ABBV-3373 / AbbVie - LARVOL DELTA

The next frontier in antibody-drug conjugates: challenges and opportunities in cancer and autoimmune therapy. (PubMed, Cancer Drug Resist) - "ADCs have also shown emerging therapeutic potential in the treatment of autoimmune diseases; for instance, ABBV-3373 has achieved initial success in this area, yet it also faces unique challenges such as the safety of long-term administration, immunogenicity, and heterogeneity of target cells. Addressing these challenges requires multidimensional innovations, including optimizing molecular design, exploring combination therapy strategies, and introducing artificial intelligence (AI)-assisted development. These efforts aim to transition ADCs from the traditional "targeted killing" paradigm to intelligent and personalized precision delivery systems, thereby offering more therapeutic options for patients with cancer and autoimmune diseases."

Journal • Review • Immunology • Oncology

An anti-TNF-glucocorticoid receptor modulator antibody-drug conjugate is efficacious against immune-mediated inflammatory diseases. (PubMed, Sci Transl Med) - "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."

Journal • Contact Dermatitis • Immunology • Inflammation • Oncology • Rheumatoid Arthritis • Rheumatology

Minimising the payload solvent exposed hydrophobic surface area optimises the antibody-drug conjugate properties. (PubMed, RSC Med Chem) - "Solving the crystal structure of compound 2, the GRM payload from ABBV-3373 and ABBV-154, in the ligand binding domain of the glucocorticoid receptor (GR) revealed key information to facilitate optimal ADC payload design. Confirmation of the stereochemistry of the acetal in compound 2 as (R) was established. Finally, the importance of minimising the exposed hydrophobic surface area of a payload to reduce the negative impact on the properties of resulting ADCs, like aggregation, was rationalised by comparison of (R)-acetal compound 2 and (S)-acetal compound 3."

Journal • Oncology

A first-in-human study of the novel immunology antibody drug conjugate, ABBV-3373, in healthy participants. (PubMed, Br J Clin Pharmacol) - "ABBV-3373 had favorable PK profiles, manageable immunogenicity, and was generally well tolerated. Except for a transient effect at 900 mg IV, there was no apparent impact on serum cortisol. Study results supported further clinical development of ABBV-3373."

Journal • P1 data • Inflammation

Discovery of ABBV-3373, an Anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody Drug Conjugate. (PubMed, J Med Chem) - "In a chronic mouse arthritis model, mouse anti-TNF GRM ADCs were efficacious after a single dose of 10 mg/kg i.p. for over 30 days. 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."

Journal • Contact Dermatitis • Immunology • Oncology • Rheumatology

[VIRTUAL] ANTI-TNF GLUCOCORTICOID RECEPTOR MODULATOR ANTIBODY DRUG CONJUGATE FOR THE TREATMENT OF AUTOIMMUNE DISEASES (EULAR 2021) - "These data suggest that an anti-TNF ADC delivering a GRM payload into activated immune cells may provide improved efficacy in immune mediated diseases, while minimizing systemic side effects associated with standard GC treatment."

Contact Dermatitis • Immunology • Inflammation • Rheumatoid Arthritis • Rheumatology

[VIRTUAL] EFFICACY AND SAFETY OF ABBV-3373, A NOVEL ANTI-TNF GLUCOCORTICOID RECEPTOR MODULATOR ANTIBODY DRUG CONJUGATE, IN PATIENTS WITH MODERATE TO SEVERE RHEUMATOID ARTHRITIS DESPITE METHOTREXATE THERAPY: A PHASE 2A PROOF OF CONCEPT STUDY (EULAR 2021) - "Background: ABBV-3373 is a novel antibody drug conjugate composed of adalimumab (ADA) linked to a proprietary and highly potent glucocorticoid receptor modulator (the anti-inflammatory payload) currently evaluated for the treatment of rheumatoid arthritis (RA). These data demonstrate the clinical efficacy of ABBV-3373 and its potential to provide improved outcomes for RA pts compared to ADA. The safety profile of ABBV-3373 was generally similar to ADA."

Clinical • P2a data • Immunology • Infectious Disease • Inflammatory Arthritis • Pneumonia • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P2; N=48; Active, not recruiting; Sponsor: AbbVie; Recruiting ➔ Active, not recruiting; Trial completion date: Jun 2021 ➔ Dec 2023

Clinical • Enrollment closed • Trial completion date • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P1; N=45; Recruiting; Sponsor: AbbVie; Trial primary completion date: Dec 2020 ➔ Jun 2021

Clinical • Trial primary completion date • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P1; N=45; Recruiting; Sponsor: AbbVie; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P2; N=45; Recruiting; Sponsor: AbbVie; Phase classification: P1 ➔ P2; Trial completion date: Aug 2020 ➔ Jun 2021; Trial primary completion date: Aug 2020 ➔ Dec 2020

Clinical • Phase classification • Trial completion date • Trial primary completion date • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P1; N=45; Not yet recruiting; Sponsor: AbbVie

Clinical • New P1 trial • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P1; N=45; Recruiting; Sponsor: AbbVie; Trial completion date: Jun 2021 ➔ Aug 2020; Trial primary completion date: Jun 2021 ➔ Aug 2020

Clinical • Trial completion date • Trial primary completion date • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P2; N=48; Completed; Sponsor: AbbVie; Recruiting ➔ Completed; N=133 ➔ 48

Clinical • Enrollment change • Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ABBV-3373 in Participants With Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P2; N=133; Recruiting; Sponsor: AbbVie; Active, not recruiting ➔ Recruiting; N=48 ➔ 133; Trial completion date: Dec 2023 ➔ Nov 2020; Trial primary completion date: Dec 2020 ➔ Jun 2020

Clinical • Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Immunology • Rheumatoid Arthritis • Rheumatology • CRP

"ABBV-3373, anti-THF antibody conjugated for rheumatoid arthritis @AbbVie. First results in humans. #ASCPT2021" (@Cortellis)

Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology