Discussions on the Company hosted by Lady Gaga and Mr Sean Parker
Operating & Financial Review
1 – Establishing and expanding access to SCENESSE®
CLINUVEL has established SCENESSE® as the standard of care for the treatment of adult EPP patients in Europe and North America. Since its commercial launch in Europe in 2016, the Company has worked to facilitate access to SCENESSE® for all eligible EPP patients who demand treatment. More recently, efforts have also focused on addressing clinical requests to treat a wider group of EPP patients, most notably adolescent EPP patients. In FY2024, CLINUVEL enabled treatment access for the largest groups of EPP patients to date, with treatment uptake increasing in both Europe and the USA. The Company expects greater uptake in the coming year as more eligible patients are identified and able to access treatment, and CLINUVEL’s team works to expand the regions where SCENESSE® is available for prescription. As of 30 June 2024, more than 16,000 doses of SCENESSE® have been administered to EPP patients worldwide.
Expert treatment network
EPP patients have traditionally received treatment from a number of different medical specialties, reflecting the complexity of the diagnosis, treatment and care needed over a patient’s lifetime. In introducing SCENESSE®, CLINUVEL has sought to encourage multi-disciplinary care and worked with clinical and academic experts
to establish a network of trained and accredited centres across Europe and the USA. The Company distributes SCENESSE® directly to centres and ensures appropriate use according to regulatory requirements.
The US Specialty Center network has grown throughout the course of FY2024, with over 85 clinics now trained and accredited to administer SCENESSE®. To better engage with this network and facilitate patient treatment, CLINUVEL has invested in new talent to work directly with prescribing physicians and their administrative teams, liaise with patients, and interact with payors, as well as ensuring compliance through a controlled distribution network. With reference to direct distribution costs, in integrating the distribution and logistics in-house, CLINUVEL is able to scale the system for future distribution of SCENESSE® and other prescription products. We are now working to expand to 120 trained and accredited centres as a foundation for the prescription of SCENESSE® for additional indication, such as vililigo.
Clinical benefit
A growing body of evidence reflects the clinical demand for the product. Feedback on SCENESSE® use is in near- real time, enabling CLINUVEL’s teams to identify and address challenges as they arise, as well as supporting global research efforts. The European EPP Disease Registry – the EEDR, created in 2016 as part of an agreed risk management plan for SCENESSE® and hosted by the Erasmus Medical Center in Rotterdam – captures pseudonymised data from the ongoing use of the treatment and is now the largest EPP registry in the world. Publications from EEDR data have demonstrated the ongoing clinical benefit from SCENESSE® treatment, as well as highlighting the long-term safety profile of the product.
Broadening access
After two years of review and interactions with the European Medicines Agency (EMA) to expand the label for SCENESSE® to include use in adolescent patients, CLINUVEL chose to withdraw its application. The variation – originally filed in 2022 – incorporated data and analyses from the use of SCENESSE® since 2006 and
narrowed the adolescent use to focus on patients aged 15-17 years with a minimum bodyweight of 60kg. 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 of the CHMP, preparing a future submission containing additional data.
The Company has continued to receive clinical requests to facilitate access to SCENESSE® for adolescent patients under conditions of use through full reimbursement as well as compassionate access programs. Seven adolescent EPP patients have received SCENESSE® treatment for up to two years under these conditions of use. None of these programs or patients have been impacted by the withdrawal of the European variation and the Company expects that further adolescent patients will receive treatment. In parallel, clinical support has been received to commence a pharmacokinetic study (CUV052) in adolescent and adult (aged 12-70) EPP patients. The study design comprises one implant administration to patients of 50kg body weight and above, comparing adolescent and adult patients and evaluating the safety and clinical benefits of SCENESSE®. Data from the CUV052 study will be submitted to global regulators to support further filings.
