Natrunix (vilamakitug) / XBiotech - LARVOL DELTA

Phase I dose-escalation study of trifluridine/tipiracil plus XB2001 and bevacizumab in chemorefractory advanced colorectal cancer: The TASKIN study (ESMO-GI 2024) - P1/2 | "This supports testing the combination of TAS-102 plus XB2001 (an IL-1α monoclonal antibody). In the phase 1/2 TASKIN study (NCT05201352), patients (pts) with chemorefractory metastatic CC after failure of oxaliplatin, irinotecan, and fluoropyrimidine were enrolled and received XB2001 from 250 mg to 1000 mg every 2 weeks plus FTD-TPI 35 mg/m2. FTD-TPI plus XB2001 and bevacizumab demonstrated acceptable safety with promising efficacy in chemorefractory metastatic CC. The study continues as a randomized phase 2 study comparing FTD-TPI and bevacizumab with or without XB2001."

IO biomarker • Metastases • P1 data • Anemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • CD8 • CTAG1B • IL6 • PD-L1

Safety and Pharmacokinetics (PK) Study of Natrunix in Healthy Volunteers (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: XBiotech, Inc. | Recruiting ➔ Completed

Trial completion

1-BETTER: XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=76 | Completed | Sponsor: XBiotech, Inc. | Active, not recruiting ➔ Completed

Trial completion • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

XBiotech Launches Phase II Clinical Trial Evaluating Vilamakitug for the Treatment of Active Axial Spondyloarthritis (The Manila Times) - "IND Application for V-SPINE Study Completes 30-Day FDA Review Without Clinical Hold, Clearing Path for U.S. Patient Enrollment...The study is now authorized to proceed with patient enrollment in the United States, marking the resumption of XBiotech’s rheumatology program....PT064 will evaluate 400 mg of vilamakitug administered as 16 weekly subcutaneous injections versus placebo in 150 adult participants with active axial spondyloarthritis (axSpA)."

IND • Trial status • Immunology • Spondylarthritis

Vilamakitug in Spondyloarthritis Placebo-controlled Investigation for Efficacy (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: XBiotech, Inc. | N=60 ➔ 150 | Trial completion date: Apr 2027 ➔ Sep 2028 | Trial primary completion date: Feb 2027 ➔ Sep 2028

Enrollment change • Trial completion date • Trial primary completion date • Ankylosing Spondylitis • Immunology • Inflammatory Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis

Natrunix in HLA-B27 Positive Subjects With Axial Spondyloarthritis (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: XBiotech, Inc. | Trial completion date: Apr 2025 ➔ Apr 2027 | Trial primary completion date: Feb 2025 ➔ Feb 2027

Trial completion date • Trial primary completion date • Ankylosing Spondylitis • Immunology • Seronegative Spondyloarthropathies • Spondylarthritis

Natrunix in Combination With Methotrexate for Rheumatoid Arthritis Treatment (clinicaltrials.gov) - P2 | N=108 | Not yet recruiting | Sponsor: XBiotech, Inc. | Trial completion date: Mar 2026 ➔ Jul 2027 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

TASKIN: Evaluation of Efficacy of Trifluridine/Tipiracil Plus an Anti-IL-1α True Human Antibody Versus Trifluridine/Tipiracil Plus Placebo in Metastatic Colorectal Cancer Patients After Failure of Oxaliplatin, Irinotecan, Fluoropyrimidine (clinicaltrials.gov) - P1/2 | N=160 | Active, not recruiting | Sponsor: Centre Georges Francois Leclerc | Recruiting ➔ Active, not recruiting

Enrollment closed • Colorectal Cancer • Oncology • Solid Tumor • BRAF • MSI

Natrunix in Combination With Methotrexate for Rheumatoid Arthritis Treatment (clinicaltrials.gov) - P2 | N=108 | Not yet recruiting | Sponsor: XBiotech, Inc. | Trial completion date: May 2025 ➔ Mar 2026 | Initiation date: Sep 2024 ➔ Jul 2025 | Trial primary completion date: Mar 2025 ➔ Jan 2026

