siplizumab (TCD601) / ITBMed - LARVOL DELTA

AURORA: A Study of TCD601 (Siplizumab) in Newly Diagnosed Adult Amyotrophic Lateral Sclerosis (ALS) Patients (clinicaltrials.gov) - P1 | N=7 | Terminated | Sponsor: ITB-Med LLC | N=48 ➔ 7 | Trial completion date: Nov 2029 ➔ Jul 2026 | Recruiting ➔ Terminated | Trial primary completion date: Nov 2029 ➔ Jul 2026; The Sponsor has decided to terminate study early due to significant enrolment challenges since restarting the study in Dec 2025. The Sponsor is concerned that the study is not feasible and ultimately the objectives of the study cannot be met.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Amyotrophic Lateral Sclerosis • CNS Disorders

A Study of TCD601 in the Induction of Tolerance in Renal Transplantation (PERSPECTIVE) (clinicaltrials.gov) - P2 | N=7 | Terminated | Sponsor: ITB-Med LLC | N=18 ➔ 7 | Trial completion date: Mar 2030 ➔ Feb 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2027 ➔ Feb 2026; Sponsor decision, indication no longer under evaluation

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

MODERNIZE1: A Study Comparing Siplizumab With Rabbit Anti-Thymocyte Globulin to Help the Body Accept a Kidney Transplant (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Nefro Avillion Clinical Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Transplant Rejection • Transplantation

Safety and Efficacy of Siplizumab Induction Therapy in Renal Transplant Recipients: An Open-Label Phase 2 Study (ATC 2026) - "Rabbit antithymocyte globulin (rATG) is an animal-derived polyclonal antibody mixture primarily of antibodies to human T-cell antigens. In this Phase 2 study, siplizumab was well-tolerated and demonstrated prevention of acute rejection comparable to an rATG based regimen. These results support the continued development of a modernized, highly targeted humanized therapy for the prevention of acute rejection in kidney transplant recipients. Clinical advantages of targeted T-cell depletion versus an animal derived antibody mixture require further investigation."

Clinical • Late-breaking abstract • P2 data • Transplant Rejection • Transplantation • CD2

Evidence for Immunomodulatory Effect of Thymus in Pig-to-Decedent Human Thymokidney Transplant (ATC 2026) - "Here, we describe a novel immunosuppressive regimen along with GGTA1KO TK transplantation in a thymectomized human decedent recipient, characterizing T cell recovery over 22 days* TKs were constructed in an SLAhh GGTA1KO miniature swine 6 months prior to transplantation of one TK into a brain-dead human recipient who received immunosuppression consistent of siplizumab, obinutuzumab, IgG degrader, belatacept, eculizumab, pegcetaloplan and steroids. Human thymocytes and T cells, including Tregs, were detected within the thymic tissue at explant, and human RTEs recovered in the blood. The presence of porcine Tregs pre-transplant and human and porcine Tregs post-transplant in the kidney portion of the graft suggests a possible "immunomodulation" mechanism that may explain the outstanding outcomes achieved in pig-to-baboon TK xenografts using donor swine bearing only the GGTA1KO modification."

Immunomodulating • Immunology • Transplant Rejection • Transplantation • CD8 • PTPRC

Evidence for Immunomodulatory Effect of Thymus in Pig-to-decedent Human Thymokidney Transplant (FOCIS 2026) - "TKs were constructed in an SLAhh GGTA1-KO miniature swine 6 months prior to transplantation of one TK into a decedent who underwent thymectomy and received immunosuppression consisting of siplizumab, obinutuzumab, IgG degrader, belatacept, eculizumab, pegcetaloplan and steroids. Human thymocytes and T cells, including Tregs, were detected within the thymic tissue at explant, and human RTEs were recovered in peripheral blood. The presence of porcine Tregs suggests a possible "immunomodulation" mechanism that may explain the outstanding outcomes achieved in pig-to-baboon TK xenografts using source pig with only the GalT-KO modification"

