Biohaven Ltd. · NYSE:BHVN
Biohaven — ObesityWeek 2025
10 slides from Biohaven's conference presentation, 2025
Slide 1: Taldefgrobep/Myostatin Complex Inhibits TGF-ß Ligand Signaling Reducing Lipid Storage in Adipocytes
Taldefgrobep/Myostatin Complex Inhibits TGF-ß Ligand Signaling Reducing Lipid Storage in Adipocytes Authors: Eric H. Ma, PhD1; Nadee Nissanka, PhD1; David Pirman, PhD1; Peter Ackerman, MD1; Christopher Jensen, PharmD1; Camille Schrier, PharmD1; Clifford Bechtold, MS1; Vlad Coric, MD1; Bruce Car, DVM
Slide 2: Taldefgrobep Alfa: A Novel Myostatin-Activin Pathway Inhibitor in Development for Obesity
Taldefgrobep Alfa: A Novel Myostatin-Activin Pathway Inhibitor (MAPI) in Development for the Treatment of Overweight and Obesity MAPIs with varied mechanisms of action have demonstrated beneficial body composition changes in people living with obesity1-4 Taldefgrobep is an investigational drug with
Slide 3: Taldefgrobep Has Direct Effects on Fat and Muscle, Potentially Optimizing Quality of Weight Loss
Taldefgrobep Has Direct Effects on Fat and Muscle, Potentially Optimizing the Quality of Weight Loss LIGANDS THAT SIGNAL THROUGH ActRII A ALK5 Inhibition in adipocytes ALK7 Taldefgrobep alfa Activins leads to lipolysis SMAD2/3/4 SIGNALING Biohaven Increased brown fat enhanced mitochondrial activity
Slide 4: In an Obese Mouse Model, Taldefgrobep Reduced Fat Mass While Increasing Lean Mass
In an Obese Mouse Model, Taldefgrobep Demonstrated Significant Reductions in Fat Mass While Increasing Lean Mass **** 20 **** 25 **** **** From Baseline at 8 Weeks (%) Change in Lean Muscle Mass Change in Fat Mass From Baseline at 8 Weeks (%) 20 0 15 10 -20 5 0 -40 -5 Vehicle T-alfa T-alfa + Semaglu
Slide 5: Taldefgrobep-Myostatin Complex Blocks Activin B Induced Dimerization of ActRIIB-ALK7
Taldefgrobep-Myostatin Complex Blocks Activin B Induced Dimerization of ActRIIB-ALK7 Assay Demonstrates Taldefgrobep-Myostatin Complex Chemiluminescent Signal Dose Curve (%) Inhibits Activin B–Mediated ActRIIB-ALK7 Dimerization T-ALFA MYOSTATIN COMPLEX ACTIVIN A M A M U2OS CELLS -6 Activin B Conc (u
Slide 6: Taldefgrobep Decreases Phospho-SMAD2/3 Signaling in Adipocytes
Taldefgrobep Decreases Phospho-SMAD2/3 Signaling in Adipocytes Taldefgrobep Decreases Phospho-SMAD2/3 Signaling Taldefgrobep Decreases Phospho-SMAD2/3 in Mouse 3T3-L1 Adipocytes1 Signaling in Primary Human Adipocytes ** ** *** ABS450 (nm) ABS450 (nm) Control T-alfa ActRII ligandsa ActRII ligandsa +
Slide 7: Reversed ActRII Ligand-Induced Alterations in Intracellular Metabolite Levels in Adipocytes
Taldefgrobep Reversed ActRII Ligand-Induced Alterations in Intracellular Metabolite Levels in Adipocytes Isoleucine Valine class Control * Relative Abundance (AU) Relative Abundance (AU) N-ACETYLASPARAGINE 8×107 T-alfa 6×107 D-MANNOSAMINE DEOXYRIBOSE Myostatin * * PANTOHENATE Myostatin + T-alfa 6×10
Slide 8: Treatment Reduces Fat Storage in Adipocytes
Taldefgrobep Treatment Reduces Fat Storage in Adipocytes Lipid Storage Myostatin Mouse 3T3-L1 Adipocytes1 Primary Human Adipocytes drives 25000 fat storage 20000 **** * BODIPY (gMFI) BODIPY (gMFI) ns 15000 10000 Taldefgrobep reduces this 5000 increased storage 0 Control T-alfa ActRII ligandsa Contro
Slide 9: Increases Mitochondrial Mass in Adipocytes
Taldefgrobep Increases Mitochondrial Mass in Adipocytes Basal Mitochondrial Oxygen Consumption Mitochondrial Mass1 **** **** 8000 **** ** ** OCR (pmol/min/protein)) MitoTracker Green (gMFI) 6000 4000 2000 0 Control T-alfa Myostatin Myostatin + T-alfa Control T-alfa ActRII ligandsa ActRII ligandsa +
Slide 10: Conclusions
Conclusions Taldefgrobep alfa is a novel myostatin-activin pathway inhibitor (MAPI) being developed for the treatment of overweight and obesity • ActRII-mediated signaling, and downstream SMAD2/3 phosphorylation, leads to muscle wasting and the accumulation of fat mass • The taldefgrobep-myostatin c