Idefirix (imlifidase) / Hansa Biopharma, Sarepta Therap - LARVOL DELTA

A Successful Pediatric Kidney Transplant in a Highly Sensitized Recipient with Compassionate Use of Imlifidase: A Case Study with One Year Follow Up (WTC 2025) - "Multiple desensitization attempts that included combinations of therapeutic plasma exchange, intravenous immunoglobulin, rituximab and tocilizumab, provided limited reduction in sensitization. This case highlights the potential role of IdeS in highly sensitized pediatric kidney transplant recipients. This patient demonstrates well-tolerated and effective transplantation where traditional desensitization strategies failed. Future studies are ongoing in US and Europe to assess long-term outcomes and optimize patient selection for IdeS therapy."

Case study • Clinical • Antibody-mediated Rejection • Pediatrics • Transplantation

The Use of Imlifidase Desensitisation in the Australian and New Zealand Paired Kidney Exchange Program (WTC 2025) - "All received rituximab 1-2 weeks prior to desensitisation. With careful patient selection and risk mitigation, Imlifidase desensitisation can be a useful tool to achieve live donor transplantation for highly sensitised patients (PRA >99%) in paired kidney exchange."

Cellular Basis of Anti-HLA Antibody Rebound and Rejection in Kidney Transplant Patients Desensitized with Imlifidase (WTC 2025) - "However, its impact on B-cell biology, alloantibody rebound, and allograft rejection remains elusive.* In 22 HS KT candidates receiving Imlifidase as desensitization therapy and a step-wise induction therapy based on thymoglobulin, rituximab and IVIG starting at day 4 after KT, we analyzed the cellular basis driving anti-HLA antibody rebound and ABMR using multidimensional spectral flow cytometry and functional cell-based assays.* During the first 6 months, 13 patients (59%) developed BPAR, 1/13 (8%) TCMR at day 5 and 12/13 (92%) ABMR at 35.3±48.9 days post-KT... In HS KT recipients receiving Imlifidase for HLA-incompatible KT, DSA rebound facilitating ABMR is driven by high pre-transplant frequencies of alloreactive mBc, especially those against previously recognized HLA antigens."

Clinical • Transplant Rejection • Transplantation

ConfIdeS: Renal Function in Highly Sensitized Patients 1 Year After Desensitization With Imlifidase Prior to DD Kidney Tx (clinicaltrials.gov) - P3 | N=64 | Completed | Sponsor: Hansa Biopharma AB | Active, not recruiting ➔ Completed

Trial completion • Transplantation

DELISTING STRATEGY IN HIGHLY SENSITISED PATIENTS WITH PREFORMED DSA (ERA 2025) - "In the case group there was greater use of rituximab in induction (p=0.052) and i.v. immunoglobulin plasmapheresis (p=0.005)... Delisting strategies are an option for highly sensitised patients with the presence of DSA, even without the use of imlifidase. The rate of AR and CMV infection was higher, but with acceptable survival data, so they can be considered in situations where the patient's immune status limits access to KT."

Clinical • Antibody-mediated Rejection • Cytomegalovirus Infection • Infectious Disease • Novel Coronavirus Disease • Transplant Rejection

Imlifidase a new treatment for severe minimal change disease? (ERA 2025) - "The patient was immediately started on prednisone 1 mg/kg...Rituximab was administered 5 days after imlifidase... Imlifidase may offer a potential add-on therapeutic option for minimal change disease (MCD) patients when used in combination with other anti-B cell targeted therapies. Methodologically rigorous studies are needed to confirm these findings. Figure: Figure 1: Evolution of renal function (urine output and plasma creatinine), proteinuria and albuminuria, in relation to the administered treatments."

Acute Kidney Injury • Glomerulonephritis • Immunology

Urinary Markers of Inflammation and Damage in Anti-GBM Disease Before and After Treatment with Imlifidase (ERA 2025) - "In conclusion, in our study the urinary markers indicate both glomerular and tubular inflammation and damage which despite improvement persists for six months in patients with anti-GBM disease. Furthermore, patients with a rebound of anti-GBM autoantibodies displayed a tendency to have elevated levels of several urinary markers. These urinary markers could therefore help predict in which patients rebound is likely to occur to allow for adaptation of treatment strategies."

Glioblastoma • Glomerulonephritis • Hematological Disorders • Inflammation • Lupus Nephritis • Nephrology • CLU • KIM1

Lymphocyte depletion post alemtuzumab administration in imlifidase enabled transplants; a UK wide case series (UKKW 2025) - No abstract available

Clinical • Transplantation

Impact of In Vitro Imlifidase on Flow Cytometric Crossmatch and Single Antigen Testing in Serum Samples From Highly Sensitized Renal Transplant Patients (EFI 2025) - "One patient saw no reduction in HLA antibodies as detected by SAB and remained FCXM positive. In vitro incubation of Imlifidase with serum from HSP did not affect the binding of FCXM detection antibodies, indicating that our current flow crossmatch protocol is suitable for Imlifidase treated patient sera without false negative results."

