SCENESSE® European Orphan Drug Designation for Variegate Porphyria

A S X A N N O U N C E M E N T Melbourne, Australia, 24 June 2024 ASX: CUV | Börse Frankfurt: UR9 | ADR Level 1: CLVLY ASX Announcement PAGE 1 OF 3 SCENESSE® European Orphan Drug Designation for Variegate Porphyria CLINUVEL’s drug afamelanotide has received a positive opinion for an orphan drug designation (ODD) from the European Medicines Agency (EMA) for the treatment of variegate porphyria (VP). This designation is a step along the regulatory pathway to extend the existing approved label for SCENESSE® (afamelanotide) to include VP, a genetic disorder resembling EPP.1 Assessing afamelanotide as a systemic photoprotective in VP The EMA accepted a submission on the use of afamelanotide as a systemic photoprotective , including data from the recently completed Phase IIa CUV040 study of SCENESSE® in VP.2 VP affects an estimated 1 in 300,000 individuals across Europe.3 The Committee for Orphan Medicinal Products (COMP) recognised the chronically severe nature of skin symptoms in VP, the high unmet need, lack of alternative therapies, and afamelanotide’s potential as a VP treatment. The EMA considered clinical evidence from the CUV040 study – an open-label six-month study of six adult VP patients – to be a sufficient proof-of-concept to enable a positive opinion on the ODD application for SCENESSE®. The Agency reviewed the study endpoints and results on disease severity, ability to expose to light, and quality of life as a potential clinical benefit for VP patients. Orphan drug designation The European ODD enables CLINUVEL to receive regulatory support and commercial incentives throughout the development of afamelanotide for VP, including post-authorisation market exclusivity of ten years. CLINUVEL received an approval from the US FDA in 2016 for the use of afamelanotide in variegate porphyria. ODDs provide structured regulatory and commercial incentives to drug developers who seek to address unmet needs in rare or neglected severe disorders. The COMP assesses clinical data alongside other evidence to determine the eligibility of a product for an ODD. SUMMARY Committee for Orphan Medicinal Products based its decision on: • medical need to treat chronic skin lesions in VP • use of SCENESSE® in EPP (similar disorder) • phase II (CUV040 study) endpoints and results Orphan drug designation provides financial incentives, scientific advice for development program ASX Announcement PAGE 2 OF 3 Commentary “The use of SCENESSE® in EPP has become standard of care, as seen from demand for treatment year on year,” CLINUVEL’s Chief Scientific Officer, Dr Dennis Wright said. “The strategy to expand the existing label to include other porphyrias is demand driven, as patients and physicians request our photoprotective treatment. Among patients and prescribers, there seems to be a growing realisation that afamelanotide mimics the body’s natural defence system of the brain and skin, which releases alpha-MSH under acute conditions.” – END – Background variegate porphyria (VP) VP is a metabolic disorder which leads to the accumulation and storage of excessive porphyrin intermediates in the skin and l iver. As a result, sun and light exposure cause severe dermatological symptoms for VP patients: dermal lesions, ulcers, and blister ing, as well as skin fragility which delays healing. There are no approved treatments to prevent or address the dermatological symptoms in VP. Notes 1. Erythropoietic protoporphyria (EPP) and VP are both porphyrias, disorders of the haem biosynthesis pathway which lead to the accumulation and storage of porphyrins and their precursors in the body, including in the skin and liver. The skin symptoms seen in VP differ from EPP but are similarly provoked by the exposure of patients’ skin to light. 2. Peltenburg, C., & Minder, A. E. (2024, March 3). Afamelanotide in Variegate Porphyria. British and Irish Porphyria Network Meeting, Dublin, Ireland. See CLINUVEL’s website for the full CUV040 results announcement: SCENESSE® provides photoprotection, improves QoL in variegate porphyria. 3. Elder, G., et al., (2013). The incidence of inherited porphyrias in Europe. Journal of Inherited Metabolic Disease, 36(5), 849–857. 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 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 ASX Announcement PAGE 3 OF 3 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 fore casts 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

The release as fetched from its publisher. clinuvel.com ↗