SMART 101 / Smart Immune - LARVOL DELTA

SMART101 Donor T-Lymphoid Progenitors to Accelerate Immune Reconstitution Post HLA Mismatched Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide: Reset-02 First-in-Human Phase I/II (ASH 2024) - P1/2 | "All patients received a haploidentical HSCT with reduced intensity conditioning and GvHD prophylaxis post-HSCT with cyclophosphamide at D3, 4 and sirolimus ±MMF. Conclusion SMART101 is the first-generation of allogeneic TLP cell therapy obtained from Smart Immune's proprietary GMP manufacturing platform. The preliminary data showed excellent safety and tolerability of the product without any dose limiting toxicity in 11 patients treated with SMART101 and very promising data regarding the early immune recovery of the patients post-HSCT."

P1/2 data • Post-transplantation • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • CD7

Smart Immune and CELLforCURE by SEQENS Partner to Industrialize SMART101 Clinical Batches Manufacturing (GlobeNewswire) - "Smart Immune...and CELLforCURE by SEQENS...announced today a strategic collaboration to expand SMART101 production capabilities....As part of this collaboration, the technology transfer will involve an intermediate manufacturing process, currently being set up at the MEARY Centre, which will bridge the gap between current clinical production methods and future fully automated steps. This evolution includes cell selection, scale-up aligned with future v2.0 requirements, and semi-automation of key steps like the implementation of mini-bioreactor-based production."

Licensing / partnership • Hematological Malignancies

Smart Immune Announces Recommended SMART101 Dose for Adult Cancer Proof-of-Concept Trials (GlobeNewswire) - P1/2 | N=40 | ReSET-02 (NCT05768035) | Sponsor: Smart Immune SAS | "Smart Immune...announced that the recommended dose for its lead candidate, SMART101, has been established following the completion of the ReSET-02 trial dose escalation segment....Patients were treated with three doses of SMART101 at 1.5, 4, and 9 million cells per kg of body weight. No toxicities and no primary graft failures were reported. Patients didn’t experience severe acute graft versus host disease or serious adverse events related to SMART101....Based on these results, Smart Immune has established the highest dose of 9 million CD7+ cells per kg of body weight to be used in adult patient proof-of-concept cancer trials....ReSET-02 dose escalation Phase I is completed. Phase II PoC randomized segment is starting."

P1 data • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome

CAR ProTcell, towards well-tolerated and persistent off-the-shelf allogeneic CAR-T cells (ESGCT 2023) - "Without the need for any TCR knock down, ProTcells pave the way toward a new generation of off-the-shelf allogeneic CAR T cells, avoiding the risk of GvHD thanks to thymic selection while harboring a functional TCR with the potential to fight infection and cancer relapse. Our algorithm for donor selection will reduce the risk of rejection and increase the likelihood of persistence of this new generation of allogeneic CAR-T cells."

CAR T-Cell Therapy • IO biomarker • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • CD34 • CD8 • CXCR4

Smart Immune treats adult acute leukemia patient at final dose level in Phase I/II ReSET-02 trial (GlobeNewswire) - "Smart Immune...announces the treatment of the first patient in the third and final dose cohort of the dose-escalation stage in its ReSET-02 trial. This is an important milestone in the evaluation of SMART101 in post-transplant hematology."

Trial status • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

SMART101 Donor T-Lymphoid Progenitors to Accelerate Immune Reconstitution Post-Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide: SI101-02 First-in-Human Phase I/II (ASH 2023) - "Conclusion SMART101 is the first-generation of allogeneic TLP cell therapy obtained from Smart Immune's proprietary GMP manufacturing platform. The duration and the depth of T cell immunodeficiency post haplo PTCy HSCT is expected to be significantly reduced by the infusion of SMART101 thereby decreasing the non-relapse mortality and morbidity rates and thus improving the overall clinical outcome of this therapy."

P1/2 data • Post-transplantation • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Myelodysplastic Syndrome • Oncology • Transplantation • CD34 • CD7

Smart Immune to Present Details of Pioneering Clinical Study at the American Society of Hematology (ASH) Annual Meeting 2023 (GlobeNewswire) - "Smart Immune...today announced that a poster featuring SMART101, the first T cell progenitor therapy product in development from the Company’s ProTcell platform, will be presented at the American Society of Hematology (ASH) Annual Meeting to be held 09-12 December 2023 in San Diego, California...The poster will present details of the ReSET-02 clinical study..."

