Linvoseltamab Regulatory review Bispecific

Antibody Information

Entry ID	1735
INN	Linvoseltamab
Status	Regulatory review
Drug code(s)	REGN5458
Brand name	Lynozyfic
mAb sequence source	mAb human
General Molecular Category	Bispecific
Format, general category	Full length Ab
Format details	None
Isotype (Fc)	IgG4
Light chain isotype	kappa
Linker	None
Ave. DAR	None
Conjugated/fused moiety	None
Discovery method/technology	VelociBi™ platform

Therapeutic information

Target(s)	BCMA, CD3
Indications of clinical studies	Chronic Kidney Disease, Multiple myeloma
Primary therapeutic area	Cancer

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)	Regulatory review EU, US
Status	Active
Start of clinical phase (IND filing or first Phase 1)	January 02, 2019
Start of Phase 2	August 15, 2022
Start of Phase 3	October 15, 2023
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	Regeneron Pharmaceuticals
Licensee/Partner	None
Comments about company or candidate	Feb 28, 2025: The CHMP recommended granting a conditional marketing authorisation for Lynozyfic (linvoseltamab) for the treatment of patients with relapsed and refractory multiple myeloma. Feb 2025: Resubmission of BLA announced; FDA decision expected by July 10, 2025 August 20, 2024 I Regeneron Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for the Biologics License Application (BLA) for linvoseltamab in relapsed/refractory (R/R) multiple myeloma (MM) that has progressed after at least three prior therapies. Feb. 02, 2024: Regeneron Pharmaceuticals, Inc. announced that the European Medicines Agency (EMA) has accepted for review the Marketing Authorization Application (MAA) for linvoseltamab to treat adult patients with relapsed/refractory (R/R) multiple myeloma (MM) who have progressed after at least three prior therapies. NCT05730036 Phase 3 started in Sep 2023. August 2023 presentation: Linvoseltamab (BCMAxCD3) – Updated pivotal Phase 2 data presented at ASCO 2023; Phase 3 study to initiate in 3Q23; received Fast-Track designation from FDA; BLA planned in 4Q23 (https://investor.regeneron.com/static-files/a73a7d9c-591d-43e4-905f-6851ac1ff04e). May 25, 2023 press release "Updated Linvoseltamab (BCMAxCD3) Data from Pivotal Trial Demonstrates Early, Deep and Durable Responses in Patients with Heavily Pre-treated Multiple Myeloma" https://investor.regeneron.com/news-releases/news-release-details/updated-linvoseltamab-bcmaxcd3-data-pivotal-trial-demonstrates . "the LINKER-MM1 trial will form the basis of planned submissions to regulatory authorities, including to the U.S. Food and Drug Administration (FDA) later this year" 2023 FDA submission expected (https://investor.regeneron.com/static-files/dbe7aad3-8aff-483f-9366-fa1678d7b738) NCT05730036 Phase 3 due to start in May 2023. June 6 2022: FDA grants orphan drug designation for multiple myeloma Listed as Phase 2 in Regeneron pipeline dated May 2021; https://investor.regeneron.com/static-files/e90481f9-321f-4a55-804e-1d6ce4557112. NCT03761108 Phase 1/2 study in MM started in Jan 2019. REGN5458 is a human bispecific antibody that binds to BCMA and CD3. In vitro, REGN5458 efficiently activates T cells and induces polyclonal T cell killing of myeloma cell lines with a range of BCMA cell-surface densities, and also induces cytotoxicity of primary human plasma cells. 2018 ASH annual meeting (Dec), abstract 1944 REGN5458, a Bispecific BCMAxCD3 T Cell Engaging Antibody, Demonstrates Robust In Vitro and In Vivo Anti-Tumor Efficacy in Multiple Myeloma Models, Comparable to That of BCMA CAR T Cell.
Full address of company	Tarrytown, New York, United States North America United States of America https://www.regeneron.com/

Description/comment

REGN5458 is a human bispecific antibody that binds to BCMA and CD3. REGN5458 and REGN5459 were invented using Regeneron's next generation VelocImmune® "human antibody mouse" technology, together with its VelociBi™ platform. These allow for the creation of bispecific antibodies that closely resemble natural human antibodies with no linkers or artificial sequences.
Hetero H, cL. Hetero HH: WT x H435R-Y436F (limits binding to Protein A, purification); HL-pairing: cL; both chains: E233P, F234V, L235A, G236del (Fc-silencing)

Additional information

Anticipated events	Approval anticipated - FDA decision expected by July 10, 2025; EC decision by end of April 2025
Factor(s) contributing to discontinuation	None