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

Targeted Inhibition of IL-18 with Tadekinig Alfa Correlates with Disease Control of Primary Monogenic IL-18-driven Hyperinflammatory Syndrome, a Serious and Potentially Life-threatening Disease in Patients with NLRC4 and XIAP mutations (ACR Convergence 2026) - No abstract available

Clinical • Pediatrics • Rheumatology • IL18 • XIAP

AB2 Bio...announced that Nippon Shinyaku Co., Ltd. has exercised its exclusive U.S. commercialization option under the companies' 2025 option and license agreement for Tadekinig alfa, AB2 Bio's lead investigational therapy (GlobeNewswire) - "The agreement covers treatment of Primary Monogenic IL-18-Driven Hyperinflammatory Syndrome in patients with NLRC4 and XIAP mutations....Under the agreement, AB2 Bio will receive a USD 30 million option exercise payment and is eligible to receive up to USD 100 million in development milestone payments and up to USD 500 million in commercial milestone and royalty payments....Nippon Shinyaku now holds exclusive commercialization rights in the United States for the licensed indication, while AB2 Bio retains exclusive rights to all other indications in the United States and to all indications outside the United States."

Commercial • Inflammation

Pyrin Inflammasome Activation Triggers an IL-18-Driven IFNγ Response in Mevalonate Kinase Deficiency. (PubMed, J Allergy Clin Immunol) - "Our findings identify a pyrin-inflammasome driven IL-18/IFNγ axis as a key signaling module of MKD-associated inflammation. This pathway may represent a novel target for therapeutic intervention in MKD."

Journal • Inflammation • GLI2 • IFNG • IL18 • IL1B

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 2026 ➔ Apr 2028 | Trial primary completion date: Jan 2026 ➔ Jan 2028

Trial completion date • Trial primary completion date • Inflammation

Potential of biomarker-based enrichment strategies to identify critically ill patients for emerging cell death interventions. (PubMed, Cell Death Differ) - "The daily monitoring of pyro- and ferroptosis signatures reveals potential intervention opportunities, such as anakinra, tadekinig alfa, lead ferroptosis inhibitors, or a combination thereof. In summary, our findings demonstrate that a targeted biomarker panel enables predictive enrichment of ICU patients, paving the way for timely intervention strategies against pyroptosis or ferroptosis."

Biomarker • Journal • Critical care • Infectious Disease • Septic Shock • GDF15 • IL10 • IL18 • IL6

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