Topigen Pharmaceuticals Inc. raised C$26 million (US$24.7 million) in the first close of a Series C financing to drive Phase II trials with TPI 1020 in chronic obstructive pulmonary disease (COPD) and TPI ASM8 in asthma.

Paul Wotton, president and CEO of Montreal-based Topigen, said the company wanted to raise money quickly to support its Phase II trials, so the first close of the Series C came predominantly from existing investors. He added that Topigen plans to keep the round open "over the balance of the year" to give new investors a chance to participate.

Topigen already has investor interest and expects to close an additional C$20 million in Series C funding before the end of the year, Wotton said.

Existing investor BDC Venture Capital, of Montreal, led the first close of the Series C, with participation from existing Montreal-based investors Desjardins Venture Capital, Caisse de dépot et placement du Québec, T2C2/BIO 2000 and Lothian Partners 27 (sarl) SICAR. Two new investors also joined the round: Toronto-based MMV Financial Inc. and NovaQuest, the investment arm of Research Triangle Park, N.C.-based Quintiles Transnational Corp.

Including the current funding, Topigen has raised C$75 million (US$71.2 million) to date. Wotton attributed about $62 million (US$58.9 million) to equity investments and the "bulk of the rest" to cash received through Canadian research and development tax credits.

The money is expected to last through the first quarter of 2010, Wotton said, adding that the company is "very cash efficient."

Most of the financing will support Phase II programs for TPI 1020 and TPI ASM8.

TPI 1020 is an inhaled, small-molecule, nitric-oxide formulation of the steroid budesonide, licensed from NicOx SA, of Sophia Antipolis, France. In preclinical models, the drug inhibited neutrophil infiltration in the airways, something not seen with other steroids, Wotton said. (See BioWorld Today, Oct. 28, 2005.)

Early clinical data also showed TPI 1020 could protect against bronchoconstriction more effectively than standard budesonide. Topigen just completed a Phase II study of the drug in asthmatic smokers, and data are expected next month. A Phase II trial in COPD will kick off within the next three months and take about a year to complete.

Approved drugs for COPD include DuoNeb (albuterol and ipratropium, DEY LP), Brovana (arformoterol, Sepracor Inc.), Perforomist (formoterol, DEY LP) and many others. There also are several in development, including Pharmaxis's Aridol in Phase II, Argenta Discovery Ltd.'s ADC4022 beginning Phase II and Aerovance Inc.'s Pulmolytic (AER 002) also in Phase II. BioMarck Pharmaceuticals Ltd.'s BIO-11006 is on the verge of beginning Phase IIa, as is ALKS 27 from Alkermes Inc. and Indevus Pharmaceuticals Inc. Additionally, AstraZeneca plc has a potential $200 million COPD discovery deal with Argenta and a potential $136 million deal with Dynavax Technologies Corp. (See BioWorld Today, Sept. 8, 2006, and Feb. 1, 2007.)

TPI ASM8 will compete in the similarly crowded asthma market but has a unique mechanism of action. The inhaled drug consists of two RNA-targeted, modified antisense oligonucleotides designed to reduce the recruitment and persistence of chronic inflammatory cells.

Initial Phase II data showed the drug demonstrated significant inhibitory effects on allergen-induced responses, inhibited the influx of eosinophil cells by nearly half and halted the increase in total cells and neutrophils after an allergen challenge. Topigen is conducting an expanded Phase II trial and expects to move into Phase IIb in the second half of 2008.

Beyond its two lead programs, Topigen has TPI 1100, a third-generation oligonucleotide derived from the TPI ASM8 technology. The inhaled drug inhibits several phosphodiesterase targets involved in COPD and is slated to enter the clinic next year.

Topigen also has an earlier-stage preclinical program, TPI ALR8, aimed at allergic rhinitis. The program is another product of the company's RNA discovery engine, like TPI ASM8 and TPI 1100, but Topigen is evaluating the drug using both inhaled delivery and topical intranasal delivery technology licensed from Novagali Pharma SA. (See BioWorld Today, March 23, 2007.)