alnuctamab (CC-93269) / BMS - LARVOL DELTA

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=250 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Celgene | Active, not recruiting ➔ Recruiting

Enrollment open • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Celgene | Active, not recruiting ➔ Recruiting | N=19 ➔ 120

Enrollment change • Enrollment open • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=220 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Celgene | N=135 ➔ 220

Enrollment change • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=183 | Terminated | Sponsor: Celgene | Active, not recruiting ➔ Terminated; Business objectives have changed

First-in-human • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=135 | Recruiting | Sponsor: Celgene | Trial completion date: Nov 2023 ➔ Nov 2026 | Trial primary completion date: Oct 2023 ➔ Oct 2026

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=115 | Recruiting | Sponsor: Celgene | Trial completion date: Jun 2022 ➔ Nov 2023 | Trial primary completion date: Jul 2021 ➔ Oct 2023

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=120 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=250 | Active, not recruiting | Sponsor: Celgene | Trial completion date: Aug 2029 ➔ Mar 2025 | Trial primary completion date: Jun 2029 ➔ Mar 2025

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting | N=125 ➔ 19

Enrollment change • Enrollment closed • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Celgene | Trial completion date: Nov 2026 ➔ Aug 2027 | Trial primary completion date: Oct 2026 ➔ Jul 2027

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=250 | Recruiting | Sponsor: Celgene | Trial completion date:Aug 2027 ➔ Aug 2029 | Trial primary completion date: Jul 2027 ➔ Jun 2029

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=250 | Recruiting | Sponsor: Celgene | Trial completion date: Aug 2027 ➔ Aug 2029 | Trial primary completion date: Jul 2027 ➔ Jun 2029

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=115 | Recruiting | Sponsor: Celgene | Active, not recruiting ➔ Recruiting

Enrollment open • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=250 | Recruiting | Sponsor: Celgene | Trial completion date: Aug 2029 ➔ Aug 2027 | Trial primary completion date: Jun 2029 ➔ Jul 2027

First-in-human • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

CC-93269-MM-001: Study of CC-93269, a BCMA x CD3 T Cell Engaging Antibody, in Participants With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=120 | Not yet recruiting | Sponsor: Celgene

First-in-human • New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Alnuctamab (ALNUC; BMS-986349; CC-93269), a B-Cell Maturation Antigen (BCMA) x CD3 T-Cell Engager (TCE), in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Results from a Phase 1 First-in-Human Clinical Study (ASH 2022) - P1 | "All CRS events were limited to grade 1 (21 pts; 45%) or grade 2 (4 pts; 9%); 20 pts received ≥ 1 concomitant medication for CRS, including tocilizumab (n = 12) and/or corticosteroids (n = 8). SC ALNUC exhibited promising dose-dependent antitumor activity with a high proportion of MRD responses. Enrollment in the phase 1 study is ongoing and updated data will be presented."

Clinical • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Neutropenia • Oncology

Alnuctamab, a bivalent B-cell maturation antigen-targeting T cell engager for patients with relapsed or refractory multiple myeloma: results from a phase 1, first-in-human study. (PubMed, Leukemia) - "These results support improved safety of SC versus IV, and corroborate a step-up dosing strategy to mitigate CRS. Importantly, a schedule that de-intensifies over time provides favorable toxicity that may be applicable to other bispecific engagers."

First-in-human • Journal • P1 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology

Alnuctamab, a bivalent B-cell maturation antigen-targeting T cell engager for patients with relapsed or refractory multiple myeloma: results from a phase 1, first-in-human study (Nature) - "Ninety-five patients received ALNUC SC; at data cutoff, 44.2% remained on treatment and median follow-up was 8.0 months. The recommended phase 2 dose was 30 mg. The most common treatment emergent adverse events (any grade/grade 3/4) were CRS (57.9%/0%), and neutropenia (53.7%/43.2%). Infections were also frequent (64.2%/14.7%). ORR was 58.9% for all ALNUC SC-treated patients and 71.4% for the 30-mg cohort; 47/95 (49.5%) were measurable residual disease (MRD) negative. Overall, the safety and efficacy of ALNUC SC were comparable to other BCMA-targeted therapies."

