medical need. Biohaven previously received orphan drug designation from the FDA for taldefgrobep in the treatment of SMA."

Fast track designation • CNS Disorders • Muscular Atrophy

RESILIENT: A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy (clinicaltrials.gov) - P3 | N=225 | Recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Trial completion date: Aug 2024 ➔ Jan 2025 | Trial primary completion date: Aug 2024 ➔ Jan 2025

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

RESILIENT: A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy (clinicaltrials.gov) - P3 | N=225 | Recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Trial primary completion date: Jul 2023 ➔ Aug 2024

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

A study to test Taldefgropeb Alfa in patients with Spinal Muscular Atrophy. (clinicaltrialsregister.eu) - P3 | N=180 | Sponsor: Biohaven Pharmaceuticals, Inc.

New P3 trial • Genetic Disorders • Movement Disorders • Muscular Atrophy • Musculoskeletal Diseases • Rare Diseases

RESILIENT: A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy (clinicaltrials.gov) - P3 | N=225 | Recruiting | Sponsor: Biohaven Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

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

RESILIENT: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy (clinicaltrials.gov) - P3 | N=225 | Not yet recruiting | Sponsor: Biohaven Pharmaceuticals, Inc.

New P3 trial • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Clinical Trial to Evaluate the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys With Duchenne Muscular Dystrophy (clinicaltrials.gov) - P2/3; N=166; Completed; Sponsor: Hoffmann-La Roche; Terminated ➔ Completed

Clinical • Trial completion • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Immunotherapy in Hodgkin and non-Hodgkin lymphoma: Innate, adaptive and targeted immunological strategies. (PubMed, Cancer Treat Rev) - "To overcome impaired antigen presentation, antibody-based cytotoxic strategies, namely antibody-drug conjugates (polatuzumab vedotin and brentuximab vedotin) and bispecific T-cell or NK-cell engagers (blinatumomab, REGN1979, RG6206, and AFM13), have rapidly evolved with promising clinical activity. As additional tools become available for lymphoma treatment, formulation of safe, rational combination strategies to combine them with standard therapy will be of paramount importance. A successful approach to the treatment of lymphoma may require both an optimized anti-tumor immune response as well as effective depletion of malignant lymphoid cells."

Journal • Review • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Immune Modulation • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Study of an Investigational Drug, RO7239361 (BMS-986089), in Ambulatory Boys With DMD (clinicaltrials.gov) - P1/2; N=43; Terminated; Sponsor: Hoffmann-La Roche; Completed ➔ Terminated; A pre-planned futility analysis indicated lack of efficacy.

Clinical • Trial termination • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Study of an Investigational Drug, RO7239361 (BMS-986089), in Ambulatory Boys With DMD (clinicaltrials.gov) - P1/2; N=43; Completed; Sponsor: Hoffmann-La Roche; Active, not recruiting ➔ Completed

Clinical • Trial completion • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy