CLINUVEL withdraws SCENESSE® label expansion for adolescent erythropoietic protoporphyria

A S X A N N O U N C E M E N T Melbourne, Australia, 03 June 2024 ASX: CUV | Börse Frankfurt: UR9 | ADR Level 1: CLVLY ASX Announcement PAGE 1 OF 3 CLINUVEL withdraws SCENESSE® label expansion for adolescent erythropoietic protoporphyria Company continues to treat adolescent patients in the European Union CLINUVEL has withdrawn a submission to expand its European marketing authorisation for SCENESSE® (afamelanotide) for adolescent patients with erythropoietic protoporphyria (EPP , absolute light intolerance). The decision not to proceed follows two years of discussions between CLINUVEL and the European Medicines Agency (EMA) , including a formal oral hearing with the Committee for Medicinal Products for Human Use (CHMP). “Based on the benefit -risk profile of SCENESSE® in adult EPP patients seen over two decades, plus data generated in adolescent patients, and the lack of alternative treatments, we disagree with the EMA’s recommendation not to expand the existing commercial label of afamelanotide to older adolescent patients,” CLINUVEL’s Chief Scientific Officer, Dr Dennis Wright said. “Hence, we will generate more data from the use of the drug in this population and will file again.” ADOLESCENT EPP PATIENT LABEL EXPANSION In response to continued patient and expert physician demand, CLINUVEL filed a variation to the European marketing authorisation in 2022 to expand the label of SCENESSE® to include adolescent EPP patients (aged 12-17 years). Following initial Agency feedba ck, and extensive analyses of data captured from the use of SCENESSE® in EPP since 2006, CLINUVEL amended the variation to focus on patients aged 15-17 years and with a minimum bodyweight of 60kg. Comparative analyses of data from both adolescent patients and a large cohort of adult patients with lower body weights were provided to the Agency which demonstrated a consistent and beneficial benefit-risk profile of the drug in EPP patients to date. After continued dialogue between the Company and the Agency, the EMA opined that it would not know whether a benefit-risk profile of SCENESSE® for adolescent EPP patients was established. CLINUVEL withdrew the variation application following an oral hearing o f the CHMP, preparing a future submission containing additional data. SCENESSE® is the only approved therapy for adult EPP patients EPP (genetic disorder) affects 1:140,000 individuals in Europe Approximately 3% of European EPP population estimated to be aged 15-17 60 adolescent patients across France, Germany, Italy, and the Netherlands Adolescent EPP patients severely affected, lack approved therapy ASX Announcement PAGE 2 OF 3 CUV052 PHARMACOKINETIC STUDY ONGOING By early 2024, European expert physicians had prescribed SCENESSE® to adolescent patients longer-term, and CLINUVEL garnered clinical support to conduct a pharmacokinetic study (CUV052) in volving adolescent EPP patients. The CUV052 study has currently enrolled 15 EPP patients (aged 12 -70) across three European EPP expert centres, while a further 13 will be included. The study design comprises one implant administration to patients of 50kg body weight and above, thereby comparing adolescent and adult patients and evaluating the safety and clinical benefits of SCENESSE®. First results are expected in 2024. CONTINUED TREATMENT ACCESS FOR ADOLESCENT PATIENTS CLINUVEL is continuing to supply SCENESSE® in a number of European countries under conditions of use to adolescent patients through full reimbursement as well as compassionate access programs. None of these programs has been impacted by the withdrawal of the European variation. COMMENTARY “Based on the data and experience we have over such a long time, I am confident that this is just a minor delay before physicians and adolescent patients gain unfettered access to SCENESSE®,” Dr Wright said. SCENESSE® FOR EPP SCENESSE® was approved by the EMA for adult EPP patients in 2014 and has been administered in porphyria expert centres under the marketing authorisation since 2016. The drug provides protection from light (photoprotection) and acts as a strong antioxidant, preventing phototoxic reactions – debilitating burns and anaphylactoid reactions – which affect EPP patients lifelong. Adult EPP patients have reported that SCENESSE® treatment enables a ‘normal’ life previously thought impossible. The drug’s safety profi le has remained consistent to date, with over 14,500 doses administered to EPP patients. In 2022, CLINUVEL facilitated expert physician requests to treat adolescent EPP patients (aged 15-17), with the treatment fully reimbursed by national insurance bodies. To date, seven adolescent EPP patients have received SCENESSE® treatment for up to two years under these conditions of use. – END – References Rocco Falchetto. (2019). The Patient Perspective: A Matter of Minutes. The Patient - Patient-Centered Outcomes Research, 13(1). O’Reilly, M., McGuire, V. A., & Dawe, R. S. (2023). Erythropoietic Protoporphyria and Afamelanotide: A Patient’s Perspective. Clinical and Experimental Dermatology, 186-187. Wensink, D., et al., (2020). Association of Afamelanotide With Improved Outcomes in Patients With Erythropoietic Protoporphyria in Clinical Practice. JAMA Dermatology, 156(5), 570–575. 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. ASX Announcement PAGE 3 OF 3 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 products; competition for our products, especially SCENESSE® (afamelanotide 16mg), PRÉNUMBRA® or NEURACTHEL®; our ability to achieve expected safety and efficacy results in a timely manner through our innovative R&D efforts; the effectiveness of our patents and other protections for innovative products, pa rticularly in view of national and regional variations in patent laws; our potential exposure to product liability claims to the extent not covered by insurance; increased government scrutiny in either Australia, the U.S., Europe, Israel, China and Japan of our agreements with third parties and suppliers; our exposure to currency fluctuations and restrictions as well as credit risks; the effects of reforms in healthcare regulation and pharmaceu tical pricing and reimbursement; that the Company may incur unex pected delays in the outsourced manufacturing of SCENESSE®, PRÉNUMBRA® or NEURACTHEL® which may lead to it being unable to supply its commercial markets and/or clinical trial programs; any failures to comply with any government payment system (i.e. Medicar e) reporting and payment obligations; uncertainties surrounding the legislative and regulatory pathways for the registration and approval of biotechnology and consumer based products; decisions by regulatory authorities regarding approval of our products a s 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 industry and related industries; potential changes to tax liabilities or legislat ion; environmental risks; and other factors that have been discussed in our 2023 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 requi red 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 a nd 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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