Preliminary results from SCENESSE® adolescent EPP study

A S X A N N O U N C E M E N T Melbourne, Australia, 10 February 2025 ASX: CUV | Börse Frankfurt: UR9 | ADR Level 1: CLVLY ASX Announcement PAGE 1 OF 3 Preliminary results from SCENESSE® adolescent EPP study Consistent s afety profile in adolescents CLINUVEL today announced preliminary results from its post-authorisation study of SCENESSE® (afamelanotide) in adult and adolescent (12–17-year-old) erythropoietic protoporphyria (EPP) patients (CUV052). SCENESSE® was well tolerated by all patients enrolled in the study , with the safety profile of the drug being consistent with that reported in long-term adult use. Biochemical analyses showed that the controlled-release profile of the SCENESSE® implant in adolescent patients was similar to that observed in earlier studies in adults. Pending final analyses, data from the CUV052 study will form part of the regulatory package to be submitted to regulatory agencies in support of expanding the SCENESSE® indication to include treatment of adolescent patients. SCENESSE® for adolescent EPP patients The first adolescent patients were treated with SCENESSE® in 2021, with strong support from expert physicians. CLINUVEL committed to the CUV052 study following feedback from the European Medicines Agency (EMA) that pharmacological and safety data in adolescent patients could support the extension of the SCENESSE® label to adolescent EPP patients, who are currently deprived of treatment. Results show consistent safety in adults and adolescents CUV052 is the first study in adolescent patients evaluating SCENESSE®. A total of 28 EPP patients (14 adults and 14 adolescents) were assessed. The study sought to analyse the pharmacology of SCENESSE®, comparing adolescents of 12 to 17 years of age with adults. EPP is an inherited genetic disorder affecting an estimated 1:140,000 individuals 21 adolescent patients have now received SCENESSE® treatment Approximately 60 EPP adolescent patients are known to reside in France, Germany, Italy and the Netherlands EXECUTIVE SUMMARY • First SCENESSE® study in adolescents EPP patients (CUV052) complete o Equivalent safety profile between adults and adolescents o Biochemical data in adolescents similar to historical range in healthy adult volunteers o All eligible patients request further treatment under special access • Data to support SCENESSE® label extension filing 2H 2025 ASX Announcement PAGE 2 OF 3 Consistent with conditions of use, SCENESSE® was well tolerated by all study participants. All treatment- related adverse events were mild in severity and resolved during the study, with no treatment-related serious adverse events reported.1 Preliminary biochemical analyses showed consistent readings among both adults and adolescents. Pharmacology measures, including the area under curve and maximum concentration, were determined. It was found that active drug detectable in blood samples was higher in adolescents compared to adults, although consistent with historical data captured in healthy volunteer studies. Final analyses of data from CUV052 are expected in the second half of 2025, with a further submission to the EMA planned to seek expansion of the SCENESSE® label. CLINUVEL is facilitating limited special access to SCENESSE® treatment for patients enrolled in the CUV052 study, with all eligible enrolled patients electing to receive further treatment in 2024 or 2025. Regulatory pathway SCENESSE® label expansion CLINUVEL engaged the EMA in 2022, requesting an expansion of the SCENESSE® label to include adolescent patients. During review of preliminary data and an oral hearing in 2024, the EMA opined that it would not know whether a risk of SCENESSE® for adolescent EPP patients would be posed and recommended further data from CLINUVEL to support a label expansion. CLINUVEL will incorporate data from CUV052 and seek label expansions in jurisdictions where the drug is approved. Commentary “Over the last three years we have diligently collected and analysed data which support a positive risk- benefit profile of SCENESSE® in adolescent EPP patients, following demand from patients and physicians to broaden access to treatment,” CLINUVEL’s Chief Scientific Officer, Dr Dennis Wright said. “As one could expect from our longer-term use, initial data from the CUV052 study demonstrate that the drug is well tolerated, consistent with that seen under conditions of use in adults. “Adolescents seem to have slightly higher drug exposure in this study but these results are consistent with historical ranges in earlier adult studies. “We understand from regulatory decision makers that pharmacology data can be used to support label expansion. It is hoped that the complete analyses of data from CUV052, now underway, will ultimately address regulatory hesitance and allow wider adolescent use,” Dr Wright said. – END – 1 Preliminary data subject to final data analyses. All treatment related adverse events listed are reported as “common” (may affect up to 1 in 10 people receiving the drug) or “very common” (may affect >1 in 10 people) in the SCENESSE® Summary of Product Characteristics available from CLINUVEL’s website. CUV052 STUDY DESIGN Study summary A Study to Evaluate the Pharmacokinetics of Afamelanotide in Patients with Erythropoietic Protoporphyria (EPP), CUV052 