Complement Factor B-modulating compositions and methods of use thereof

A compound comprising a first modified oligonucleotide 14 to 23 linked nucleosides in length having a nucleobase sequence comprising at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or at least 20 contiguous nucleobases of the nucleobase sequence of SEQ ID NO:

• 109 and a second modified oligonucleotide 14 to 23 linked nucleosides in length having a region of complementarity to the first modified oligonucleotide, wherein one or more GalNAc are attached to the first modified oligonucleotide, wherein the 5′ nucleoside of the first modified oligonucleotide is of the following formula:
• wherein:
• R9 is H, adenine, guanine, thymine, cytosine, uracil, adenine comprising a protecting group (PG), guanine comprising a PG, thymine comprising a PG, cytosine comprising a PG, uracil comprising a PG, a modified nucleobase, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, or a nucleobase isostere;
• L is a bond, a phosphodiester bond, a phosphorothioate bond, a triazole, a tetrazole, an amide, a reverse-amide, a carbamate, a carbonate, urea, alkyl, or heteroalkyl;
• R2 is an oligonucleotide sequence or modified oligonucleotide;
• Y1 is O, CH2, CH2O, or optionally substituted NH;
• Y2 is O, CH2, CH2O, or optionally substituted NH;
• Y3 is CO, SO2, P (O) O, CH2—O—C(O), CH2—NH—C(O), CH2—NH—SO2, or CH2;
• Y4 is CO, SO2, P (O) O, CH2—O—C(O), CH2—NH—C(O), CH2—NH—SO2, or CH2;
• n2 is 0, 1, 2, 3, 4, 5, or 6;
• and
• each n1, n3, n4 and n5 is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.