TARGETS AND PIPELINE

Tech and Hearts Orbiting Recovery

TARGETS

Receptor-level GFRAL inhibition and novel mechanisms for oncologic, cachectic and systemic therapeutics

GDF15 is a stress-induced cytokine secreted by tumors that binds exclusively to GFRAL - a receptor expressed in the hindbrain. This interaction triggers a cascade of pathological responses: appetite loss, progressive muscle and fat wasting, sympathetic hyperactivation and suppression of anti-tumor immunity. In cancer patients, this translates to treatment intolerance, reduced response to immunotherapy and shortened survival. Critically, no approved therapy currently addresses this cascade directly.

THOR's programs intervene at the receptor level. By targeting the D3 domain of GFRAL - the binding site for the RET co-receptor, we block the formation of the GFRAL-RET signaling complex and halt downstream pathogenic signaling at its source. This approach is mechanistically distinct from GDF15-neutralizing antibodies, which act upstream in circulation and do not directly prevent receptor activation.
The GDF15-GFRAL axis extends beyond oncology. Elevated GDF15 levels have been documented in heart failure, sarcopenia, lung fibrosis, kidney failure and neurodegenerative conditions - each representing a potential expansion of THOR's therapeutic platform. Our pipeline is designed to address this broader landscape through a combination of anti-GFRAL antibodies and antisense oligonucleotides, developed in parallel across multiple disease contexts.

PIPELINE

THOR Therapeutics is advancing candidates targeting the GDF15-GFRAL axis:


Pipeline Modality Mechanism Indications Stage
THOR-017 Anti-GFRAL mAb (IgG1) GFRAL D3 domain blocker; inhibits GDF15-GFRAL-RET signaling Cancer cachexia,
IO booster		 IND-enabling
THOR-019 Bifunctional binder Dual GFRAL inhibition + GDF15 neutralization Cancer cachexia,
heart failure,
IO booster,
sarcopenia		 Discovery
THOR-427 GFRAL-targeting ASO ASO-mediated GFRAL knockdown Refractory Cachexia,
IO booster		 IND-enabling