Preclinical • Transplantation

Establishing a Delisting Strategy for Highly Sensitised Renal Patients Considered as Potential Imlifidase Candidates (EFI 2025) - "In conclusion, an active HLA antibody delisting strategy can lead to transplantation without the use of Imlifidase. Combining patient's SAB with C3d antibody testing and dilution of serum to 1:16, it is possible to better stratify candidates who are more likely to respond to Imlifidase treatment and those who may not."

Clinical • Nephrology

Imlifidase in Highly Sensitized Kidney Transplant Recipients with a Positive Crossmatch Against a Deceased Donor: Real-World Results from the First 30 Cases in France (EFI 2025) - "Patients received thymoglobulin, rituximab, tacrolimus, mycophenolate mofetil, and intravenous immunoglobulins in addition to imlifidase...A total of 22 patients (73%) developed at least one infection (1.7 ± 0.71 per patient). These real-world data demonstrate that imlifidase has an acceptable efficacy and safety profile in the medium term for selected patients, despite a high incidence of DSA rebound and rejection."

Clinical • Real-world • Real-world evidence • Antibody-mediated Rejection • Infectious Disease • Transplantation

VTX-PID Mediated Optimal Depletion of Anti-AAV3B Neutralizing Antibodies in Human Subjects allows to Expand Patient Eligibility for future AAV-Based Gene Therapies (ASGCT 2025) - "VTX-PID (imlifidase) is a streptococcal protease that specifically and rapidly cleaves IgG antibodies into F(ab')2 and Fc fragments...2 of these subjects also experienced a transient LFT elevation, which triggered the addition of prophylactic prednisone in the 6 next subjects treated at the highest dose. Based on these data, a PK/PD model has been built including variables from patient-specific factors (e.g. ADA, PK, NAbs level…) to define the most suitable dosing schedule to achieve the optimal window for AAV3B-based treatment. Therefore, VTX-PID-mediated anti AAV NAb removal provides an opportunity to expand the patient population that may benefit from AAV-based systemic gene therapies."

Clinical • Gene therapy • Gene Therapies • Musculoskeletal Diseases • Musculoskeletal Pain • Pain

Depletion of AAV8 Antibodies in Seropositive Individuals Treated with the IgG Cleaving Enzyme Imlifidase (ASGCT 2025) - "Disclaimer: Imlifidase is an investigational product and is not approved in the USA for any use. Disease Focus of Abstract:None"

Clinical • Gene Therapies

SUCCESSFUL POTENT REDUCTION OF DONOR-SPECIFIC ANTI-HLA ANTIBODIES USING IMLIFIDASE IN A PATIENT UNDERGOING HAPLOIDENTICAL STEM CELL TRANSPLANTATION (EBMT 2025) - "Due to ongoing minimal residual disease (MRD) positivity, she was switched to Decitabine and Venetoclax, with the aim of consolidation by allogeneic stem cell transplant...Desensitisation was performed using 3-weekly IV Rituximab 375mg/m2 and SC Bortezomib 2mg with twice weekly plasmapheresis...Compassionate access to 2 doses of Imlifidase was obtained to further attempt reduction of DSA levels.The patient underwent reduced intensity conditioning with Fludarabine, Cyclophosphamide and 2 Gy TBI and post-transplant Cyclophosphamide, with Ciclosporin and Mycophenolate Mofetil for graft versus host disease prophylaxis... To our knowledge, this was the first use of Imlifidase for this indication. This case demonstrates the potency of Imlifidase to achieve rapid transient reduction in DSA with high MFI. More studies e.g., frequency of infusion and incorporation to desensitisation regimens are required."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Transplantation • DNMT3A • IDH1

Hansa Biopharma publishes 2024 Annual and Sustainability Reports (PRNewswire) - "'2024 was a momentum-building year for Hansa. With year-on-year IDEFIRIX sales growth of 83%, a successful financing round'...Preparation for commercialization in the US is progressing, with complete randomization of the pivotal Phase 3 trial - ConfIdeS - announced in May 2024. Data readout for the trial and submission of a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) are planned in 2H 2025...The company plans to align with regulatory authorities in the first half of 2025 on a clinical development path for HNSA-5487 in MG...In Autoimmune, enrolment was completed for the GOOD-IDES-02 Phase 3 trial in anti-glomerular basement membrane (anti-GBM) disease in December, with data readout expected in the second half of 2025."

