ABBV-154 / AbbVie - LARVOL DELTA

Development of a scalable route to an immunology ADC drug-linker for ABBV-154 (ACS-Fall 2024) - "A scalable route has been developed to the bromoacetamide glucocorticoid drug-linker used in conjugation with the monoclonal antibody (mAb) adalimumab to produce antibody-drug conjugate ABBV-154. Notably, the final step involves a global acidic deprotection of three t-butyl protecting groups that proceeds through several intermediates and is complicated by acetal epimerization. This complex reaction was initially optimized in a batch setup, but scaling issues prompted the development of a flow process with an impinging jet mixing element."

Investigational agents for polymyalgia rheumatica treatment: assessing the critical needs for future development. (PubMed, Expert Opin Investig Drugs) - "Currently, there are 12 ongoing clinical trials exploring potential treatments such as leflunomide, low-dose IL-2, rituximab, abatacept, secukinumab, Janus kinase inhibitors, and selective inhibitors like SPI-62 and ABBV 154...The development of internationally accepted definitions for remission and relapse is urgently needed. Early referral strategies to specialist settings would improve disease stratification and personalized treatment."

Journal • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatoid Arthritis • Rheumatology • IL6R

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

Discovery of ABBV-154, an anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody-Drug Conjugate (iADC). (PubMed, J Med Chem) - "Additionally, BrAc also offers multiple benefits over maleimide, especially with respect to homogeneity of the ADC structure. In combination with a short, hydrophilic linker and phosphate prodrug on the payload, this afforded a stable ADC (ABBV-154) with the desired properties to enable long-term stability to facilitate subcutaneous self-administration."

Journal

AIM-RA: Study to Evaluate Adverse Events and Change in Disease Activity in Participants Between 18 to 75 Years of Age Treated With Subcutaneous (SC) Injections of ABBV-154 for Moderately to Severely Active Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P2 | N=473 | Terminated | Sponsor: AbbVie | Trial completion date: Feb 2026 ➔ Aug 2023 | Active, not recruiting ➔ Terminated; Business decision

Adverse events • Trial completion date • Trial termination • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

AIM-PMR: A Study to Evaluate the Change in Disease State and Adverse Events in Adult Participants With Polymyalgia Rheumatica (PMR) Dependent on Glucocorticoid Treatment, Receiving Subcutaneous Injections of ABBV-154 (clinicaltrials.gov) - P2 | N=181 | Terminated | Sponsor: AbbVie | Trial completion date: Apr 2024 ➔ Jul 2023 | Active, not recruiting ➔ Terminated; Business Decision

Adverse events • Trial completion date • Trial termination • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology

AIM-CD: A Study to Evaluate Adverse Events and Change in Disease Activity in Participants Between 18 to 75 Years of Age Treated With Intravenous (IV) Infusion and Subcutaneous (SC) Injections of ABBV-154 for Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P2 | N=176 | Terminated | Sponsor: AbbVie | N=265 ➔ 176 | Trial completion date: Jul 2026 ➔ Jul 2023 | Recruiting ➔ Terminated | Trial primary completion date: Jan 2024 ➔ Jul 2023; Strategic considerations

Adverse events • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

"@abbvie is shutting down development of Humira-steroid antibody-drug congugate (Abbv154) after interim analysis. Very disappointing news for our hopes of novel combo strategies." (@ShomronH)

Study to Assess Adverse Events and Compare How Two Subcutaneous ABBV-154 Injection Formulations Move Through the Body of Adult Healthy Participants (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Adverse events • Trial completion

Discovery of ABBV-154, an anti-TNF glucocorticoid receptor modulator immunology antibody drug conjugate (iADC) (ACS-Sp 2023) - "The design considerations for an Immunology Antibody Drug Conjugate (iADC) need to enable self-administration by the patient via subcutaneous injection and support chronic dosing. This talk will discuss aspects of drug-linker design in conjunction with the screening assays that were used for efficacy, safety and ADC property assessment to identify ABBV-154."

Immunology • Oncology

AIM-PMR: A Study to Evaluate the Change in Disease State and Adverse Events in Adult Participants With Polymyalgia Rheumatica (PMR) Dependent on Glucocorticoid Treatment, Receiving Subcutaneous Injections of ABBV-154 (clinicaltrials.gov) - P2 | N=181 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology

Study to Assess Adverse Events and Compare How Two Subcutaneous ABBV-154 Injection Formulations Move Through the Body of Adult Healthy Participants (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed

AIM-RA: Study to Evaluate Adverse Events and Change in Disease Activity in Participants Between 18 to 75 Years of Age Treated With Subcutaneous (SC) Injections of ABBV-154 for Moderately to Severely Active Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P2 | N=473 | Active, not recruiting | Sponsor: AbbVie | Trial completion date: May 2024 ➔ Feb 2026 | Trial primary completion date: Nov 2022 ➔ Aug 2022

Adverse events • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

ABBV-154: Data from P2 AIM-CD trial (NCT05068284) for Crohn’s disease in 2024 (AbbVie) - Q3 2022 Results

