Products and
Pipeline – Modakafusp Alfa (TAK-573)

Overview^1-2

Modakafusp alfa is a first-in-class innate immunity enhancer that functions through targeted next generation IFN signaling

Mechanism of Action (Proposed)^1-2

- Modakafusp alfa is an attenuated IFNα2b fused to an anti-CD38 IgG4 mAb backbone, driving preferential IFN signaling in immune cells and MM cells

- It binds to a unique CD38 epitope therefore does not currently compete with approved monoclonal antibodies

- Modakafusp alfa activates innate and adaptive immune cells, and elicits direct anti-proliferation and apoptotic signals in MM cells via targeted next generation IFN signaling, which has the potential to help MM patients

CD38, cluster of differentiation 38; IFN, interferon; IFNα2b, interferon alfa-2b; IgG4, immunoglobulin G4; mAb, monoclonal antibody; MM, Multiple Myeloma

CD, cluster of differentiation; DC, dendritic cell, Fc, fragment crystallizable region; hIgG4b, human immunoglobulin G4b; IFN, interferon; IFNAR, interferon α/ß receptor; IFNα, interferon alfa MDSC, myeloid-derived suppressor cell; MM, multiple myeloma; NK, natural killer; Treg, regulatory T cell

Clinical Trials

Study Name

A Phase 1/2 Open-label Study to Investigate the Safety and Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of Modakafusp Alfa (TAK-573) as a Single Agent in Patients With Relapsed Refractory Multiple Myeloma (iinnovate-1)

Study Name

A Phase 1b Open-label Study to Evaluate the Safety and Tolerability of Intravenous Modakafusp Alfa as Part of Combination Therapy in Adult Patients With Multiple Myeloma (iinnovate-2)

Study Name

A Phase 1/2a Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Modakafusp Alfa in Combination With Daratumumab Subcutaneous in Patients With Relapsed or Refractory Multiple Myeloma (iinnovate-3)

Study Name

An Open-Label, Dose-Escalation Phase 1b/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Antitumor Activity of Modakafusp Alfa (TAK-573) as a Single Agent and in Combination With Pembrolizumab in Adult Patients with Advanced or Metastatic Solid Tumors

References

1. Vogl DT, Kaufman JL, Holstein SA, et al. TAK-573, an anti-CD38/Attenuated ifnα fusion protein, has clinical activity and modulates the ifnα receptor (IFNAR) pathway in patients with Relapsed/Refractory multiple myeloma. Blood. 2020;136:37-38. Web Link

2. Pogue SL, Taura T, Bi M, et al. Targeting Attenuated Interferon-α to Myeloma Cells with a CD38 Antibody Induces Potent Tumor Regression with Reduced Off-Target Activity. PLoS One. 2016;11(9):e0162472. Published 2016 Sep 9. doi:10.1371/journal.pone.0162472

3. Anguille S, Lion E, Willemen Y, Van Tendeloo VF, Berneman ZN, Smits EL. Interferon-α in acute myeloid leukemia: an old drug revisited. Leukemia. 2011;25(5):739-748. doi:10.1038/leu.2010.324

4. Crescioli S, Correa I, Karagiannis P, et al. IgG4 Characteristics and Functions in Cancer Immunity. Curr Allergy Asthma Rep. 2016;16(1):7. doi:10.1007/s11882-015-0580-7

5. Calabretta E, Carlo-Stella C. The Many Facets of CD38 in Lymphoma: From Tumor-Microenvironment Cell Interactions to Acquired Resistance to Immunotherapy. Cells. 2020;9(4):802. Published 2020 Mar 26. doi:10.3390/cells9040802