afimetoran (BMS-986256) / BMS, Beeline Medicines - LARVOL DELTA

Afimetoran, an Oral Equipotent Dual Antagonist of Toll-Like Receptor 7 (TLR7) and TLR8, in Combination with an Anti-TNF Results in Increased Efficacy in a Collagen-Induced Arthritis Model (ACR Convergence 2026) - No abstract available

Clinical • Combination therapy • Immunology • Rheumatology • TLR7 • TLR8

TLR7/8 Blockade by BMS-905, a Structural Analog of Afimetoran, Drives Transcriptional Rewiring of Kidney Inflammation in a Mouse Model of SLE (ACR Convergence 2026) - No abstract available

Preclinical • Inflammation • Inflammatory Arthritis • TLR7

Beeline Medicines Announces Positive Topline Results from Global Phase 2 Study of Afimetoran in Systemic Lupus Erythematosus (GlobeNewswire) - "Study met its primary endpoint, with afimetoran demonstrating higher SRI-4 response rates versus placebo at Week 48 (p-value <0.001 across all dose groups); Secondary endpoints demonstrated improvements consistent with the primary endpoint findings; Afimetoran was generally well tolerated, with a safety profile consistent with previous Phase 1 clinical trial experience and no new safety signals observed"

P2 data • Systemic Lupus Erythematosus

Development of Kilogram-Scale Electrochemical Ni-Catalyzed Cross Electrophile Coupling in Flow. (PubMed, Org Process Res Dev) - "In this work, we report a kilogram-scale flow electrochemical Ni-catalyzed cross-electrophile coupling (XEC) to prepare a key intermediate in the synthesis of the toll-like receptor (TLR) 7/8 inhibitor afimetoran...Key design aspects of our custom parallel-plate reactor are discussed that enabled kilogram-scale synthesis with a single electrode stack. This report showcases that with proper reaction engineering, electrochemical Ni-catalyzed XEC is a viable alternative to existing Pd-catalyzed cross-coupling methods."

Journal

Beeline Medicines…announced the closing of a $126.3 million Series A extension, bringing its total Series A financing round to $426.3 million. (GlobeNewswire) - "The proceeds from the upsized Series A will support the initiation of several clinical studies across the Company’s broad immunology portfolio, including planned pivotal development of its lead program, afimetoran, in lupus...The Company has commenced pivotal development preparations in lupus ahead of the expected Phase 2 readout of afimetoran in systemic lupus erythematosus in the second half of 2026...Over the next 12 months, the Company expects to initiate additional clinical trials across its pipeline, including for lomedeucitinib...and BLN-481 (formerly BMS-986481)."

Financing • P2 data • Pipeline update • Atopic Dermatitis • Immunology • Inflammation • Systemic Lupus Erythematosus

A Study to Assess the Effect of Famotidine on the Drug Levels of Afimetoran in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed | N=76 ➔ 32

Enrollment change • Trial completion

Beeline Medicines formally launched Wednesday with $300 million in series A financing and a ready-made pipeline of immunology assets in-licensed from Bristol Myers Squibb that it hopes will help reshape how autoimmune and inflammatory diseases are treated. (Firstwordpharma Press Release) - "Beeline's lead programme, afimetoran (BMS-986256), is a once-daily oral small molecule designed to inhibit toll-like receptors 7 and 8 (TLR7/8), components of the innate immune system linked to the aberrant activation seen in systemic lupus erythematosus...'we expect several additional clinical trials to start across our pipeline over the next 12 months.'...Beyond afimetoran, the pipeline also includes an IL-2-CD25 fusion protein dubbed BMS-986326...The company is also working on a once-daily oral TYK2 inhibitor called lomedeucitinib (BMS-986322)....Additionally, the pipeline includes two IND-stage biologics, BMS-986481 and BMS-986498..."

Financing • New trial • Atopic Dermatitis • Immunology • Psoriasis • Systemic Lupus Erythematosus

Disease Activity Modulation and Pharmacodynamic Biomarkers Observed upon Afimetoran Treatment in Patients with Cutaneous Lupus Erythematosus (LUPUS 2026) - P1b | "This decreased presence of subsets of DCs and monocytes in afimetoran-treated patients was further demonstrated by WB flow cytometry. Although PD effects were seen in the lesional skin of both Rs and NRs, the reduction in the immune cells signature scores was more pronounced in Rs.Abstract PO:02:027 Figure 1Mean changes from baseline in CLASI-A scores for Rs versus NRs and placebo-treated subjectsAbstract PO:02:027 Figure 2WB transcriptional signature enrichment scores at baseline versus Wk 16 Conclusions In patients with CLE, afimetoran-treated patients that achieved CLASI-50 showed a distinct profile from NRs, based on the magnitude and duration of clinical improvements, robust PD effects in blood and lesional skin, and the reduced presence of activated DCs and monocytes in the lesional skin."

