NaPi2b-targeted antibody-drug conjugates and methods of use thereof

A conjugate having Formula:

• wherein:
• the conjugate comprises a polymeric scaffold comprising poly(l-hydroxymethylethylene hydroxymethyl-formal) (PHF), wherein the PHF has a molecular weight ranging from 5 kDa to 10 kDa;
• m is an integer from 1 to 75,
• m1 is an integer from about 2 to about 35,
• m2 is an integer from about 2 to about 10,
• m3a is an integer from 0 to about 4,
• m3b is an integer from 1 to about 5,
• the sum of m, m1, m2, m3a, and m3b ranges from about 40 to about 75,
• XMT-1535 comprises a variable light chain complementarity determining region 1 (CDRL1) comprising the amino acid sequence SASQDIGNFLN (SEQ ID NO:
• 8);
• a variable light chain complementarity determining region 2 (CDRL2) comprising the amino acid sequence YTSSLYS (SEQ ID NO:
• 9);
• a variable light chain complementarity determining region 3 (CDRL3) comprising the amino acid sequence QQYSKLPLT (SEQ ID NO:
• 10);
• a variable heavy chain complementarity determining region 1 (CDRH1) comprising the amino acid sequence GYTFTGYNIH (SEQ ID NO:
• 5);
• a variable heavy chain complementarity determining region 2 (CDRH2) comprising the amino acid sequence AIYPGNGDTSYKQKFRG (SEQ ID NO:
• 6);
• and a variable heavy chain complementarity determining region 3 (CDRH3) comprising the amino acid sequence GETARATFAY (SEQ ID NO:
• 7);
• and
• wherein the ratio between the PHF and XMT-1535 is an integer from 2 to about 6.