Pharma Update
Anti-latent myostatin mAb to promote muscle growth in SMA
Ph II/III combination trial with Evrysdi ongoing
GYM329 (Anti-latent myostatin mAb)
Circulating Myostatin
Propeptide Complex
Latent Myostatin
Dimer/Propeptide Complex
100
-1000-13*
GYM329
Pre-clinical data in a mouse models of muscle disease
Efficent inhibition of latent myostatin,
but not GDF11
Latent myostatin
Increase in muscle mass and strength
in mouse models
250
Combination rationale
Roche
•
Evrysdi treats the underlying
SMA disease by increasing SMN
M M
Muscle Cell Membrane
ActRIIB
Alk4/Alk5
Muscle Fiber
Smad 3
Smad 2
℗
Smad 4
Smad Complex
Gene activation leading to skeletal
muscle growth and strength
• GYM329 binds latent myostatin, a key negative
regulator of skeletal muscle growth and strength
Unique sweeping and recycling technology
allows less frequent SC dosing and highly
specific myostatin inhibition
% Inhibition
120
Latent GDF11
100
Mature myostatin
Mature GDF11
282842089
0
0.01
0.1 110
Antibody concentration (pg/ml.)
100
Change in muscle mass (g)
8
7
200
Change in grip strength (g)
الله الله
B10 Vehicle 3
10
GYM-mFc
B10 Vehicle
GYM-mFe
protein throughout the CNS and
in peripheral tissues
GYM329 targets skeletal
muscles to increase their size
and strength
• GYM329 efficiently inhibits myostatin, but not the related muscle hormone GDF11, making it highly
specific compared to other anti-myostatin Abs tested²
• GDF11 and myostatin act in opposite directions in muscle strength enhancement
• The combination of GYM329 + Evrysdi improved muscle size and strength in an animal model of SMA
Ph II/III (MANATEE) of GYM329 and Evrysdi in SMA ongoing
1. A sweeping antibody is a recycling antibody that has been further engineered to bind to FcRn at neutral pH; 2.Muramatsu H. et al., Nature Scientific Reports. 2021; SC=subcutaneous; CNS-central nervous system;
mAb-antibody; SMA-spinal muscular atrophy; SMN=survival motor neuron; GDF11-growth differentiation factor 11; GYM329 in collaboration with Chugai
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