Proteolix Inc. closed a Series B financing, bringing in $45 million to support clinical development of its proteasome inhibitor pipeline in cancer and immune diseases.

To date, the San Francisco-based company has raised more than $63 million since its 2003 inception. Proteolix was founded only a few months after the first proteasome inhibitor - Cambridge, Mass.-based Millennium Pharmaceuticals Inc.'s Velcade (bortezomib) - gained FDA approval in multiple myeloma.

Bolstered by that outcome, Proteolix began building its pipeline of drugs, led by PR-171, a proteasome inhibitor that has demonstrated early promise against multiple tumor types, including multiple myeloma cells that are resistant to existing therapy. Proteasomes are cellular complexes that control protein turnover in cells, and research has shown that blocking proteasome activity can provoke apoptosis, particularly in cancer cells.

The company could not be reached for comment, but in a statement said that funds from the Series B would be used to expand ongoing clinical trials of PR-171, an intravenously administered candidate in Phase I studies in multiple myeloma and lymphoma.

PR-171, an analogue of epoxomicin, is designed to work by inhibiting the chymotrypsin-like protease in the core of the proteasome. Results from animal models have suggested that Proteolix's compound could demonstrate better efficacy compared to existing proteasome inhibitors, such as Velcade, due to PR-171's ability to dose at higher levels.

For the first quarter of 2006, Millennium reported U.S. Velcade sales of $53.4 million, and it is conducting studies to broaden the product's label. Velcade is in Phase II trials, either as a monotherapy or in combination therapy, in mantle-cell lymphoma, non-Hodgkin's lymphoma, bronchioloalveolar carcinoma and advanced non-small-cell lung cancer. Earlier testing is evaluating Velcade against lung, breast, prostate and ovarian cancers.

San Diego-based Nereus Pharmaceuticals Inc. also is developing its own proteasome inhibitor, NPI-0052, a small molecule in a Phase I trial in patients with advanced solid tumors or refractory lymphomas. Nereus also is planning a second trial in multiple myeloma.

Beyond PR-171, Proteolix has an oral proteasome inhibitor in preclinical development and is conducting lead optimization work on an inhibitor aimed at immunoproteasomes, which are found in immune cells. Early research has shown that modulating immunoproteasomes could attack hematological diseases and tumor disorders with fewer side effects compared to existing therapies.

Delphi Ventures, of Menlo Park, Calif., led the financing round, and Delphi's Deepa Pakianathan joined Proteolix's board. Existing investors Menlo Park, Calif.-based U.S. Venture Partners; Palo Alto, Calif.-based Advanced Technology Ventures; San Francisco-based Latterell Venture Partners and Summit, N.J.-based The Vertical Group also participated.