Sarcomas are rare neoplasms that arise from the mesenchymal tissues of the body. In the United States, there are approximately 12,000 cases diagnosed each year, representing less than 1% of all new cancers. Of these cases, roughly 80% originate from soft tissue, with the remainder originating from bone. Prognosis remains poor, with more than 4000 patients in the US dying of the disease each year. Metastases may occur to multiple organs in this disease but approximately 20% of patients with extremity sarcomas will have isolated lung metastasis at some point during their disease course.

Osteosarcomas, rhabdomyosarcomas, and other non-rhabdomyosarcomas are high risk sarcomas that occur most commonly in teens and young adults. Approximately 30% of patients will present with metastases or recur with metastatic disease. The prognosis for these patients remains unacceptably poor despite multimodality treatment with chemotherapy, surgery, and/or radiation therapy. While >90% of these patients can be rendered free of detectable disease, the overwhelming majority will succumb to recurrent, chemoresistant disease. New targeted therapies are desperately needed for these metastatic sarcomas.

MabVax plans to initially target sarcoma due to its high metastatic potential and generally poor long term prognosis due to recurrent disease and its orphan drug designation. This quick disease recurrence provides for the rapid determination of the clinical endpoints of progression free survival and overall survival which can result in shorter clinical trial time periods, lower development costs and a faster time to market. Additionally, since sarcoma shares the majority of its target antigens with neuroblastoma and melanoma, a single product could form the basis for treatment of all three cancers. This could accelerate revenues from the product while the company follows-up with clinical trials to gain the additional indications.

Neuroblastoma is a rare cancer of the sympathetic nervous system, a nerve network that carries messages from the brain throughout the body. The cancer generally occurs in young children with about 650 children in the United States diagnosed on an annual basis. These solid tumors which form in a lump or a mass account for half of all malignancies in infants. Neuroblastoma comprises 6-10% of all childhood cancers, and 15% of cancer deaths in children. The cause of neuroblastoma is currently unknown although many physicians believe it is due to accidental cell growth in the adrenal glands. Current treatment methods for the disease include chemotherapy, radiation therapy, stem cell transplantation, and immunotherapy and while prognosis is generally positive in low risk disease states, the cure rate in high risk neuroblastoma, which accounts for about 50% of the cases, is less than 30%.

Small cell lung cancer is a disease in which malignant cells form in the tissues of the lung and it is divided into three subcategories: small cell carcinoma, mixed small cell/large cell carcinoma, and combined small cell carcinoma. This type of lung cancer is strongly associated with smoking, and for the most part, the current treatment options of chemotherapy and/or radiation do not cure the cancer.

Small cell lung cancer is a cancer with a high unmet medical need and the largest patient population of the cancers that are the initial focus of the company. The current prognosis for patients with small cell lung cancer is unsatisfactory even though considerable improvements in diagnosis and therapy have been made over the past 10 to 15 years. Without treatment, small cell carcinoma of the lung has the most aggressive clinical course of any type of pulmonary tumor, with median survival from diagnosis of only 2 to 4 months. Compared with other cell types of lung cancer, small cell carcinoma has a greater tendency to be widely disseminated by the time of diagnosis but is responsive to chemotherapy and irradiation in the initial treatment period. Because patients with small cell lung cancer tend to develop distant metastases, localized forms of treatment, such as surgical resection or radiation therapy, rarely produce long-term survival.

Estimated new cases and deaths from lung cancer (small cell and non-small cell combined) in the United States in 2006:

Type of Lung Cancer	New Cases	Deaths	5 Year Survival
Small Cell	30,000	29,000	5% to 10%
Non Small Cell	140,000	130,000	15%

In patients with limited-stage small cell lung cancer, combination chemotherapy produces results that are clearly superior to single-agent treatment, and moderately intensive doses of drugs are superior to doses that produce only minimal or mild hematologic toxic effects. Current programs yield overall objective response rates of 65% to 90% and complete response rates of 45% to 75%. Because of the frequent presence of occult metastatic disease, chemotherapy is the cornerstone of treatment for patients with limited-stage small cell lung cancer. No clear evidence is available from reported data that maintenance chemotherapy will improve survival duration.

Treatment for patients with extensive-stage disease follows a similar pattern as that for limited-stage disease. Combination chemotherapy produces early results however surgical resection is not indicated and radiation treatment centers on providing palliative therapy.

Because the prognosis for small cell lung cancer patients is poor and metastatic disease is the typical presentation, it is expected that most patients who have reached the adjuvant setting (approximately 50% or more) would be given the MabVax antibody product or the vaccine. These products would be adjunctive therapy delivered at the end of the initial treatment phase and so would not have to displace a current treatment modality.

In 2007 there were over 100,000 cases of melanoma in the United States. According to the American Cancer Society, the incidence of melanoma is increasing at a rate of 3-5% per year. While melanoma is 85-90% curable if identified and treated early, melanoma that has metastasized is deadly. Today, the five-year survival rate for metastatic melanoma, even after surgery, is only 20%-50%. Current treatment methods for melanoma include: surgical removal of the tumor; adjuvant treatment; chemo- and immunotherapy, or radiation therapy.