Trial completion date • Trial initiation date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

1-BETTER: XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=76 | Active, not recruiting | Sponsor: XBiotech, Inc. | Completed ➔ Active, not recruiting | Trial completion date: Jun 2024 ➔ Jun 2025

Enrollment closed • Trial completion date • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Safety and efficacy of trifluridine/tipiracil +/- bevacizumab plus XB2001 (anti-IL-1α antibody): a single-center phase 1 trial. (PubMed, Signal Transduct Target Ther) - P1/2 | "XB2001, a fully human monoclonal antibody neutralizing IL-1α, was evaluated for safety and preliminary efficacy with trifluridine/tipiracil (FTD/TPI) and bevacizumab in metastatic colorectal cancer patients previously treated with oxaliplatin- and irinotecan-based chemotherapies. High intratumoral IL-1α expression at baseline and CD8/PD-L1 infiltration are associated with a better progression-free survival. The combination of XB2001 with FTD/TPI and bevacizumab is feasible and safe, and showed encouraging clinical activity in chemotherapy-resistant mCRC."

IO biomarker • Journal • P1 data • Cardiovascular • Colorectal Cancer • Hematological Disorders • Hypertension • Infectious Disease • Neutropenia • Oncology • Solid Tumor • CD8 • IL6 • PD-L1

Natrunix or Placebo in Combination With Methotrexate in Rheumatoid Arthritis (clinicaltrials.gov) - P2 | N=243 | Completed | Sponsor: XBiotech, Inc. | Recruiting ➔ Completed

Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

XBiotech Pauses Rheumatology program (GlobeNewswire) - P2 | N=210 | NCT05363891 | Sponsor: XBiotech, Inc. | "XBiotech...announced today data that it is halting its clinical program in rheumatological disease while it seeks to understand the outcome from its recently completed Phase II, Double-Blind, Placebo-Controlled, Randomized study in Rheumatoid Arthritis. The Phase II study failed to meet its primary endpoint amid substantial irregularities that make unequivocal interpretation of the findings difficult. XBiotech was planning launch of additional studies in arthritis as well as other areas of rheumatology, including ankylosing spondylitis, which are now on hold while recent findings are evaluated...Although the study did not meet efficacy endpoints, discrepancies found during data analysis suggest caution in interpreting results."

P2 data • Trial suspension • Rheumatoid Arthritis

Natrunix in Combination with Methotrexate for Rheumatoid Arthritis Treatment (clinicaltrials.gov) - P2 | N=108 | Not yet recruiting | Sponsor: XBiotech, Inc.

Combination therapy • New P2 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Natrunix in HLA-B27 Positive Subjects With Axial Spondyloarthritis (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: XBiotech, Inc.

Combination therapy • New P2 trial • Ankylosing Spondylitis • Immunology • Seronegative Spondyloarthropathies • Spondylarthritis

1-BETTER: XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=76 | Completed | Sponsor: XBiotech, Inc. | Active, not recruiting ➔ Completed | Trial primary completion date: Feb 2024 ➔ Oct 2023

Combination therapy • Metastases • Trial completion • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

XBiotech Results from Randomized Double-Blinded Phase 1/2 Study Suggest Potential Breakthrough Treatment for Advanced Pancreatic Cancer (GlobeNewswire) - P1/2 | N=69 | 1-BETTER (NCT04825288) | Sponsor: XBiotech, Inc. | "The Phase 1 portion was a dose escalation study in metastatic pancreatic cancer patients to determine if dose limiting toxicities (DLTs) occurred in combination with the ON+5FU+LV regimen in second- or third-line setting. DLTs were not expected with Natrunix and none were seen....The primary endpoint for the Phase 2 study was to assess the safety and tolerability of Natrunix when used with the ON+5FU+LV combination. Overall, there were fewer adverse events (AEs) of any kind during the 24-week treatment period for the Natrunix arm compared to placebo (297 vs 336), with markedly fewer events in specific categories of adverse events during that time."

