A handful of companies have expressed interest in applying RNA interference to the field of dermatology — L’Oreal, for instance, holds an international patent application on the use of double-stranded RNAs for cosmetic purposes, and Atugen has said that it is evaluating the gene-silencing technology in wound healing (see RNAi News, 2/13/2004).
But no company has moved as aggressively as Sirna Therapeutics, which announced this week the formation of a dermatology division following the acquisition of privately held dermatology firm Skinetics Biosciences.
Driving the acquisition is Skinetics’ discovery of hairless, a gene associated with hair growth. According to Sirna, preclinical in vitro and in vivo research it performed in collaboration with Skinetics has shown that topically applied siRNAs targeting the hairless gene can be used to block the growth of hair.
As such, “Sirna Dermatology’s first clinical program will be the application of siRNAs for permanent hair removal — an estimated $4 billion market in the United States alone,” Howard Robin, president and CEO of Sirna, said during a conference call this week. He added that the “world market is expected to grow to an estimated $11.1 billion in 2005.”
According to Angela Christiano, a Skinetics co-founder and associate professor of dermatology, genetics, and development at Columbia University, the hairless gene was discovered her lab following a genetic linkage study that began with several families from Pakistan affected with an extreme form of alopecia. “The search for the gene led us to identify [hairless] using a genomic approach comparing regions of DNA between human families and hairless mice,” she said during the conference call.
The hairless gene, she added, “is expressed during a critical window [in] the hair follicle cycle, and in its absence, such as in hairless mice, the hair follicle is destroyed during the catagen … stage in a manner that causes permanent alteration so that no further hair growth can occur.”
Robin said during the conference call that Sirna expects to advance a topical, siRNA-based drug targeting hairless into phase I testing “in the early part” of 2006.
But before that occurs, he said, Sirna still must “finalize [the] selection of the chemical modifications of the siRNAs needed to stabilize [them] and give the highest level of activity.” Additionally, the company needs to “develop the proper type of … cream formulation,” Robin said. “That type of work will take us … the next six months or so.”
Another key finding that Robin said would be worked out during preclinical development is the number of doses of the RNAi drug required to achieve permanent hair removal.
“Since you can only knock down the hairless gene at certain points in the hair-growth cycle, we would envision that [treatment] would [involve multiple] … topical application[s] that would go on for a number of months before the permanent hair removal takes place,” he said. “It could be that this takes regular dosing of a cream for three or four or five months until you’ve approached all the hairs in their growth cycle.”
Christiano added that a hair-removal drug is “bound by the limits of how fast hairs can cycle, and we have to catch them all at the precise time when hairless is expressed. So, certainly more than one dosing would be required.”
Robin said that the preclinical data already in hand indicate that there is no significant toxicity associated with the siRNA treatment, nor are there any systemic effects since the majority of the drug does not penetrate the skin. He said that while no date has been set for the public release of any preclinical data, information is expected to be made available in the “not too-distant future.”
In terms of developing the hair removal drug, Robin said that “we haven’t made a decision about how far we will take [the drug through development ourselves]. It’s certainly possible that we take this right through phase III, and it’s also possible that we find a partner early.”
But given the size of the hair-removal market, “this is not a drug that you give away on the cheap,” he added. “If we do find a partner, [the drug] will only be acquired at a very high price.”
Skinetics to Sirna
Under the terms of the companies’ agreement, Sirna will acquire from Skinetics all intellectual property rights and research related to the development of siRNAs for permanent hair removal. Nassim Usman, senior vice president and COO of Sirna, told RNAi News this week that his company also acquired rights to the use of siRNAs against other undisclosed gene targets.
In exchange, Sirna granted stock to Skinetics shareholders and consultants. Additional shares are to be granted upon the achievement of certain clinical milestones, and royalties will be paid upon product commercialization.
Sirna did not specify the exact number of shares it has granted already under the arrangement, but a recent Sirna filing with the US Securities and Exchange Commission indicates that it was 680,272 shares of common stock (see RNAi News, 11/26/2004). On Wednesday, shares of Sirna closed at $3.671, giving the initial stock payout to Skinetics’ shareholders and consultants a value of about $2.5 million.
Skinetics will form the basis of Sirna’s new dermatology division, with Joseph Carroll, a Skinetics co-founder and former Millennium Pharmaceuticals senior scientist, heading up the research activities of the unit. Carroll will report to Barry Polisky, Sirna’s senior vice president of research.
Usman noted that the business structure of the dermatology branch has not been finalized.
A scientific advisory board has also established for Sirna Dermatology. The members include Paul Khavari, a professor of dermatology at Stanford University School of Medicine; James Krueger, a professor of investigative dermatology at Rockefeller University; Thomas Kupper, a professor of dermatology at Harvard Medical School; Elise Olsen, a professor of medicine and dermatology at Duke University Medical Center; and Fiona Watt, head of the keratinocyte laboratory at Cancer Research UK. Christiano will act as an exclusive RNAi consultant to the dermatology division.
While Sirna Dermatology’s initial focus will be on advancing its hair-removal product, Usman noted that the division is expected to branch out into other indications. “But we haven’t chosen those yet,” he said. “As in other fields, you try to find the simplest things first, and [hair removal] was the first one we decided to go after.”
Giving a possible preview of where Sirna Dermatology may be headed next, Christiano noted during the conference call that aside from its use for permanent hair removal, an RNAi drug targeting hairless could also have therapeutic potential for treating trachoma.
Trachoma is a condition in which the conjunctival lining of the eyelids become infected with a bacteria that, over the long term, causes inflammation, she said. The disorder also shortens the eyelid, which causes eyelashes to turn inward — a development that can irritate the cornea and lead to impaired vision and blindness.