T-Guard (SPV-T3a-RTA/WT1-RTA) / Xenikos - LARVOL DELTA

A randomized study evaluating tailoring of advanced/metastatic colorectal cancer (mCRC) therapy using circulating tumor DNA (ctDNA): TACT-D. (ASCO 2024) - P2 | "Research Funding: MD Anderson Cancer Center, Houston, TXGuardant Health Inc., Redwood City, CA...Background: Identifying non-responders to expensive salvage therapies with modest benefits and substantial treatment related adverse events (TRAEs) (e.g. regorafenib [Reg] or TAS102 [Tas] in mCRC) is key to precision care... In the first prospective study of clinical utility of monitoring ctDNA in mCRC, baseline ctDNA was strongly prognostic for clinical benefit from salvage therapies in mCRC. Adjusted for this prognostic impact, ΔctDNA between C1D1 and C1D15 was predictive of clinical outcomes. Efforts are needed to establish novel signatures, optimal cutoffs/intervals for assessing ctDNA response in mCRC, tailored to pts and their therapy."

Circulating tumor DNA • Clinical • Late-breaking abstract • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Establishment of a Biorepository for Down Syndrome: Experience of the Inter-Institutional Multidisciplinary BioBank - BioBIM. (PubMed, Discov Med) - "By establishing this biobank, we have gathered a significant number of biological samples and clinical data from individuals with Down syndrome, thereby fostering collaboration between different research groups in an open and transparent manner. Sharing expertise and resources among scientists will ultimately facilitate the transfer of knowledge to clinical practice, leading to the development of more effective therapeutic treatments to improve the outcomes and quality of life of patients with Down syndrome."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Developmental Disorders • Genetic Disorders • Heart Failure • Hematological Malignancies • Immunology • Leukemia • Oncology

Anti-CD3/CD7 immunoconjugate (T-Guard) for severe, steroid-refractory GVHD: final report of BMT CTN 2002. (PubMed, Bone Marrow Transplant) - No abstract available

Journal • Graft versus Host Disease • Immunology • CD7

"He’s a likable guy who gets hot from 3 and can’t guard a statue." (@realmikesmall)

A Phase I/II Study on the Anti-CD3/CD7 Immunotoxin Combination (T-GuardTM) for the Treatment of Steroid-Refractory Acute Gvhd (ASH 2017) - P1/2; "...The outcomes compared favorably with historical controls receiving either infliximab (N=21) or inolimomab/etanercept (N=21) were the ORR was 52% and the 6-month OS 29% (Figure 1 and 2)...Treatment of SR-aGVHD with a short course of the T-GuardTM proved to be safe and well tolerated, and resulted in a high rate of CR and a promising 6-month OS of 60%, especially considering the high-risk setting (90% GI involvement, 50% high-risk biomarker profile). A pivotal multicentre international controlled trial, comparing T-GuardTM with best-available therapy for SR-aGVHD is scheduled for the end of 2017."

Biomarker • Clinical • P1/2 data • Biosimilar • Cytomegalovirus Infection • Graft versus Host Disease • Leukemia • Venous Thromboembolism

A Study to Compare T-Guard vs Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-vs-Host Disease (BMT CTN 2002) (clinicaltrials.gov) - P3 | N=12 | Terminated | Sponsor: Xenikos | N=246 ➔ 12 | Trial completion date: Jun 2026 ➔ Jan 2023 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2025 ➔ Nov 2022; The study met the protocol defined stopping boundary for Day 60 mortality when comparing mortality between the T-Guard and ruxolitinib arms

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

A Study to Compare T-Guard vs Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease (SR-aGVHD) (BMT CTN 2002) (clinicaltrials.gov) - P3 | N=246 | Recruiting | Sponsor: Xenikos | Trial completion date: Jan 2026 ➔ Apr 2026 | Initiation date: Dec 2021 ➔ Mar 2022 | Trial primary completion date: Jan 2025 ➔ Apr 2025