Immunomodulating • Immunology • Transplant Rejection • PTPRC

CD2-targeted Therapy in Type 1 Diabetes Promotes Treg and Exhausted T Cells (FOCIS 2026) - P1/2, P2 | "The phase 2 T1DAL trial (ITN045AI, NCT00965458), using a CD2-targeting fusion protein, alefacept, demonstrated preserved beta cell function with depletion of the effector T cell population and relative sparing of Treg. In a new clinical study, DESIGNATE (ITN095AI, NCT05574335), we evaluated whether CD2 T cell depletion with a monoclonal antibody, siplizumab (TCD-601, ITB-MED), resulted in a similar mechanistic outcome. In T1D participants, a monoclonal antibody targeting CD2 increased relative levels of Treg and exhausted CD4 T cells but was associated with significant T cell depletion. These findings support the continued study of CD2-targeting molecules to develop new therapies for T1D"

IO biomarker • Immune Modulation • Immunology • CD2 • CD4 • PD-1 • TIGIT

Engineering Stable and Lymphodepletion-resistant Regulatory T Cell Therapy for Inducing Immune Tolerance in Transplantation and Autoimmunity (FOCIS 2026) - "Using CRISPR/Cas9 editing, we deleted CD2 (a co-stimulatory receptor) from Tregs to render them resistant to siplizumab-mediated lymphodepletion...We observed that that the phenotype, functionality and metabolism of CD2-KO Tregs exhibited a trend resembling rapamycin-treated Tregs, implicating a mechanism wherein the PI3K-AKT-mTOR axis is potentially downmodulated. Phosphoproteomic analysis revealed decreased mTOR-mediated signaling as an underlying mechanism for the improved metabolic phenotype and lineage stability of CD2-KO Tregs. Together, these findings have potential to advance clinical implementation of Treg-based therapies in organ transplantation as well as autoimmune disorders."

IO biomarker • Immunology • Transplant Rejection • CD2 • FOXP3 • PD-1

Engineering Stable and Lymphodepletion-resistant Regulatory T Cell Therapy for Inducing Immune Tolerance in Transplantation and Autoimmunity (FOCIS 2026) - "Using CRISPR/Cas9 editing, we deleted CD2 (a co-stimulatory receptor) from Tregs to render them resistant to siplizumab-mediated lymphodepletion...We observed that that the phenotype, functionality and metabolism of CD2-KO Tregs exhibited a trend resembling rapamycin-treated Tregs, implicating a mechanism wherein the PI3K-AKT-mTOR axis is potentially downmodulated. Phosphoproteomic analysis revealed decreased mTOR-mediated signaling as an underlying mechanism for the improved metabolic phenotype and lineage stability of CD2-KO Tregs. Together, these findings have potential to advance clinical implementation of Treg-based therapies in organ transplantation as well as autoimmune disorders."

IO biomarker • Late-breaking abstract • Immunology • Transplant Rejection • CD2 • FOXP3 • PD-1

Evaluate the Safety and Efficacy of Subcutaneous Siplizumab in the Treatment of Hidradenitis Suppurativa. (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Jul 2027 ➔ Jul 2028 | Trial primary completion date: Dec 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Dermatology • Hidradenitis Suppurativa • Immunology

ASCEND: A Study of TCD601 in de Novo Renal Transplant Recipients (clinicaltrials.gov) - P2 | N=76 | Completed | Sponsor: ITB-Med LLC | Active, not recruiting ➔ Completed

Trial completion • Nephrology • Transplantation

MODERNIZE1: A Study Comparing Siplizumab With Rabbit Anti-Thymocyte Globulin to Help the Body Accept a Kidney Transplant (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Nefro Avillion Clinical Development, LLC

New P2 trial • Transplant Rejection • Transplantation

AURORA: A Study of TCD601 (Siplizumab) in Newly Diagnosed Adult Amyotrophic Lateral Sclerosis (ALS) Patients (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: ITB-Med LLC | Active, not recruiting ➔ Recruiting | Trial completion date: Nov 2026 ➔ Nov 2029 | Trial completion date: Nov 2026 ➔ Nov 2029 | Trial primary completion date: Nov 2026 ➔ Nov 2029 | Trial primary completion date: Nov 2026 ➔ Nov 2029

Enrollment open • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

A Dose Escalation Study of TCD601 Compared to ATG in de Novo Renal Transplantation (clinicaltrials.gov) - P2 | N=33 | Terminated | Sponsor: ITB-Med LLC | Completed ➔ Terminated; After enrolment was complete, and sufficient data was collected to fully characterize the highest dose cohort, study follow up was terminated by the sponsor for non-safety related reasons.

