SuperGen Inc.

4140 Dublin Blvd., Suite 200
Dublin, CA 94568

USA

Phone: (925) 560-0100
Fax: (925) 560-0101
Email: investor_relations@supergen.com
Web Site: http://www.supergen.com

 

A. Company Profile

 

SuperGen (NASDAQ:SUGN) is a pharmaceutical company whose mission is to prolong, improve the quality of and ultimately, to save the lives of those people afflicted with life-threatening diseases, especially cancer. The company possesses a broad portfolio of proprietary cancer therapies that target a variety of solid tumors, hematological malignancies and blood disorders.

 

B. Products

 

 

Product Pipelines

 

Product	Indication	Clinical Status
Avicine	Colorectal cancer	Phase III
Decitabine	Myelodysplastic syndrome	Phase III
Lucanthone	Brain tumor	Phase II
MitoExtra, DaunoExtra, and PaxoExtra	Various tumors	Phase I-III
Rubitecan	Colorectal cancer	Phase II
Orathecin	Pancreatic cancer	Phase III

 

1. Avicine

Avicine is a therapeutic cancer vaccine. It elicits a highly specific immune response to the hormone human chorionic gonadotropin (hCG), a cancer-associated oncofetal protein. In its role as a pregnancy hormone, hCG is only produced by fetal cells and the placenta. Cancer is the only significant exception to this phenomenon. In fact, hCG is a biochemical marker of malignancy associated with all the major types of cancer. The expression of hCG has been shown to correlate with tumor aggressiveness, i.e., the greater the hCG expression, the more aggressive the tumor.

2. Decitabine

Decitabine is a chemotherapeutic agent that has been shown to have a broad spectrum of activity in several hematological malignancies as well as solid tumors. Decitabine belongs to a new class of drugs called hypomethylating agents, with a unique mechanism of action. Methylation is a process in which methyl (CH3) groups are added to DNA to inactivate or "silence" genes. Recent research demonstrates tumor suppressor genes and DNA repair genes are hypermethylated and silenced in a majority of cancers, typically at an early stage of the disease. Hypermethylation, then, is an early warning sign that may prove useful for early cancer detection and screening of cancer patients.

3. Lucanthone

Lucanthone is a topoisomerase II inhibitor, an enzyme involved in the replication of DNA. Lucanthone has marked radiosensitizing activity in advanced brain tumors in humans.

4. MitoExtra, DaunoExtra, and PaxoExtra

 

Most anti-cancer drugs also are cytotoxic and must be administered intravenously. If a vein is missed on injection, the drug can extravasate to surrounding tissue, causing ulceration that sometimes requires even plastic surgery to correct. Extra technology is designed to shield the injection site from the drug, thus providing the patient protection from tissue ulceration. Various anti-cancer drugs that would benefit from reformulation with Extra technology, including MitoExtra[TM] (mitomycin for injection), DaunoExtra[TM] (daunorubicin), and PaxoExtra[TM] (paclitaxel injection).

 

 

5. Rubitecan

 

Rubitecan is an oral chemotherapeutic drug developed for the treatment of pancreatic cancer and other solid tumors. Rubitecan is a topoisomerase I inhibitor, a patented analogue of a natural compound derived from the Camptotheca acuminata tree. Topoisomerase I is an enzyme that "unwinds" DNA in the nucleus of cells in preparation for DNA replication and cell division. Topoisomerase I inhibitors prevent the DNA from unwinding, thus interfering with the cell's replication. All cells require topoisomerase I, but fast-growing cancer cells need more of it. By inhibiting the enzyme, rubitecan selectively inflicts more damage on cancer cells than on normal cells.

 Dacogen[TM] (decitabine) for Injection

SuperGen's development of Dacogen for myelodysplastic syndrome (MDS) has been completed, and approved for use by FDA on May 3, 2006. SuperGen has licensed the worldwide rights for marketing and commercial development of Dacogen to MGI PHARMA.

 

Orathecin[TM] (rubitecan) Capsules

SuperGen has completed over 40 Phase II and Phase III trials in solid tumors. SuperGen continues to investigate the potential benefit of Orathecin in combination with gemcitabine in patients with newly diagnosed pancreatic cancer.

 

MP529 - Aurora Kinase Inhibitor

Aurora kinases are a family of oncogenic serine/threonine kinases that localize to the mitotic apparatus (centrosome, poles of the bipolar spindle, or midbody) and regulate completion of centrosome separation, bipolar spindle assembly and chromosome segregation. MP529 is a novel inhibitor of Aurora kinases which exhibits potent activity against pancreatic tumors bearing this target, while remaining bioavailable and showing low toxicity in animal models. MP529 is undergoing IND-enabling studies for entry into the clinic in Q1 of 2007.

