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

Elimination of alloantibody responses using chimeric HLA-II antibody receptor T cells (ASH 2025) - "Additionally, solid organ transplant recipients can form denovo donor-specific alloantibodies (DSAs) after transplantation and these may lead to allograft rejection.Current strategies aimed at eliminating pre-existing alloantibodies (desensitization) such as intravenousimmunoglobulin (IVIG), plasmapheresis, rituximab, proteasome inhibitors, and imlifidase havedemonstrated inconsistent efficacy or fail to produce sustained reductions in alloantibodies. CHAR-II T cells selectively depletedalloantibodies that were specific or cross-reactive to the HLA alleles expressed on the CHARs. Finally, wemodeled targeting of patient's alloantibody-specific B cells in vitro and confirmed that CHAR-II T cellseliminate primary B cell clones, and HLA class-II alloantibodies, with high specificity.ConclusionOverall, our findings provide proof of concept for the use of the CHAR-II platform as an efficient andselective therapeutic strategy for desensitization or treatment of..."

Antibody-mediated Rejection • Bone Marrow Transplantation • Solid Organ Transplantation • Transplant Rejection

Degradation of IgG autoantibodies associated with platelet disorders by a half-life extended IgG protease (ASH 2025) - "Treatment options for ITP include IVIG, rituximab, or plasmapheresis toreduce anti-platelet autoantibodies (Mititelu A, et al...Wild type (WT) IdeS (drug name imlifidase) has enabled platelettransfusion in a patient with severe alloimmune platelet refractoriness (Qamar A, et al...Pharmacokinetics (PK) in C57BL/6 mice, humanized FcRn mice, and hFcRn/Albumin-KO micesupported modeling of long human PK with an elimination half-life of 9.6 days.Overall, the data show CYR212 achieves rapid and deep depletion of IgG, with low immunogenicity foreffective repeat doses. The profile is well suited for rapidly addressing antibody-mediated hematologicalemergencies and long-term maintenance therapy."

Cardiovascular • Hematological Disorders • Immune Thrombocytopenic Purpura • Rheumatology • Thrombocytopenia • Thrombocytopenic Purpura • Thrombosis

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=5 | Terminated | Sponsor: Sarepta Therapeutics, Inc. | Trial completion date: Oct 2027 ➔ Oct 2025 | Enrolling by invitation ➔ Terminated | Trial primary completion date: Jan 2026 ➔ Oct 2025; Study is being terminated due to a business decision.

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

ConfIdeSLTFU: Survival and Dialysis Independency in Highly Sensitized Patients After Desensitization With Imlifidase and Tx of Kidneys (clinicaltrials.gov) - P=N/A | N=64 | Active, not recruiting | Sponsor: Hansa Biopharma AB | Recruiting ➔ Active, not recruiting

Enrollment closed • Transplantation

Alloantibody Levels, Immunoglobulin Degradation Products, and Platelet Transfusion Response over Successful Desensitization of Severe Alloimmune Platelet Refractoriness with a Novel IgG-Targeted Enzyme Therapeutic (ASH 2023) - "METHODS With IRB approval, patient data and samples (D-16; D-1 post-conventional desensitization with rituximab and therapeutic plasma exchange; D0 post-imlifidase dose 1; D2 post-imlifidase dose 2; and D7, D14 and D29 follow-up samples) were collected. These results suggest imlifidase is capable of effective desensitization despite profound baseline sensitization, with rapid cleavage of intact IgG to F(ab'), resulting in the temporary reduction of unacceptable antigens. Larger scale investigation of imlifidase in desensitization of APR patients requiring significant transfusion over a limited period of time, along with investigation into transfusion strategies in desensitized APR, are warranted."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Diagnostic Dilemma: When Pyelonephritis Masks Anti-GBM Disease (KIDNEY WEEK 2025) - "While plasmapheresis, steroids, and cyclophosphamide are standard therapy, rituximab was chosen due to gonadotoxic concerns, highlighting individualized treatment approaches. Emerging therapies like Imlifidase offer potential renal benefit, reinforcing the importance of early diagnosis in atypical presentations. Although the patient received a COVID booster vaccination three months ago, no causal association has been described in the literature."

Glioblastoma • Glomerulonephritis • Infectious Disease • Lupus Nephritis • Nephrology • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases • Vasculitis

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

The Cost-Effectiveness of Imlifidase Idefirix® for Desensitization Treatment of Highly Sensitized Adult Kidney Transplant Patients in Ireland (ISPOR-EU 2025) - "Imlifidase-enabled kidney transplantation with a deceased donor kidney is a cost-effective treatment strategy compared with lifelong dialysis for highly sensitised adult patients in Ireland."

Clinical • Cost effectiveness • HEOR • Transplantation

Depletion of AAV8 antibodies in seropositive healthy subjects and patients treated with the IgG cleaving enzyme imlifidase (ESGCT 2024) - "The results from this small in vitro study on serum from imlifidase treated individuals, supports the rational for further clinical studies, as antibody depletion with imlifidase could offer a simple and elegant way to enable gene therapy in currently ineligible patient groups. The potential of imlifidase in removing AAV antibodies has previously been demonstrated in both in vivo and in vitro studies and is under further evaluation in collaboration with our gene therapy company partners."

Clinical • Gene Therapies

Treatment of Patients with Donor-Specific Anti-HLA Antibodies (ICBMT 2025) - "Rituximab induces B-cell depletion by targeting CD20, reducing DSA production. Proteasome inhibitors like bortezomib or carfilzomib target plasma cells, inducing apoptosis by disrupting the ubiquitin-proteasome pathway...Post-transplant cyclophosphamide (PTCy) has demonstrated particular efficacy in the context of haploidentical HSCT, owing to its capacity to selectively eliminate alloreactive T cells...Complement inhibition strategies, utilizing agents such as eculizumab (a monoclonal antibody targeting C5) or next-generation complement inhibitors like ravulizumab, aim to abrogate complement-mediated HSC destruction. Imlifidase, a bacterial-derived IgG-degrading enzyme (IdeS), is currently under investigation for its capacity to rapidly and profoundly reduce DSA levels by cleaving IgG antibodies...Continued collaboration among clinicians, researchers, and immunologists is essential to advance HSCT. By leveraging our expanding knowledge of DSA biology, refining risk..."

Clinical • Bone Marrow Transplantation • Hematological Disorders • Immunology • Targeted Protein Degradation

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

Overcoming AAV8 Immunity: First Seropositive Crigler-Najjar Patient Treated with GNT0003 Following Imlifidase Pretreatment (GNT-018-IDES clinical trial) (ESGCT 2025) - No abstract available

Clinical • Metabolic Disorders

VTX-PID (imlifidase) Mediated Optimal Depletion of Anti-AAV3B Neutralizing Antibodies in Human Subjects allows to Expand Patient Eligibility for future AAV-Based Gene Therapies : Results of a dose ranging and PK/PD modeling approach (ESGCT 2025) - No abstract available

Clinical • Gene therapy • PK/PD data • Gene Therapies

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

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