Litifilimab Clinical Naked monospecific

Antibody Information

Entry ID	438
INN	Litifilimab
Status	Clinical
Drug code(s)	BIIB059
Brand name	None
mAb sequence source	mAb humanized
General Molecular Category	Naked monospecific
Format, general category	Full length Ab
Format details	None
Isotype (Fc)	IgG1
Light chain isotype	kappa
Linker	None
Ave. DAR	None
Conjugated/fused moiety	None
Discovery method/technology	None

Therapeutic information

Target(s)	BDCA2
Indications of clinical studies	Cutaneous Lupus Erythematosus, Systemic Lupus Erythematosus
Primary therapeutic area	Immune-mediated / inflammatory disorders

Development stage information

Phase lengths*

*The graph represents early-stage clinical development phase lengths. For molecules approved or under evaluation for marketing authorization in the US is provided a complete overview of all clinical development phase lengths. Phase lengths are calculated from the start of the first in human (FIH) study (Start of clinical phase). “Start of Phase 2” bar represents Phase 1 length (Start of clinical phase to start of Phase 2); “Start of Phase 3” bar represents Phase 1+2 length (Start of clinical phase to start of Phase 3); “Date BLA/NDA submitted” bar represents Phase 1+2+3 length (Start of clinical phase to Date BLA/NDA submitted); and “Date of first US approval” bar represents Phase 1 to first US approval length (Start of clinical phase to Date of first US approval).

Most advanced stage of development (global)	Phase 3
Status	Active
Start of clinical phase (IND filing or first Phase 1)	September 01, 2014
Start of Phase 2	August 15, 2016
Start of Phase 3	May 25, 2021
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 information

Company	Biogen
Licensee/Partner	Royalty Pharma
Comments about company or candidate	Feb 2025: Royalty Pharma will provide up to $250 million over six quarters to Biogen to support the development of litifilimab in exchange for regulatory milestones and mid-single digit royalties on annual worldwide sales. Phase 3 studies NCT06044337 (for Systemic lupus erythematosus) and NCT05352919 (for cutaneous lupus Erythematosus) Phase 3 studies are enrolling by invitation as of November 2024. Phase 2/3 study for Cutaneous lupus erythematosus (NCT05531565) is recruiting as of May 2023; phase 3 studies for Systemic lupus erythematosus (NCT04961567, NCT04895241) are recruiting as of August-November 2024. July 2022 Biogen presentation: Phase 3 study discussed, but no mention of regulatory filings. NCT04895241 and NCT04961567 Phase 3 studies have primary completion dates in 2025. NCT04961567 Phase 3 TOPAZ-2 study started in Aug 2021. NCT04895241 Phase 3 study in SLE started in May 2021. June 17, 2021 I Biogen Inc. (Nasdaq: BIIB) today announced that the first patient has been dosed in the global clinical study, TOPAZ-1. The Phase 3 study will evaluate the clinical efficacy and assess the safety of BIIB059, a first in-class, humanized IgG1 monoclonal antibody (mAb) targeting blood dendritic cell antigen 2 (BDCA2), as compared to placebo, in participants with active systemic lupus erythematosus (SLE). Nov 2020: The LILAC study (part A) met its primary endpoint and a key secondary endpoint (SRI-4). These results, and the observed safety profile, support the continued development of BIIB059 in SLE. Dec 2019: The Phase 2 LILAC study met its primary endpoints, demonstrating statistically significant reduction of disease activity in patients with CLE and SLE who received BIIB059 compared to placebo. Listed as Phase 2 in Biogen pipeline accessed Aug 12, 2019. March 2019: Results of NCT02106897 published (Furie et al. Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus. J Clin Invest. 2019 Mar 1;129(3):1359-1371. doi: 10.1172/JCI124466). NCT02847598 Phase 2 study in SLE still recruiting as of July 2018. NCT02106897 Phase 1 study complete. Target is blood dendritic cell antigen 2 (BDCA2). Blood dendritic cell antigen 2 (BDCA2) is a C-type lectin expressed on human plasmacytoid dendritic cells (pDCs) (Dzionek et al, J. Immunol, 165:6037-6046 (2000)), a specialized population of bone marrow-derived cells that secrete type I interferons (IFNs) in response to toll-like receptor (TLR) ligands. BDCA2 consists of a single extracellular carbohydrate recognition domain (CRD), which belongs to the type II C-type lectin group, at its C-terminus, a transmembrane region, and a short cytoplasmic tail at its N- terminus that does not harbor a signaling motif. BDCA2 transmits intracellular signals through an associated transmembrane adaptor, the FcsRIy, and induces a B cell receptor (BCR)-like signaling cascade.
Full address of company	Cambridge, MA 02142, United States North America United States of America https://www.biogen.com/company/contact-us.html

Description/comment

BIIB059 is a humanized IgG1 mAb that specifically recognizes blood DC antigen 2 (BDCA2), which is uniquely expressed on the surface of human pDCs (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391094/)

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	None