Orano - Annual Activity Report 2025 28 2 SITUATION AND ACTIVITIES OF THE COMPANY AND ITS SUBSIDIARIES DURING THE PAST FINANCIAL YEAR Highlights of the financial year ● the transfer on January 1, 2026, with a favorable opinion from the employee bodies, of some of the employees of Orano Projects and certain employees of Orano Recyclage to the Orano Aval du Futur (OAdF) entity, which has approximately 300 employees on January 1, 2026; the creation of an Economic and Social Unit (ESU) between Orano Projects and OAdF in order to ensure uniform social conditions; ● the transition to the APS phase of the storage pool project (ADEC) as well as the MOX recycled fuel manufacturing plant project, which confirms that the commissioning deadlines planned for 2040 for these facilities will be met; ● the start of site preparation work consisting of the deconstruction of certain tertiary buildings located on the site of the program; and ● the signing of a preliminary agreement between OAdF and EDF securing the financing of a major part of the program’s expenses for 2025 and 2026; the start of discussions between OAdF and EDF, in accordance with the conclusions of the CPN of March 2025, to establish long-term financing for the program. 2.1.2.4 Other activities Nuclear Medicine Orano Med continues its development with the achievement of major milestones, both in the field of cancer treatments (https:// www.Oranomed.com/en/pipeline) and in that of its unique industrial platform in the world (https://www.Oranomed.com/en/ industrial-platform): ● In 2025, Phase 2 clinical trials were completed for AlphaMedix, a drug candidate for the treatment of neuroendocrine tumors (NETs). The results underscore the promising therapeutic potential of this treatment as a first-in-class therapeutic pioneer in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Detailed results from the phase 2 trial in patients with GEP-NETs who had or had not previously been treated with internal beam radiotherapy (IBR) were presented in two oral presentations at the European Society for Medical Oncology (ESMO 2025) Congress in Berlin, Germany. This announcement comes one year after the signing of the strategic partnership with Sanofi, a leading pharmaceutical player with recognized capabilities in marketing on an international scale. Subject to obtaining regulatory authorizations, the agreement provides that Sanofi will be responsible for the worldwide marketing of AlphaMedix, while Orano Med will ensure its production thanks to its industrial platform currently under development; ● Orano Med is also developing the program targeting the GRPR (Gastrin-Releasing Peptide Receptor), expressed in several types of cancers, including breast and prostate cancer. Phase 1 of this program is currently under development; ● In addition, the partnership between Orano Med and Molecular Partners, a Swiss biotechnology company developing targeting molecules adapted to lead-212 targeted alphatherapy, continues. A first program, MP0712, a radio-DARPin targeting DLL3 (delta-like ligand 3), will enter a first-in-human study in 2026, for the treatment of small cell lung cancer in particular; ● In 2025, Orano Med also took another step forward in its longstanding partnership with the pharmaceutical group Roche. The two-stage pre-targeted radioimmunotherapy (PRIT), combining the administration of a bispecific antibody and, a few days later, chelated lead-212, is now ready to move from the preclinical phase to clinical trials in humans. A phase 1 trial will begin in the first semester of 2026 and will evaluate the effectiveness of this new treatment for different types of cancers, such as colorectal, pancreatic or gastric cancers; ● Finally, Orano Med strengthened its Research and Development capabilities by inaugurating the extension of its DDPU (Drug Development & Preclinical Unit) facility in Plano, Texas. This strategic site is dedicated to the development of new radiopharmaceuticals and the preclinical research of targeted alpha therapies with lead-212. This investment of more than 5 million US dollars has enabled the expansion of the center by approximately 1,000 m², including nearly 465 m² of new laboratories and 511 m² of offices to support the strong growth in the workforce. In addition, Orano Med announced in September that it was moving into The Hive building on the Grand Parc Campus in Villejuif, France, led by the Paris Saclay Cancer Cluster (PSCC), the first French biocluster dedicated to oncology. These new premises will become the head office of Orano Med and will house a Research and Development (R&D) laboratory for chemical vectors for targeted alpha-therapy applications. This establishment will enable the biotech to strengthen its R&D capabilities and accelerate the internal development of new innovative cancer therapies, in line with Orano Med’s investments in France; ● In parallel with these preclinical, clinical and partnership advances, Orano Med is continuing to develop its integrated industrial platform, designed to support the long-term production and availability of its internal lead-212-vectored radiotherapies. Construction of the Advanced Thorium Extraction Facility (ATEF) continues. This facility is intended to centralize production of thorium-228, a precursor of lead212, from thorium-232 inventories coming from the Orano group’s historical mining activities. Its construction began in November 2024 and will supply the two Orano Med ATLabs (Alpha Therapy Labs) located in Valenciennes (France) and Indianapolis (United States), whose construction and commissioning are ongoing. These will be entirely dedicated to the manufacture and commercial distribution of lead-212based medicines, marking a key milestone in Orano Med’s global industrial deployment.
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