When Sirna Therapeutics acquired privately held dermatology firm Skinetics Biosciences in late 2004 (see RNAi News, 12/10/2004), it predicted that it would move its first RNAi-based dermatology product, a permanent hair removal drug, into the clinic two years later.
Sirna never achieved this goal, in part because the company’s dermatology unit was shut down after Merck acquired the RNAi shop early last year (see RNAi News, 1/4/2007). But in the end, technological hurdles facing topical delivery of siRNAs may have been mostly to blame for the failure, according to a former Skinetics offical.
Skinetics CSO and co-founder Joseph Carroll, who headed up Sirna’s dermatology division, said the company was unable to achieve “knockdown consistently in vivo to move the [hair-removal] program forward.”
Carroll, who is now a consultant, noted that while delivery has always been a major issue for the RNAi therapeutics field, transdermal delivery is particularly difficult since the skin is by design a barrier.
“The first hurdle is just getting [siRNA] through the stratum corneum, [the outermost layer of the epidermis, and] into the skin,” he told RNAi News last week. “That’s a challenge because you have this macromolecule that’s … pretty big.” But even if delivery through this layer is achieved, “the second challenge is [getting] cells to take it up,” he noted.
Carroll said that before being acquired by Merck, Sirna had both been working on its own topical delivery approaches and evaluating technologies under development elsewhere, but “we just weren’t finding viable delivery options.
“We tried a range of delivery systems for skin and were looking for high levels of consistent knockdown in vivo,” he said. “It just wasn’t achievable using the systems we looked at.”
Carroll said he remains optimistic about the future of topical RNAi drugs, but suggested that a solution to the transdermal delivery problem may not be immediately forthcoming.
“Every organ is a unique challenge, and there will someday be delivery to the skin [of] a topically delivered siRNA,” he said. Still, “the magic bullet hasn’t been found yet.”
Hair Today, Gone Tomorrow
Although a handful of RNAi drug firms have been eyeing the dermatology field, Sirna became the most high profile to do so when it bought Skinetics.
Under the terms of that deal, Sirna paid an estimated $2.5 million in stock for the company and its intellectual property portfolio, which included rights to hairless, a hair growth-related gene discovered by Columbia University researcher and Skinetics co-founder Angela Christiano.
Following the transaction, Sirna established Sirna Dermatology, a business unit focused exclusively on developing the permanent hair-removal drug and RNAi-based treatments for skin disorders including psoriasis and atopic dermatitis.
“We tried a range of delivery systems for skin and were looking for high levels of consistent knockdown in vivo. It just wasn’t achievable using the systems we looked at.”
Despite the fanfare that accompanied the creation of Sirna Dermatology, the unit was quietly shut down a few months after Merck acquired Sirna, according to Carroll.
Merck was “realigning [Sirna] for a couple of key programs, and dermatology was not one of them,” he said. Dermatology “was clearly just not part of their portfolio and not something they wanted to pursue.”
Indeed, Merck has publicly stated that its main areas of interest are Alzheimer's disease, atherosclerosis, cardiovascular disease, diabetes, vaccines, obesity, cancer, pain, and sleep disorders.
Carroll noted that he and Skinetics’ other co-founders had an option to re-acquire the Skinetics IP from Merck, “but it wasn’t very feasible at that point – we didn’t have a lab, we didn’t have funding, [and] we didn’t have a company.”
More importantly, “I had some concerns about the status of topical siRNA delivery,” he said. “I had explored the idea of starting another venture around siRNA and dermatology, but I think that’s just not going to happen right now” since it would likely be difficult to secure funding for this kind of effort.
Carroll added that the Skinetics IP has since been returned to Columbia.
Sirna Dermatology isn’t the only company to find the topical delivery nut hard to crack.
TransDerm, which is developing RNAi drugs for skin disorders, is developing a topical delivery technology called gene cream for its lead drug candidate, a pachyonychia congenita therapy called TD101.
Last week, however, the company announced that its recently initiated phase Ib study of TD101 would examine the drug when it is administered as an intradermal injection (see RNAi News, 1/17/2007).
According to TransDerm’s Founder and CEO Roger Kaspar, the company continues to work on getting the gene cream ready for human testing, but is waiting for an indication that the RNAi component of TD101 is effective before stepping up this effort.
Carroll noted that he is “very encouraged” by the gene cream data to which he has been privy, but noted that it isn’t yet apparent whether the delivery technology will be applicable to a variety of skin disorders even if it is successfully developed for TD101.
“I’m wondering how amenable [gene cream] is going to be for a range of dermatologic indications or whether it is really specific for” pachyonychia congenita, he said.