Database for
Therapeutic Antibodies
Therapeutic Antibodies
| Entry ID | 347 |
| INN | None |
| Status | Clinical |
| Drug code(s) | AZD0486, TNB-486 |
| Brand name | None |
| mAb sequence source | mAb human |
| General Molecular Category | Bispecific |
| Format, general category | Fragment-Fc |
| Format details | 1+1 asymmetric, VH-CH2-CH3 x Fab-CH2-CH3 |
| Isotype (Fc) | IgG4 |
| Light chain isotype | kappa |
| Linker | None |
| Ave. DAR | None |
| Conjugated/fused moiety | None |
| Discovery method/technology | Transgenic rat (OmniFlic), human heavy chain sdAb (UniRats) |
| Target(s) | CD19, CD3 |
| Indications of clinical studies | Follicular lymphoma, Non-Hodgkin's lymphoma |
| Primary therapeutic area | Cancer |
| Most advanced stage of development (global) | Phase 3 |
| Status | Active |
| Start of clinical phase (IND filing or first Phase 1) | August 01, 2020 |
| Start of Phase 2 | |
| Start of Phase 3 | August 07, 2024 |
| 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 | AstraZeneca |
| Licensee/Partner | None |
| Comments about company or candidate | NCT06549595 Phase 3 in FL start in Aug 2024. NCT06526793 Phase 2 study in NHL due to start in Oct 2024. NCT06137118 Phase 1/2 started in Dec 2023. July 2022: AstraZeneca announced an agreement to acquire TeneoTwo, Inc. (TeneoTwo), including its Phase I clinical-stage CD19/CD3 T-cell engager, TNB-486, currently under evaluation in relapsed and refractory B-cell non-Hodgkin lymphoma1. Oct 2021: Three previous affiliates of Teneobio, including TeneoTwo, Inc. (TNB-486, anti-CD19xCD3), TeneoFour, Inc. (anti-CD38 enzyme inhibitor TNB-738) and TeneoTen, Inc. (anti-HBVxCD3) were not part of the acquisition by Amgen of Teneobio. NCT04594642 in NHL started in Feb 2021. Oct. 01, 2020: Teneobio, Inc. and its affiliate TeneoTwo, Inc. announced today that their investigational new drug application (IND) for TNB-486, a bispecific T-cell engaging antibody for the treatment of B-Cell Non-Hodgkin’s lymphoma (B-NHL) was cleared for the initiation of Phase I clinical studies by the US Food and Drug Administration (FDA) on September 30, 2020. TNB-486 is a fully human bispecific antibody that binds CD19 with one arm and incorporates a unique anti-CD3 on the other. In preclinical studies, TNB-486 induced T-cell dependent killing of CD19-positive B-cell leukemia and lymphoma cells while inducing minimal cytokine secretion, a feature that could limit immune mediated toxicities while retaining cytotoxic activity. |
| Full address of company | Cambridge, United Kingdom Europe United Kingdom https://www.astrazeneca.com/our-company/contact-us.html |
TNB-486 is a novel CD19xCD3 bispecific T-cell engager (TCE) that incorporates a unique anti-CD3 moiety designed to reduce cytokine release syndrome by binding to CD3 on T-cells with low affinity. A silenced IgG4 backbone confers a long half-life suitable for intermittent administration. TNB-486 is a fully human bispecific antibody composed by a heavy chain only arm targeting CD19 and a fixed-light-chain arm targeting CD3 joined with knob in a hole technology with a silenced IgG4 Fc https://doi.org/10.1080/19420862.2021.1890411 In preclinical studies, TNB-486 induced T-cell dependent killing of CD19-positive B-cell leukemia and lymphoma cells while inducing minimal cytokine secretion, a feature that could limit immune mediated toxicities while retaining cytotoxic activity.
| Anticipated events | None |
| Factor(s) contributing to discontinuation | None |