Full dose escalation data show favorable safety profile of ISB 2001 for Multiple Myeloma: Ichnos Glenmark Innovation

New York: Ichnos Glenmark Innovation (IGI), a global, fully integrated clinical-stage biotechnology company focused on developing multispecifics in oncology, has presented promising full dose-escalation results from its Phase 1 TRIgnite-1 study of ISB 2001, an investigational first-in-class BCMA × CD38 × CD3-targeting trispecific antibody for the treatment of patients with relapsed or refractory multiple myeloma (RRMM).

These data, presented as a rapid oral presentation (Abstract #7514) at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, demonstrated a sustained overall response rate (ORR) of 79% and a high complete/stringent complete response (CR/sCR) rate of 30% across seven active dose levels (≥ 50 µg/kg) in a heavily pretreated patient population, with a favorable safety profile. The ORR was 74% in all treated patients, including two patients treated at lower dose levels. ISB 2001 was designed to simultaneously target multiple myeloma by binding to the tumor associated antigens BCMA and CD38, even when expressed at low levels, while engaging T cells to trigger an immune response. This novel trispecific design enhances tumor-specific cytotoxicity and aims to overcome resistance mechanisms seen with first-generation bispecific antibodies and CAR T-cell therapies, while minimizing off-tumor toxicity.

Professor Hang Quach, M.D., Professor of Haematology at the University of Melbourne and Director of Haematology at St. Vincent’s Hospital Melbourne, said, “Responses to ISB 2001 highlight the remarkable anti-myeloma activity of this first-in-class anti-BCMA × CD38 × CD3 trispecific antibody-T cell engager in heavily pretreated RRMM patients, including those who have exhausted prior T cell-redirecting, BCMA-targeted, or anti-CD38 therapies - an especially challenging, quad-exposed patient population. With its unprecedented potency and tolerability, ISB 2001 has the potential to redefine the treatment landscape for RRMM, offering new hope for patients with limited therapeutic options.”

A total of 35 patients with at least one month of follow-up had received a median of six prior lines of therapy (range: 3–11) at study entry, underscoring a heavily pretreated population. ISB 2001 demonstrated high response rates at active dose levels, with 33 patients treated at ≥ 50 µg/kg (dose levels 3–9).

Responses were durable and deepened over time, irrespective of prior lines of therapy or refractoriness status, reinforcing the strength of earlier findings reported at ASH 2024 Annual Meeting in 18 patients treated with ISB 2001 at doses ≥ 50 µg/kg:

• The ORR was 79% (26/33), including a CR/sCR rate of 30% (10/33), with a median followup of 6.3 months (range: 1–16).

• Of the 10 patients achieving CR/sCR, eight were evaluable for minimal residual disease (MRD), and six achieved MRD negativity, indicating no detection of myeloma cells by molecular or flow cytometry assays with 10-5 sensitivity, and reinforcing the depth of response.

• Among 25 patients refractory to anti-CD38 therapies, the ORR was 72%, with a CR/sCR rate of 24%.

• In 19 patients without prior T-cell directed therapy (TCDT), including bispecific antibodies and/or CAR T-cell therapy, the ORR was 84%, with CR/sCR rate of 32%.

• Among 14 patients previously treated with TCDT, the ORR remained strong at 71% with a CR/sCR rate of 28%.

• In 15 patients who had received prior BCMA-targeted therapies, the ORR was 73%, with a CR/sCR rate of 27%.

• The median half-life of ISB 2001 was approximately 17 days, supporting the potential for less-frequent dosing.