Biomarker • Clinical • PK/PD data • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • TLR7

Structural and immunological impacts of TOLLIP nsSNPs: A computational biology approach to drug discovery and immune system modulation. (PubMed, PLoS One) - "Notably, molecular docking and dynamic simulations revealed that T40M and R200C variants significantly enhance binding affinity for the Afimetoran. Additionally, molecular dynamics (MD) simulations highlighted the altered flexibility, solvent accessibility and modified hydrogen bonds in mutant proteins structure, suggesting potential mechanisms for functional disruption. Collectively, these findings elucidate the structural and functional consequences of nsSNPs on TOLLIP protein stability, and provide a rational base for targeted therapeutic strategies in immune related diseases."

IO biomarker • Journal

Bristol Myers Squibb and Bain Capital Create New Company Dedicated to Developing Innovative Immunology Therapies that Address the Unmet Medical Needs of Patients (The Globe and Mail) - "Bristol Myers Squibb...and Bain Capital today announced the creation of a new independent biopharmaceutical company ('NewCo') focused on developing new therapies for autoimmune diseases that address significant unmet needs of patients. The newly formed company launches with five immunology assets in-licensed from BMS and a $300 million financing commitment that was led by Bain Capital...The NewCo has a broad pipeline consisting of three clinical-stage and two Phase 1-ready investigational medicines that each target promising mechanisms in autoimmune diseases. The most advanced assets in the NewCo’s portfolio are afimetoran, an oral, potential best-in-class TLR7/8 inhibitor that is currently being studied in a Phase 2 clinical trial for systemic lupus erythematosus (SLE), and BMS-986322, an oral TYK2 inhibitor, which successfully established proof-of-concept in a positive plaque psoriasis Phase 2 trial..."

Commercial • Atopic Dermatitis • Psoriasis • Systemic Lupus Erythematosus

Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Afimetoran, a Toll-Like Receptor 7 and 8 Inhibitor, in Patients With Cutaneous Lupus Erythematosus: A Phase 1b Randomized, Double-Blind, Placebo-Controlled Study. (PubMed, ACR Open Rheumatol) - P1b | "These findings support afimetoran's potential as a once daily oral treatment for patients with CLE and suggest a possibly substantial therapeutic benefit, warranting further clinical investigation of afimetoran for lupus."

Clinical • IO biomarker • Journal • P1 data • PK/PD data • Cutaneous Lupus Erythematosus • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Novel Coronavirus Disease • TLR7

In Vitro and In Vivo Evidence of the Steroid-Sparing Potential of Afimetoran, an Equipotent Toll-Like Receptor 7/8 Dual Antagonist (EULAR 2025) - "These translational and preclinical data further demonstrate that afimetoran can block TLR7/8 and has steroid-sparing potential in patients with SLE, lupus nephritis, and other autoimmune conditions requiring immunosuppressant therapy."

IO biomarker • Preclinical • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus • ANXA5

A Study to Assess the Effect of Famotidine on the Drug Levels of Afimetoran in Healthy Participants (clinicaltrials.gov) - P1 | N=76 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Apr 2024 ➔ Mar 2026 | Trial primary completion date: Mar 2024 ➔ Mar 2026

Trial completion date • Trial primary completion date

In Vitro and In Vivo Evidence of the Steroid-Sparing Potential of Afimetoran, an Equipotent Toll-Like Receptor 7/8 Dual Antagonist (ACR Convergence 2024) - "These translational and preclinical data further demonstrate that afimetoran can block TLR7/8 and has steroid-sparing potential in patients with SLE, lupus nephritis, and other autoimmune conditions requiring immunosuppressant therapy."

IO biomarker • Preclinical • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Sjogren's Syndrome • ANXA5

A Study to Assess the Effect of Phenytoin on the Drug Levels of Afimetoran and the Effect of Afimetoran on the Drug Levels of Midazolam (clinicaltrials.gov) - P1 | N=65 | Completed | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Completed | N=50 ➔ 65 | Trial completion date: Oct 2023 ➔ Apr 2024 | Trial primary completion date: Oct 2023 ➔ Apr 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date

Design and synthesis of heteroarene-based antagonists of toll-like receptors 7 and 8 (TLR7/8) (ACS-Fall 2024) - "Our program to identify small molecule dual antagonists of TLR7/8 resulted in the discovery of afimetoran, an indole-based antagonist currently in clinical trials for lupus...In vivo performance will be described for select compounds. This presentation will also describe my personal journey of being an out, gay professional from entry level into leadership roles and my efforts to advocate for LGBTQ visibility in chemistry."

