A. Company Profile

Cell Therapeutics, Inc. (NASDAQ:CTIC) develops, acquires, and commercializes novel treatments for cancer. The company's goal is to build a vertically integrated biopharmaceutical company with a diversified portfolio of oncology drugs focused on identifying new, less toxic and more effective cancer therapies

B. Technology

Novel drug delivery technology are developing a new way to deliver cancer drugs more selectively to tumor tissue with the goal of reducing the toxic side effects and improving the anti-tumor activity of existing chemotherapy agents. The technology links cancer drugs to proprietary polymers, such as polyglutamate (PG). PG is a biodegradable polymer of glutamic acid, a naturally occurring amino acid. PG is constructed by linking glutamic acid molecules together to an optimal size. The polymer technology takes advantage of a well-described difference between tumor blood vessels and blood vessels in normal tissues. The blood vessels in tumor tissues are more porous than those in normal tissues, and they are therefore more permeable to large molecules, such as the polymers, that are within a specific size range. As the polymer, carrying its tumor-killing drug, circulates in the bloodstream and passes through the tumor blood vessels, it becomes trapped in the tumor tissue allowing a significantly greater percentage of the anti-cancer drug to accumulate in tumor tissue compared to normal tissue. The toxicity of the chemotherapy drug to normal tissues also may be reduced because the drug appears to be inactive as long as it is bound to the polymer. Once the polymer backbone is digested in the tumor, the cancer-killing drug is released directly into the cancer tissues. The polymer-chemotherapy drug conjugates may be able to achieve a number of benefits over existing chemotherapy drugs: 1. Enrich drug in the tumor; 2. Increase active drug efficacy; 3. Use higher doses of the active drug; 4. Reduce toxicity at the same or higher doses of active drug; 5. Broaden applicability due to differentiated tumor uptake mechanism.

C. Products

Product Pipelines

Product

Indication

Clinical Status

CT-2106 (PG-CPT)

Advanced Solid Tumor

Phase I

Trisenox

(Arsenic Trioxide)

Acute Promyelocytic Leukemia

Market

Multiple Myeloma

Phase II

Myelodysplasia

Phase II

Neuroblastoma

Phase II

Hepatocellular Carcinoma

Phase I

Xyotax (CT-2103)

Non-Small Cell Lung Cancer

Phase III

Recurrent Colorectal Cancer

Phase II

Metastatic Breast Cancer

Phase II

1. CT-2106 (PG-CPT)

CT-2106 (polyglutamate camptothecin) is camptothecin attached to PG. In preclinical models, the PG technology appears to be capable of delivering more chemotherapy directly to the tumor, making each dose potentially more effective without increasing side effects.

Camptothecins are important and rapidly growing class of anti-cancer drugs. However, like taxanes, their full clinical benefit is limited by poor solubility and significant toxicity. To avert solubility limitations, oral analogs such as Hycamtin and Camptosar were developed. However, conversion to oral dosage forms has been accompanied by a reduction in anti-tumor potency. Despite these limitations, camptothecins are becoming standard drugs in the treatment of advanced colon, lung, and ovarian cancer.

Linking a camptothecin to PG renders it water soluble, and animal studies suggest that it permits up to 400% more drug to be administered without an increase in toxicity. PG-CPT showed significantly enhanced anti-tumor activity in animal models of lung, colon and breast cancer, with up to 500% improvement over the free drug.

2. Trisenox (arsenic trioxide)

Trisenox (arsenic trioxide) is indicated for the treatment of induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy. The mechanism of action of Trisenox is not completely understood. The possible actions include: (1) Causes morphological changes of cancer cells; (2) Results in DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells; (3) Inhibit the growth of myeloma cells; (3) Induce apoptosis (programmed cell death) of myeloma cells; (4) Block the ability of myeloma cells to "stick" to bone marrow stromal cells. It does this by inhibiting the production of adhesion molecules on the surface of both cell types. This, in turn, inhibits the secretion of interleukin 6 (IL-6), a growth factor for myeloma cells, by the stromal cells; (5) Inhibit the growth of new blood vessels (angiogenesis) by stimulating apoptosis of tumor-supporting endothelial cells and inhibiting the production of vascular endothelial growth factor (VEGF).

A multi-center pivotal trial was held, led by Memorial Sloan-Kettering Cancer Center, consisting of 40 patients ranging in age from 5 to 72. The drug was shown to be effective with 70% of the patients achieving complete remission. 86% showed clearing of the chromosomal abnormality that causes APL. Total remission was reached, on average, within two months after treatment with Trisenox began. At a median follow-up time of 16 months, 68% of patients who had achieved complete remission were still alive and 58% were disease free.

Common side effects include, but are not limited to: leukocytosis, nausea, vomiting, diarrhea, abdominal pain, fatigue, edema, hyperglycemia, dyspnea, cough, rash or itching, headaches, and dizziness.

Approx. 23% of patients showed symptoms of APL-differentiation syndrome during or after their treatment with Trisenox. These symptoms include fever, weight gain, shortness of breath, and musculoskeletal pain. High-dose steroids and diuretics were used to manage these symptoms and the majority of patients were able to continue their treatment with Trisenox. Hyperleukocytosis occurred in aprox. 50% of patients undergoing Trisenox therapy. It did not require them to stop treatment.

3. Xyotax

Paclitaxel (Taxol) is the most commonly used chemotherapy agent in the world. However, some side effects caused by paclitaxel may decrease a patient's quality of life and cause a reduction in the dose of therapy. Researchers recently created a new form of paclitaxel, which involves the active form of the drug bound to molecules called polyglutamate polymers. These molecules tends to allow for the delivery of higher levels of the active drug to cancer cells, while sparing healthy cells from side effects.

A. Company Profile

B. Technology

C. Products

1. CT-2106 (PG-CPT)

2. Trisenox (arsenic trioxide)

3. Xyotax

D. Job Opportunities at Cell Therapeuticals

E. Information for Investor

F. Others