tadekinig alfa (IL-18BP) / AB2 Bio - LARVOL DELTA

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency As Open Label Extension (clinicaltrials.gov) - P3 | N=11 | Completed | Sponsor: AB2 Bio Ltd. | Trial completion date: Oct 2024 ➔ May 2024 | Trial primary completion date: Sep 2024 ➔ Apr 2024 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • XIAP

Tadekinig Alfa (IL-18BP) Rescue Therapy for CAR T Cell Related Cytokine Release Syndrome (CRS) and HLH-like Syndrome (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: University of Pennsylvania | Trial completion date: Apr 2025 ➔ Apr 2026 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Inflammation

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency as Open Label Extension (clinicaltrials.gov) - P3 | N=10 | Active, not recruiting | Sponsor: AB2 Bio Ltd. | Trial completion date: May 2024 ➔ Oct 2024 | Trial primary completion date: Apr 2024 ➔ Sep 2024

Trial completion date • Trial primary completion date • IL18 • XIAP

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency (clinicaltrials.gov) - P3 | N=15 | Completed | Sponsor: AB2 Bio Ltd. | Active, not recruiting ➔ Completed

Trial completion • XIAP

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency as Open Label Extension (clinicaltrials.gov) - P3 | N=10 | Active, not recruiting | Sponsor: AB2 Bio Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • IL18 • XIAP

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency as Open Label Extension (clinicaltrials.gov) - P3 | N=10 | Recruiting | Sponsor: AB2 Bio Ltd. | Trial completion date: Jan 2024 ➔ May 2024 | Trial primary completion date: Nov 2023 ➔ Apr 2024

Trial completion date • Trial primary completion date • IL18 • XIAP

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency (clinicaltrials.gov) - P3 | N=15 | Active, not recruiting | Sponsor: AB2 Bio Ltd. | Trial completion date: Jul 2023 ➔ Oct 2023 | Trial primary completion date: May 2023 ➔ Oct 2023

Trial completion date • Trial primary completion date • XIAP

A natural goldmine of binding proteins and soluble receptors simplified their translation to blockbuster drugs, all in one decade. (PubMed, Front Immunol) - "IFNβ proved beneficial in Multiple Sclerosis and is a blockbuster drug, Rebif. TNF mAbs translated into Remicade to treat Crohn's disease. Enbrel based on TBPII is for Rheumatoid Arthritis...Seven years of continuous compassionate use of Tadekinig alfa™ in children born with mutations (NLRC4, XIAP) proved life-saving and is an example of tailored made medicine. IL-18 is a checkpoint biomarker in cancer and IL-18BP is planned recently to target cytokine storms resulting from CAR-T treatment and in COVID 19."

IO biomarker • Journal • Review • CNS Disorders • Crohn's disease • Gastroenterology • Immunology • Infectious Disease • Inflammatory Arthritis • Inflammatory Bowel Disease • Multiple Sclerosis • Novel Coronavirus Disease • Oncology • Rheumatoid Arthritis • Rheumatology • IFNAR2 • IFNB1 • IFNG • IL18 • IL32 • IL6 • RETN • XIAP

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency (clinicaltrials.gov) - P3 | N=15 | Active, not recruiting | Sponsor: AB2 Bio Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • XIAP

Tadekinig Alfa (IL-18BP) Rescue Therapy for CAR T Cell Related Cytokine Release Syndrome (CRS) and HLH-like Syndrome (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: University of Pennsylvania | Trial completion date: Apr 2023 ➔ Apr 2025 | Trial primary completion date: Jan 2023 ➔ Jan 2025

CAR T-Cell Therapy • Cytokine release syndrome • Trial completion date • Trial primary completion date • Inflammation

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency (clinicaltrials.gov) - P3 | N=15 | Recruiting | Sponsor: AB2 Bio Ltd. | N=10 ➔ 15 | Trial completion date: Jul 2022 ➔ Jul 2023 | Trial primary completion date: May 2022 ➔ May 2023

Enrollment change • Trial completion date • Trial primary completion date • XIAP

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency as Open Label Extension (clinicaltrials.gov) - P3 | N=10 | Recruiting | Sponsor: AB2 Bio Ltd. | Trial completion date: Jan 2023 ➔ Jan 2024 | Trial primary completion date: Nov 2022 ➔ Nov 2023

Trial completion date • Trial primary completion date • IL18 • XIAP

Tadekinig Alfa (IL-18BP) Rescue Therapy for CAR T Cell Related Cytokine Release Syndrome (CRS) and HLH-like Syndrome (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: University of Pennsylvania | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Cytokine release syndrome • Enrollment open • Inflammation

"IL-18, Iike IL-1, is a produced by activation of the inflammasome. IL-18 is a potential bioimarker for #AOSD, closely linked to Dz activity & could be a Tx target, either as IL-18 binding protein (Tadekinig alfa) or mAb against IL-18 (phase 1b) https://t.co/ex231f27rg" (@RheumNow)

IL18

Current treatment options for monogenic periodic fever syndromes - the role of interleukin 1 inhibitors. (PubMed, Cas Lek Cesk) - "The most available are anakinra, canakinumab and rilonacept. Moreover, several clinical trials are currently underway with other very promising drugs, such as gevokizumab, tadekinig alfa or tranilast. In the following review, we provide a new perspective on the efficacy and safety of IL-1 inhibitors that have provided the novel results coming from recently published clinical trials."