Trial completion date • Trial initiation date • Trial primary completion date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Xenikos Enrolls First Patient in Global Pivotal Phase 3 Study Evaluating T-Guard in Patients with Steroid-Refractory Acute Graft-Versus-Host Disease (GlobeNewswire) - "Xenikos...today announced enrollment of the first patient in a global pivotal Phase 3 clinical study designed to evaluate T-Guard® versus ruxolitinib for the treatment of patients with Grade III or IV steroid-refractory acute graft-versus-host disease (SR-aGVHD) following allogeneic hematopoietic stem cell transplant (allo-HSCT)....There will be a safety run-in phase at the beginning of the study whereby the Data and Safety Monitoring Board (DSMB) will evaluate the first 24 patients. Xenikos expects to report results from the safety run-in phase during the first half of 2023....Xenikos expects the data from this study to support the submission of a Biologics License Application (BLA) in the US based on Day 28 data from the first 150 patients. Data from the full 246 patients is expected to support the submission of a Marketing Authorization Application (MAA) in the EU."

Enrollment open • P3 data • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

A Study to Compare T-Guard vs Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease (SR-aGVHD) (BMT CTN 2002) (clinicaltrials.gov) - P3; N=246; Recruiting; Sponsor: Xenikos; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

A Study to Compare T-Guard vs Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease (SR-aGVHD) (BMT CTN 2002) (clinicaltrials.gov) - P3; N=246; Not yet recruiting; Sponsor: Xenikos; Initiation date: Sep 2021 ➔ Dec 2021

Clinical • Trial initiation date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

A study to compare the experimental medicine T-Guard to Ruxolitinib for treating acute Graft-versus-Host Disease that does not sufficiently improve with the standard steroid treatment (clinicaltrialsregister.eu) - P3; N=246; Ongoing; Sponsor: Xenikos B.V.

Clinical • New P3 trial • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Xenikos Secures €40 Million in Convertible Debt Financing, Veloxis Pharmaceuticals Joins as Strategic Investor (PRNewswire) - “Xenikos B.V…announced today the closing of €40 million in convertible debt consisting of two equal tranches of €20 million. The financing was led by Veloxis Pharmaceuticals, with participation from existing investors, Medicxi, RA Capital Management, Oost NL and Sanquinnovate. In connection with the financing, Veloxis will obtain two sequential call options to acquire the company and a Board seat. Xenikos will use the proceeds of the financing to initiate a registrational Phase 3 clinical trial in the US and EU, which is designed to evaluate the efficacy and safety of their flagship product T-Guard® for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD) in patients following allogeneic stem cell transplantation versus ruxolitinib….A randomized Phase 3 registration trial…is expected to begin in the US and Europe in the second half of 2021.”

Financing • Trial initiation date • Acute Graft versus Host Disease • Graft versus Host Disease • Immunology

Xenikos Announces T-Guard Phase 3 Clinical Update and Outlines 2021-2022 Corporate Objectives (GlobeNewswire) - "Xenikos B.V...announced that it has reached agreement with the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) on the design of its pivotal randomized Phase 3 clinical study (BMT CTN 2002) to evaluate T-Guard® versus ruxolitinib for the treatment of patients with Grade III or IV steroid-refractory acute graft-versus-host disease (SR-aGVHD) following allogeneic hematopoietic stem cell transplant (allo-HSCT)....Xenikos expects to commence this Phase 3 study in the second half of 2021....Complete safety run-in phase of Phase 3 study mid 2022. Complete futility analyses portion of the Phase 3 study during the first half of 2023."

P3 data • Trial initiation date • Graft versus Host Disease • Immunology

BMT CTN 2002: A Study to Compare T-Guard vs Ruxolitinib for Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease (SR-aGVHD) (clinicaltrials.gov) - P3; N=246; Not yet recruiting; Sponsor: Xenikos

Clinical • New P3 trial • Graft versus Host Disease • Immunology

T-Guard as Treatment for Steroid Refractory Acute GVHD (clinicaltrials.gov) - P3; N=3; Terminated; Sponsor: Xenikos; N=47 ➔ 3; Trial completion date: Sep 2021 ➔ Feb 2020; Suspended ➔ Terminated; Initiated a new randomized trial per discussion with FDA

Enrollment change • Trial completion date • Trial termination • Graft versus Host Disease • Immunology

Dutch company Xenikos secures USD 30 Million in series B financing (Xenikos Press Release) - "Xenikos...announced today the receipt of USD 30 million from a Series B financing...funds will be used to advance the development of Xenikos' lead compound, T-Guard, including conducting clinical Phase 3 registration trials in the US and EU, arranging commercial-scale production, and submitting the relevant applications for market approval."