Patients enrolled (n=) 28: 14 adults / 14 adolescents Age range 13-55 Study period 90 days Objectives Pharmacological objectives Safety (adverse events, drug tolerability) ASX Announcement PAGE 3 OF 3 Changes in melanin density Sites Three European EPP Expert Centres Safety reports 22 treatment-related adverse events reported by 14 patients (8 adult/6 adolescent) Most common treatment related adverse events: • headache (5 patients – 3 adult/2 adolescent) • nausea (4 patients – 2/2) • flu-like symptoms (3 patients – 3/0) • diarrhea (3 patients – 2/1) • Implant site reaction (3 patients 1/2) About CLINUVEL PHARMACEUTICALS LIMITED CLINUVEL (ASX: CUV; ADR LEVEL 1: CLVLY; Börse Frankfurt: UR9) is a global specialty pharmaceutical group focused on developin g and commercialising treatments for patients with genetic, metabolic, systemic, and life -threatening, acute disorders, as well as healthcare solutions for specialised populations. As pioneers in photomedicine and the family of melanocortin peptides, CLINUVEL’s resea rch and development has led to innovative treatments for patient populations with a clinical need for systemic photoprot ection, assisted DNA repair, repigmentation and acute or life-threatening conditions who lack alternatives. CLINUVEL’s lead therapy, SCENESSE® (afamelanotide 16mg), is approved for commercial distribution in Europe, the USA, Israel, and Australia as the world’s first systemic photoprotective drug for the prevention of phototoxicity (anaphylactoid reactions and burns) in adult patients with erythropoietic protoporphyria (EPP). Headquartered in Melbourne, Australia, CLINUVEL has operations in Eu rope, Singapore, and the USA. For more information, please go to https://www.clinuvel.com. Authorised for ASX release by the Board of Directors of CLINUVEL PHARMACEUTICALS LTD. Head of Investor Relations Mr Malcolm Bull, CLINUVEL PHARMACEUTICALS LTD Investor Enquiries https://www.clinuvel.com/investors/contact-us Forward-Looking Statements This release contains forward -looking statements, which reflect the current beliefs and expectations of CLINUVEL’s management. Statements may involve a number of known and unknown risks that could cause our future results, performance, or achievements to differ significantly from those expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to: our ability to develop and commercialise pharmaceutical products; the COVID-19 pandemic and/or other world, regional or national events affecting the supply chain for a protracted period of time, including our ability to develop, manufacture, market and sell biopharmaceutical and PhotoCosmetic products; competition for our pro ducts, especially SCENESSE® (afamelanotide 16mg), CYACÊLLE, PRÉNUMBRA®, NEURACTHEL® or products developed and characterised by us as PhotoCosmetics; our ability to achieve expected safety and efficacy results in a timely manner through our innovative R&D e fforts; the effectiveness of our patents and other protections for innovative products, particularly in view of national and regional variations in patent laws; our potential exposure to product liability claims to the extent not covered by insurance; incr eased government scrutiny in either Australia, the U.S., Europe, the UK, Israel, China, Japan, and/or LATAM regions of our agreements with third parties and suppliers; our exposure to currency fluctuations and restrictions as well as credit risks; the effe cts of reforms in healthcare regulation and pharmaceutical pricing and reimbursement; that the Company may incur unexpected delays in the outsourced manufacturing of SCENESSE®, CYACÊLLE, PRÉNUMBRA®, NEURACTHEL® or products developed as PhotoCosmetics which may lead to the Company being unable to launch, supply or serve its commercial markets, special access programs and/or clinical trial programs; any failures to comply with any gove rnment payment system (i.e. Medicare, Medicaid, and U.S. Department of Vete ran’s Affairs) reporting and payment obligations; uncertainties surrounding the legislative and regulatory pathways for the registration and approval of biotechnology, cosmetic and consumer based products; decisions by regulatory authorities regarding appr oval of our products as well as their decisions regarding label claims; our ability to retain or attract key personnel and managerial talent; the impact of broader change within the pharmaceutical indu stry, cosmetic industry and related industries; potenti al changes to tax liabilities or legislation; environmental risks; and other factors that have been discussed in our 2024 Annual Report. Forward-looking statements speak only as of the date on which they are made, and the Company undertakes no obligation, outside of those required under applicable laws or relevant listing rules of the Australian Securities Exchange, to update or revise any forward -looking statement, whether as a result of new information, future events or otherwise. More information on preliminary and uncertain forecasts and estimates is available on request, whereby it is stated that past performance is not an indicator of future performance. Contact: Tel: +61 3 9660 4900 Fax: +61 3 9660 4909 Email: [email protected] Australia (Head Office), Level 22, 535 Bourke Street, Melbourne, Victoria, 3000, Australia

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