siplizumab (TCD601) / ITBMed - LARVOL DELTA

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

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