National Institute for Health & Care Excellence

Genetic testing to identify women with Lynch Syndrome is likely to need to increase dramatically to ensure that carriers are not missed, a new analysis has found. A study by The Institute of Cancer Research, London, and published in the Journal of Medical Genetics, has revealed that only a fraction of women diagnosed with endometrial (womb) cancer were tested for Lynch Syndrome in 2019, according to an analysis of lab data. Lynch Syndrome is an inherited condition that greatly increases the lifetime risk of certain types of cancer, including bowel, ovarian, pancreatic and womb cancers. It is thought to affect 175,000 people in England, although currently only approximately five per cent are aware they have it. Because womb cancer is often the first cancer that women with Lynch Syndrome develop, genetic testing is an effective way to spot cases. In 2020, the National Institute for Health and Care Excellence (NICE) introduced guidelines which recommended that everyone diagnosed with womb cancer should be tested for Lynch. However, a baseline analysis, carried out by a team from The Institute of Cancer Research (ICR) found that of the 7,928 women who were diagnosed with womb cancer in 2019, just 1408 (17.8 per cent) were given a tumour test (typically an immunohistochemistry (IHC) test) to check for abnormal cells. Of the 104 patients who were then identified as being eligible for genetic testing, only 25 per cent had a test result recorded. Of these 26 patients, 15 had Lynch Syndrome. The study, which received funding from The Wellcome Trust, and Cancer Research UK, and was conducted in partnership with the National Disease Registration Service, also showed there were significant delays between patients getting their cancer diagnosis and receiving a genetic test. The median time from cancer diagnosis to germline testing was 315 days, with the longest wait time from diagnosis to testing at over two years (837 days). Earlier this year, the National Disease Registration Service (NDRS), NHS Genomic Medicine Service Alliances (GMSAs) and NHS Regional Clinical Genetics Services, together with researchers from the ICR, set up The English National Lynch Syndrome Registry. The database, which comprises of 9,000 patients with Lynch Syndrome, will ensure participants are called up for regular bowel cancer screening to detect the disease in earlier stages, when treatment is more successful. In addition, researchers will be able to find patients who are eligible for clinical trials, speeding up the process and ensuring that treatments can reach patients faster. Dr Catherine Huntley, a specialist public health doctor at The Institute of Cancer Research, who conducted the analyses, said: “For female patients with Lynch Syndrome, endometrial cancer is often their first cancer diagnosis. Tumour testing followed by genetic testing is an effective way of identifying the three per cent of cases – approximately 240 people with endometrial cancer – every year caused by Lynch Syndrome. “However, our study shows that historically, testing rates appeared to be very low. It’s imperative that women with endometrial cancer have routine testing of their tumours to prevent opportunities to diagnose Lynch Syndrome being missed. Identifying patients with Lynch Syndrome provides us with a valuable opportunity to prevent further cancers in that patient. Delays in starting preventative strategies such as taking aspirin and having regular colonoscopies could lead to bowel cancers being diagnosed at later stages when they are much harder to treat. Professor Clare Turnbull, Professor of Translational Cancer Genetics at The Institute of Cancer Research, London, and Consultant in Clinical Cancer Genetics at The Royal Marsden NHS Foundation Trust, who led the analysis, said: “Having a Lynch Syndrome diagnosis helps to guide more personalised cancer treatment but also enables families and relatives of that patient to be offered testing too. Relatives who have Lynch Syndrome can be referred to genetic services to help catch any cancers as early as possible.”