Dermatology • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Psoriasis • Rheumatoid Arthritis • Rheumatology • TLR7

Optimization of antagonists of toll-like receptors 7 and 8 (TLR7/8) leading to the discovery of afimetoran (ACS-Fall 2024) - "The successful assessment of afimetoran in patients with cutaneous lupus (CLE) marked the first clinical validation of this innovative lupus treatment approach. This positive evaluation supports the ongoing trial of afimetoran in patients with systemic lupus (SLE)."

Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • TLR7

PHARMACODYNAMIC EFFECTS AND EXPLORATORY EFFICACY OF AFIMETORAN, A TLR7/8 INHIBITOR, IN PATIENTS WITH CUTANEOUS LUPUS ERYTHEMATOSUS (EULAR 2024) - P1b | "In pts with CLE, afimetoran was safe and well tolerated compared with PBO, and demonstrated treatment efficacy and potent pharmacodynamic effects early, throughout, and beyond the treatment period. The positive impact of afimetoran on the molecular disease profile and its potent pharmacodynamic and clinical effects suggest potentially substantial therapeutic benefit for patients with CLE."

Clinical • IO biomarker • PK/PD data • Cutaneous Lupus Erythematosus • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Novel Coronavirus Disease • Systemic Lupus Erythematosus • CCL3 • IFNG • IL18 • IL6 • TLR7 • TLR8 • TNFA

A Study Evaluating the Efficacy and Safety of Afimetoran Compared With Placebo in Participants With Active Systemic Lupus Erythematosus (SLE) (clinicaltrials.gov) - P2 | N=268 | Recruiting | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Recruiting | Trial completion date: May 2026 ➔ Apr 2029 | Trial primary completion date: May 2025 ➔ Mar 2026

Enrollment open • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Study Evaluating the Efficacy and Safety of Afimetoran Compared With Placebo in Participants With Active Systemic Lupus Erythematosus (SLE) (clinicaltrials.gov) - P2 | N=268 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Safety, Tolerability, and Exploratory Efficacy of Afimetoran, a TLR7/8 Inhibitor, in Patients with Cutaneous Lupus Erythematosus: A Phase 1b Randomized, Double-Blind, Placebo-Controlled Study (ACR Convergence 2023) - P1b, P2 | "Afimetoran demonstrated a favorable safety profile and was well tolerated vs placebo in patients with CLE. These results provide the first clinical evidence to suggest that afimetoran may offer a clinical benefit as indicated by an early and sustained clinical response vs placebo as measured by CLASI-A. As such, these results support the continued clinical investigation of afimetoran in lupus, including the ongoing phase 2b study in SLE (NCT04895696)."

Clinical • Late-breaking abstract • P1 data • Cutaneous Lupus Erythematosus • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Novel Coronavirus Disease • TLR7 • TLR8

Steroid-sparing Effects of Afimetoran (BMS-986256), an Equipotent Toll-like Receptor (TLR)7 and TLR8 Antagonist, in a Lupus Mouse Model (ACR Convergence 2023) - "Afimetoran, alone or in combination with low-dose (1mg/kg) prednisolone, showed robust efficacy in NZB/W mice with moderate disease. Bone marrow pDCs and B cells showed afimetoran-induced reversal of resistance to prednisolone-induced apoptosis. These data confirm that afimetoran has the clinical potential to be steroid sparing."

IO biomarker • Preclinical • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Renal Disease • Systemic Lupus Erythematosus • ANXA5 • LCN2 • TIMP1 • TLR8

Phenoxythiazoline (FTz)-Cobalt(II) Precatalysts Enable C(sp2)-C(sp3) Bond Formation for Key Intermediates in the Synthesis of Toll-like Receptor 7/8 Antagonists. (PubMed, Angew Chem Int Ed Engl) - "An air-stable cobalt(II) precatalyst, (FTz)CoBr(py)3 was synthesized and applied to the cross-coupling of an indole-5-boronic ester nucleophile with a piperidine-4-bromide electrophile that is relevant to the synthesis of reported toll-like receptor (TLR) 7/8 antagonist molecules including afimetoran...Determination of the experimental rate law established a first-order dependence on the cobalt precatalyst and a saturation regime in heterogeneous potassium aryl boronate (apparent zeroth order), supporting turnover-limiting transmetalation and the origin of the observed trends in N-imine substitution. The optimized cobalt precatalyst and reaction conditions were applied to the multigram-scale synthesis of an intermediate used in both the discovery and process routes for toll-like receptor (TLR) 7/8 antagonist molecules."

Journal

A Study to Assess the Effect of Famotidine on the Drug Levels of Afimetoran in Healthy Participants (clinicaltrials.gov) - P1 | N=76 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Assess the Effect of Phenytoin on the Drug Levels of Afimetoran and the Effect of Afimetoran on the Drug Levels of Midazolam (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open