Toviblideg (BMS-986458) is a highly selective, orally active cereblon-based BCL6 PROTAC degrader and antitumor agent. Toviblideg selectively degrades BCL6 by binding cereblon to the BTB domain of BCL6, thereby regulating the cell cycle, antiproliferative and interferon signaling pathways, and upregulating the expression and distribution of CD20. Toviblideg modulates the phenotype of follicular helper T cells and reduces circulating tumor DNA levels. The combination of Toviblideg with CD20xCD3 bispecific antibody also enhances the efficiency of T cell tumor infiltration and expansion. Toviblideg induces regression of BCL6-positive tumors and prolongs survival, and it is suitable for research related to B-cell non-Hodgkin lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, and relapsed/refractory lymphoma [1] [2] [3]. (Pink: BCL6 ligand; Blue: Cereblon ligand; Black: linker ).
In Vivo, Toviblideg (BMS-986458) phenotypically modulates lymph-resident Tfh populations in immunocompetent mice without reducing cellular viability[1]. Toviblideg (BMS-986458) (5 mg/kg; p.o.; BID) monotherapy induces tumor volume reduction and modest CD3+ cell infiltration at the tumor edge, and its combination with Glofitamab demonstrates synergistic antitumor efficacy with enhanced CD3+ cell tumor infiltration in a humanized DLBCL mouse model[3].
References:
[1]. Groocock L, et al. BMS-986458 a potential first-in-class, highly selective, potent and well tolerated BCL6 ligand directed degrader (LDD) demonstrates multi-modal anti-tumor efficacy for the treatment of B-cell non-Hodgkin's lymphoma[J]. Blood, 2024, 144: 957.
[2]. Morschhauser F, et al. BMS-986458, a first-in-class, bifunctional cereblon-dependent ligand-directed degrader of B-cell lymphoma 6 (BCL6) in patients with Relapsed/Refractory (R/R) non-Hodgkin lymphoma (NHL): Updated results from the Phase 1 dose escalation study[J]. 2025.
[3]. Deb G, et al. BMS-986458, a first-in-class, highly selective, and potent ligand-directed degrader (LDD) of B-cell lymphoma 6 (BCL6) combined with T-cell engagers (TCEs) demonstrates preclinical synergistic antitumor efficacy for the treatment of B-cell non-Hodgkin lymphoma (NHL)[J]. Blood, 2025, 146: 5090.
In Vivo, Toviblideg (BMS-986458) phenotypically modulates lymph-resident Tfh populations in immunocompetent mice without reducing cellular viability[1]. Toviblideg (BMS-986458) (5 mg/kg; p.o.; BID) monotherapy induces tumor volume reduction and modest CD3+ cell infiltration at the tumor edge, and its combination with Glofitamab demonstrates synergistic antitumor efficacy with enhanced CD3+ cell tumor infiltration in a humanized DLBCL mouse model[3].
References:
[1]. Groocock L, et al. BMS-986458 a potential first-in-class, highly selective, potent and well tolerated BCL6 ligand directed degrader (LDD) demonstrates multi-modal anti-tumor efficacy for the treatment of B-cell non-Hodgkin's lymphoma[J]. Blood, 2024, 144: 957.
[2]. Morschhauser F, et al. BMS-986458, a first-in-class, bifunctional cereblon-dependent ligand-directed degrader of B-cell lymphoma 6 (BCL6) in patients with Relapsed/Refractory (R/R) non-Hodgkin lymphoma (NHL): Updated results from the Phase 1 dose escalation study[J]. 2025.
[3]. Deb G, et al. BMS-986458, a first-in-class, highly selective, and potent ligand-directed degrader (LDD) of B-cell lymphoma 6 (BCL6) combined with T-cell engagers (TCEs) demonstrates preclinical synergistic antitumor efficacy for the treatment of B-cell non-Hodgkin lymphoma (NHL)[J]. Blood, 2025, 146: 5090.