Proteolix, Inc. announced data from ongoing Phase 2 and Phase 1b clinical trials of carfilzomib for the treatment of multiple myeloma at the 14th Congress of the European Hematology Association (EHA) in Berlin, Germany. Carfilzomib is the first in a new class of selective, irreversible proteasome inhibitors being developed by Proteolix for the treatment of hematologic malignancies and solid tumors.

Relapsed Multiple Myeloma Patients Achieve Responses with SingleAgent Carfilzomib

Keith Stewart, M.B., Ch.B., Professor, Division of Hematology/Oncology at the Mayo Clinic, Arizona presented positive data from an ongoing Phase 2 clinical trial of singleagent carfilzomib in relapsed multiple myeloma patients. Patients in the study have relapsed after receiving one to three prior therapies and are stratified according to prior exposure to bortezomib.

A total of 31 patients have been enrolled in the Phase 2 clinical trial to date, of which 45 percent had no prior bortezomib experience and 55 percent relapsed following bortezomib treatment. In both arms, substantial response rates were achieved and sustained. Bortezomibnaive patients achieved an overall response rate of 57 percent with a median duration of response of 8.5 months. The median time to progression in this cohort has not been reached.

Among patients with prior bortezomib exposure, 18 percent achieved partial responses and the median duration of response has not yet been reached in this population. The median time to progression for patients in this cohort was 8.9 months. Ten additional patients achieved stable disease.

“Carfilzomib monotherapy achieves durable responses in relapsed multiple myeloma patients regardless of their prior exposure to bortezomib, and notably, a number of patients remain progression free after twelve cycles,” said Dr. Stewart. “Further, carfilzomib has been generally well tolerated, and the compounds selectivity appears to avoid the offtarget effects, such as peripheral neuropathy, associated with currently available proteasome inhibitors.”

Adverse events were generally mild and manageable and carfilzomib has been well tolerated for up to one year. Of 31 patients treated, 29 percent have received 12 full cycles of treatment.

These data were reported by Dr. Stewart in an oral presentation, titled “# 0474 Safety and Efficacy Update of PX171004, an Openlabel Phase II Trial of Carfilzomib in Relapsed Multiple Myeloma,” on Saturday, June 6, 2009.

Carfilzomib Combination with Lenalidomide is WellTolerated; Achieves Responses in Heavily Pretreated Patients at Low Doses

Positive preliminary data from an ongoing Phase 1b doseescalating trial of carfilzomib in combination with lenalidomide and lowdose dexamethasone in relapsed and refractory patients was presented by Michael Wang, M.D., of the University of Texas MD Anderson Cancer Center on Sunday, June 7, 2009. The Phase 1b clinical trial is designed to evaluate safety and to establish a maximumtolerated dose of carfilzomib in combination with lenalidomide and dexamethasone administered on a 28day treatment cycle. Lenalidomide in combination with dexamethasone is currently indicated for use in patients with multiple myeloma who have had at least one prior therapy.

To date, the combination of carfilzomib and lenalidomide was well tolerated in heavily pretreated patients and adverse events were manageable. The most common adverse events reported include anemia and fatigue. No cases of peripheral neuropathy, a common adverse event associated with approved proteasome inhibitors, have been reported. A maximumtolerated dose has not yet been established and doseescalation in this trial continues.

Sixtyone percent of the 18 patients evaluable for efficacy achieved very good partial, partial or minor responses. Responses occurred in the first 28day cycle of treatment at doses well below the maximumtolerated dose for either lenalidomide or carfilzomib alone. Initial responses improved with continued therapy. Potent inhibition of the proteasome has been observed and the lenalidomide/dexamethasone combination does not appear to interfere with carfilzomibs activity.

“Results observed to date in our Phase 1b combination study of carfilzomib are very promising,” said Michael Kauffman, M.D., Ph.D., Chief Medical Officer of Proteolix. “We believe that carfilzomib in combination with lenalidomide and dexamethasone should provide superior activity to lenalidomide and dexamethasone alone. In addition, the lack of overlapping toxicities and absence of peripheral neuropathy may allow for longterm dosing and ultimately, sustained clinical benefit.”

Dr. Wang presented interim data from the Phase 1b clinical trial during the Novel Therapeutics and Drug Resistance session in an oral talk, titled “#1070 PX171006 Phase IB Multicenter Dose Escalation Study of Carfilzomib (CFZ) plus Lenalidomide (LEN) and Low Dose Dexamethasone (LODEX) in Relapsed and Refractory Multiple Myeloma (MM) Preliminary Results.”

About Multiple Myeloma

According to the American Cancer Society, in 2009, approximately 20,500 new cases of multiple myeloma will be diagnosed in the United States. Newly diagnosed patients have treatment options that include combination chemotherapeutic agents and stem cell transplantation. While many patients respond to treatment, most eventually relapse and require subsequent treatment. Few patients are ultimately cured of their disease. In spite of advances in the treatment of multiple myeloma, this year alone, approximately 10,500 patients are expected to die of the disease.

About Carfilzomib

Carfilzomib is the first in a new class of selective, irreversible proteasome inhibitors. Carfilzomib produces specific and sustained inhibition of the proteasome, leading to apoptosis in cancer cells with minimal offtarget effects. In Phase 1 and Phase 2 clinical trials, carfilzomib has demonstrated singleagent activity in hematologic malignancies and solid tumors, including multiple myeloma, Waldenstroms macroglobulinemia, mantle cell lymphoma and renal cell carcinoma.

Proteolix is conducting a comprehensive clinical development program evaluating carfilzomib for the treatment of multiple myeloma, including an ongoing accelerated approval study in heavily pretreated relapsed/refractory patients and a Phase 2 clinical trial in relapsed patients stratified by prior treatment with bortezomib. Both Phase 2 clinical trials are being conducted by Proteolix in collaboration with the Multiple Myeloma Research Consortium (MMRC). A Phase Ib clinical trial of carfilzomib in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma is also ongoing. In addition, Proteolix is conducting a singleagent Phase 2 clinical trial of carfilzomib in patients with recurrent or advanced solid tumors.

About Proteolix

Founded in December 2003, Proteolix, Inc. is a privatelyheld biotechnology company, headquartered in South San Francisco, dedicated to discovering, developing and commercializing novel therapeutics that target protein degradation pathways for cancer and autoimmune diseases. Proteolixs lead product, carfilzomib, is the first in a new class of selective, irreversible proteasome inhibitors. Proteolix is also developing a pipeline of novel proteasome inhibitors, including a selective, oral proteasome inhibitor and a selective immunoproteasome inhibitor.