Hospital Universitário

– Simultaneously Published by the Journal of Clinical Oncology – FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced detailed results from the Phase 3 EVOKE-01 study that will be presented during an oral session (Abstract #LBA8500) today (2:45-5:45pm CT) at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The results were also published simultaneously in the Journal of Clinical Oncology. The company previously announced that the study did not meet the primary endpoint of overall survival (OS) in previously treated metastatic non-small cell lung cancer (NSCLC). EVOKE-01, evaluating Trodelvy® (sacituzumab govitecan-hziy; SG) vs. docetaxel, showed a 16% reduction in the risk of death (median OS: 11.1 vs. 9.8 months; HR: 0.84; 95% CI: 0.68-1.04; 1-sided p=0.0534) in patients with metastatic or advanced NSCLC that had progressed on or after platinum-based chemotherapy and anti-PD-(L)1-therapy. This numerical improvement in OS was observed consistently across both squamous and non-squamous histology. In patients with high unmet medical need whose tumors did not respond to last anti-PD-(L)1-containing treatment, a meaningful OS improvement of 3.5 months was seen when treated with Trodelvy vs. docetaxel (mOS: 11.8 vs. 8.3 months; HR: 0.75; 95% CI: 0.58-0.97). This subgroup represents approximately 2/3 of the study population. This pre-specified subgroup analysis was not alpha-controlled for formal statistical testing. For the subgroup of patients whose mNSCLC was responsive to last anti-PD-(L)1-containing treatment, median OS was 9.6 vs. 10.6 months when treated with Trodelvy vs. docetaxel (HR: 1.09; 95% CI: 0.76-1.56). In the overall study population numerically more patients were alive at 12-months when treated with Trodelvy compared to docetaxel (46.6% vs. 36.7%). In the study, Grade ≥3 adverse events (AEs) were lower among patients receiving Trodelvy (66.6%) vs. docetaxel (75.7%), and AEs leading to discontinuation were lower with Trodelvy (9.8%) vs. docetaxel (16.7%). The most common AEs of any grade for Trodelvy were fatigue (57%), diarrhea (53%), and alopecia (43%) and for docetaxel were fatigue (56%), neutropenia (43%) and diarrhea (34%). Patients treated with docetaxel had a greater incidence of neutropenia of any grade compared with Trodelvy (43% vs. 38%, respectively), while patients treated with Trodelvy experienced more diarrhea of any grade vs. docetaxel (53% vs. 34%, respectively). The safety pro Trodelvy was consistent with prior studies, with no new safety signals identified in this patient population. “Treating patients with metastatic NSCLC who have progressed on available treatments continues to be a challenge. After progression, standard of care for most patients is limited to single-agent chemotherapy, which offers modest benefit,” said Dr. Luis Paz-Ares, PhD, Head of the Medical Oncology Service at the Hospital Universitario 12 de Octubre, Madrid. “These data, including the meaningful benefit observed in the sub-group of patients, are encouraging and warrants further investigation as these patients have a great unmet need.” “Our data in metastatic NSCLC demonstrating Trodelvy’s activity continue to advance our understanding of the potential to build on our impact for patients,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “We look forward to further investigating how these data may positively impact patients in the second-line setting. We would also like to thank the patients, families, investigators and advocates who contributed to this important research.” In addition to the EVOKE-01 presentation at the 2024 ASCO Annual Meeting, Gilead will present data from its broader lung cancer clinical development program. Longer-term results from Cohort A of the Phase 2 EVOKE-02 study of Trodelvy in combination with KEYTRUDA® (pembrolizumab) in first-line metastatic PD-L1 ≥50% NSCLC will also be presented in a poster session (Abstract #8592) on June 3, 2024. These data show a median progression-free survival (PFS) of 13.1 months and support promising activity in this patient population in both squamous and non-squamous histologies. These data continue to support our ongoing Phase 3 EVOKE-03 study in PD-L1-high mNSCLC. In addition, Gilead has a broad clinical development program in lung cancer with domvanalimab, the first Fc-silent investigational anti-TIGIT antibody, and the investigational anti-PD-L1, zimberelimab. Trodelvy is the first approved Trop-2-directed antibody-drug conjugate (ADC) that has demonstrated meaningful survival advantages in two different types of metastatic breast cancers and shown improved clinical outcomes for certain people with 2L advanced or metastatic urothelial cancer. Trodelvy has not been approved by any regulatory agency for the treatment of metastatic NSCLC. Its safety and efficacy have not been established for this indication. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for the approved U.S. Indication and additional Important Safety Information. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About Metastatic Non-Small Cell Lung Cancer Worldwide, more than two million people were diagnosed with lung cancer in 2020. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for up to 85% of diagnoses. About half of NSCLC cases are diagnosed at the metastatic stage (57%), when treatment is especially difficult. Even in patients whose disease is caught early, half will eventually progress to the metastatic stage within five years. Newly diagnosed patients have several treatment options including platinum-based therapy, checkpoint inhibitors and targeted therapies. However, there are limited treatment options once patients with metastatic NSCLC progress on or after platinum-based chemotherapy and checkpoint inhibitors. About the EVOKE-01 Study The EVOKE-01 study is a global, multi-center, open-label Phase 3 study randomized 1:1 to evaluate Trodelvy vs. docetaxel in patients with advanced or metastatic NSCLC that has progressed on or after platinum-based chemotherapy and checkpoint inhibitor therapy. The study enrolled 603 participants. The primary endpoint is overall survival (OS). Key secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and disease control rate (DCR) as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and safety. Additional efficacy measures include time to first deterioration in shortness of breath domain as measured by NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ) Score and time to first deterioration NSCLC-SAQ Total Score. Further study details are available on clinicaltrials.gov (NCT05089734). About Trodelvy Trodelvy® (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast, bladder and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect. Trodelvy is approved in almost 50 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Trodelvy is also approved in multiple countries globally to treat certain patients with pre-treated HR+/HER2- metastatic breast cancer in