In Main Objective 1, we conducted research that has clarified that also a subgroup of patients with acute myeloid leukemia (AML) express TdT, providing a rationale for including also this patient group in a clinical trial. By screening biobanked cryopreserved samples from 239 AML patients with an extensive immunophenotyping panel, we showed that 22% expressed high levels of TdT. We demonstrated that TdT+ AML blasts were efficiently killed by TdT TCR T cells in vitro. AML patients have an overall 5-year survival of only 30% and hence a great medical need that potentially could be met by TTT-therapy.
In Main Objective 2, the Project Leader worked together with her strong team of advisers with expertise in business development, clinical development, IPR and financial aspects needed for commercialization. In-depth interviews with Key Opinion Leaders in acute myeloid leukemia treatment and drug development was performed, resulting in development of a Target Product Profile and drafted clinical strategy. Moreover, an IPR and business strategy was developed, and the PCT phase of the approved TdT TCR patent and platform technology patent was secured. A clinical trial application (CTA) for TTT-therapy was submitted to EMA in March 2025 for a phase I/IIa clinical in r/r ALL, and this trial can be amended if future experimental in vivo data provide additional support for therapeutic efficacy in AML. A process for manufacturing of cells (part of the CTA) has been developed and technology transfer successfully performed to an academic GMP facility that will manufacture the gene-modified T cells for the trial. Validation runs were completed.
