SMART-101

PRESS RELEASE | Paris, France – December 3, 2024 Smart Immune, a clinical-stage biotechnology company, and CELLforCURE by SEQENS, a Contract Development and Manufacturing Organization (CDMO) for Advanced Therapy Medical Products (ATMPs), announced today a strategic collaboration to expand SMART101 production capabilities. SMART101 is an innovative therapy in Phase I/II trials for patients with acute leukemia or primary immunodeficiencies (PID), in the EU and the US. Enhanced Production Capacity This partnership will complement Smart Immune's existing capabilities at the MEARY Center for Cell and Gene Therapy and Necker Children Hospital in Paris, supporting the company's expanding clinical development with patients’ inclusions expected to rapidly increase in 2025.The collaboration will enable the production of SMART101 for the ReSET trials in primary immune deficiencies and hematological malignancies post-transplant, as well as for new proof-of-concept trials in solid tumors. CELLforCURE brings a robust and strongly established commercial manufacturing experience, positioning itself as a highly reliable partner for Smart Immune at a critical development stage of its ProTcell platform. Manufacturing Process Evolution 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. Accelerating Patient Access "This collaboration marks a significant step in our mission to bring innovative cell therapies to more patients," says Karine Rossignol, Co-Founder and Chief Executive Officer of Smart Immune. "By partnering with CELLforCURE, we're establishing a robust manufacturing framework to support our growing clinical programs and future commercialization needs.” “We are very proud to collaborate with Smart Immune and contribute to the ambition of bringing innovative cell therapies to more patients,” says Pierre-Noël Lirsac, President of CELLforCURE. “CELLforCURE will leverage its historical expertise as a CDMO as well as its “real-life” experience to manufacture SMART101 clinical batches.” Pierre Heimendinger, Chief Technical Officer of Smart Immune, adds: "The enhanced manufacturing process, featuring rapid sterility testing, will enable a vein-to-vein time of just two weeks. This is particularly crucial for patients receiving fresh allogeneic hematopoietic stem cell transplants within the European and Middle Eastern zones." Strategic Choice of European Manufacturing The choice of CELLforCURE, with its established track record in commercial cell therapy manufacturing, aligns with Smart Immune's commitment to maintaining production excellence in France and Europe. This decision builds upon the foundation established with the MEARY Center at Saint-Louis Hospital and Necker Children Hospital, reflecting the company's dedication to leveraging French and European expertise in advanced therapy manufacturing. A commitment also shared by the SEQENS Group, who capitalized and invested in France and Europe to maintain and develop essential and strategic capabilities for the healthcare sector. About CELLforCURE and SEQENS: CELLforCURE SAS (commercial name: CELLforCURE by SEQENS) is a CDMO authorized by ANSM, dedicated to ATMPs production from concept to commercialization. With advanced technologies, extensive capabilities, and large scale capacity, CELLforCURE offers a seamless journey from early-stage development to commercial manufacturing of a wide range of cell therapies. CELLforCURE is part of the SEQENS Group, a global partner in health, personal care and specialty ingredients, leveraging 3300 employees, 16 manufacturing sites and 9 R&D centers in 9 countries. press@seqens.com / www.seqens.com / LinkedIn: SEQENS and CELLforCURE by SEQENS About Smart Immune: Smart Immune is a clinical-stage biotechnology company developing ProTcell, a thymus-empowered T-cell progenitor platform to rapidly re-arm the immune system against cancer and infection. The company aims to radically improve outcomes for patients in hematology and immuno-oncology. Its main asset SMART101 is in Phase I/II trials for patients with acute leukemia or primary immunodeficiencies (PID), in the EU and the US. Additional clinical applications are planned to be evaluated in combination with innovative cancer therapies. lwormser@ulysse-communication.com (+33) 06 13 12 04 04 / www.smart-immune.com / LinkedIn: Smart Immune

ReSET-02 dose escalation Phase I is completedPhase II PoC randomized segment is starting No dose-limiting toxicities, no safety or tolerability issuesThe highest dose is to be used in both hematological and solid tumors Paris, France – October 23, 2024 – Smart Immune, a clinical-stage biotechnology company pioneering ProTcell, a thymus-empowered T-cell progenitor therapy platform, today announced that the recommended dose for its lead candidate, SMART101, has been established following the completion of the ReSET-02 trial dose escalation segment. This international multicenter study is evaluating the safety and efficacy of a single infusion of SMART101 administered after a standard-of-care HLA-mismatched allogeneic stem cell transplant in adult patients with hematological malignancies such as acute leukemia or myelodysplastic syndrome. 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. This data demonstrates an excellent tolerability and safety profile of 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 evaluating SMART101 in hematology and solid tumors. The recommended dose choice was endorsed by the Chair of the Independent Data Monitoring Review Committee after examining all the data from segment 1 of the trial. In addition, the preliminary data on immune recovery is very promising in patients treated with intermediate and high doses of SMART101 and should be further confirmed by the randomized part of the trial. Dr. Raynier DEVILLIER, Team Leader, Allogeneic Immunotherapy – Paoli-Calmettes Institute, Comprehensive Cancer Center at Marseille, France, said: “As an investigator for the ReSET-02 study, I've been pleased by the tolerability and safety profile of SMART101 among our cohort, which is composed of elderly and fragile patients. As it may offer the greatest potential for efficacy, establishing the maximum dose level as the recommended regimen for adult cancer patients is very promising. I'm thrilled to continue contributing to this line of research. ” Dr. Rahim FANDI, Chief Medical Officer of Smart Immune, added: “This is an important step in the development of SMART101. Following the determination of the recommended dose, we have launched the randomized part of the ReSET-02 study, and we are preparing new proof-of-concept trials in immune-oncology, notably in solid tumor indications. This is a major milestone for Smart Immune to contribute to the fight against cancer and bring new therapeutic options to patients.” About Smart Immune Smart Immune is a clinical-stage biotechnology company developing ProTcell, a thymus-empowered T-cell progenitor platform to rapidly re-arm the immune system against cancer and infection. The company aims to radically improve outcomes for patients in hematology and immuno-oncology. SMART101 is in Phase I/II trials for patients with acute leukemia or primary immunodeficiencies (PID), in the EU and the US. Additional clinical applications are planned to be evaluated in combination with innovative cancer therapies. https://www.smart-immune.com/LinkedIn | X (formerly Twitter) About the ReSET-02 clinical trial ReSET-02 is a first-in-human, open-label, randomized, multicenter phase I/II study evaluating the safety and activity of a single infusion of SMART101 post-HSCT in adult patients with hematological malignancies eligible for an HLA-mismatched PT-Cy HSCT as standard of care. In the Phase II segment, patients will be randomized to receive SMART101 after HSCT (SMART101 arm) or the standard of care with HSCT (SoC; control arm). This will allow generating an internal control group. The trial is currently conducted at multiple sites in France and Italy and coordinated by Fabio Ciceri (San Raffaele Hospital, Milan, IT). For more information, visit www.clinicaltrials.gov, study identifier number NCT05768035. About SMART101 SMART101 is generated ex vivo in 7 days from allogeneic blood stem cells, using Smart Immune’s ProTcell T-cell therapy platform. Once injected into the patient, the SMART101 human T-cell progenitors travel to the thymus where they are educated to become fully functional and self-tolerant T-cells. Preclinical data suggest that the ProTcell platform 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. Media contact: Pauline Rodrigue info@smart-immune.com