Australia, Brazil, Canada, the European Union, Israel, United Arab Emirates and the United States. In the U.S., Trodelvy has an accelerated approval for treatment of certain patients with second-line or later advanced or metastatic urothelial cancer; see below for full indication statements and please see yesterday’s announcement of topline results from Gilead’s Phase 3 TROPiCS-04 study in locally advanced or metastatic urothelial cancer. Trodelvy is being explored for potential investigational use in other TNBC, HR+/HER2- and metastatic UC populations, as well as a range of tumor types where Trop-2 is highly expressed, including metastatic non-small cell lung cancer (NSCLC), head and neck cancer, gynecological cancer, and gastrointestinal cancers. U.S. Indications for Trodelvy In the United States, Trodelvy is indicated for the treatment of adult patients with: Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. U.S. Important Safety Information for Trodelvy BOXED WARNING: NEUTROPENIA AND DIARRHEA Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay. Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses. CONTRAINDICATIONS Severe hypersensitivity reaction to Trodelvy. WARNINGS AND PRECAUTIONS Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 64% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Withhold Trodelvy for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever. Administer G-CSF as clinically indicated or indicated in Table 1 of USPI. Diarrhea: Diarrhea occurred in 64% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments. Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions. Nausea and Vomiting: Nausea occurred in 64% of all patients treated with Trodelvy and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1. Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting. Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function. Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose. ADVERSE REACTIONS In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%). In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes. In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes. In the TROPHY study (locally advanced or metastatic urothelial cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, any infection, alopecia, decreased appetite, constipation, vomiting, rash, and abdominal pain. The most frequent serious adverse reactions (SAR) (≥5%) were infection (18%), neutropenia (12%, including febrile neutropenia in 10%), acute kidney injury (6%), urinary tract infection (6%), and sepsis or bacteremia (5%). SAR were reported in 44% of patients, and 10% discontinued due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPHY study were reduced neutrophils, leukocytes, and lymphocytes. DRUG INTERACTIONS UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy. UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy. Please see full Prescribing Information, including BOXED WARNING. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials, including the EVOKE-01 study and those involving Trodelvy and domvanalimab; uncertainties relating to regulatory applications and related filing and approval timelines, including pending or potential applications for Trodelvy for the treatment of metastatic and other TNBC, HR+/HER2- metastatic breast cancer, metastatic UC, metastatic NSCLC, head and neck cancer, gynecological cancer and gastrointestinal cancer, and for domvanalimab; Gilead’s ability to receive regulatory approvals for programs and/or indications that are currently under evaluation in a timely manner or at all, and the risk that any such approvals may be subject to significant limitations on use; the possibility that Gilead may make a strategic decision to discontinue development of programs for indications that are currently under evaluation, including Trodelvy for treatment of metastatic NSCLC and domvanalimab, and as a result, these programs may never be commercialized for such indications; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. U.S. Prescribing Information for Trodelvy including BOXED WARNING, is available at . Trodelvy, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies. For more information about Gilead, please visit the company’s website at or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Pictured: Oncology tracker over the Chicago skyline/ Nicole Bean for BioSpace The American Society of Clinical Oncology (ASCO)’s annual meeting kicks off Friday in Chicago, with more than 5,000 abstracts highlighting investigational therapies for various malignancies. Analysts have expressed particular excitement for a new bispecific antibody, ADCs and a BCMA-targeted CAR-T cell therapy. Stay tuned to BioSpace as we keep you updated on all of the biggest data and news from the conference. Updated: May 31, 11:00 EST/10:00 CST Novartis' Leukemia Drug Prevails Over Older Therapies in Phase III Novartis’ kinase inhibitor Scemblix aced a Phase III trial in chronic myeloid leukemia (CML), the pharma reported at ASCO on Friday. In the ASC4FIRST trial, where Scemblix was pitted against current standard-of-care tyrosine kinase inhibitor (TKI) therapies, Novartis’ drug elicited a major molecular response in 68% of patients compared to 49% in the TKI arm. A deep molecular response, which is often considered a remission in chronic myeloid leukemia, was seen in 39% of patients treated with Scemblix versus 21% in the comparison arms, one of which was Novartis’ Gleevec. Scemblix was designed to elicit high potency and high specificity in order to minimize side effects and toxicities—an effect that was also born out in the trial, where 86% of patients on Scemblix remained on the treatment at the cutoff date compared to only 62% of patients on Gleevec and 75% on a second generation TKI. Gilead Shares Details on Failed Trodelvy NSCLC Trial In January, Gilead Sciences announced that its antibody-drug conjugate, Trodelvy, missed the primary endpoint of overall survival in non-small cell lung cancer (NSCLC). On Friday at ASCO, the company revealed more details. In the EVOKE-01 trial, the ADC showed a 16% reduction in the risk of death compared with the chemotherapy docetaxel, while the median survival benefit was just 1.3 months for those treated with Trodelvy, Endpoints News reported. However, the OS margin was greater for those patients whose tumors did not respond to their last anti-PD(L)1-containing treatment, at 11.8 months for Trodelvy and 8.3 months for docetaxel. Trodelvy’s safety pro also superior to docetaxel, Endpoints reported, with fewer grade 3 or worse adverse events and fewer discontinuations from toxicities compared with chemotherapy. “These data, including the meaningful benefit observed in the sub-group of patients, are encouraging and warrants further investigation as these patients have a great unmet need,” Luis Paz-Ares, head of medical oncology service at Hospital Universitario 12 de Octubre in Madrid, said in a press release, according to Endpoints.