Journal • Cardiovascular • Genetic Disorders • Inflammation • Oncology • TNFA

Tadekinig Alfa (IL-18BP) Rescue Therapy for CAR T Cell Related Cytokine Release Syndrome (CRS) and HLH-like Syndrome (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: University of Pennsylvania

CAR T-Cell Therapy • Cytokine release syndrome • New P1 trial • Inflammation

A Case of XIAP Deficiency Successfully Managed with Tadekinig Alfa (rhIL-18BP). (PubMed, J Clin Immunol) - No abstract available

Journal • XIAP

Update on the therapy of adult-onset Still's disease with a focus on IL-1-inhibition: a systematic review. (PubMed, Ther Adv Musculoskelet Dis) - "We conducted searches using Medline, Biosis, Embase, and Cochrane databases between 2016 and 2021 using the terms AOSD, IL1, IL-18, canakinumab, anakinra, tadekinig, and rilonacept and if applicable their trade names. The overall efficacy-safety profile of the IL-1 inhibitors is favorable reflecting a targeted approach as standard of care. We can expect that the successful treatment of AOSD with IL-1 inhibition will facilitate further clinical and basic research with impact on other auto-inflammatory and hyper-inflammatory conditions."

Clinical • Journal • Review • Idiopathic Arthritis • Immunology • Rare Diseases • Rheumatoid Arthritis • Rheumatology • IL18

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency (clinicaltrials.gov) - P3; N=10; Recruiting; Sponsor: AB2 Bio Ltd.; Trial completion date: Dec 2021 ➔ Jul 2022; Trial primary completion date: Oct 2021 ➔ May 2022

Clinical • Trial completion date • Trial primary completion date • XIAP

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency as Open Label Extension (clinicaltrials.gov) - P3; N=10; Recruiting; Sponsor: AB2 Bio Ltd.; Trial completion date: Feb 2022 ➔ Jan 2023; Trial primary completion date: Jun 2021 ➔ Nov 2022

Clinical • Trial completion date • Trial primary completion date • IL18 • XIAP

Interleukin-1 Blockade in Polygenic Autoinflammatory Disorders: Where Are We now? (PubMed, Front Pharmacol) - "Most of the current data are focused on the therapeutic use of anakinra, an IL-1 receptor antagonist, canakinumab, an anti-IL-1β monoclonal antibody, and rilonacept, a soluble decoy receptor. However, other promising agents, such as gevokizumab, IL-1β blocking monoclonal antibody, tadekinig alfa, a human recombinant IL-18-binding protein, and tranilast, an analog of a tryptophan metabolite, are currently being tested...Furthermore, the anti-IL-1 therapy allowed corticosteroid tapering and, in some cases, even withdrawal. This article reviews the current IL-1 inhibitors and the results of all clinical trials in which they have been tested for the management of broad spectrum of polygenic AIDs."

Journal • Review • Cardiovascular • Gout • Human Immunodeficiency Virus • Idiopathic Arthritis • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Musculoskeletal Diseases • Rheumatoid Arthritis • Rheumatology • CD123 • IL18 • IL1B

IL-1 Inhibitors in the Treatment of Monogenic Periodic Fever Syndromes: From the Past to the Future Perspectives. (PubMed, Front Immunol) - "Most of the available data regarding the efficacy and safety of IL-1 inhibitors are related to anakinra, canakinumab, and rilonacept. Other promising therapeutics, such as gevokizumab, tadekinig alfa, and tranilast are currently undergoing clinical trials. In this review, we provide sophisticated and up-to-date insight into the therapeutic uses of different IL-1 inhibitors in monogenic periodic fever syndromes."

Journal • Review • Amyloidosis • Cardiovascular • Genetic Disorders • Human Immunodeficiency Virus • Idiopathic Arthritis • Immunology • Infectious Disease • Inflammation • Musculoskeletal Diseases • Rheumatoid Arthritis • Rheumatology • CD123 • IL18 • IL1B • IL1R1 • TNFA

Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency (clinicaltrials.gov) - P3; N=10; Recruiting; Sponsor: AB2 Bio Ltd.; Trial completion date: May 2021 ➔ Dec 2021; Trial primary completion date: Dec 2020 ➔ Oct 2021

Clinical • Trial completion date • Trial primary completion date

WuXi Biologics and AB2 Bio Announce Collaboration to Accelerate Commercial-Scale Manufacturing of Tadekinig alfa (PRNewswire) - "WuXi Biologics...and AB2 Bio Ltd....today announced that they have entered into a collaboration to set-up and accelerate commercial-scale manufacturing of Tadekinig alfa, AB2 Bio's novel recombinant IL-18 binding protein. Per the agreement, AB2 Bio is in the process of transferring manufacturing of Tadekinig alfa to WuXi Biologics, where commercial-scale manufacturing will be conducted. AB2 Bio will prepare the submission of the license application to the U.S. Food and Drug Administration (FDA) and initiate commercialization activities...The pivotal Phase 3 trial with Tadekinig alfa in primary, monogenic HLH, is expected to read-out in mid-2021, after which the Biologics License Application (BLA) application process will be initiated."

Licensing / partnership • P3 data • Immunology • Rare Diseases

"$WXXWY WuXi Biologics and AB2 Bio Announce Collaboration to Accelerate Commercial-Scale Manufacturing of Tadekinig alfa https://t.co/HwUzSqiWqE" (@otcdynamics)