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 106

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