Santhera has begun launch preparations for AGAMREE® in UK with first sales expected in this quarter Pratteln, Switzerland, January 16, 2025 – Santhera Pharmaceuticals (SIX: SANN) announces that the National Institute for Health and Care Excellence (NICE) has issued positive Final Guidance that recommends AGAMREE® (vamorolone) for use in the National Health Service (NHS) in England, Wales and Northern Ireland for the treatment of Duchenne muscular dystrophy (DMD) in patients 4 years of age and older. This follows confirmation that no appeals were received against the Final Draft Guidance (FDG) recommendation announced on December 10, 2024. Following this, Santhera has already started launch preparations for AGAMREE in the UK and expect first sales in this quarter. AGAMREE is the first and only medicinal product for DMD to have received full approval in the EU, US, and UK. This recommendation follows the Medicines and Healthcare products Regulatory Agency’s (MHRA) approval of AGAMREE on January 11, 2024, which, alongside the European Medicines Agency (EMA), acknowledged clinically important tolerability benefits with regards to maintaining normal bone metabolism, density, and growth compared to standard of care corticosteroids, alongside similar efficacy from clinical trials. The Final Guidance is available on the NICE website: www.nice.org.uk/guidance/TA1031 For more information about AGAMREE in Great Britain, including Scotland: Summary of Product Characteristics About AGAMREE® (vamorolone) AGAMREE is a novel drug with a mode of action based on binding to the same receptor as glucocorticoids but modifying its downstream activity. Moreover, it is not a substrate for the 11-β-hydroxysteroid dehydrogenase (11β-HSD) enzymes that may be responsible for local drug amplification and corticosteroid-associated toxicity in local tissues [1-4]. This mechanism has shown the potential to ‘dissociate’ efficacy from steroid safety concerns and therefore AGAMREE is positioned as a dissociative anti-inflammatory drug and an alternative to existing corticosteroids, the current standard of care in children and adolescent patients with DMD [1-4]. In the pivotal VISION-DMD study, AGAMREE met the primary endpoint Time to Stand (TTSTAND) velocity versus placebo (p=0.002) at 24 weeks of treatment and showed a good safety and tolerability profile [1, 4]. The most commonly reported side effects were cushingoid features, vomiting, weight increase and irritability. Side effects were generally of mild to moderate severity. Currently available data show that AGAMREE, unlike corticosteroids, has no restriction of growth [5] and no negative effects on bone metabolism as demonstrated by normal bone formation and bone resorption serum markers [6]. ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. References:[1] Dang UJ et al. (2024) Neurology 2024;102:e208112. doi.org/10.1212/WNL.0000000000208112. Link.[2] Guglieri M et al (2022). JAMA Neurol. 2022;79(10):1005-1014. doi:10.1001/jamaneurol.2022.2480. Link. [3] Liu X et al (2020). Proc Natl Acad Sci USA 117:24285-24293[4] Heier CR et al (2019). Life Science Alliance DOI: 10.26508[5] Ward et al., WMS 2022, FP.27 - Poster 71. Link.[6] Hasham et al., MDA 2022 Poster presentation. Link. About SantheraSanthera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical company focused on the development and commercialization of innovative medicines for rare neuromuscular diseases with high unmet medical need. The Company has an exclusive license from ReveraGen for all indications worldwide to AGAMREE® (vamorolone), a dissociative steroid with novel mode of action, which was investigated in a pivotal study in patients with Duchenne muscular dystrophy (DMD) as an alternative to standard corticosteroids. AGAMREE for the treatment of DMD is approved in the U.S. by the Food and Drug Administration (FDA), in the EU by the European Medicines Agency (EMA), in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA), in China by the National Medical Products Administration (NMPA) and Hong Kong by the Department of Health (DoH). Santhera has out-licensed rights to AGAMREE for North America to Catalyst Pharmaceuticals and for China and certain countries in Southeast Asia to Sperogenix Therapeutics. For further information, please visit www.santhera.com. AGAMREE® is a trademark of Santhera Pharmaceuticals. For further information please contact: public-relations@santhera.com or Elodie Denjean, General Manager UK, France & Beneluxelodie.denjean@santhera.comPhone +44 7437 865600 Disclaimer / Forward-looking statements This communication does not constitute an offer or invitation to subscribe for or purchase any securities of Santhera Pharmaceuticals Holding AG. This publication may contain certain forward-looking statements concerning the Company and its business. Such statements involve certain risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of the Company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. The Company disclaims any obligation to update these forward-looking statements. # # # Attachment 250116 NICE guidance_FINAL_English

Santhera Pharmaceuticals’ Agamree (vamorolone) has been accepted by the Scottish Medicines Consortium (SMC) to treat Duchenne muscular dystrophy (DMD) in patients aged four years and older. The decision, which allows patients with the rare muscle-wasting disorder to access Agamree on the NHS in Scotland, comes one month after the National Institute for Health and Care Excellence (NICE) recommended the drug for use on the NHS in England, Wales and Northern Ireland. Estimated to affect 2,500 males in the UK at any one time, DMD is caused by a change or mutation in the gene that encodes instructions for dystrophin, which is required to strengthen and protect muscles. The disease causes progressive muscle degeneration and weakness, and its major milestones are the loss of ambulation and self-feeding, the start of assisted ventilation, and the development of cardiomyopathy. Agamree is a dissociative anti-inflammatory drug that works in a similar way to existing corticosteroids, the current standard of care for children and adolescents with DMD, but without the same safety concerns. The SMC’s decision follows the Medicines and Healthcare products Regulatory Agency’s approval of the therapy in January 2024, which was supported by results from the pivotal VISION-DMD study and three open-label studies. In VISION-DMD, patients treated with Agamree on average maintained growth similar to those treated with placebo, while those treated with the corticosteroid prednisone on average experienced growth stunting. The trial also showed that patients who switched from prednisone to Agamree after 24 weeks were on average able to resume growing in height over the remainder of the study. Additionally, unlike corticosteroids, Agamree did not result in a reduction of bone metabolism or a significant reduction in bone mineralisation in the spine after 48 weeks in the clinical studies. Commenting on the latest authorisation for the therapy, Santhera’s chief executive officer, Dario Eklund, said: “I am delighted that the team has secured this latest approval, which will ensure Scottish patients can benefit from this important treatment for DMD. “We will work closely with NHS Scotland, along with all the key regulatory and health authorities in all our approved markets, to ensure patients have access to Agamree.”