PERTH, Australia – With the launch of its lead product, Scenesse (afamelanotide), in the U.S. and Europe, Melbourne-based Clinuvel Pharmaceuticals Ltd. is expanding its global footprint and widening its pipeline as it opens a new R&D center in Singapore and builds up its franchise in photo medicine.

What sets Clinuvel apart is its old-fashioned approach to handling all activities in-house and its single focus on one drug.

“We opted to focus on one drug and then slowly started adding other products to the pipeline,” Clinuvel CEO Philippe Wolgen told BioWorld.

The FDA approved Clinuvel’s Scenesse in October 2019 to increase pain-free light exposure in adults with a history of skin damage from the rare inherited disorder erythropoietic protoporphyria (EPP). The drug was approved in Europe in late 2014.

EPP is a rare disorder caused by mutations leading to impaired activity of ferrochelatase, an enzyme involved in heme production. That decrease in ferrochelatase activity leads to an accumulation of protoporphyrin IX in the body, causing intense skin pain and skin changes when light enters the body. Scenesse, a melanocortin-1 receptor (MC1-R) agonist, increases the production of eumelanin in the skin independent of exposure to sunlight or artificial light sources.

Prior to the U.S. approval, there were no FDA-approved treatments to help EPP patients increase their light exposure. The FDA granted the application a priority review as well as affording the program orphan drug status.

The company is still working its way through reimbursement in the U.S.

“We fought our way through reimbursement in the world. It’s a game of stalling and delaying,” Wolgen said, noting that Europe is 80% done.

“In the U.S., we have to go through every single insurer for every single patient in every single state to fight our way through. And then they delay and delay.”

The move has been particularly frustrating since Clinuvel has a uniform pricing policy, and because it’s an orphan indication, it can accurately count the number of patients to be treated and the associated costs.

“In Europe, we’ve done really well. We know exactly how much it will cost, and we’ve always come in under budget,” he said.

Staged approach to R&D

Clinuvel has taken a staged approach to R&D, focusing on just one product to keep costs low.

“Many investors don’t understand our approach. But to me it’s all about laying a foundation of a company that survives over time,” Wolgen said.

“Now that the EPP indication is done, we can finally open the R&D spectrum, because it’s a family of hormones and it does a multitude of things. We’ve always known that, but we just didn’t want to do it in parallel; we did it sequentially.”

Reversing sun damage was always the key characteristic of Scenesse, he said. In early trials in 2006, the drug was given to 82 Australian volunteers in Queensland, where biopsies taken from patients with sun damage saw reversal of that damage with treatment.

Wolgen said it would have been impossible to get approval for the broad sun damage indication because there wasn’t a disease attached to it, so the EPP route was the first stage of the company’s journey.

“Now that we have convinced regulators that the drug photoprotects, the next stage is whether we can eliminate the photo products and repair DNA,” he said.

He explained that skin incurs DNA damage following ultraviolet exposure. Non-ionizing light penetrates the nucleus of skin cells and causes distortions to the DNA helix, known as photoproducts. If left unrepaired, those chemical changes to DNA may replicate as mutations, leading to irreversible damage and then progress to skin cancer.

“Eventually you want to take fragments of this hormone and put it in topical treatments, but that’s the dream of every cosmetic company that claims to rejuvenate skin,” Wolgen said. “That’s the final part of the puzzle, because you have something that will benefit everyone.”

Expanding the pipeline

The company is now progressing its DNA repair program, starting first with patients with xeroderma pigmentosum (XP), a rare genetic disorder that leads to a 10,000-fold increase in the risk of skin cancer.

XP is a “horrendous and mutilating disease and is characterized by an inability to repair DNA,” Wolgen said, and Scenesse can help repair those patients’ DNA. Patients with XP usually only live 25 to 30 years, and they often lose their facial features because they develop skin cancer at a very high rate. They live in “NASA-like spacesuits” and cannot go outside during the day.

“We always wanted to treat this disease, but we couldn’t get ethics approval, because most hospitals are very protective of these patients, and EPP gave us the right to speak to these patients and to the hospitals, and the regulators finally agreed,” he said.

Clinical trials in patients with XP will begin in the coming weeks.

The trial protocol for those patients is tricky because they can only travel at night, so there are logistics around that, and Clinuvel has a team in place that handles the transport of patients from door to door.

Two more indications will be announced in the coming weeks, he said.

Singapore R&D center

Clinuvel has opened a new R&D center in Singapore that will be operated by its subsidiary, Vallaurix Pte Ltd. The company built its first R&D center in Singapore in 2014. Construction of the new facilities began in 2019, but the COVID-19 pandemic caused a four-month delay.

The Singapore lab was built in six months, he said, which would have taken two years in Australia and even longer in the U.S. The only glitch was the COVID-19 pandemic, he said.

In 2014, the emphasis for the Singapore R&D center was on experimental and analytical output, including developing novel products and melanocortins. Initial research focused on early discovery, in vitro testing, and analyses of new molecules.

Singapore’s Economic Development Board also invested $365,000 to complement Clinuvel’s financial commitment to constructing its state-of-the-art facility in the country.

The new Singapore R&D center will house full integration and cross-functional operations within the Clinuvel Group, whereby staff will operate under Clinuvel’s global policies.

Manufacturing will be the next stage, he said, noting that this is the missing piece in the company. He stressed that Clinuvel does not use third parties.

“My view is you want to be independent, so you build these functions in-house. I want to have a vertically integrated company, because in my old-fashioned view, a pharma company is the aggregate of that individual talent, and you can’t outsource that. You want to retain that talent and grow it,” Wolgen said.

The company has raised $95 million since 2006. It reported a 5% increase in revenue to AU$32.5 million (US$23.66 million) compared to the previous year and net profit of AU$13.13 million for financial year 2020 that ended June 30. The company invested AU$9.6 million in R&D, 40% more than the previous year.

Clinuvel’s shares on the Australian Securities Exchange (ASX:CUV) were trading at AU$21.31 at close of trading Sept. 14.

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