With Japanese investors holding the majority of its shares and a lead product in-licensed from a Tokyo-based company, Acologix Inc. filed to conduct a $115 million initial public offering on the Tokyo Stock Exchange.

The Hayward, Calif.-based company is one of a handful of American firms this year that have turned to more receptive foreign markets to go public. In July, South San Francisco-based Napo Pharmaceuticals Inc. completed a $22 million IPO on the London Stock Exchange, and a month earlier, PuriCore Inc., of Malvern, Pa., through its parent company, PuriCore plc, raised $54.7 million through a London IPO.

If Acologix is successful in raising $115 million on the Tokyo exchange, it would be more money than a U.S. biotech company has raised in an IPO this year on American exchanges. While two companies - Affymax Inc., of Palo Alto, Calif., and Perlegen Sciences Inc., of Mountain View, Calif. - have pending IPOs aimed at raising $115 million, the highest amount raised so far this year was $105 million in January by Cambridge, Mass.-based Altus Pharmaceuticals Inc., according to BioWorld Industry Snapshots. The next highest raised was $59.6 million in April by Vanda Pharmaceuticals Inc., of Rockville, Md.

Only one IPO in 2005 - conducted by San Diego-based MediciNova Inc. - surpassed the $115 million mark. The company raised $122.5 million in February, but the IPO, notably, was done in Japan on the Osaka Securities Exchange under the Hercules market.

Acologix was founded in 1992 by the company's current president, CEO and director, Yoshinari Kumagai. It since has raised $72 million through three rounds of financing, including a $25 million Series C round conducted last December. (See BioWorld Today, Dec. 22, 2005.)

That money was expected to take the company to the end of 2007. As of June 30, Acologix had cash, cash equivalents and short-term investments of $42 million. The company, which is in a quiet period, did not return phone calls Thursday.

Its prospectus filed with the SEC said the funds would be used for clinical and preclinical trial activities, for prosecuting and maintaining patents, and for building a sales and marketing organization to commercialize Acologix's first product candidate. The sales force would target the renal market. For other indications, the company likely would partner.

In June 2005, Acologix in-licensed the late-stage compound TRK-820 from Tokyo-based Toray Industries Inc., and Acologix holds exclusive commercial rights in North America. Toray is entitled to milestones and royalties related to the product.

A kappa-opioid receptor agonist, the lead drug is in Phase III development to treat uremic pruritus, a severe systemic itch associated with end-stage renal disease (ESRD) for which there is no FDA-approved product. In 2003, there were about 450,000 ESRD patients in the U.S.

Acologix intends to start a Phase III U.S. trial of intravenous TRK-820 in 2007 under a special protocol assessment agreed upon with the FDA. An intravenous form of TRK-820 already is in development with Toray in Europe, where the two companies share costs of an ongoing Phase III study. Acologix has exclusive rights to commercialize TRK-820 in Europe and expects to pay Toray royalties on eventual sales.

The two Phase III trials are focused on the intravenous form of the drug, although Toray separately has completed a Phase III study of an oral formulation of TRK-820 in Japan, which demonstrated a statistically significant reduction in itching intensity in uremic pruritus patients.

Acologix also is pursuing development of AC-100, or Dentonin, a synthetic peptide for bone and dental tissue regeneration applications. It was well tolerated in a Phase I trial. Phase II data showed it stimulated the formation of new human dentin following a typical tooth restoration procedure, but it did not do so well when evaluated in periodontal disease in a separate Phase II trial. The company suspects it did not use an optimal dose for that study. A sustained-release formulation of AC-100 is being evaluated as a therapy to improve the healing of orthopedic bone fractures. Since it targets indications outside the realm of renal disease, Acologix likely will seek a partner for the product.

At the preclinical stage, Acologix is studying AC-200, or Phosphatonin, a recombinant protein to treat hyperphosphatemia, which often occurs in patients with advanced renal failure. The candidate was identified through academic research sponsored by Acologix and in June was partnered in Japan with Toray.

Other preclinical work at Acologix is focused on potential therapies for interstitial cystitis.

The company's top investors are JAIC (Japan Asia Investment Co.), which has a 13.4 percent stake, and Acologix's CEO, Kumagai, who holds a 14.2 percent stake. Other stockholders, each owning more than 5 percent of Acologix are Aqua RIMCO Funds, Nomura R&A II Venture Capital Fund LP, Life Science Venture Fund and Tokio Marine and Nichido Fire Insurance Co. Ltd. All are based in Japan.