First-in-human • P1 data • Multiple Myeloma

Alnuctamab for Refractory SLE (LATTE Study) (clinicaltrials.gov) - P1 | N=21 | Recruiting | Sponsor: Icahn School of Medicine at Mount Sinai | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Safety and Efficacy of Anti-B-cell Maturation Antigen (Anti-BCMA) Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma: A Systematic Review of Clinical Trials. (PubMed, Cureus) - "AMG-420, AMG-701, elranatamab, REGN5458, teclistamab (Tec), alnuctamab (ALNUC), and ABBV-383 are the seven anti-BCMA-CD3 bispecific Abs currently being assessed in clinical trials as monotherapy and in combination with immunomodulators/proteasome inhibitors against RRMM. Our analysis of the trials revealed that bispecific Abs showed efficacy in RRMM, with CRS and hematologic toxicities being the most common adverse events, mostly low-grade and manageable. Based on the promising efficacy and safety of BCMA targeting bispecific Abs, these drugs are emerging as a new therapeutic option for patients with advanced and RRMM."

Journal • Review • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

Pooled Analysis on Bispecific Antibody-Related Toxicities in Multiple Myeloma (ASH 2023) - "BsAb included in our study were the following: Teclistamab, Elranatamab, REGN-5458, AMG420, AMG701, CC-93269, TNB-383B, Linvoseltamab, Talquetamab, and Cevostamab. The use of BsAbs in MM has demonstrated remarkable efficacy; however, these have been linked to a unique adverse event profile. Our results showed that non-BCMA bsAb were associated less hematotoxicity (combined grade 3-4 events and hypogammaglobulinemia), whereas BCMA bsAb were associated with less CRS rates. This is important information for treatment selection and mitigation strategy development aiming to optimize patient outcomes."

Retrospective data • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

MODULE 4: Bispecific Antibodies in the Treatment of MM (ASH 2023) - "Supported by AbbVie Inc, GSK, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Karyopharm Therapeutics, Legend Biotech, Regeneron Pharmaceuticals Inc, and Sanofi. Similarities and differences in the cellular targets and mechanisms of action among bispecific antibodies for MM Antitumor activity observed with teclistamab in the Phase I/II MajesTEC-1 study leading to its recent FDA approval for R/R MM; optimal incorporation into the treatment paradigm Rate, depth and duration of response observed with elranatamab in the pivotal Phase II MagnetisMM-3 trial for patients with R/R MM; FDA approval and current clinical role Key findings with other promising anti-BCMA bispecific antibody constructions, such as alnuctamab, linvoseltamab and ABBV-383, for heavily pretreated MM Available efficacy and safety findings with non-BCMA-targeted bispecific antibodies for MM, such as talquetamab, cevostamab and RG6234; FDA approval of talquetamab for patients with R/R MM..."

Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Mantle Cell Lymphoma • Oncology

MODULE 4: Bispecific Antibodies for the Treatment of MM (ASH 2024) - "This program is supported by educational grants from GSK, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC and Karyopharm Therapeutics.Available efficacy and safety findings leading to the FDA approvals of the BCMA-directed bispecific antibodies teclistamab and elranatamab for R/R MM; optimal incorporation into management algorithms Efficacy and safety documented with investigational anti-BCMA bispecific antibodies for pretreated MM, such as linvoseltamab and alnuctamab Available efficacy and safety findings with non-BCMA-targeted bispecific antibodies for MM, such as talquetamab and cevostamab Recent FDA approval and optimal incorporation of talquetamab into disease management Spectrum, incidence and severity of CRS and other toxicities with various BCMA- and non-BCMA-directed bispecific antibodies; optimal mitigation and management strategies Rationale for and early-phase data with bispecific antibodies in combination with other systemic therapies,..."

Hematological Malignancies • Multiple Myeloma • Oncology