In May 2024, CLINUVEL announced the signing of a strategic partnership with rare disease specialists Valentech Pharma to introduce SCENESSE® as a treatment for erythropoietic protoporphyria (EPP) patients in Latin America. The two companies are now working to enable patient access through both special access programs and regulatory pathways. Recently enacted legislation in a range of Latin American countries has supported the introduction and use of drugs for patients with severe and rare conditions, reflecting similar statutes in Europe and North America. An estimated 1 in 200,000 individuals in Latin America are burdened by EPP.
CLINUVEL continues to evaluate new opportunities to expand patient access to SCENESSE®.
2 – Pharmaceutical Product Development & Clinical Programs
CLINUVEL is a global leader in the development and commercialisation of melanocortins. Having established SCENESSE® as the standard of care for EPP, the Company is now working to address unmet patient need in a range of severe and live-threatening disorders of skin and brain with melanocortin- based products.
CLINUVEL’s clinical development program follows a decision model whereby the introduction of melanocortins to address disorders must have a high level of clinical and academic support, where there is a strong rationale for the introduction of technology and the ability to conduct a clinical program, and where the program is likely to result in a product which is commercially viable. This relies heavily on the team’s existing knowledge of the potential of melanocortins, while working closely with global experts in a range of relevant fields.
Afamelanotide, the active ingredient in the SCENESSE® controlled-release injectable implant and the instant- release PRÉNUMBRA® injectable formulation, binds to melanocortin receptors on cells across the body and is recognised as playing a role in photoprotection, DNA repair, melanogenesis, and as an anti- oxidative and anti-oncotic. Throughout FY2024 CLINUVEL has pursued clinical programs with afamelanotide for a range of disorders of the skin and brain. Highlights for the year include:
- Commencement of the first Phase III study of SCENESSE® for vitiligo patients. The CUV105 study seeks to confirm earlier clinical results that showed SCENESSE® – in combination with narrowband ultraviolet B (NB- UVB) phototherapy – resulted in faster, deeper repigmentation in vitiligo patients than NB-UVB monotherapy. Up to 200 patients will be enrolled in the study across sites worldwide. In August, the Company announced a change to the inclusion criterion of the study, retaining all patients in the study, extending its recruitment to June 2025.
- A new case study on the clinical efficacy of SCENESSE® in vitiligo was presented to the American Academy of Dermatology (AAD) meeting in San Diego in March 2024. The patient presenting with a Fitzpatrick Skin Type IV was diagnosed with vitiligo and had historically been unresponsive to other treatments. The patient had received seven SCENESSE® implants and 39 NB-UVB treatments over 134 days. Significant repigmentation of vitiliginous lesions on the face, neck, torso, and back was observed. The patient was reported to be thrilled with the repigmentation and to have regained her identity.
- Positive results from the DNA Repair Program. Biopsy analyses from the CUV151 study, evaluating the DNA repair capacity of afamelanotide on skin of healthy volunteers exposed to UV radiation, showed that DNA photodamage was significantly reduced following afamelanotide treatment. Further analyses from CUV151 – released on 5 July 2024 – use RNA sequencing to show that afamelanotide significantly reduced the number of differentially expressed genes (DEGs) following UV irradiation. The genes evaluated are found as being central in the regulation of DNA repair and inflammatory reactions following solar and UV exposure.
- Positive results from the first study of SCENESSE® as a treatment for variegate porphyria patients. The six-month CUV040 study evaluated whether the drug could offer systemic photoprotection to VP patients and reduce the impact of dermatological symptoms. All six patients experienced a positive change – improvement of symptoms and ability to expose to light up to three times baseline scores using the validated Clinical Global Impression of Change tool – in disease severity after treatment. Two physician assessment tools determined the degree of skin dysfunction and disease at a given timepoint, with a median decline in disease severity compared to baseline. Counts of new skin lesions (wounds, blisters and/or ulcers) on light-exposed skin revealed a decrease over time with the median lesion count decreased from 10.5 to 3 across the treatment period. All patients also experienced decreased fragility of sun exposed skin following treatment.