Financing • New P3 trial • Graft versus Host Disease • Immunology

Xenikos partners with the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) to conduct a U.S.-based phase 3 trial to test T-Guard in acute graft-versus-host disease (Xenikos Press Release) - "Xenikos B.V. announced today that they have partnered with the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) to conduct a U.S.-based Phase 3 registration trial to test the efficacy of T-Guard in treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) in patients following an allogeneic stem cell transplant...the Phase 3 trial design is based on input received from the U.S. Food and Drug Administration at the End-of-Phase 2 meeting. Xenikos plans to file an Investigational New Drug application in 2019."

IND • New P3 trial • Graft versus Host Disease • Immunology

1802: T-Guard as Treatment for Steroid Refractory Acute GVHD (clinicaltrials.gov) - P3; N=47; Suspended; Sponsor: Xenikos; Recruiting ➔ Suspended

Clinical • Trial suspension

Xenikos announces first patient receives T-Guard(R) for steroid-refractory acute GVHD in pivotal U.S.-based phase 3 trial (Yahoo Finance) - "The Dutch company Xenikos B.V....announced today that the first patient has been treated in their U.S.-based Phase 3 registration trial designed to evaluate the use of T-Guard for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) in patients following allogeneic stem cell transplantation....A total of 47 patients will be enrolled through up to 25 transplant centers in the U.S."

Trial status

Results from an Expanded Access Program of Anti-CD3/CD7 Immunotoxin Combination (T-Guard®) for the Treatment of Steroid-Refractory Acute Gvhd (ASH 2019) - "T-Guard was given as the second-line therapy to 10 patients; the remaining 2 patients received T-Guard as the third-line therapy after receiving ruxolitinib (N=1) or cyclosporin-UVB (N=1). Conclusion Consistent with our recent phase I/II trial, our expanded access program in which 12 patients with high-risk SR-aGVHD received T-guard confirms that this treatment is safe and significantly improves patient outcome. A multicenter phase III study is planned to start in 2019 (BMT-CTN 1802)."

Xenikos presents promising new data from Expanded Access Program (EAP) using T-Guard(R) to treat steroid-refractory acute GVHD at ASH annual meeting (Digital Journal) - P1/2, N=NA; "The Dutch company Xenikos B.V....reports today data from an expanded access program (EAP) using T-Guard to treat steroid-refractory acute graft-versus-host disease (SR-aGVHD) in patients following allogeneic stem cell transplantation. These data are being presented later today at the 61st annual meeting of the American Society of Hematology in Orlando, FL...By treatment day 28, 75% of patients had achieved a clinical response...In addition, the 6-month and 1-year overall survival rate was 75% and 58%, respectively....'We are now recruiting patients for our US-based Phase 3 registration trial, marking the next step in taking T-Guard to market.' "

Enrollment open • P1/2 data

1802: T-Guard as Treatment for Steroid Refractory Acute GVHD (clinicaltrials.gov) - P3; N=47; Recruiting; Sponsor: Xenikos; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

1802: T-Guard as Treatment for Steroid Refractory Acute GVHD (clinicaltrials.gov) - P3; N=47; Not yet recruiting; Sponsor: Xenikos

Clinical • New P3 trial

Xenikos receives Fast-track status from the FDA for T-Guard (R) for the treatment of steroid-refractory acute graft-versus-host disease [Google Translation] (DGAP-EQS Group) - "Xenikos BV...announced today that the US Food and Drug Administration...'Xenikos' lead product, T-Guard, has given fast track status to patients with steroid refractory acute graft-versus-host disease (SR-aGVHD) after allogeneic stem cell transplantation. Xenikos is currently preparing to launch a pivotal Phase 3 trial in the US with T-Guard."

Fast track designation • New P3 trial

"Yes, super easy to care for and manage, totally agree. Adaptable to anything. They just aren't guard dogs like a German Shepherd." (@XBIObserver)