Researchers have demonstrated that some childhood leukemia originate during embryonic development, although they do not manifest after a few months after birth. Researchers from the Institute of Oncology of the University of Oviedo (IUOPA), the Josep Carreras Leukaemia Research Institute, the University of Barcelona and the Centre for Biomedical Research in Cancer Network (CIBERONC) have demonstrated that some childhood leukaemia originate during embryonic development, although they do not manifest after a few months after birth. Acute myeloid leukaemia is the second most common type of acute leukaemia in childhood and can be diagnosed within a few months of life. The early onset of the disease had led to the suspicion that the tumour could have a prenatal origin. However, proving this theory has been challenging due to the lack of prenatal or birth samples. 'The opportunity to study the origin of this leukaemia arose from the case of a five-month-old baby diagnosed with acute myeloid leukaemia at the Hospital Niño Jesús in Madrid,' explains Pablo Menéndez, ICREA professor at the University of Barcelona and the Josep Carreras Institute. 'The parents, who had preserved the umbilical cord blood, opened a line of research that until now had not been possible to address,' adds the researcher. Using precision medicine techniques, researchers analysed the complete genome of the tumour. Unlike tumours in adults, where thousands of mutations are detected, only two chromosomal alterations were identified in this leukaemia. 'Genome analysis allowed us to design a personalised diagnostic method to monitor the disease,' says Xose S. Puente, Professor of Biochemistry at the University of Barcelona. Puente, Professor of Biochemistry and Molecular Biology at the University of Oviedo. 'But these data raise new questions, such as when the tumour arose and in what order these mutations have appeared,' he highlights. These questions are difficult to answer, since such research requires blood samples from the baby before the diagnosis, something that is impossible in the vast majority of cases. However, in this particular case, the existence of a frozen umbilical cord sample allowed researchers to separate different populations of blood cells at birth and to study whether any of the chromosomal alterations detected in the tumour were already present during foetal development. The study revealed that a translocation between chromosome 7 and 12 was already present in some haematopoietic stem cells in the umbilical cord. In contrast, the other chromosomal alteration, a trisomy of chromosome 19, was not present in the foetus, but was found in all tumour cells, suggesting that it contributes to increasing the malignancy of the leukemic cells. 'These data are highly relevant for understanding the development of a devastating disease, and the existence of this umbilical cord sample was crucial to be able for conducting a study that had been impossible until now in acute myeloid leukaemia', adds Talía Velasco, researcher at the Josep Carreras Institute and the University of Barcelona and co-leader of the study. In addition to reconstructing the genomic alterations that the cells undergo to generate this leukaemia, the study has also identified a molecular mechanism that had not been observed before in this type of leukaemia and which causes the activation of a gene, called MNX1, which is frequently altered in this type of tumour. Knowledge of these alterations is essential for developing cell and animal models that allow us to understand the disease's evolution and develop new therapies for treating these pathologies. The study has been led by Xose S. Puente, Professor of Biochemistry and Molecular Biology at the University of Oviedo-IUOPA, Talía Velasco and Pablo Menéndez, from the Josep Carreras Institute and the University of Barcelona, with participation from researchers from four other institutions, including the Hospital Infantil Universitario Niño Jesús, the Hospital Universitario Central de Asturias, the Instituto de Biomedicina y Biotecnología de Cantabria and the Instituto de Investigación Sanitaria La Princesa de Madrid. This research has been made possible thanks to the collaboration of the parents and funding from the Ministry of Science, Innovation and Universities, the European Research Council, the AECC Scientific Foundation, the Foundation Unoentrecienmil, the "La Caixa" Foundation, the Government of Catalonia, CIBERONC and the III Health Institute.