Trial termination • Nephrology • Transplantation

CD2 SCD: Siplizumab for Sickle Cell Disease Transplant (clinicaltrials.gov) - P1/2 | N=1 | Terminated | Sponsor: Columbia University | N=18 ➔ 1 | Trial completion date: Jul 2029 ➔ Dec 2025 | Recruiting ➔ Terminated; Closed by the industry collaborator

Enrollment change • Trial completion date • Trial termination • Anemia • Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation • CD34 • HLA-B • HLA-C • HLA-DPB1 • HLA-DQB1 • HLA-DRB1

A Study of TCD601 in the Induction of Tolerance in Renal Transplantation (PANORAMA) (clinicaltrials.gov) - P2 | N=4 | Terminated | Sponsor: ITB-Med LLC | N=18 ➔ 4 | Trial completion date: Jul 2030 ➔ Oct 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jul 2027 ➔ Oct 2025; Sponsor decision, indication no longer under evaluation

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

SET-SAIL: A Study of SIPLIZUMAB in AILD and LT Patients (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Elizabeth C. Verna | Trial completion date: Mar 2026 ➔ Mar 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Trial completion date • Trial primary completion date • Autoimmune Hepatitis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Transplantation

DESIGNATE: Siplizumab in T1DM (clinicaltrials.gov) - P1/2 | N=8 | Terminated | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | N=120 ➔ 8 | Active, not recruiting ➔ Terminated; Prior to termination the DESIGNATE study was an on enrollment hold due to greater than anticipated lymphodepletion. The pharmaceutical partner decided not to reopen its own T1D trial and ceased development of siplizumab in autoimmunity.

Enrollment change • Trial termination • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Tolerance Through Mixed Chimerism (Sip-Tego) (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Tatsuo Kawai, MD, PhD | Not yet recruiting ➔ Recruiting

Enrollment open • Renal Disease • Transplantation

ASCEND: A Study of TCD601 in de Novo Renal Transplant Recipients (clinicaltrials.gov) - P2 | N=90 | Active, not recruiting | Sponsor: ITB-Med LLC | Trial completion date: Oct 2026 ➔ Apr 2026 | Trial primary completion date: Jul 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Nephrology • Transplantation

STRIDE: A Study of TCD601 (Siplizumab) in New Onset Type 1 Diabetes Patients (clinicaltrials.gov) - P2 | N=9 | Terminated | Sponsor: ITB-Med LLC | N=96 ➔ 9 | Trial completion date: Jan 2027 ➔ Jul 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2027 ➔ Jul 2025; The study has been early terminated due to business reasons. This decision is not related to any safety, efficacy, or regulatory concerns.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Study of Siplizumab Induction: Effect of an Anti-CD2 mAb on T-Cell Subsets in Kidney Transplant Recipients (WTC 2025) - "Increasing doses of siplizumab were associated with deep and durable Tmem depletion while preferentially sparing Tn populations, leading to an immunophenotypic shift in CD4+ and CD8+ T-cells toward a naïve-dominant and memory depleted profile in the post-transplant period compared to rATG. These findings suggest that CD2-targeted induction with siplizumab provides a specific, differentiated, immunomodulatory response warranting continued development for the treatment of kidney transplant recipients."

Clinical • Transplant Rejection • Transplantation • CCR7 • CD8

DESIGNATE: Siplizumab in T1DM (clinicaltrials.gov) - P1/2 | N=120 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Dec 2027 ➔ Oct 2025 | Trial primary completion date: Dec 2026 ➔ May 2025

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Delayed Tolerance Through Mixed Chimerism (clinicaltrials.gov) - P1/2 | N=20 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Recruiting ➔ Active, not recruiting

Enrollment closed • Renal Disease • Transplantation • CD34

Renal Allograft Tolerance Through Mixed Chimerism - SMC/MGH (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2025 ➔ Jun 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2027

Enrollment closed • Trial completion date • Trial primary completion date