galunisertib + nerandomilast

Galunisertib + nerandomilast is an investigational combination therapy being developed by Gipfel Life Sciences for the treatment of amyotrophic lateral sclerosis (ALS), specifically targeting patients with elevated Gremlin-2 (GREM2) biomarkers. The combination employs two distinct mechanisms to address neurodegeneration and neuroinflammation: galunisertib is a selective ATP-competitive inhibitor of the TGF-β receptor type I (TGF-βR1/ALK5), which blocks SMAD2/3 phosphorylation to attenuate maladaptive astrocytic activity and fibrotic gene programs; nerandomilast (formerly BI 1015550) is a selective phosphodiesterase 4B (PDE4B) inhibitor that increases intracellular cAMP levels to resolve pro-inflammatory signaling and reduce glial toxicity. This dual-targeting approach is hypothesized to slow disease progression by mitigating the synergistic effects of dysregulated TGF-β signaling and chronic inflammation in the central nervous system.

Other names

Galunisertib + Nerandomilast CombinationGalunisertib and Nerandomilast in GREM2-Positive ALSNerandomilast + Galunisertib