Commercial • FDA filing • P3 data • Regulatory • Immunology • Myasthenia Gravis • Rare Diseases • Transplantation

PAES: Efficacy and Safety in Imlifidase Desensitized Kidney Tx Patients, Including Two Non-Comparative Reference Cohorts (clinicaltrials.gov) - P3 | N=225 | Active, not recruiting | Sponsor: Hansa Biopharma AB | Recruiting ➔ Active, not recruiting

Enrollment closed • Transplantation

LIVEDES: Imlifidase in Living Donor Renal Transplantation Highly Sensitized Recipients (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Fundacion Clinic per a la Recerca Biomédica | N=10 ➔ 0 | Trial completion date: Dec 2026 ➔ May 2027 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Jul 2026 ➔ Dec 2026

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Nephrology • Transplantation

Hansa Biopharma completes enrolment in European Phase 3 20-HMedIdeS-19 Post Authorization Efficacy and Safety study in highly sensitized kidney transplant patients (PRNewswire) - "Hansa Biopharma AB...announced today that it has completed enrolment of its 20-HMedIdeS-19 Post Authorization Efficacy and Safety (PAES) study, an open-label Phase 3 confirmatory study in Europe investigating the one-year patient and graft survival in highly sensitized patients who have undergone HLA-incompatible kidney transplantation following desensitization treatment with imlifidase...The Company anticipates data readout in the second half of 2026 followed by submission to the European Medicines Agency to seek full authorization....The PAES study is a controlled, open-label post-authorization efficacy and safety study to determine the one-year graft failure-free survival in highly sensitized kidney transplant patients with positive crossmatch against a deceased donor who received desensitization treatment with imlifidase followed by an HLA-incompatible kidney transplantation."

Enrollment closed • P3 data • Transplantation

Industry sponsored symposium: Clinical Experience with Imlifidase-Enabled Kidney Transplants in UK & France (BTS-NHSBT JAC 2025) - "Sponsored by HANSA BIOPHARMA"

Clinical • Transplantation

A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) Following Imlifidase Infusion in Participants With Duchenne Muscular Dystrophy (DMD) Determined to Have Pre-existing Antibodies to Recombinant Adeno-Associated Virus Serotype (rAAVrh74) (clinicaltrials.gov) - P1 | N=6 | Enrolling by invitation | Sponsor: Sarepta Therapeutics, Inc. | Trial completion date: Sep 2026 ➔ Oct 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

PAES: Efficacy and Safety in Imlifidase Desensitized Kidney Tx Patients, Including Two Non-Comparative Reference Cohorts (clinicaltrials.gov) - P3 | N=225 | Recruiting | Sponsor: Hansa Biopharma AB | Trial completion date: Dec 2024 ➔ Apr 2026 | Trial primary completion date: Dec 2024 ➔ Apr 2026

Trial completion date • Trial primary completion date • Transplantation

PAES-LTFU: A Long-term Follow-up Trial of Patients Previously Treated With Imlifidase Prior to Kidney Transplantation and a Non-comparative Transplanted Patient Group (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Hansa Biopharma AB | Trial completion date: Dec 2028 ➔ Apr 2030 | Trial primary completion date: Dec 2028 ➔ Apr 2030

Trial completion date • Trial primary completion date • Transplantation

DINKY: Imlifidase Prior to Kidney Transplant in Highly Sensitised Children (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Hansa Biopharma AB | Trial completion date: Sep 2029 ➔ Aug 2031 | Trial primary completion date: Sep 2024 ➔ Feb 2027

Trial completion date • Trial primary completion date • Transplantation

Anti-HLA-I IgG Subclass Influences Antibody-Mediated Platelet Activation in the Context of Platelet Transfusion Refractoriness (ASH 2024) - "In some conditions, platelets were incubated either with Eculizumab (100 µg/mL), IV.3 (10µg/mL) or IdeS (Imlifidase, 20 µg/mL) before incubation with the different chimeric antibodies in order to inhibit certain activation pathways. Our research reveals that platelet activation mechanisms in response to anti-HLA-I antibodies depend on the IgG subclass. Cleavage of anti-HLA-I IgG by IdeS abolishes platelet activation mediated by antibodies, which opens the door for developing strategies to safely transfuse platelets despite the limitations imposed by alloantibodies."

Hematological Disorders • ANXA5 • FCGR2A

GOOD-IDES-02: A Study With Imlifidase in Anti-GBM Disease (clinicaltrials.gov) - P3 | N=50 | Active, not recruiting | Sponsor: Hansa Biopharma AB | Recruiting ➔ Active, not recruiting

Enrollment closed • Glomerulonephritis • Renal Disease