Teclistamab Approved Bispecific

Antibody Information

Entry ID	86
INN	Teclistamab
Status	Approved
Drug code(s)	JNJ-64007957
Brand name	TECVAYLI
mAb sequence source	mAb chimeric/human
General Molecular Category	Bispecific
Format, general category	Full length Ab
Format details	1+1 asymmetric, Duobody
Isotype (Fc)	IgG4
Light chain isotype	lambda
Linker	None
Ave. DAR	None
Conjugated/fused moiety	None
Discovery method/technology	Transgenic (OmniRat technology) and DuoBody technology

Therapeutic information

Target(s)	BCMA, CD3
Indications of clinical studies	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)	Approved EU, US, Japan, China, Australia, Russia
Status	Active
Start of clinical phase (IND filing or first Phase 1)	March 15, 2017
Start of Phase 2	September 17, 2020
Start of Phase 3	October 15, 2021
Date BLA/NDA submitted to FDA	December 28, 2021
Year of first approval (global)	2022
Date of first US approval	October 25, 2022
INN, US product name	Teclistamab, teclistamab-cqyv
US or EU approved indications	US: First approval for Multiple Myeloma (TECVAYLI is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody) (as of first label in 2022 and as of May 28, 2024 label). EU: First approval for Multiple Myeloma (TECVAYLI is indicated as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.) (as per EPAR-Product Information last updated on October 21, 2024)

Company information

Company	Janssen Research & Development
Licensee/Partner	Genmab
Comments about company or candidate	Submission of MAA announced Jan 31, 2022; approved on August 3 NCT05083169 Phase 3 due to start on Oct 15, 2021. June 2021: Teclistamab was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration for the treatment of relapsed or refractory multiple myeloma. This mAb also received PRIME (PRIority MEdicines) designation from the European Medicines Agency (EMA) earlier this year. November 2020: Teclistamab Received FDA Orphan Drug Designation for Treatment of Multiple Myeloma NCT04557098 Phase 2 study in multiple myeloma started in Sep 2020. May 18, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson announced today results reported for the first time from a Phase 1 first-in-human dose escalation study (NCT03145181) of teclistamab (JNJ-7957), an investigational bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3 receptors on T-cells in the treatment of patients with relapsed or refractory multiple myeloma. Initial results suggest a manageable safety profile across all teclistamab doses evaluated. Investigators reported that patients achieved deep responses which persisted, including some minimal residual disease (MRD)-negative complete responses (CR) at 10-6, with one durable beyond 12 months.1 The data will be featured during the American Society of Clinical Oncology (ASCO) Virtual Scientific Program as an oral presentation on Saturday, May 30 at 1:00 p.m. ET (Abstract #100). NCT04108195 Phase 1b in MM started in Feb 2020. Phase 1 NCT03145181 in MM patients started in May 2017 still recruiting as of Aug 2019; listed in Janssen pipeline dated July 16, 2019. IND filing by Janssen affiliate CAN Development LLC announced in March 2017 by Ligand Pharma Inc.
Full address of company	1125 Trenton-Harbourton Road Titusville, NJ 08560 North America United States of America https://www.janssen.com/us/contact-us

Description/comment

JNJ-64007957 or teclistamab is a DuoBody antibody generated by controlled Fab-arm exchange of a BCMA antibody and a CD3 parental antibody derived from SP34 clone following the method developed by Genmab. For the BCMA arm, OmniRats (Open Monoclonal Technology) were immunized with BCMA-Fc recombinant protein (R&D Systems) to generate anti-BCMA antibodies, and hits were re-cloned on a relatively silent IgG4-PAA scaffold. The Fc portion of teclistamab is engineered with the following mutations: F405L-R409K x WT (R409) (Hetero HH, heterodimerization) both chains: S228P (hinge stabilization) and F234A, L235A (reduced Fc effector function). https://doi.org/10.1182/bloodadvances.2020002393

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	None