siplizumab (TCD601) / ITBMed - LARVOL DELTA

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

An Open-label, Time-lagged, Dose-escalation Study to Evalaute 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 | Not yet recruiting ➔ Recruiting | Trial completion date: Oct 2026 ➔ Jul 2027 | Trial primary completion date: Apr 2026 ➔ Dec 2026

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

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

New P1 trial • Renal Disease • Transplantation

A Study of TCD601 in the Induction of Tolerance in Renal Transplantation (PANORAMA) (clinicaltrials.gov) - P2 | N=18 | Active, not recruiting | Sponsor: ITB-Med LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Nephrology • Transplantation

A Study of TCD601 in the Induction of Tolerance in Renal Transplantation (PERSPECTIVE) (clinicaltrials.gov) - P2 | N=18 | Active, not recruiting | Sponsor: ITB-Med LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Nephrology • Transplantation

ASCEND: A Study of TCD601 in de Novo Renal Transplant Recipients (clinicaltrials.gov) - P2 | N=90 | Active, not recruiting | Sponsor: ITB-Med LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Nephrology • Transplantation

STRIDE: A Study of TCD601 (siplizumab) in New Onset Type 1 Diabetes Patients (clinicaltrials.gov) - P2 | N=96 | Active, not recruiting | Sponsor: ITB-Med LLC | Trial completion date: Jan 2025 ➔ Jan 2027 | Trial primary completion date: Jan 2025 ➔ Jan 2027

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

A Study to Demonstrate the Safety and Efficacy of Siplizumab in the Treatment of Hidradenitis Suppurativa (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Dec 2025 ➔ Oct 2026 | Initiation date: Jan 2025 ➔ May 2025 | Trial primary completion date: Sep 2025 ➔ Apr 2026

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

A Dose Escalation Study of TCD601 Compared to ATG in de Novo Renal Transplantation (clinicaltrials.gov) - P2 | N=33 | Completed | Sponsor: ITB-Med LLC | Active, not recruiting ➔ Completed | Trial completion date: Jul 2025 ➔ Dec 2024 | Trial primary completion date: Jul 2025 ➔ Dec 2024

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

A Study of TCD601 in the Induction of Tolerance in de Novo Liver Transplantation (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: ITB-Med LLC | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Hepatology • Transplantation

SET-SAIL: A Study of SIPLIZUMAB in AILD and LT Patients (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Elizabeth C. Verna | Not yet recruiting ➔ Recruiting | Initiation date: Jun 2024 ➔ Sep 2024

Enrollment open • Trial initiation date • Autoimmune Hepatitis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Transplantation

STRIDE: A Study of TCD601 (Siplizumab) in New Onset Type 1 Diabetes Patients (clinicaltrials.gov) - P2 | N=96 | Active, not recruiting | Sponsor: ITB-Med LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

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

Enrollment closed • Amyotrophic Lateral Sclerosis • CNS Disorders

A Dose Escalation Study of TCD601 Compared to ATG in de Novo Renal Transplantation (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: ITB-Med LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Nephrology • Transplantation

Revised Siplizumab-based conditioning regimen for combined kidney and bone marrow transplantation improved mixed hematopoietic chimerism with significant enrichment of regulatory T cells (TTS 2024) - "To overcome CTS, a revised conditioning regimen was evaluated in eight patients. Our previous conditioning regimen that included anti-CD2 mAb (Siplizumab), rituximab, cyclophosphamide (CY: 60 mg/kg x2), and thymic irradiation, was modified by adding low-dose fludarabine (Flu: 10 mg/m2 x3) while lowering the dose of CY (22.5 mg/kg x2) (Fig. A modified preconditioning regimen has successfully overcome CTS with improved mixed transient hematopoietic chimerism. Markedly enriched Tregs have been observed long-term after CKBMT."

Acute Kidney Injury • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Nephrology • Transplantation • CD4 • IL2RA • IL7R • ISG20

A Study of TCD601 in the Induction of Tolerance in de Novo Renal Transplantation (PANORAMA) (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: ITB-Med LLC | Trial completion date: Jan 2030 ➔ Jul 2030 | Trial primary completion date: Jan 2027 ➔ Jul 2027

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

A Study of TCD601 in the Induction of Tolerance in Renal Transplantation (PERSPECTIVE) (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: ITB-Med LLC | N=12 ➔ 18 | Trial completion date: Dec 2027 ➔ Mar 2030 | Trial primary completion date: Dec 2024 ➔ Mar 2027

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

SET-SAIL: SIPLIZUMAB in AILD and LT (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Elizabeth C. Verna

New P1 trial • Autoimmune Hepatitis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • 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

New P1 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

A Dose Escalation Study of TCD601 Compared to ATG in de Novo Renal Transplantation (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: ITB-Med LLC

New P2 trial • Nephrology • Transplantation

A Dose Escalation Study in de Novo Renal Transplantation (clinicaltrials.gov) - P2 | N=13 | Completed | Sponsor: ITB-Med LLC | Recruiting ➔ Completed | N=24 ➔ 13 | Trial completion date: Mar 2026 ➔ Oct 2023 | Trial primary completion date: Jan 2026 ➔ Oct 2023

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

Delayed Tolerance Through Mixed Chimerism (clinicaltrials.gov) - P1/2 | N=20 | Recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Dec 2029 ➔ Dec 2030 | Trial primary completion date: Dec 2026 ➔ Dec 2028

Trial completion date • Trial primary completion date • Renal Disease • Transplantation • CD34