Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 1766 |
| INN | None |
| Status | Terminated |
| Drug code(s) | ABBV-3373, adalimumab-ADC |
| Brand name | None |
| mAb sequence source | mAb human |
| General Molecular Category | Immunoconjugate, Unconventional ADC, Antibody-steroid conjugate |
| Format, general category | Full length Ab conjugate |
| Format details | None |
| Isotype (Fc) | IgG1 |
| Light chain isotype | kappa |
| Linker | mal-Gly-Ala-Ala (Cleavable linker) |
| Ave. DAR | 4 |
| Conjugated/fused moiety | Glucocorticoid receptor modulator steroid payload 17 |
| Discovery method/technology | None |
| Target(s) | TNF |
| Indications of clinical studies | Rheumatoid arthritis |
| Primary therapeutic area | Immune-mediated / inflammatory disorders |
| Most advanced stage of development (global) | Terminated at Phase 2 |
| Status | Inactive |
| Start of clinical phase (IND filing or first Phase 1) | May 01, 2018 |
| Start of Phase 2 | March 15, 2019 |
| Start of Phase 3 | |
| Date BLA/NDA submitted to FDA | |
| Year of first approval (global) | None |
| Date of first US approval | |
| INN, US product name | None |
| US or EU approved indications | None |
| Company | AbbVie |
| Licensee/Partner | None |
| Comments about company or candidate | Mar 2024: Phase 1 data published. "Clinical data for a human anti–TNF-GRM ADC (ABBV-3373) from a single ascending dose phase 1 study in healthy volunteers demonstrated antibody-like pharmacokinetic profiles and a lack of impact on serum cortisol concentrations at predicted therapeutic doses. These data suggest that an anti–TNF-GRM ADC may provide improved efficacy beyond anti-TNF alone in immune mediated diseases while minimizing systemic side effects associated with standard GC treatment." (https://www.science.org/doi/10.1126/scitranslmed.add8936). Not listed in AbbVie pipeline as of Sep 2021; NCT03823391 completed as of last update in July 2021. NCT03823391 changed to Phase 2 in April 2020. Listed as Phase 1b/2a in AbbVie pipeline dated June 25, 2019. NCT03823391 Phase 1 study recruting as of March 21, 2019. ABBV-3373 is an anti-TNF GRM steroid ADC being investigated to treat rheumatoid arthritis; listed as Phase 1 on AbbVie website accessed Aug 8 2018. |
| Full address of company | North Chicago, Illinois, United States North America United States of America https://www.abbvie.com/ |
ABBV-3373 is an anti-TNF GRM steroid ADC being investigated to treat rheumatoid arthritis; listed as Phase 1 on AbbVie website accessed Aug 8 2018. As described in "Discovery of ABBV-3373, an Anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody Drug Conjugate" (J Med Chem. 2022 Dec 8;65(23):15893-15934. doi: 10.1021/acs.jmedchem.2c01579), data on the unconjugated payloads and mouse surrogate anti-TNF ADCs identified payload 17 which was conjugated to a human anti-TNF antibody and advanced to the clinic as ABBV-3373. INN may be Adalimumab fosimdesonide?
We have developed a plasma-stable antibody drug conjugate (ADC) that has glucocorticoid receptor modulator (GRM) molecules linked to an anti-TNF-α mAb. This ADC is targeted to TNF-α expressing inflammatory cells and internalized into lysosomes where GRM payload is released. This significantly reduces the efficacious GRM dose to below levels that induce undesired side effects. (PEGS Boston 2020). DAR = 4; mal-Gly-Ala-Ala linker. As per INN description: conjugated at the S
atoms of the reduced cysteinyl 224, 214', 224'' and 214''' with four 2-{[2-({(2S)-4-carboxy-1-[4-({4-[11βhydroxy-3,20-dioxo-21-(phosphonooxy)-2'H,16βH-[1,3]dioxolo[4',5':16,17]pregna-1,4-dien-2'αyl]phenyl}methyl)anilino]-1-oxobutan-2-yl}amino)-2-
oxoethyl]amino}-2-oxoethyl (fosimdesonide) groups
| Anticipated events | None |
| Factor(s) contributing to discontinuation | None |