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    DRUG CLASS:

    SIRPA inhibitor

    Related drugs:
    4ms
    A Dose Escalation and Expansion Trial With BYON4228 Alone and in Combination in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=85, Recruiting, Byondis B.V. | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Keytruda (pembrolizumab) • BYON4228
    6ms
    ELA026 CP002: Open-label Study of ELA026 in Participants With Secondary Hemophagocytic Lymphohistiocytosis (sHLH) (clinicaltrials.gov)
    P2/3, N=156, Recruiting, Electra Therapeutics Inc. | Active, not recruiting --> Recruiting
    Enrollment open
    8ms
    A Dose Escalation and Expansion Trial With BYON4228 Alone and in Combination in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=85, Not yet recruiting, Byondis B.V.
    New P1 trial
    |
    Keytruda (pembrolizumab) • BYON4228
    9ms
    ELA026 CP002: Open-label Study of ELA026 in Participants with Secondary Hemophagocytic Lymphohistiocytosis (sHLH) (clinicaltrials.gov)
    P2/3, N=156, Active, not recruiting, Electra Therapeutics Inc. | Recruiting --> Active, not recruiting | Phase classification: P1 --> P2/3 | N=24 --> 156 | Trial completion date: Mar 2025 --> Jun 2029 | Trial primary completion date: Dec 2024 --> Jun 2027
    Enrollment closed • Phase classification • Enrollment change • Trial completion date • Trial primary completion date
    1year
    BYON4228.001: First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228 (clinicaltrials.gov)
    P1, N=100, Recruiting, Byondis B.V. | Trial primary completion date: Oct 2024 --> Oct 2025
    Trial primary completion date • Combination therapy
    |
    CD20 (Membrane Spanning 4-Domains A1)
    |
    CD20 expression
    |
    Rituxan (rituximab) • Truxima (rituximab-abbs) • BYON4228
    1year
    A pan-allelic human SIRPα-blocking antibody, ES004-B5, promotes tumor killing by enhancing macrophage phagocytosis and subsequently inducing an effective T-cell response. (PubMed, Antib Ther)
    Unlike CD47-targeted agents, ES004-B5 exhibits an excellent safety profile in nonhuman primates. ES004-B5 has potential to be an important backbone for SIRPα-based combination therapy and/or bispecific antibodies, which will likely overcome the limitations of CD47-targeted agents encountered in clinical settings.
    Journal • IO biomarker
    |
    CD47 (CD47 Molecule) • SIRPA (Signal Regulatory Protein Alpha)
    |
    CD47 expression
    over1year
    ELA026 CP002: Evaluation of the Safety and Efficacy of ELA026 in Participants With Secondary Hemophagocytic Lymphohistiocytosis (clinicaltrials.gov)
    P1, N=24, Recruiting, Electra Therapeutics Inc. | Phase classification: P1b --> P1 | Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Dec 2024
    Phase classification • Trial completion date • Trial primary completion date
    over1year
    Blockade of SIRPα-CD47 axis by anti-SIRPα antibody enhances anti-tumor activity of DXd antibody-drug conjugates. (PubMed, PLoS One)
    To this end, DS-1103a, a newly developed anti-human SIRPα antibody (Ab), was assessed for the potential combination benefit with datopotamab deruxtecan (Dato-DXd) and trastuzumab deruxtecan (T-DXd), DXd-ADCs targeting human trophoblast cell-surface antigen 2 and human epidermal growth factor receptor 2, respectively. Furthermore, in syngeneic mouse models, both Dato-DXd and T-DXd combination with anti-mSIRPα Ab showed stronger anti-tumor activity over the monotherapies. Taken together, this study provides a preclinical rationale of novel therapies for solid tumors combining SIRPα-CD47 blockers with DXd-ADCs.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • SIRPA (Signal Regulatory Protein Alpha)
    |
    Enhertu (fam-trastuzumab deruxtecan-nxki) • Datroway (datopotamab deruxtecan-dlnk) • DS-1103
    over1year
    Evaluation of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ELA026 in Single and Multiple Doses in Healthy Volunteers (clinicaltrials.gov)
    P1, N=91, Completed, Electra Therapeutics Inc. | Recruiting --> Completed | Trial completion date: Apr 2024 --> Nov 2023 | Trial primary completion date: Apr 2024 --> Nov 2023
    Trial completion • Trial completion date • Trial primary completion date
    almost2years
    Muc4 is a biomarker of metastasis in TNBC and its downregulation by blocking soluble TNF prevents metastasis in combination with immunotherapy (AACR 2024)
    We have demonstrated that TNF induces trastuzumab resistance through mucin 4 (MUC4) upregulation and it is an independent biomarker of poor response to therapy in HER2+ breast cancer...TNF blockade was achieved with etanercept (E), which blocks the soluble (sTNF) and transmembrane isoform of TNF, or with the dominant negative protein INB03 (DN) which neutralizes only sTNF...MUC4 is associated with poorly-infiltrated TNBC, and sTNF blockade downregulates its expression decreasing MTS when combined with anti-PD-1. We propose the TNF as a new target for the treatment of TNBC, and MUC4 as a predictive biomarker to guide a combined treatment of TNF blockers with immunotherapy.
    Combination therapy • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • AR (Androgen receptor) • MUC4 (Mucin 4, Cell Surface Associated) • KRT5 (Keratin 5)
    |
    MUC4 expression
    |
    VENTANA PD-L1 (SP142) Assay
    |
    Herceptin (trastuzumab) • INB03
    2years
    First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228 (clinicaltrials.gov)
    P1, N=100, Recruiting, Byondis B.V.
    Trial initiation date
    |
    CD20 (Membrane Spanning 4-Domains A1)
    |
    CD20 expression
    |
    Rituxan (rituximab) • BYON4228
    2years
    First-in-Human Dose-Escalation and -Expansion Trial with Sirpα Antibody BYON4228 in R/R B-Cell NHL (ASH 2023)
    Phase 1 clinical trial design: BYON4228.001 (NCT05737628) is the first-in-human clinical trial of BYON4228, in combination with rituximab, in relapsed or refractory (R/R) B-cell Non-Hodgkin's lymphoma (NHL). Tumor response is determined according to Lugano and LYRIC criteria. An extensive biomarker program in the peripheral blood and bone marrow is included in the trial.
    P1 data • IO biomarker
    |
    CD20 (Membrane Spanning 4-Domains A1) • SIRPA (Signal Regulatory Protein Alpha)
    |
    CD20 expression
    |
    Rituxan (rituximab) • BYON4228