A Phase 1b, Open-label, Single-arm, Multicenter Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Multiple Doses of ELA026 in Adults and Adolescents with Secondary Hemophagocytic Lymphohistiocytosis (sHLH). - N/A

Start Date-

Sponsor / Collaborator

Electra Therapeutics, Inc.Startup

NCT05416307 / RecruitingPhase 1

An Open-label, Single-arm, Multicenter Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Multiple Doses of ELA026 in Participants With Secondary Hemophagocytic Lymphohistiocytosis (sHLH)

Hemophagocytic lymphohistiocytosis is a rare, aggressive and life-threatening syndrome of excessive immune activation. ELA026 is a fully human IgG1 SIRP-directed monoclonal antibody designed to reduce the myeloid and T cells driving the inflammation. The purpose of this study is to assess the safety, efficacy pharmacokinetics and pharmacodynamics of ELA026 in participants with secondary hemophagocytic lymphohistiocytosis.

Start Date19 May 2022

Sponsor / Collaborator

Electra Therapeutics, Inc.Startup

NCT05556863 / CompletedPhase 1

A Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ELA026 Following Intravenous and/or Subcutaneous Administration of Single and Multiple Doses in Healthy Adults

ELA026 is a fully human IgG1 SIRP-directed monoclonal antibody designed to reduce the myeloid and T cells driving the inflammation. The purpose of this study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of ELA026 in Single and Multiple Doses in Healthy Adults.

Start Date18 Oct 2021

Sponsor / Collaborator

Electra Therapeutics, Inc.Startup

100 Clinical Results associated with SIRPβ1 x SIRPγ x SIRPα

100 Translational Medicine associated with SIRPβ1 x SIRPγ x SIRPα

0 Patents (Medical) associated with SIRPβ1 x SIRPγ x SIRPα

Literatures (Medical) associated with SIRPβ1 x SIRPγ x SIRPα

01 Dec 2019·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

Functional characterization of the selective pan-allele anti-SIRPα antibody ADU-1805 that blocks the SIRPα–CD47 innate immune checkpoint

Q2 · MEDICINE

ArticleOA

Author: Kreijtz, Joost ; Spijkers, Sanne ; van den Tillaart, Gilbert ; Reinieren-Beeren, Inge ; van Duijnhoven, Sander ; Paradé, Marc ; Habraken, Maurice ; van Zandvoort, Peter ; van Eenennaam, Hans ; Janssen, Wout ; Lutje Hulsik, David ; Vink, Paul ; van Elsas, Andrea ; Rens, Joost ; Voets, Erik ; Driessen, Lilian

BACKGROUNDAccumulating preclinical data indicate that targeting the SIRPα/CD47 axis alone or in combination with existing targeted therapies or immune checkpoint inhibitors enhances tumor rejection. Although several CD47-targeting agents are currently in phase I clinical trials and demonstrate activity in combination therapy, high and frequent dosing was required and safety signals (acute anemia, thrombocytopenia) were recorded frequently as adverse events. Based on the restricted expression pattern of SIRPα we hypothesized that antibodies targeting SIRPα might avoid some of the concerns noted for CD47-targeting agents.METHODSSIRPα-targeting antibodies were generated and characterized for binding to human SIRPα alleles and blockade of the interaction with CD47. Functional activity was established in vitro using human macrophages or neutrophils co-cultured with human Burkitt's lymphoma cell lines. The effect of SIRPα versus CD47 targeting on human T-cell activation was studied using an allogeneic mixed lymphocyte reaction and a Staphylococcus enterotoxin B-induced T-cell proliferation assay. Potential safety concerns of the selected SIRPα-targeting antibody were addressed in vitro using a hemagglutination assay and a whole blood cytokine release assay, and in vivo in a single-dose toxicity study in cynomolgus monkeys.RESULTSThe humanized monoclonal IgG2 antibody ADU-1805 binds to all known human SIRPα alleles, showing minimal binding to SIRPβ1, while cross-reacting with SIRPγ, and potently blocking the interaction of SIRPα with CD47. Reduced FcγR binding proved critical to retaining its function towards phagocyte activation. In vitro characterization demonstrated that ADU-1805 promotes macrophage phagocytosis, with similar potency to anti-CD47 antibodies, and enhances neutrophil trogocytosis. Unlike CD47-targeting agents, ADU-1805 does not interfere with T-cell activation and is not expected to require frequent and extensive dosing due to the restricted expression of SIRPα to cells of the myeloid lineage. ADU-1805 is cross-reactive to cynomolgus monkey SIRPα and upon single-dose intravenous administration in these non-human primates (NHPs) did not show any signs of anemia, thrombocytopenia or other toxicities.CONCLUSIONSBlocking the SIRPα-CD47 interaction via SIRPα, while similarly efficacious in vitro, differentiates ADU-1805 from CD47-targeting agents with respect to safety and absence of inhibition of T-cell activation. The data presented herein support further advancement of ADU-1805 towards clinical development.

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