Rethymic (allogeneic processed thymus tissue-agdc) / Sumitomo Pharma - LARVOL DELTA

HLA Matching is Not Required For T-Cell Engraftment Following Cultured Thymic Tissue Implantation (CTTI) in Children with Congenital Athymia (AAAAI-WAO 2025) - "Rationale Allogeneic processed thymus tissue-agdc is approved to treat congenital athymia...Conclusions HLA mismatch does not impair T-cell reconstitution in children who received CTTI. However, younger age is associated with higher naïve and total T-cells post implantation."

CD8

Real World Experience in the United States Following FDA Approval of Cultured Thymus Tissue Implantation in Congenital Athymia Patients at Duke University. (TCT-ASTCT-CIBMTR 2025) - "Introduction: Cultured thymus tissue implantation (CTTI), pioneered at Duke University (Durham, NC) received US Food and Drug Administration (FDA) approval in 2021 (RETHYMIC, Sumitomo USA), for the treatment of congenital athymia (CA)...One patient with atypical phenotype (AP) developed EBV+ post-transplant lymphoproliferative disorder and was successfully treated with 4 doses of rituximab... While viral reactivation is common post-CTTI, the procedure is associated with high OS and evidence of immune reconstitution. Since FDA approval, early CTTI patients were older primarily due to no previously approved therapies available and time to insurance approval. With improvements in access, insurance authorization and medical clearance to reduce time to treatment, CTTI shows promise in enhancing patient survival and immune recovery."

Real-world • Real-world evidence • Anemia • Autoimmune Hemolytic Anemia • Cerebral Hemorrhage • CNS Disorders • Developmental Disorders • Graft versus Host Disease • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Oncology • Orthopedics • Thrombocytopenic Purpura

An Observational Cohort Study to Evaluate the Efficacy and Safety ofAllogeneic Processed Thymus Tissue-agdc Post-FDA Approval: The Congenital Athymia Patient Registry (CIS 2024) - "There were 17 participants who experienced ≥1 SAE or AESI; 11experienced AKI. The data collected provide supplemental safety andefficacy results following clinical trials of allogeneic processed thymustissue-agdc and evidence for future guidelines for patient care."

Clinical • Observational data • Acute Kidney Injury • Graft versus Host Disease • Hematological Disorders • Immunology • Nephrology • Pediatrics • CD4

Clinical Characteristics Associated With Mortality Among Patients With Congenital Athymia Treated With Allogeneic Processed Thymus Tissueagdc (CIS 2024) - "Furtherfollow-up is needed to better understand the factors contributing to bestoutcomes of allogeneic processed thymus tissue-agdc implantation.Figure 1A. Distribution of time post-treatment to death Figure 1B: Naive T cellcounts in patients who died."

Clinical • Infectious Disease • Nephrology • Pediatrics • Renal Disease • Respiratory Diseases • CD4

Clinical Characteristics Associated with Early Immune Reconstitution in Patients with Congenital Athymia After Treatment with Allogeneic Processed Thymus Tissue-agdc (FOCIS 2023) - No abstract available

Clinical • Immunology

Timing of Immune Reconstitution in Patients With Congenital Athymia After Treatment With Allogeneic Processed Thymus Tissue-agdc (CIS 2023) - "b Includes methylprednisolone with anti-thymocyte globulin [rabbit] administered just before implantation. a Based on available naïve CD4 + T-cell data. b Naïve CD4 + T-cell data at the year 1 visit was not available for these patients."

Clinical • Developmental Disorders • Immunology • Infectious Disease • Otorhinolaryngology • Pediatrics • Primary Immunodeficiency • Renal Disease • Respiratory Diseases • CD4

The Congenital Athymia Patient Registry: An Observational Cohort Study to Evaluate the Real-World Efficacy and Safety of Allogeneic Processed Thymus Tissue-agdc (CIS 2023) - "The study will end when all patients have achieved at least 2 years of follow-up, died, or withdrawn consent. Data from this ongoing registry will provide real-world evidence to supplement safety and efficacy results from clinical trials of allogeneic processed thymus tissue-agdc and may inform future guidelines for patient care after administration."

Clinical • Observational data • Real-world • Real-world effectiveness • Real-world evidence • Immunology • Pediatrics • CD4 • CD8

Use of Immunosuppressive Medications in Patients With Congenital Athymia Following Treatment With Allogeneic Processed Thymus Tissue-agdc (AAAAI 2023) - "Common immunosuppressive therapies administered at any time included glucocorticoids (n=59, 62.1%; including methylprednisolone, n=57, 60.0%), selective immunosuppressants (n=58, 61.1%; including anti-thymocyte globulin [rabbit] [ATG-R], n=56, 58.9%), and calcineurin inhibitors (n=45, 47.4%). Immunosuppressive medication use decreased after allogeneic processed thymus tissue-agdc treatment."

