Therapeutic inhibitors of gdf15 signalling

An antibody that binds human GFRAL, comprising an antibody heavy chain variable (VH) domain and an antibody light chain variable (VL) domain, wherein:

• (i) the VH domain comprises the QUEL-0201 set of heavy chain complementarity determining regions (HCDRs) HCDR1 SEQ ID NO:
• 13, HCDR2 SEQ ID NO:
• 14 and HCDR3 SEQ ID NO:
• 15, and
• the VL domain comprises the QUEL-0201 set of light chain complementarity determining regions (LCDRs) LCDR1 SEQ ID NO:
• 18, LCDR2 SEQ ID NO:
• 19 and LCDR3 SEQ ID NO:
• 20,
• (ii) the VH domain comprises the QUEL-0301 set of heavy chain complementarity determining regions (HCDRs) HCDR1 SEQ ID NO:
• 23, HCDR2 SEQ ID NO:
• 24 and HCDR3 SEQ ID NO:
• 25, and
• the VL domain comprises the QUEL-0301 set of light chain complementarity determining regions (LCDRs) LCDR1 SEQ ID NO:
• 28, LCDR2 SEQ ID NO:
• 29 and LCDR3 SEQ ID NO:
• 30,
• (iii) the VH domain comprises the QUEL-0101 set of heavy chain complementarity determining regions (HCDRs) HCDR1 SEQ ID NO:
• 3, HCDR2 SEQ ID NO:
• 4 and HCDR3 SEQ ID NO:
• 5, and
• the VL domain comprises the QUEL-0101 set of light chain complementarity determining regions (LCDRs) LCDR1 SEQ ID NO:
• 8, LCDR2 SEQ ID NO:
• 9 and LCDR3 SEQ ID NO:
• 10,
• (iv) the VH domain has at least 90% amino acid sequence identity to the QUEL-0201 VH domain SEQ ID NO:
• 12 and
• the VL domain has at least 90% amino acid sequence identity to the QUEL-0201 VL domain SEQ ID NO:
• 17,
• (v) the VH domain has at least 90% amino acid sequence identity to the QUEL-0301 VH domain SEQ ID NO:
• 22 and
• the VL domain has at least 90% amino acid sequence identity to the QUEL-0301 VL domain SEQ ID NO:
• 27, or
• (vi) the VH domain has at least 90% amino acid sequence identity to the QUEL-0101 VH domain SEQ ID NO:
• 2 and
• the VL domain having at least 90% amino acid sequence identity to the QUEL-0101 VL domain SEQ ID NO:
• 7.