P1/2 data • Hematological Malignancies • Leukemia • Oncology

Safety and Efficacy of SMART101 in Adult Patients With Hematological Malignancies After Haploidentical HSCT With Post-transplant Cyclophosphamide (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: Smart Immune SAS | Trial completion date: Oct 2026 ➔ Jul 2026 | Trial primary completion date: Jan 2025 ➔ Jul 2025

Post-transplantation • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Transplantation • CD4

Smart Immune Doses First Leukemia Patients with ProTcell Therapy SMART101 in ReSET-02 Phase I/II Trial (GlobeNewswire) - P1/2 | N=40 | ReSET-02 (NCT05768035) | Sponsor: Smart Immune SAS | "Smart Immune...announced today that the first patients have been dosed in its ReSET-02 Phase I/II trial for adult acute leukemia and myelodysplasia syndrome patients. Two patients have now received the first dose level of SMART101, an allogeneic cell therapy produced from donor mobilized peripheral blood stem cells and differentiated into T-cell progenitors through Smart Immune’s ProTcell therapy platform. Early data show that SMART101 is being well tolerated and has a safety profile in line with that observed in patients enrolled in the ongoing ReSET-01 clinical trial in the T-cell-depleted allogeneic HSCT setting."

P1 data • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Safety and Efficacy of SMART101 in Adult Patients With Hematological Malignancies After Haploidentical HSCT With Post-transplant Cyclophosphamide (clinicaltrials.gov) - P1/2 | N=34 | Recruiting | Sponsor: Smart Immune SAS | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2023 ➔ Jun 2023

Enrollment open • Trial initiation date • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Transplantation • CD4

SI101-01 PHASE I/II STUDY EVALUATING SAFETY AND EFFICACY OF ALLOGENEIC SMART101 T-LYMPHOID PROGENITOR INJECTION TO ACCELERATE IMMUNE RECONSTITUTION AFTER T-CELL DEPLETED ALLOGENEIC HSCT (EHA 2023) - P1/2 | "SMART101 is the first-generation of allogeneic T lymphoid progenitor cells obtained through Smart Immune's ProTcell platform, the first scalable progenitor T-cell manufacturing system in clinics. The early data indicate that SMART101 is well tolerated with a good safety profile. Thymic function, Post-transplant, CD4+ T cells, Allogeneic hematopoietic stem cell transplant"

Clinical • P1/2 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Myelodysplastic Syndrome • Oncology • Pediatrics • Transplantation • CD1a • CD34 • CD7 • CXCR4 • KLRB1 • MLANA

SMART101 DONOR T-LYMPHOID PROGENITORS TO ACCELERATE IMMUNE RECONSTITUTION POST-HAPLOIDENTICAL PERIPHERAL BLOOD STEM CELL TRANSPLANTATION WITH POST-TRANSPLANT CYCLOPHOSPHAMIDE: SI101-02 PHASE I/II (EHA 2023) - "SMART101 is the first-generation of allogeneic T lymphoid progenitor cell therapy obtained from Smart Immune's proprietary ProTcell platform, the first scalable progenitor T-cell manufacturing system in clinics. Notch, Thymus, Post-transplant, Allogeneic hematopoietic stem cell transplant"

P1/2 data • Post-transplantation • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Myelodysplastic Syndrome • Oncology • Transplantation • CD34 • CD7 • CXCR4 • KLRB1 • MLANA • SELP

Smart Immune to present details of the phase I/II studies of new T-cell therapy SMART101 at the European Hematology Association (EHA) (GlobeNewswire) - "Smart Immune...announced today that it will be presenting posters of two abstracts, detailing the phase I/II clinical trials of SMART101, at the 2023 European Hematology Association (EHA) Annual Meeting....The two trials are evaluating the safety and preliminary efficacy of increasing dose levels of SMART101, a cell therapy using allogeneic CD34-CD7+ T-lymphoid progenitors generated ex vivo in 7 days, from mobilized peripheral blood CD34+ cells from a donor via Smart Immune’s ProTcell platform. Once infused to the patient, the SMART101 T-cell progenitors migrate to the thymus where they are educated to become fully functional T-cells. Preclinical data suggest that SMART101 could reconstitute the immune system in 100 days instead of the 12 to 18 months observed in physiology, thereby protecting patients from infection and relapse."

P1/2 data • Preclinical • Hematological Malignancies • Oncology

Rapid and Safe T Cell Immune Reconstitution By T Cell Progenitor Injection Following Haploidentical Transplantation for Severe Combined Immunodeficiency (SCID) (ASH 2021) - P1/2 | "T cell progenitors in this trial are generated in vitro within 7 days from mobilized peripheral blood (mPB) CD34 + hematopoietic stem and precursor cells (HSPCs) using our Notch ligand Delta-like 4 GMP culture platform so called SMART Immune’s SMART101 product...The conditioning regimen is based on Busulfan and Fludarabine according to IE-WP/EBMT guidelines with upfront administration of ATG to prevent graft rejection...He received Defibrotide prophylaxis from D0 until D+21, as well as Ursodeoxycholic acid until D+80...The preliminary results obtained after injection of Human T lymphoid progenitors in P1 are encouraging. While deserving confirmation in larger numbers of patients they could represent an important step forward in improving the outcome of haploidentical HSCT for SCID."

Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Genetic Disorders • Graft versus Host Disease • Immunology • Infectious Disease • Primary Immunodeficiency • Transplant Rejection • Transplantation • CD19 • CD34 • CD7 • CD8 • MLANA • NCAM1 • RAG1

Safety and Efficacy of SMART101 in Pediatric and Adult Patients With Hematological Malignancies After T Cell Depleted Allo-HSCT (clinicaltrials.gov) - P1/2 | N=36 | Recruiting | Sponsor: Smart Immune SAS | Trial completion date: Dec 2026 ➔ May 2027 | Trial primary completion date: Mar 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Pediatrics • Transplantation • CD4 • TP53

Safety and Efficacy of SMART101 in Adult Patients With Hematological Malignancies After Haploidentical HSCT With Post-transplant Cyclophosphamide (clinicaltrials.gov) - P1/2 | N=34 | Not yet recruiting | Sponsor: Smart Immune SAS

New P1/2 trial • Post-transplantation • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Transplantation • CD4

First US leukemia patient dosed with Smart Immune’s investigational SMART101 cell therapy (GlobeNewswire) - "Smart Immune SAS...announced today that the first adult leukemia patient has been dosed with SMART101, a T-cell progenitor cell injection derived from donor stem cells using ProTcell at Memorial Sloan Kettering Cancer Center (MSK)....The first enrolled patient received a SMART101 injection in December 2022; no related adverse events have been reported."

Trial status • Hematological Malignancies • Leukemia • Oncology

Safety and Efficacy of SMART101 in Pediatric and Adult Patients With Acute Leukemia After T Cell Depleted Allo-HSCT (clinicaltrials.gov) - P1/2; N=36; Recruiting; Sponsor: Smart Immune SAS; Not yet recruiting ➔ Recruiting; Trial completion date: Sep 2026 ➔ Dec 2026; Initiation date: Sep 2021 ➔ Dec 2021; Trial primary completion date: Dec 2024 ➔ Mar 2025

Clinical • Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Transplantation • CD4

Smart Immune Announces Acceptance of Two Abstracts Covering Preclinical Research and Clinical Data at the American Society of Hematology - “Smart Immune SAS, a T-cell medicine company utilizing its proprietary ex-vivo biomimetic “thymus in a dish” technology to develop allogeneic T-cell progenitors Smart-101 (ProTcell™) for rapid immune reconstitution, announced today the presentation of clinical data and preclinical research at the 63rd annual meeting of the American Society of Hematology (ASH), taking place December 11-14 in Atlanta, Georgia. Preliminary data in these abstracts became available on the ASH conference website 9:00 AM ET yesterday. Recently, Smart-Immune has also announced the commencement of its first US clinical trial using its T-cell progenitor product (Smart-101) for the treatment of patients with AML and ALL who receive allogeneic hematopoietic stem cell transplant (allo-HSCT).”

Clinical data • Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Smart Immune Receives IRB Approval For Phase 1/2 Clinical Trial of Proprietary Allogeneic T-cell Product Smart-101 (ProTcell) for AML and ALL (GlobeNewswire) - "Smart Immune SAS...announced today that the institutional review board (IRB) of the Memorial Sloan Kettering Cancer Center (MSK) has approved the commencement of the Company’s phase 1/2 clinical trial. MSK will start enrolling patients in November, 2021...The Smart-101 study protocol (ClinicalTrials.gov Identifier: NCT04959903) encompasses two experimental arms in adult and pediatric leukemia patients, respectively, and will enroll up to 36 patients. Study subjects chosen are AML/ALL patients who are eligible for allogeneic hematopoetic stem cell transplant (HSCT) and will receive their routine stem-cell transplant of CD34+ cells at first, and then Smart-101 at approximately day 7 after initial transplant."

DSMB • Trial status • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

Safety and Efficacy of SMART101 in Pediatric and Adult Patients With Acute Leukemia After T Cell Depleted Allo-HSCT (clinicaltrials.gov) - P1/2; N=36; Not yet recruiting; Sponsor: Smart Immune SAS

Clinical • New P1/2 trial • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Pediatrics • Transplantation • CD4

Smart Immune Announces FDA Orphan Drug Status, IND Acceptance and Fast-Track Designation to Commence Phase 1/2 Clinical Trial of Proprietary Allogeneic T cell Progenitor Product SMART 101 (ProTcell) for AML and ALL (GlobeNewswire) - “Smart Immune…announced today that its Investigational New Drug (IND) for Acute lymphocytic leukemia (ALL) and Acute myelocytic leukemia (AML) has been accepted by the FDA. The FDA has also granted SMART 101 fast-track designation under its Expedited Program for Serious Conditions…The clinical trials that are part of the FDA accepted U.S. IND are on track to begin in fall of 2021.”

Fast track designation • IND • New P1/2 trial • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology