Smart Immune Recommends SMART101 Dose for Adult Cancer Trials

Smart Immune, a biotechnology company based in Paris, announced the completion of the ReSET-02 dose escalation Phase I trial, establishing a recommended dose for its lead candidate, SMART101. The dose-escalation study assessed the safety and efficacy of SMART101, administered as a single infusion, following a standard-of-care HLA-mismatched allogeneic stem cell transplant in adult patients with hematological malignancies, such as acute leukemia and myelodysplastic syndrome.

The ReSET-02 trial involved an international multicenter study where patients were treated with three escalating doses of SMART101: 1.5, 4, and 9 million cells per kilogram of body weight. The trial results indicated no dose-limiting toxicities or primary graft failures, and patients did not suffer from severe acute graft versus host disease or serious adverse events attributable to SMART101. This favorable outcome underscored the excellent safety and tolerability of SMART101.

Following these promising results, Smart Immune has decided to use the highest dose of 9 million CD7+ cells per kilogram for future proof-of-concept trials involving adult patients with hematological and solid tumors. The decision was strongly supported by the Independent Data Monitoring Review Committee Chair after a thorough analysis of the trial's first segment data.

Preliminary data from the study also suggested that immune recovery in patients treated with intermediate and high doses of SMART101 was promising, warranting further validation in upcoming randomized trial segments.

Dr. Raynier Devillier, leading the Allogeneic Immunotherapy Team at the Paoli-Calmettes Institute in Marseille, France, expressed satisfaction with SMART101's tolerability and safety in the trial's cohort, which included elderly and fragile patients. He emphasized that establishing the maximum dose level as the recommended regimen for adult cancer patients holds great potential for efficacy, and he looks forward to continuing his contributions to this research.

Dr. Rahim Fandi, Chief Medical Officer of Smart Immune, highlighted the significance of determining the recommended dose, marking an important milestone. Following this achievement, the randomized phase of the ReSET-02 study has commenced. Smart Immune is also preparing new proof-of-concept trials in immune-oncology, particularly for solid tumor indications. Dr. Fandi emphasized that this progress is crucial in advancing Smart Immune's contributions to cancer treatment and providing new therapeutic options to patients.

Smart Immune is a clinical-stage biotechnology company focused on developing ProTcell, a thymus-empowered T-cell progenitor platform designed to enhance the immune system's response against cancer and infections. The company aims to improve outcomes for patients dealing with hematological and immuno-oncological diseases. SMART101 is currently undergoing Phase I/II trials for patients with acute leukemia or primary immunodeficiencies in both the EU and the US, with plans for further clinical applications in combination with innovative cancer therapies.

The ReSET-02 clinical trial is a pioneering, open-label, randomized multicenter Phase I/II study. It evaluates the safety and activity of a single infusion of SMART101 post-HSCT in adult patients with hematological malignancies who are eligible for an HLA-mismatched PT-Cy HSCT as a standard of care. In the Phase II segment, patients will be randomized to receive either SMART101 after HSCT or the standard of care with HSCT, allowing for an internal control group. The trial is being conducted at multiple sites in France and Italy and is coordinated by Fabio Ciceri at San Raffaele Hospital in Milan, Italy.

SMART101 is developed ex vivo within seven days from allogeneic blood stem cells using Smart Immune's ProTcell T-cell therapy platform. Upon injection, SMART101 human T-cell progenitors migrate to the thymus, where they mature into fully functional and self-tolerant T-cells. Preclinical data suggest that this platform could significantly expedite immune system reconstitution, reducing the timeframe from the typical 12 to 18 months to just 100 days, thereby enhancing patient protection against infections and relapse.