- European orphan drug designations (ODDs) were granted for afamelanotide for both xeroderma pigmentosum and variegate porphyria, recognising the drug’s potential to treat these patients. CLINUVEL submitted clinical evidence from both programs to support the ODD applications, the first time a global regulator has reviewed data on the use of afamelanotide in either XP or VP. The ODDs entitle CLINUVEL to receive incentives throughout the development programs and, importantly, post-authorisation. This includes reduced fees for regulatory activities and ten years of market exclusivity post-approval. As SCENESSE® is already an approved medication, marketing authorisation for XP or VP would be added as a label extension (type II variation) for the drug, rather than through a completely new authorisation application process.
- The commencement of the CUV052 study to generate pharmacokinetic data on the use of SCENESSE® in adolescent and adult EPP patients. CLINUVEL aims to enrol 28 EPP patients (aged 12-70) in the study across three European EPP Expert Centres. 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®. Data from CUV052 will be submitted to global regulatory agencies to support an extension of the SCENESSE® label to treat adolescent patients. Prior to the commencement of CUV052, seven adolescent EPP patients had received fully reimbursed SCENESSE® treatment for up to two years under conditions of use.
“Afamelanotide is massive for me, I feel extremely fortunate that this drug has been made available in Scotland and my wish is that everyone living with EPP gets access to this life-changing treatment.”
| Indication | Product | Trials/program status |
|---|---|---|
| Adolescent EPP | SCENESSE® | CUV052 ongoing, n=28, Pharmacokinetic study in adolescent and adult EPP patients |
| Vitiligo, adolescents and adults | SCENESSE® |
CUV104 ongoing, Phase II n=6 CUV105 ongoing, Phase III n=200, Combination afamelanotide + NB-UVB vs NB-UVB monotherapy CUV107 in setup, Phase III n=200 |
| Variegate porphyria | SCENESSE® | CUV040 complete, further studies in development |
| DNA repair, xeroderma pigmentosum, adolescents and adults | SCENESSE® |
CUV156 ongoing, Phase II n=6, XPC patients CUV151, healthy volunteer study complete CUV152 ongoing, Phase II n=6, XPC and XPV patients CUV154 in setup, Phase II n=26, XPA, XPC, XPE and XPV patients CUV158 in setup, healthy volunteer study n=10 |
| Arterial Ischaemic Stroke | PRÉNUMBRA® instant | CUV803 ongoing, Phase II n=12, evaluating safety, changes in neurological and cognitive functions |
| Parkinson's Disease | PRÉNUMBRA® instant | CUV901 in setup, Phase IIa n=6, evaluating safety, impact on α-synuclein in blood |
| Infantile spasms, multiple sclerosis | NEURACTHEL® instant | Program in setup |
| Undisclosed CNS disorders | NEURACTHEL® modified release | Program in setup |
3 – PhotoCosmetic Products
Translating technology from unmet medical needs to the demands of many CLINUVEL is a leader in photomedicine by developing novel products to provide photoprotection, DNA repair and repigmentation of the skin to people in need of treatment:
- First evaluated in clinical trials in 2006, CLINUVEL’s pharmaceutical drug, SCENESSE® has been providing photoprotection to EPP patients since 2010 in Italy and 2012 in Switzerland under special access schemes. Following regulatory approvals, EPP patients have been treated in the EU since 2016 and the USA since 2020.
- The results to date of the DNA Repair Program have generated clinical evidence to support the use of melanocortins to prevent and repair photodamage.
- CLINUVEL’s work in the pigment loss disorder vitiligo promises to break new ground in the understanding of the health and function of melanocytes, the cells that produce pigmentation in skin.
We are evolving our proposition from biopharmaceutical products that address the unmet needs of patient groups, to the provision of solutions to meet the contemporary global desires of the wider population. Mirroring our expertise in photomedicine, our focus is on three PhotoCosmetic product lines that:
- PROTECT the skin from the life-threatening risks of sun exposure.
- PRESERVE the skin, preventing premature ageing through photodamage and increasing longevity to the body’s biggest organ; and
- BRONZE the skin for overall health and well-being, not only without solar risk, but also as a means of protection.
The PROTECT line offers polychromatic screens, CYACÊLLE and CYACÊLLE Radiant, and the PRESERVE and BRONZE product lines, the “M-lines”, will contain melanocortins.
Progress in the past year
The focus of the year has been on:
- Promotion of CLINUVEL as an emerging brand in PhotoCosmetics; and
- Ongoing formulation work in the Singapore RD&I Centre which resulted in the launch of two new polychromatic products.
During the year we rebranded the business through a new website and corporate campaigns that have raised the visibility of the organisation. We continue to grow our audience to create a base of support and drive our mission forward.
The highest profile event of the year was held in February at the Malibu home of home of Ms Stefani Germanotta (Lady Gaga) and and her partner Michael Polansky. CLINUVEL’s pioneering technology and the PhotoMedicine Foundation (refer page 76) was introduced to the most prolific investors and philanthropists in Silicon Valley, and key influencers and advocates in health and beauty. We thank Stefani Germanotta, who is vested in health and well-being as an owner of a beauty business, and many long-term stateside supporters of CLINUVEL who came to the fore to support the event. The event was a success achieving 3.4 million Instagram views and:
- Highlighted the support of CLINUVEL by long-term investors, Mr Sean Parker and Mr Michael Polansky, who are industry-leading entrepreneurs renowned for spotting companies on an explosive upward trajectory;
- Raised awareness of CLINUVEL to new influential circles in beauty, business and global entertainment, and probably most importantly;
- Gained a strategic footfall into the beauty industry thanks to a feature in the Business Of Fashion, an established luxury publication part-owned by the Financial Times, and the main reference for the fashion and beauty industry today.
May 2024 signalled a new chapter for CLINUVEL’s PhotoCosmetics with the launch of two new products in the PROTECT line, CYACÊLLE Radiant in gold and bronze tints. These pioneering tinted mineral solar shields repel UVB, UVA and blue light, and high energy wavelengths that penetrate the skin’s deepest layers. This triple protection is designed to optimise the skin’s longevity, while a skin smoothing tint acts as foundation and enhances your natural radiance. This launch is a prelude to our M-line range, PRESERVE, which will accelerate the skin process of renewal and BRONZE, which stimulates the body’s natural bronzing.
This was also an opportunity to re-set of the social strategy and start an Instagram account for cosmetics (CLINUVEL DNA). Since the launch in June, we have reached over 7 million people with our brand story, with a following increase of over 100%. Reaching our desired target audience and building an audience will be the key focus of the next year with social, aided by our ambassador programme (CUVAs).
May 2024 also saw the launch of our global e-commerce site for our PhotoCosmetic products, available in five languages, which sets the foundation for our global launches. All this communication work has been done with the work of a growing in-house creative and marketing team, which will continue to grow to fulfill the mission ahead.
4 – Financial Review
CLINUVEL’s financial performance for fiscal year 2024 marked another successful year of revenue growth and sustained profitability for the Company. Our continued success is a testament to our strategic focus on building a high-performing life sciences company and delivering year-on-year returns.
CLINUVEL’s ongoing expansion is evident as we continue to grow our primary revenue stream by reaching more patients across more trained and accredited treatment centres. Simultaneously we are investing strategically in the foundations of our future through key personnel, clinical programs, and infrastructure that will enable us to diversify our revenue base to support long-term stability and growth.
Our commitment to retaining and investing in our most critical asset – our people – remains a priority. Over the past 12 months, we have bolstered our teams across several critical areas including clinical development, operations, and communications, marketing, and branding. This expansion is integral to supporting the Company’s ongoing growth and reinforcing our strategic initiatives.
