Onyx Pharmaceuticals Inc.'s new multiple myeloma drug Kyprolis (carfilzomib) will get a $358.6 million boost following a new public offering of stock from the South San Francisco-based company.

The offering of 4.4 million shares will fund clinical development of carfilzomib and oprozomib, as well as sales and marketing of Kyprolis, which gained accelerated approval as a third-line treatment in patients with relapsed and refractory disease last year.

Proceeds from the large offering may also be used to make milestone payments to Proteolix Inc., to pay some or all of its $230 million in debt or to acquire businesses or products to supplement its peptide.

Onyx's business is based on two franchise platforms: kinase inhibitors and proteasome inhbitors. Nexavar (sorafenib) is its lead product on the kinase inhibition side. Onyx markets the drug for unresectable liver cancer and advanced kidney cancer with Bayer HealthCare Pharmaceuticals Inc.

Onyx also receives a 20 percent royalty on Bayer's oral multikinase inhibitor, Stivarga (regorafenib), which is marketed for metastatic colorectal cancer, and is also under review for the additional indication of gastrointestinal stromal tumors.

Bayer has submitted marketing applications in Europe and Japan for Stivarga, and the drug is under priority review in Japan.

Kyprolis leads Onyx's proteasome inhibitor franchise. It won a unanimous 11-1 vote in favor of approval from the FDA's Oncologic Drugs Advisory Committee (ODAC) in June 2012, and was approved soon after, in spite of concerns by some reviewers of severe cardiac toxicities and questions about its superiority to existing myeloma therpies. (See BioWorld Today, Dec. 13, 2011, June 19, 2012, June 21 , 2012, and July 23, 2012.)

Kyprolis is indicated for patients who have received at least two prior therapies, including Velcade (bortezomib, Millennium: The Takeda Oncology Co.) and an immunomodulatory therapy, and have demonstrated disease progression on or within 60 days of completion of last therapy.

Kyprolis has its own sales group separate from Onyx's sales team for the kinase inhibitor franchise. Cowen and Co. analyst Phil Nadeau projected 2013 Kyprolis sales of as much as $200 million, with U.S. sales reaching $750 million in 2016.

Onyx acquired Kyprolis through its 2009 acquisition of Proteolix, in a deal worth up to $851 million. Onyx paid $276 million up front, with the rest in milestones, including $170 million that was due to Proteolix shareholders upon accelerated FDA approval. (See BioWorld Today, Oct. 13, 2009.)

Ligand Pharmaceuticals Inc. also is entitled to milestone payments and royalties on Kyprolis sales, having contributed its Captisol technology to the product.

In a Phase IIb trial in 266 heavily pretreated patients with relapsed or refractory multiple myeloma, the overall response rate was 24 percent, and median duration of response was 7.8 months.

Onyx continues to study Kyprolis. It has completed enrollment in the Phase III ASPIRE trial, testing the drug in combination with Revlimid (lenalidomide, Celgene Corp.) and low-dose dexamethasone vs. Revlimid and dexamethasone alone in relapsed multiple myeloma patients who have received one to three prior therapies. That trial is being carried out under a special protocol assessment with the FDA.

Another study, ENDEAVOR, is testing Kyprolis plus low-dose dexamethasone against Velcade plus low-dose dexamethasone, and Onyx's FOCUS trial will evaluate Kyprolis as a single agent in patients with relapsed and refractory disease who have received one to three prior therapies.

Onyx has two other proteasome inhibitors in development: oral proteasome inhibitor oprosomib (ONX 0912) and immunoproteasome inhibitor (ONX 0914).

Underwriters may exercise an option to purchase an additional 660,000 shares of common stock to cover overallotments.

BofA Merrill Lynch and Barclays were joint book-running managers for the offering.

Onyx reported cash, cash equivalents and marketable securities of $573 million as of Sept. 30.

Onyx's stock (NASDAQ:ONXX) lost $4.15, to close at $79.28 Wednesday.