BioWorld Today Correspondent

Creabilis SA raised €15 million (US$20 million) in a Series B round to advance a pipeline of three compounds in development for dermatology, inflammation and pain indications.

The Luxembourg-based firm, which raised €20 million in a Series A round three years ago, aims to have Phase IIb data in psoriasis from its lead compound, CT327, around 12 months from now. The trial, which will recruit several hundred patients, will get under way later this year.

The drug, a topically applied TrkA kinase inhibitor, has already completed Phase IIa studies in psoriasis vulgaris (plaque psoriasis) and atopic dermatitis. A proof-of-concept trial in pain is ongoing.

"We expect that [data] in the first quarter of next year," CEO Eliot Forster told BioWorld Today.

TrkA kinase is a high-affinity receptor tyrosine kinase that binds to and transduces signals from nerve growth factor (NGF). Mutations in the Ntrk1gene, which encodes TrkA, are associated with congenital insensitivity to pain. In psoriasis, TrkA mediates the stimulatory effect of NGF on keratinocytes, the predominant cell type in the epidermis.

"Psoriasis is a hyperproliferation of keratinocytes," Forster said.

CT327 was developed using Creabilis' proprietary Low Systemic Exposure (LSE) conjugation technology, which links a molecule of interest to low molecular weight polyoxyethylene, thereby minimizing systemic exposure. The drug is based on a highly potent but toxic predecessor, K252a.

Most psoriasis patients receive steroids and vitamin D analogues at present, Forster said. Severe cases – about 10 percent of the overall population – receive systemic biologic therapy, such as the TNF-alpha inhibitors Remicade (infliximab) or Humira (adalimumab), or the interleukin-12 (IL-12) and IL-23 inhibitor Stelara (ustekinumab).

"They do quite well on this, but clearly that comes with everything from black-box warnings to immune suppression," Forster said.

Moreover, even those in the latter category continue to receive topical medication, such as steroid creams and retinoids, as well. Those too have shortcomings – excessive use of steroids can lead to skin thinning, for example, while retinoids can have limited efficacy, he said. Should CT327 gain approval in psoriasis, Forster estimated peak sales at $500 million to $700 million.

Whether the company will seek a partner or undertake full development and commercialization on its own remains an open question for now. The Phase IIb data will drive that decision.

As the most advanced molecule in the Creabilis pipeline, CT327 was the drug that whetted investor appetites during the company's road show.

"We were well positioned with some clinical data, and we were able to take that out," Forster said. However, investors also took note, he added, of its two other compounds, both of which are due to enter the clinic in the first half of 2012.

CT340, another topical therapy, is, like CT327, a TrkA kinase inhibitor, but it also acts on a second, undisclosed target associated with inflammation. It is being lined up for development in arthritis and pain.

The company's third pipeline project, CT637, is a biologic drug, also in development for inflammatory indications. It comprises a pegylated mutant of the A-box of the high-mobility group box 1 protein (HMGB1), a damage-associated molecular pattern molecule.

HMGB1, a late-acting mediator of inflammation, is released after TNF-alpha and IL-1. It is released passively after tissue injury or secreted actively following immune activation. It elicits an inflammatory response via Toll-like receptor 4 (TLR-4) and possibly other receptors. CT637 is designed to block HMGB1 receptor sites and thereby interrupt the immune cascade.

An earlier drug candidate, CT200, a modified form of alpha interferon in development for Behcet's disease, an inflammatory condition most prevalent in Turkey and among people of Turkish descent, has been parked owing to manufacturing issues.

Abbott Biotech Ventures, the venture capital arm of Abbott, of Abbott Park, Ill., led the funding round. It was joined by existing investors Neomed, of Oslo, Norway, and Paris-based Sofinnova Partners, as well as by private Italian investors.

Although headquartered in Luxembourg, Creabilis' operations are based in Colleretto Giacosa, Italy, and Womenswold, UK.

In other financing news:

• Arrowhead Research Corp., of Pasadena, Calif., said it raised $5.5 million in a private placement of about 14.5 million shares of common stock priced at 38 cents apiece. Proceeds will be used to fund current operations. Arrowhead develops nanomedicines and operates several subsidiaries, including Calando Pharmaceuticals Inc. and Ablaris Therapeutics Inc.

• Cel-Sci Corp., of Vienna, Va., is raising about $4 million through the sale of about 13.3 million shares of common stock priced at 30 cents per share in a registered direct offering. Investors also will get warrants to purchase up to 12 million shares. Proceeds will support general and administrative expenses, as well as the firm's ongoing Phase III program involving Multikine (leukocyte interleukin, injection. Shares of Cel-Sci (AMEX:CVM) fell 5 cents, or 14.7 percent, to close Tuesday at 29 cents.