Table 3.

Compounds in clinical development for C9ORF72-related frontotemporal dementia and amyotrophic lateral sclerosis

Compound	BIIB078a	WVE-004b	Afinersen ASO	Apilimod	TPN-101	Metformin
Structure	Phosphothioate backbone ASO	Stereopure phosphoryl guanidine backbone ASO	Modified phosphothiorate backbone ASO	Small molecule	Small molecule	Small molecule
Target	RNA variants V1 and V3 (via exon 1a); reduces poly(GP) and poly(GA)	RNA variant V3 selective	RNA variants V1 and V3; reduces poly(GP)	PIKFYVE inhibitor	LINE-1 retrotransposon inhibitor	RAN protein
Indication	ALS	ALS and FTD	ALS	ALS	ALS and FTD	ALS
Trial identifier	NCT03626012	ClinicalTrials.gov: NCT04931862	Not applicable	NCT05163886	NCT04993755	NCT04220021
Clinical trial cohort, N	106	35	1	14	42	18
Clinical outcomes	Safety, ALSFRS-R, HHD, SVC, IOPI	Safety, PK, PD	Safety, ALSFRS-R	Safety, tolerability, PK, biomarker change, ALSFRS-R, VC, ALS-CBS	Safety, tolerability, PK, PD, ALSFRS-R	Safety, change in RAN protein levels, ALSFRS-R

ALS-CBS Amyotrophic lateral sclerosis cognitive behavioral scale, ALSFRS-R revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ASO antisense oligonucleotide, CSF cerebrospinal fluid, DPR dipeptide repeat protein, HHD hand-held dynamometry, IOPI Iowa oral pressure instrument, PD pharmacodynamics, PK pharmacokinetics, RAN repeat-associated non-standard, SVC slow vital capacity, VC vital capacity

^aThis trial was halted in March 2022

^bThis trial was halted in May 2023