 

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MP470 - c-Kit Kinase Inhibitor

Activating or gain-of-function mutations in the c-Kit proto-oncogene have been identified in a variety of tumors including gastrointestinal stromal tumors (GIST), a very difficult tumor type to treat. MP470 was developed using the CLIMB[TM] process to specifically bind to mutant forms of the c-Kit receptor which are insensitive to current therapies. While a potent inhibitor of wild-type c-Kit, MP470 displays even greater effectiveness against clinically relevant mutants, including V560G, D816V, N822K and K642E, due to its unique binding mode. MP470 is completing late-stage IND-enabling studies, for entry into the clinic in Q4 2006.

 

MP371 - Multi-Targeted Kinase Inhibitor

In recent years, multi-targeted kinase inhibitors have begun to rise to the forefront of small-molecule drug development, no doubt due to their reduced chance of encountering resistance, a challenge faced by single-target inhibitors. SuperGen, Inc. has developed a new compound, MP371, which has activity against several therapeutic tyrosine kinase targets, including mutant forms of c-Kit, which have been reticent to inhibition by Gleevec (opening a niche for this inhibitor) as well as Ret (involved in medullary thyroid carcinoma), PDGFRa and b, and members of the Src family, all of which have been documented and validated as therapeutic targets.  MP371 is in late-stage preclinical development.

 

Polo-Like Kinase Inhibitor

 Pancreas cancer is one of the most aggressive tumor types in man, ranking as the 4th leading cause of deaths due to cancer for both men and women. This is due to the extremely high mortality rate of this cancer, which has a mean survival time of only 4 months. Currently, therapies to combat pancreatic cancer have resulted in only moderate increases in patient survival, and thus, new therapeutic strategies are needed in order to fight this disease. One enzyme, Polo-like kinase-1 (plk1) has recently emerged as a potential new target in for novel therapeutic pancreas cancer drug development. Because of its widespread expression across the spectrum of cancer diseases, especially pancreatic carcinoma, SuperGen has committed itself to creating a novel inhibitor of Polo-like kinase-1 using the CLIMB process for use in patients with pancreatic cancer.

 

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Pim-1 Kinase Inhibitor

Pim-1 is believed to play a part in tumorigenesis of a number of malignancies, including Burkitt's Lymphoma, prostate cancer and oral cancer, as well as diffuse large cell lymphomas, among others, in which it is believed to be involved, often with the c-Myc oncoprotein, in either the initiation or progression of malignant transformation. The downstream pathways activated by Pim-1 mediate progression through the G1/S and G2/M checkpoints, and inhibition of apoptosis. Using the CLIMB process, SuperGen is hard at work on the design, synthesis and testing of a novel class of kinase inhibitor, targeting Pim-1 kinase for the treatment of various tumor types, using a combined computational and medium-throughput biological approach.

 

Axl Kinase Inhibitor

Axl kinase was first discovered to be a transforming oncogene in chronic myelogenous leukemia, and has since been found in a variety of other cancer diseases. Its tumorigenic function results from its ability to signal to pathways of apoptosis inhibition, protecting tumors from the pro-apoptotic effects of numerous chemotherapeutics. SuperGen is in the process of identifying an Axl-inhibitory lead compound to be used in combination chemotherapy for CML and other tumor types.

 

Novel Protease Inhibitor

The transcription factors known as sterol regulatory element-binding proteins (SREBPs) are involved in stimulating lipid and cholesterol synthesis in hepatocytes and other cells. SREBPs are activated by proteolytic cleavage, and abrogation of the enzyme which carries out this cleavage in the liver is expected to lead to decreased lipid synthesis and reduced lipid accumulation in the blood, liver and other organs. SuperGen has identified a need for compounds that can decrease the level of serum cholesterol, and has set out to create such a drug for the treatment of lipid-related cardiovascular disorders.

 

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Eg5 Kinesin Inhibitor

Drugs which target microtubules (taxanes, vinca alkaloids and epothilones) are commonly used as anti-cancer agents, but cause significant toxicity due to the importance of microtubules in critical cellular processes outside of cell division. Eg5 is a kinesin motor protein which is required for mitosis, and is only used in this process. SuperGen is currently identifying compounds to be used for inhibition of Eg5 in the treatment of B-cell leukemias and other tumor targets.

 

DMT1 Inhibitor

Silencing of unnecessary genes is commonly carried out by DNA methylation, through the action of DNA Methyltransferase enzymes. However, this machinery can be usurped during the process of tumorigenesis, resulting in the inactivation of tumor suppressor genes and ultimately cancer. SuperGen is employing its proprietary CLIMB process to develop novel inhibitors of DNA Methyltransferase 1 to reverse this process in a clinical setting.