Givinostat Hydrochloride

Phase 3 EPIDYS MRI data quantify givinostat’s potential to preserve functional muscle tissue and reduce fat infiltration in patients with Duchenne muscular dystrophy 1 Updated open-label extension data contribute to the understanding of long-term outcomes and safety of givinostat with up to 10+ years of treatment in a clinical trial setting 3 MILAN, Italy, July 7, 2026 – Italfarmaco S.p.A. today announced the presentation of new data from its clinical development programme for givinostat in patients with Duchenne muscular dystrophy (DMD) at the 19 th International Congress on Neuromuscular Diseases (ICNMD) 2026, taking place from July 7-11 in Florence, Italy. The presentations highlight findings from the pivotal Phase 3 EPIDYS trial and its ongoing open-label extension (OLE) study, including quantitative magnetic resonance imaging (MRI) data and insights into long-term loss-of-ambulation (LoA) and safety. "These analyses contribute to the growing body of evidence on givinostat in DMD,” said Scott Baver, Ph.D., VP, Head of Global Medical Affairs, Rare Diseases, Italfarmaco . “The MRI findings and long-term observational data provide additional insights into disease progression and treatment outcomes in this patient population." Key findings: Quantitative MRI measures of DMD disease progression from the Phase 3 EPIDYS trial were associated with statistically significant differences between treatment group vs. placebo in measures of muscle composition, including contractile cross-sectional area (cCSA) and fat fraction, across selected lower limb muscles 1 Observed differences in cCSA, a measure of muscle tissue mass, ranged from 0.43 to 1.20 cm² between treatment group vs. placebo 1 Differences in fat fraction, a measure of fat infiltration, ranged from -3.4% to -4.6% between treatment group vs. placebo 1 Interim analyses from the OLE study (n=225) describe long-term follow-up of patients treated with givinostat. Median age at persistent LoA was 17.3 years (95% CI: 15.5–18.1 years) in the study population, compared with previously published natural history data (11.0–13.4 years for corticosteroid-treated patients) 2 Long-term follow-up of patients treated with givinostat for up to 10+ years in the OLE study setting was generally consistent with the known safety profile, with no new safety signals 3 For the complete scientific programme, visit icnmd.org . About Givinostat (Duvyzat ® ) Givinostat was discovered through Italfarmaco’s research and development efforts in collaboration with Telethon and Duchenne Parent Project (Italy). Givinostat is an orally administered histone deacetylase (HDAC) inhibitor that regulates the excessive HDAC activity characteristic of DMD muscles. By doing so, it helps restore the expression of key genes and biological processes essential for muscle maintenance and repair. Its mechanism of action is independent of the specific dystrophin gene mutation causing the disease. The EPIDYS Phase 3 study is a randomized, placebo-controlled clinical trial designed to evaluate the efficacy and safety of givinostat in patients with DMD. MRI-based assessments of muscle composition were included as exploratory endpoints to better characterize disease progression. The ongoing open-label extension study is intended to provide additional information on longer-term outcomes in patients previously enrolled in clinical trials. Givinostat is approved as a treatment of DMD in multiple regions, including the US, EU, UAE and UK, for patients aged 6 years and older, with differences across regions in ambulatory status criteria and subject to local prescribing information. About ITALFARMACO Founded in 1938 in Milan, Italy, Italfarmaco is a private global pharmaceutical company that has led the successful development and approval of many pharmaceutical products around the world. The Italfarmaco group has operations in more than 90 countries through directly controlled or affiliated companies. The company is a leader in pharmaceutical research, product development, production, and commercialization with proven success in many therapeutic areas including immuno-oncology, gynaecology, neurology, cardiovascular disease and rare diseases. Italfarmaco's rare disease unit includes programs in Duchenne muscular dystrophy, Becker muscular dystrophy, amyotrophic lateral sclerosis and polycythaemia vera. For more information visit . Contacts Media inquiries: Anja Heuer / Adolfo Luna | +49 (0) 151 106 199 05 | italfarmaco@trophic.eu Other inquiries: Samantha Parker | Patient Advocacy and Communications Lead | RDEnquiries@italfarmacogroup.com References: Mercuri E. An HDAC inhibitor reduces decline of contractile cross-sectional area and decreases fat infiltration in Duchenne muscular dystrophy. Oral presentation at: 19th International Congress on Neuromuscular Diseases (ICNMD); July 7-11, 2026; Florence, Italy. Sansone V. Open-label extension analysis suggests givinostat delays age at loss of ambulation in patients with DMD. Poster presented at: 19th International Congress on Neuromuscular Diseases (ICNMD); July 7-11, 2026; Florence, Italy. Bettica P. Interim safety results from an open-label extension study of givinostat treatment for Duchenne muscular dystrophy. Poster presented at: 19th International Congress on Neuromuscular Diseases (ICNMD); July 7-11, 2026; Florence, Italy. Attachment Italfarmaco Presentation of New Clinical Data on Givinostat in Duchenne Muscular Dystrophy at ICNMD 2026

Health Canada Priority Review targets an expedited 180-day review period for givinostat, reflecting Italfarmaco’s commitment to Canadian DMD community NDS is based on Italfarmaco’s Phase 3 EPIDYS trial data demonstrating meaningful treatment benefits in DMD patients MILAN, Italy, June 10, 2026 – Italfarmaco S.p.A. today announced that Health Canada has accepted for review the New Drug Submission (NDS) for givinostat (Duvyzat ® ) for the treatment of Duchenne muscular dystrophy (DMD). Health Canada has granted givinostat Priority Review status, a designation reserved for drugs that may provide a significant improvement in the benefit-risk pro existing therapies. “Families affected by Duchenne muscular dystrophy in Canada currently have limited access to treatment options that can slow functional decline,” said Dr. Jean K. Mah, a Canadian investigator for the EPIDYS and OLE studies and Director of the Pediatric Neuromuscular Program at the Alberta Children’s Hospital in Calgary, Alberta . “As a clinician treating DMD patients, I am encouraged by this positive step in the Canadian regulatory progress and givinostat’s therapeutic potential demonstrated in the EPIDYS Phase 3 study." An estimated 1000 boys in Canada are living with DMD, one of the most severe and common forms of childhood muscular dystrophy. 1 As part of its commitment to the Canadian DMD community, Italfarmaco will establish a local Canadian affiliate to lead ongoing discussions with health authorities throughout the regulatory review process and to support patients and their families as well as healthcare providers. Subject to Health Canada’s review, marketing authorisation could be granted before the end of 2026. “Duchenne muscular dystrophy places an enormous burden on boys and their families, and we understand the urgency of bringing new treatment options to communities where significant unmet need remains,” said Francesco Di Marco, Chief Executive Officer of Italfarmaco Group. “Health Canada’s acceptance of the New Drug Submission for givinostat with Priority Review is an encouraging step forward. As we expand our presence in Canada, we are committed to working with clinicians, patient organisations, and other stakeholders to support the Duchenne community and help advance access for appropriate patients, if approved.” The submission builds on many years of clinical research, including contributions from Canadian patients, families, investigators, and three clinical trial sites in Canada. It is supported by data from the EPIDYS Phase 3 multicentre, randomized, double-blind, placebo-controlled trial ( NCT02851797 ) evaluating givinostat in ambulant boys with DMD aged six and older. The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful difference in time to complete the four-stair climb assessment in patients treated with givinostat twice daily, in addition to corticosteroids, compared to placebo and corticosteroids. During the study, the most common treatment-related adverse events (frequency ≥1/10 boys) associated with givinostat were decreased platelet count/thrombocytopenia, increased blood triglyceride/hypertriglyceridemia, diarrhoea and abdominal pain; none of the severe or serious adverse events were treatment-related or resulted in study withdrawal. givinostat tolerability was managed with appropriate monitoring and dose adjustments. No other safety concerns were observed. 2 Patients from the EPIDYS study remain under observation in a long-term study assessing tolerability and efficacy, with follow-up extending up to eleven years ( NCT03373968 ). Givinostat has received regulatory approvals in multiple regions, including the US, the UK, the EU, and the UAE for the treatment of DMD. Additional regulatory submissions are ongoing in other geographies, reflecting Italfarmaco’s commitment to enabling access for as many individuals living with DMD as possible. About Duchenne Muscular Dystrophy Duchenne muscular dystrophy (DMD) is a rare, progressive neuromuscular disorder caused by mutations in the DMD gene. Mutations in the DMD gene prevent the production of functional dystrophin, causing