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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

MILAN--( BUSINESS WIRE )--Aptadir Therapeutics (Aptadir), a biotech company developing RNA inhibitor-based therapeutics for treating intractable cancers and genetic conditions, announces its launch and the appointment of Giovanni Amabile as Executive Chairman and acting CEO. Aptadir was founded by Dr Annalisa Di Ruscio and Dr Vittorio De Franciscis, both leaders in the field of RNA biology and DNA methylation, alongside Prof. Daniel Tenen, an expert in MDS and leukaemia, and Prof. Marcin Kortylewski, an expert in oligonucleotide immunotherapeutics. They are based at world class institutions: the Beth Israel Deaconess Medical Center of the Harvard Medical School, the Italian Research National Council, the Cancer Science Institute of Singapore and City of Hope National Medical Center. The basis for the Company was the landmark discovery of a new class of RNA inhibitors called DNMTs Interacting RNAs (DiRs) 1,2 . DiRs are capable of blocking aberrant DNA methylation at a single gene level reactivating previously hypermethylated genes – a key feature in cancer and genetic disorders. By reactivating specific genes, there is the opportunity to target the underlying cause of and potentially reverse specific intractable cancers and genetic conditions in adults, such as Myelodysplastic Syndrome (MDS) and, in children, such as Fragile X Syndrome. Aptadir’s proprietary platform can generate multiple DiRs for specific genes suppressed in cancer and genetic conditions, re-establishing the pathway functionality. The first programme, Aptadir Ce-49 is being developed in MDS and the aim is to enter the clinic by the end of 2025. Leading the management team is Giovanni Amabile who has been appointed Executive Chairman and acting CEO; he is also Entrepreneur in Residence of EXTEND. Previously, he was CEO at Enthera and before then, CSO at ADIENNE Pharma. He has a successful track record in raising seed and Series A funds, and for leading IND approvals, complex clinical trials and regulatory approvals in the US. Giovanni Amabile, Executive Chairman and CEO , said: “ Today represents the launch of Aptadir Therapeutics and is an exciting day for the founders and team. Aptadir’s business is based on real innovation - a landmark discovery of a new class of molecules which have the potential to be best-in-class therapeutics for intractable conditions. From data already generated, DiRs are highly selective, stable and non-toxic, and have the potential to be used across multiple indications. This is a really exciting new field and we are looking forward to pushing our first candidate forward into the clinic.” Aptadir has received $1.6m in pre-seed funding from the EXTEND initiative to optimize its lead asset, Aptadir Ce-49. The Company is the first to receive funding from EXTEND, which is the Italian National Technology Transfer Hub wholly dedicated to the biopharmaceutical sector for the development of new therapeutic approaches. The Hub was initiated by CDP Venture Capital SGR, and joint funded with co-investors, Angelini Ventures and Evotec SE. Its purpose is to develop translational drug discovery partnerships with highly renowned universities and research centers in Italy to accelerate their promising therapeutics for commercialization. Claudia Pingue, senior partner and head of the Technology Transfer Fund of CDP Venture Capital SGR , added: “ Aptadir is the first biotech company born from EXTEND, National Technology Transfer hub established on the initiative of CDP Venture Capital and funded with co-investment partners, Angelini Ventures and Evotec. EXTEND aims to develop high quality science coming from top Italian universities and to help build new start-ups that can develop that science for the benefit of future patients. Aptadir represents one of the best examples of where science innovation can create a new potential therapeutic for underserved conditions in adults and children, such as MDS and Fragile X Syndrome. We’ll be watching its progress with great interest.” Di Ruscio A et al 2013, Nature Esposito CL et al 2023, Nature Communication Notes to Editors About Aptadir Therapeutics Aptadir Therapeutics is a preclinical biotech company developing a new class of RNA therapeutics. The Company’s therapeutic focus is underserved intractable cancers and genetic conditions, including underserved intractable conditions in the oncology and rare diseases fields such as Myelodysplastic Syndrome and Fragile X Syndrome. The technology was developed and validated by a group of key opinion leaders in the field of RNA therapeutics based at three world class institutions: the Harvard Medical School, Cancer Science institute of Singapore, Italian CNR Institute and City of Hope National Medical Center. The platform is based on a landmark discovery of a new class of RNA inhibitors called DNMTs Interacting RNAs (DiRs) 1,2 . DiRs are capable of blocking aberrant DNA methylation at a single gene level reactivating previously hypermethylated genes – a key feature in cancer and genetic disorders. The first programme is developing a treatment for Myelodysplastic Neoplasms (MDS), a group of blood cancers that occur when immature blood cells in the bone marrow don't mature into healthy blood cells. Sufferers of MDS go on to develop acute myeloid leukaemia (AML). To find out more, please see: www.aptadir.com About EXTEND EXTEND is the Italian National Technology Transfer Hub (the Hub) wholly dedicated to the biopharmaceutical sector for the development of new therapeutic approaches and it was formed as an initiative of CDP Venture Capital to transform the results of this scientific research into new companies. Alongside CDP Venture Capital, the Hub is funded by co-investors, Evotec, which also acts as an entrepreneurial partner by supporting research groups along the path of scientific study up to the establishment of startups ready to raise capital on the market to start the clinical phase, and Angelini Ventures, the new Angelini Industries Group company operating in the VC sector with a focus on digital health and biotech. The scientific promoters of the initiative are IRSCC San Raffaele Hospital in Milan, the Universities of Milan, Florence, Modena and Reggio Emilia, Padua, Trento, La Sapienza in Rome, the regional research district of Puglia through H-Bio, and Human Technopole. To learn more, please visit: www.extend-tt.vc

CHICAGO, June 10, 2024 /PRNewswire/ -- The 2024 edition of the American Society of Clinical Oncology (ASCO) Congress highlighted a concerning rise in cancer cases in Western countries. In the United States, cancer diagnoses have exceeded 2 million. This exponential growth, common to all Western countries, requires prevention focused on the investigation and monitoring of the physiopathological conditions that drive cancer, rather than early diagnosis, which saves many lives from cancer but doesn't prevent the disease. Continue Reading from ASCO "The ASCO 2024 Congress delivered a clear message: to combat the cancer epidemic, it is essential to invest in active prevention strategies and correct unhealthy lifestyles. Research and innovation, such as the HELIXAFE protocol, are crucial tools to reduce the disease burden and improve public health." Saverio Cinieri, President of the AIOM Foundation (Italian Association of Medical Oncology), raised: "High costs of cancer risk make healthcare systems unsustainable. As AIOM Foundation, we prioritize promoting healthy lifestyles and emphasizing Cancer Driver Interception, as the new frontier of active prevention." Cancer Driver Interception: The New Frontier of Prevention Developed by a spin-off of the University of Rome Tor Vergata, the HELIXAFE protocol, using the Cancer Driver Inteception methodology, represents an active prevention strategy against conditions that can lead to cancer development. Professor Adriana Albini, Head of the Cancer Prevention Working Group at AACR (American Association for Cancer Research), and Board Member of Bioscience Foundation, explained: "Carcinogenesis takes years. Initially, there are predisposing molecular conditions that, if intercepted and modified, can halt the process preventing the onset of the cancer. These conditions are now clearly studied and can be monitored with HELIXAFE protocol tests." Dr. Giuseppe Mucci, President of Bioscience Foundation, outlined the main indicators of the prodromal conditions of cancer development that anticipate the early detection. "Genomic instability is the driver condition from which cancer originates and corresponds to the progressive accumulation of damages in the DNA that are not repaired by onco-suppressor genes. The macroenvironment, which promotes and accelerates the transformation from genomic instability to cancer, is assessable by the analysis of inflammatory signals that induce systemic inflammation, by the parameters that indicate the efficiency of the immune system and the balance of the intestinal bacterial flora." Conclusions The ASCO 2024 Congress delivered a clear message: to combat the cancer epidemic, it is essential to invest in active prevention strategies and correct unhealthy lifestyles. Research and innovation, such as the HELIXAFE protocol, are crucial tools to reduce the disease burden and improve public health. BIOSCIENCE FOUNDATION Dedicated to understanding the root causes of cancer and advocating for preventive strategies since 2005. Born from a collaboration with University of Rome Tor Vergata and located at San Raffaele Hospital, Milan. As an NGO whose mission is to shift the cancer prevention paradigm from early detection to Cancer Driver Interception, we aim to introduce methodologies and services globally to identify physiological conditions driving solid tumor development in symptom-free individuals. Leveraging our AI-based monitoring program, HELIXAFE, we screen for cancer driver conditions with high accuracy and sensitivity. We believe it will become a scientific preventive tool for all solid cancers, complementing healthy lifestyle recommendations. Photo - Logo - SOURCE Bioscience Foundation