P1/2 data • Gastrointestinal Cancer • Pancreatic Cancer

TASKIN: Evaluation of Efficacy of Trifluridine/Tipiracil Plus an Anti-IL-1α True Human Antibody Versus Trifluridine/Tipiracil Plus Placebo in Metastatic Colorectal Cancer Patients After Failure of Oxaliplatin, Irinotecan, Fluoropyrimidine (clinicaltrials.gov) - P1/2 | N=160 | Recruiting | Sponsor: Centre Georges Francois Leclerc | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2026 ➔ Oct 2026 | Trial primary completion date: Mar 2024 ➔ Oct 2026

Enrollment open • Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • MSI

Natrunix or Placebo in Combination With Methotrexate in Rheumatoid Arthritis (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: XBiotech, Inc. | Not yet recruiting ➔ Recruiting | N=150 ➔ 210 | Trial completion date: Feb 2023 ➔ Aug 2024 | Trial primary completion date: Dec 2022 ➔ Jun 2024

Combination therapy • Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

1-BETTER: XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=69 | Active, not recruiting | Sponsor: XBiotech, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2023 ➔ May 2024 | Trial primary completion date: Jul 2023 ➔ Feb 2024

Combination therapy • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

XBiotech Announces Enrollment Completion of Phase II, Placebo Controlled, Multicenter Study for Natrunix in Pancreatic Cancer (GlobeNewswire) - "XBiotech Inc. announced today completion of enrollment of the Phase II portion of its 1-BETTER study—a Phase I/II randomized, double-blind, placebo-controlled clinical study for Natrunix in combination with chemotherapy for treating pancreatic cancer....Twenty-two leading cancer centers across the United States have been involved in the Phase I/II study....The Phase II portion enrolled 65 subjects using the maximum dose studied from the Phase I study that were randomized on a 1:1 basis to receive either Natrunix in combination with ONIVYDE+LV+5-FU (Arm 1), or placebo plus the chemotherapy combination."

Enrollment closed • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

XBiotech Announces First Patient Begins Novel Natrunix Therapy in Phase II Rheumatoid Arthritis (RA) Clinical Trial (GlobeNewswire) - "XBiotech Inc...today began treating the first patient in a phase II, double-blind, placebo-controlled, randomized clinical study to evaluate Natrunix as a new treatment for Arthritis. Natrunix blocks a key cause of inflammation involved in pain and joint destruction in rheumatoid arthritis (RA)."

Trial status • Immunology • Rheumatoid Arthritis • Rheumatology

XBiotech Inc. - FDA Authorizes Phase II Study for Natrunix in Rheumatoid Arthritis Patients (Market Screener) - "XBiotech Inc...reports that the FDA's Division of Rheumatology has authorized the Company to initiate a Phase II clinical study to test Natrunix as a treatment for Rheumatoid Arthritis. The randomized, double-blind, placebo-controlled, trial will examine the effectiveness of Natrunix to treat rheumatoid arthritis compared to placebo in subjects already receiving stable but inadequate treatment with methotrexate (MTX)."

Trial status • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

1-BETTER: XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=69 | Recruiting | Sponsor: XBiotech, Inc. | Trial completion date: Oct 2022 ➔ Aug 2023 | Trial primary completion date: Apr 2022 ➔ Jul 2023

Combination therapy • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD14

XBiotech Announces First Patient Enrolled into the French National Cancer Institute (INCA) Sponsored Phase I/II/III Clinical Study for Natrunix Therapy for Colorectal Cancer (GlobeNewswire) - "XBiotech...announced today the enrollment of the first patient in a multicenter, randomized clinical study for Natrunix in combination with trifluridine/tipiracil for the treatment of colorectal cancer. The much anticipated clinical study for XBiotech’s candidate cancer treatment is being funded by the French National Cancer Institute (INCA)....Subjects are randomized to receive Natrunix plus trifluridine/tipiracil chemotherapy or placebo plus the chemotherapy. The study is designed to seamlessly proceed through Phase III development based on achievement of certain efficacy milestones in the Phase I/II portions."

Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor