Progress of CLINUVEL’s DNA Repair Program

Executive Summary:

• First systemic therapy globally in genetic disorder XP
• Afamelanotide expanded from systemic photoprotection to DNA repair therapy of the skin
• Two XP-C patients have received afamelanotide in study CUV156
• No safety issues have been observed to date

CLINUVEL PHARMACEUTICALS LTD today announced that two xeroderma pigmentosum (XP) patients have received afamelanotide treatments in the CUV156 study, part of the Company’s DNA Repair Program. The patients have been diagnosed with the XP-C complementation variant, a genetic defect which causes insufficient repair of ultraviolet (UV) provoked DNA damage of the skin. As a consequence of a specific genetic defect, XP-C patients belong to the group at highest risk of skin cancer following UV light exposure, necessitating multiple surgical interventions and often having a relatively short life span.

Afamelanotide DNA Repair Program in XP

It is believed that afamelanotide is able to assist the DNA damage repair process, known as nucleotide excision repair (NER), in XP patients. A first European XP expert centre has been trained to administer afamelanotide implants as part of the Phase II CUV156 study. The main objective of this first DNA Repair study is to evaluate the safety of afamelanotide in XP patients. To date, no safety issues have been observed.

Clinically, afamelanotide has been confirmed to show reduction of photoproducts (oxidative damage and pyrimidine dimers) caused by UV radiation and visible light. Further research has shown the ability of afamelanotide and other melanocortin molecules to assist skin cells in DNA repair mechanisms (NER and BER) as well as protecting skin from UV damage.

The CUV156 study focuses on the safety profile of afamelanotide in XP patients and seeks to

1. quantify whether treatment can increase protection from UV,
2. reduce DNA photoproducts, and
3. increase the cellular signalling levels which lead to increased levels of DNA repair.

Up to six XP-C patients will be enrolled for treatment with skin samples (biopsies) of exposed skin areas taken for laboratory analyses of DNA damage before and after drug administration. CLINUVEL has collaborated with expert physicians to develop global assessment tools and patient reported outcomes for use in the study, in order to evaluate disease severity in this population.

In 2022, further studies in the DNA Repair Program are planned to evaluate patients with both the XP-C and XP-V complementation variants, and healthy volunteers of fair skin complexion serving as a control group.

Commentary

“As no other attempt has ever been made to treat XP patients systemically, the significance of conducting this study with afamelanotide is regarded as a breakthrough by the medical community and regulatory authorities,” CLINUVEL’s Head of Clinical Operations, Dr Pilar Bilbao said.

“Since XP-C patients have a relatively short life span, and given the high frequency of skin cancers, our aim is to evaluate the safety of the proposed afamelanotide therapy in the first six patients as part of CUV156 study.

“CLINUVEL’s overall aim is distinct and clear: we expand from systemic photoprotection to DNA repair therapy. All our systemic and topical products in the DNA Repair Program will address patients and individuals at highest risk of solar damage”, Dr Bilbao concluded.