TBS-2025: VISTA-inhibiting Monoclonal Antibody 

Through our acquisition of Kineta, Inc. in June 2025, we added TBS-2025, a novel VISTA- inhibiting monoclonal antibody to our portfolio. Unlike other checkpoints, which are mostly present on activated T cells, VISTA is predominately expressed on myeloid cells, notably myeloid-derived suppressor cells (MDSCs), and on quiescent T cells. Research has demonstrated that when mutated, NPM1 and DNM3-TA, two of the most common mutations in AML and typically co-mutated in myelodysplasia (MDS), result in high expression of VISTA on the surface of leukemic blasts. The presence of VISTA on these cells is believed to be the primary mechanism by which leukemic cells escape immune recognition and attack, resulting in a low treatment response rate and a high level of relapse in AML. 

TBS-2025 was previously investigated in a Phase 1/2 dose escalation trial, both as a monotherapy and in combination with pembrolizumab, in patients with relapsed and/or treatment-refractory advanced solid tumors. TBS-2025 was well tolerated when administered every 2 weeks at doses up to 1,000mg both in the monotherapy arm (n=24) or in the pembrolizumab combination therapy arm (n=16). Pharmacokinetic and pharmacodynamic data demonstrated greater than 90% receptor occupancy across the every two- week dosing interval. Immunocytokine analysis was consistent with the mechanism of action for VISTA inhibition on immune cells. 

As a next step, we are planning on investigating TBS-2025 in a Phase 2 trial to determine if TBS-2025 as a monotherapy or in combination with a menin inhibitor can augment the response rates seen with menin inhibitors and decrease the rate of relapse in patients with mutNMP1 relapsed or refractory AML where menin inhibitors are the current standard of care.