P2 data • Crohn's disease • Immunology • Inflammatory Bowel Disease

Study to Assess Adverse Events and Compare How Two Subcutaneous ABBV-154 Injection Formulations Move Through the Body of Adult Healthy Participants (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open

Study to Assess Adverse Events and Compare How Two Subcutaneous ABBV-154 Injection Formulations Move Through the Body of Adult Healthy Participants (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: AbbVie

Adverse events • New P1 trial

AIM-CD: A Study to Evaluate Adverse Events and Change in Disease Activity in Participants Between 18 to 75 Years of Age Treated With Intravenous (IV) Infusion and Subcutaneous (SC) Injections of ABBV-154 for Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P2 | N=265 | Recruiting | Sponsor: AbbVie | Trial completion date: Feb 2025 ➔ Jul 2026

Adverse events • Trial completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

AIM-CD: A Study to Evaluate Adverse Events and Change in Disease Activity in Participants Between 18 to 75 Years of Age Treated With Intravenous (IV) Infusion and Subcutaneous (SC) Injections of ABBV-154 for Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P2 | N=265 | Recruiting | Sponsor: AbbVie | Trial completion date: Jul 2026 ➔ Feb 2025

Adverse events • Trial completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

AIM-PMR: A Study to Evaluate the Change in Disease State and Adverse Events in Adult Participants With Polymyalgia Rheumatica (PMR) Dependent on Glucocorticoid Treatment, Receiving Subcutaneous Injections of ABBV-154 (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: AbbVie | Trial completion date: Sep 2023 ➔ Apr 2024 | Trial primary completion date: Dec 2022 ➔ Jul 2023

Adverse events • Trial completion date • Trial primary completion date • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology

AIM-CD: A Study to Evaluate Adverse Events and Change in Disease Activity in Participants Between 18 to 75 Years of Age Treated With Intravenous (IV) Infusion and Subcutaneous (SC) Injections of ABBV-154 for Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P2 | N=265 | Recruiting | Sponsor: AbbVie | Trial completion date: Apr 2025 ➔ Jul 2026

Adverse events • Trial completion date • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

AIM-RA: Study to Evaluate Adverse Events and Change in Disease Activity in Participants Between 18 to 75 Years of Age Treated With Subcutaneous (SC) Injections of ABBV-154 for Moderately to Severely Active Rheumatoid Arthritis (RA) (clinicaltrials.gov) - P2 | N=473 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

AbbVie (ABBV) Q4 2021 Earnings Call Transcript (The Motley Fool) - "We also have regulatory applications under review for Rinvoq in ulcerative colitis, ankylosing spondylitis, and non-radiographic axial SpA. We expect an FDA approval decision next month for ulcerative colitis, in the second quarter for ankylosing spondylitis, and in the fourth quarter for non-radiographic axial SpA. In Europe, we anticipate approval decisions for ulcerative colitis and non-radiographic axial SpA in the second half of the year....We expect to see results from the second Phase 3 Crohn's induction study and from the maintenance study in the first half of this year with regulatory submissions anticipated in the second half of 2022....We also have regulatory applications under review for Skyrizi in Crohn's disease with approval decisions expected in the U.S. next month and in Europe later this year. Our anti-TNF steroid ADC, ABBV-154....We also expect to see Phase 2 proof-of-concept data in PMR and Crohn's disease in 2023."

European regulatory • P2 data • P3 data • Regulatory • sNDA • Crohn's disease • Immunology • Inflammation • Inflammatory Bowel Disease • Spondylarthritis • Ulcerative Colitis

Active development of Crohn's disease treatment … Approval of 3 clinical trials simultaneously [Google translation] (Health Korea News) - "...the Ministry of Food and Drug Safety approved three clinical trials targeting Crohn's disease, including the clinical trials of Janssen Korea's Guselkumab, AbbVie Korea's ABBV-154, and Seoul Asan Medical Center's Remsima....Janssen Korea will conduct a phase 3 clinical trial for 'Guselkumab' (product name Tremfya)...The total number of subjects was 318, and the number of domestic subjects was 24. Implementing institutions are Pusan ​​National University Hospital, Ajou University Hospital, Wonju Severance Hospital, Yeungnam University Hospital, and Kangbuk Samsung Hospital...AbbVie Korea is conducting a phase 2 clinical trial for 'ABBV-154'...A total of 265 subjects and 15 domestic subjects were reported. Implementing institutions are Samsung Seoul Hospital, Asan Medical Center, and Catholic Daejeon St. Mary's Hospital."

New P2 trial • New P3 trial • Crohn's disease • Immunology • Inflammatory Bowel Disease

ABBV-154: Early proof of concept data from P2 AIM-CD trial (NCT05068284) for Crohn’s disease in 2023 (40th Annual J.P. Morgan Healthcare Conference (Virtual Meeting), AbbVie)

P2 data • Crohn's disease • Inflammatory Bowel Disease

ABBV-154: Early proof of concept data from P2 AIM-CD trial (NCT05068284) for Crohn’s disease in 2023 (40th Annual J.P. Morgan Healthcare Conference (Virtual Meeting), AbbVie)

P2 data • Crohn's disease • Inflammatory Bowel Disease