Clinical • Graft versus Host Disease • Immunology

Enzyvant Announces Merger with Altavant (GlobeNewswire) - "Enzyvant Therapeutics...announced a merger to form a biopharmaceutical company focused on delivering life-altering therapies for people with rare diseases. The combined company retains the name Enzyvant and is equipped with a full range of capabilities spanning non-clinical and clinical development and commercialization and is in the process of developing in-house manufacturing."

M&A • Immunology

Global Pricing, Reimbursement and Market Access Trends for Regenerative Medicines, Atmps, Cell & Gene Therapies (ISPOR-EU 2022) - "Only 5 cell/gene therapies (including 4 CAR-Ts and Zolgensma) overlap across these jurisdictions Cell/gene therapy with highest annual visible ex-factory vary: US was Rethymic (Allogeneic processed thymus tissue–agdc) at €2.59M; Europe was Libmeldy (atidarsagene autotemcel) at €3.33M; and Japan was Zolgensma (onasemnogene abeparvovec) €1.17 million European net therapy cost following negotiation is often 10% to 40% below visible ex-factory price Average time to reimbursed access post regulatory approval was 3 weeks in the US, ~15 weeks in Japan and ranged from 32 weeks in Germany to 88 weeks in France... Regenerative medicines markets are still developing as evidenced by the fragmented regulatory and market access landscape. Type of therapy impacts access, with CAR-Ts and gene therapies for rare paediatric conditions more likely to be approved and reimbursed across jurisdictions relative to “tissue engineered therapies.” The value of cell/gene therapies is being..."

Clinical • Pricing • Reimbursement • Gene Therapies • Pediatrics

Pricing, Reimbursement and Market Access Trends for Cell and Gene Therapies in the US and Europe (ISPOR 2022) - " Cell/gene therapies approved as of November 2021 US: 14 authorized by the FDA, 12 of which are marketed and 9 are reimbursed Europe: 19 authorized by the EC, of which 6 therapies have been withdrawn for clinical/commercial reasons Only 7 cell/gene therapies overlap in both jurisdictions (US/EU) Cell/gene therapy with highest annual visible ex-factory in the US was Rethymic (Allogeneic processed thymus tissue–agdc) at $2.7M in and in Europe was Libmeldy (atidarsagene autotemcel) at $3.24M Generally, net cost of therapy in Europe following negotiations was 10% to 40% below visible ex-factory price Average time to reimbursed access post regulatory approval was 3 weeks in the US and ranged from 32 weeks in Germany to 88 weeks in France Market access status of available cell/gene therapies varied considerably in the US and Europe Market access of cell/gene therapies remains challenging particularly in Europe. Market access of cell/gene therapies remains challenging..."

Pricing • Reimbursement • Gene Therapies

Congenital Athymia Patient Registry (clinicaltrials.gov) - P=N/A | N=75 | Recruiting | Sponsor: Enzyvant Therapeutics GmBH | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Primary Immunodeficiency • CD4 • CD8

Congenital Athymia Patient Registry (clinicaltrials.gov) - P=N/A | N=75 | Not yet recruiting | Sponsor: Enzyvant Therapeutics GmBH

New trial • Immunology • Primary Immunodeficiency • CD4 • CD8

Experience with cultured thymus tissue in 105 children. (PubMed, J Allergy Clin Immunol) - "Treatment with CTT led to development of naive T cells with a 1-year survival rate of 77% and a median follow-up time of 7.6 years. Immune reconstitution sufficient to prevent infections and support survival typically develops 6 to12 months after administration of CTT."

Journal • Alopecia • CNS Disorders • Dermatology • Graft versus Host Disease • Hematological Disorders • Hepatology • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Mental Retardation • Otorhinolaryngology • Primary Immunodeficiency • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Transplantation

Investigational Cultured Thymus Tissue Transplantation (RVT-802) Following Failed Stem Cell Transplantation in Athymic Patients (CIS 2019) - "...Subject 1 was treated with corticosteroids, cyclosporine, cidofovir and infliximab...The post-thymic transplant course included immune thrombocytopenia requiring rituximab and splenectomy and generalized adenopathy for 3 years but no GVHD... RVT-802 can improve T cell immunity after poor or failed correction with allogeneic hematopoietic transplants. In subject 1, GVHD post RVT-802 was related to an acute viral infection; cord T cells attacked HLA mismatches in the recipient. Subjects 2 and 3 were given RVT-802 matched to recipient alleles that were not expressed in the hematopoietic donor."

Guidance for the Care of Patients Undergoing Cultured Thymus Tissue Transplantation (RVT-802) (CIS 2019) - "Clinical care that maintains a well-nourished, clinically stable, infection free patient yields the best chance for successful T cell development. Guidance documents supporting these goals ensure patients are best prepared to receive RVT-802 and develop long lasting thymic function."