the dystrophin-associated protein complex (DAPC) to break down. This makes muscle fibres more vulnerable to damage and increases histone deacetylase (HDAC) levels in the muscle cells, blocking the activation of important genes needed for muscle maintenance and repair. As a result, muscle fibres experience ongoing damage, leading to chronic inflammation and poor regeneration. Over time, muscle cells die and are replaced by scar tissue and fat. 3-6 DMD primarily affects males, with symptoms typically appearing between the ages of two and five. As the condition progresses, muscle weakness worsens, leading to loss of ambulation; eventually, the heart and respiratory muscles are also affected, which are the leading causes of premature death. 7 DMD is one of the most severe and common forms of childhood muscular dystrophy, with a global birth incidence of approximately 1 in 5,050 boys. 8 About Givinostat Givinostat was discovered through Italfarmaco’s research and development efforts in collaboration with Telethon and Duchenne Parent Project (Italy). Givinostat is an orally administered histone deacetylase (HDAC) inhibitor that regulates the excessive HDAC activity characteristic of DMD muscles. By doing so, it helps restore the expression of key genes and biological processes essential for muscle maintenance and repair. Its mechanism of action is independent of the specific dystrophin gene mutation causing the disease. 9,10 Givinostat is an investigational medicine in Canada. Its safety and efficacy are currently under investigation, and Health Canada has not yet granted market authorization for this product. About ITALFARMACO Founded in 1938 in Milan, Italy, Italfarmaco is a private global pharmaceutical company that has led the successful development and approval of many pharmaceutical products around the world. The Italfarmaco group has operations in more than 90 countries through directly controlled or affiliated companies. The company is a leader in pharmaceutical research, product development, production and commercialisation with proven success in many therapeutic areas including immuno-oncology, gynaecology, neurology, cardiovascular disease and rare diseases. Italfarmaco's rare disease unit includes programmes in Duchenne muscular dystrophy, Becker muscular dystrophy, amyotrophic lateral sclerosis and polycythaemia vera. Contacts Media enquiries: Anja Heuer / Adolfo Luna | +49 (0) 151 106 199 05 | italfarmaco@trophic.eu Other enquiries: Samantha Parker | Patient Advocacy and Communications Lead | RDEnquiries@italfarmacogroup.com References Lorenz, C., Kapoor, A., Tomar, A. et al. Modelling the epidemiology of Duchenne muscular dystrophy provides insights into the overall population and selected subpopulations in nine countries. J Rare Dis 4, 73 (2025). doi.org/10.1007/s44162-025-00132-8 Mercuri E, Vilchez J, Boespflug-Tanguy O et al. Safety and efficacy of givinostat in boys with Duchenne muscular dystrophy (EPIDYS): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Neurology, 23, 393-403. doi.org/10.1016/s1474-4422(24)00036-x . Sandonà M, Cavioli G, Renzini A, et al. Histone Deacetylases: Molecular Mechanisms and Therapeutic Implications for Muscular Dystrophies. Int J Mol Sci. 2023;24(5):4306. doi.org/10.3390/ijms24054306 . Consalvi S, Saccone V, Giordani L, Minetti G, Mozzetta C, Puri PL. Histone Deacetylase Inhibitors in the Treatment of Muscular Dystrophies: Epigenetic Drugs for Genetic Diseases. Mol Med. 2011;17(5):457–465. doi.org/10.2119/molmed.2011.00049 . Bez Batti Angulski A, Hosny N, Cohen H, et al. Duchenne muscular dystrophy: disease mechanism and therapeutic strategies. Front Physiol. 2023;14:1183101. doi.org/10.3389/fphys.2023.1183101 . Giuliani G, Rosina M, Reggio A. Signaling pathways regulating the fate of fibro/adipogenic progenitors (FAPs) in skeletal muscle regeneration and disease. FEBS J. 2022;289(21):64846517. doi.org/10.1111/febs.16080 . Crisafulli S, Sultana J, Fontana A, Salvo F, Messina S, Trifirò G. Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta-analysis. Orphanet J Rare Dis. 2020;15(1):141. doi.org/10.1186/s13023-020-01430-8 . Walter MC, Reilich P. Recent developments in Duchenne muscular dystrophy: facts and numbers. J Cachexia Sarcopenia Muscle. 2017;8(5):681–685. doi.org/10.1002/jcsm.12245 . Comi G, Bertini E, Vita G, et al. S22.008: Development of the histone deacetylases inhibitor Givinostat in Duchenne Muscular Dystrophy. Poster. Neurology. 2018;90(15 (Supplement)). Licandro SA, Crippa L, Pomarico R, et al. The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene. Skelet Muscle. 2021;11(1):19. doi.org/10.1186/s13395-021-00273-6 . Attachment Italfarmaco Announces Health Canada Acceptance and Priority Review of New Drug Submission for Givinostat as a Duchenne Muscular Dystrophy Treatment