Profile: Astex Pharmaceuticals Inc (ASTX.O)
17 May 2013
Astex Pharmaceuticals, Inc., formerly SuperGen, Inc., incorporated in March 1991, is a pharmaceutical company. The Company is primarily engaged in the discovery and development of small molecule therapeutics with a focus on oncology and hematology. The Company is developing a pipeline of medicines for partnership with pharmaceutical companies. It is also engaged in the application of fragment-based drug discovery and development of small-molecule therapeutics. Using its fragment-based drug discovery platform, Pyramid, Astex Therapeutics Limited, a wholly owned subsidiary, has built a pipeline of molecularly-targeted drugs for large pharmaceutical partners and internal development that are at various stages of clinical, pre-clinical and early discovery development. On July 20, 2011, it completed the acquisition of Astex Therapeutics Limited.
The Company’s two lead internal programs are AT13387, a HSP 90 inhibitor, and SGI-110, a second generation hypomethylating agent. The third product in its clinical pipeline is amuvatinib (MP-470), its multi-targeted kinase inhibitor and Deoxyribonucleic acid (DNA) repair suppressor. It also have partnered clinical trials ongoing for AT7519, a CDK inhibitor, and AT9283, an aurora/JAK2 inhibitor.
Dacogen Hypomethylator (MDS)
Dacogen is a DNA hypomethylating agent approved in selected markets for treatment of patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS of all French-American-British (FAB) subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia), and Intermediate-1, Intermediate-2 and High-Risk International Prognostic Scoring System (IPSS) groups. Dacogen is approved for the treatment of MDS in more than 30 countries worldwide, including markets, such as the United States, Brazil, China, India, Russia and Turkey.
Dacogen Hypomethylator (AML)
The Company's 485-patient Phase III trial in elderly patients with AML has been completed. Its partners Eisai Inc. and Janssen-Cilag International NV have previously filed for regulatory approval for this indication in the United States and the European Union.
AT13387 Hsp90 inhibitor (GIST)
AT13387 is a small molecule inhibitor of Hsp90 (also called Heat Shock protein), which is responsible for supporting many tumor cells becoming cancerous. Hsp90 acts as a molecular chaperone stabilizing and preventing the breakdown of key cancer-forming (oncogenic) proteins. These client proteins and their association with different tumor types include HER2 (the target for Herceptin in breast cancer), the androgen receptor (the target for hormone therapy in prostate cancer), mutant B-raf (melanoma), c-kit (the target for Gleevec in gastrointestinal tumors) and mutant EGFr (the target for Tarceva and Iressa in the treatment of non small cell lung cancers). Although AT13387 is a targeted inhibitor of Hsp90, the functional role of Hsp90 means the product has the potential to control the proliferation of multiple solid tumors and hematological malignancies where uncontrolled cell growth is dependent on the interaction between Hsp90 and its client proteins. These include tumor types that have become resistant to initial therapy. It is completing a Phase I dose escalation safety and tolerability study with AT13387 in advanced cancer patients and have initiated a Phase II study in combination with imatinib (Gleevec) for treatment of refractory GIST patients.
SGI-110 DNMT Inhibitor (MDS and AML)
The Company has developed a compound called SGI-110, which targets and blocks the mechanism by which methylation is copied to newly forming cells, thus allowing re-expression of silenced genes in tumors. The initial Phase I/II study will evaluate multiple schedules in patients with intermediate-2 or high-risk MDS and acute myeloid leukemia (AML).
Amuvatinib-Multi-targeted Kinase Inhibitor and DNA Repair Suppressor (SCLC)
Amuvatinib is an oral multi-targeted Tyrosine Kinase Inhibitor that was designed to hit mutant forms of protein kinase targets called c-kit and PDGFR. These protein kinase targets are involved in the growth and proliferation of cancer cells. Amuvatinib is also a suppressor of Rad51, a DNA repair protein, which is involved in resistance to a variety of chemotherapy agents and radiation. Amuvatinib has a therapeutic window and shows minimal toxicity in the expected therapeutic dose range, despite suppressing several signaling pathways within cells. It is conducting a Phase II, multi-center, open-label, single-arm study of amuvatinib in combination with platinum-etoposide in up to 50 subjects with small cell lung cancer who are not responding to standard treatment or relapsed shortly after standard treatment. Eligible subjects receive amuvatinib lipid suspension capsules at the dose of 300 mg orally three times a day on a continuous basis in 21 day cycles together with their platinum-etoposide treatment. The primary endpoint will be tumor objective response.
AT7519 CDK inhibitor (Multiple Myeloma)
AT7519 is a small molecule targeted inhibitor of several cyclin-dependent kinases (CDK's) that regulate two important disease processes: the cell replication cycle and gene expression. CDK's 1 and 2 act as controls of the cell cycle, and the inhibition of these enzymes both prevents cell proliferation and initiates cell death. AT7519 is an inhibitor of both CDK I and II and in preclinical testing induces tumor shrinkage in multiple animal models of cancer. In addition to its direct effects on the cell cycle, AT7519 is also a potent inhibitor of ribo nucleic acid (RNA) polymerase II dependent transcription.
AT9283 Aurora/Jak2 Inhibitor (MM)
AT9283 is a small molecule inhibitor of kinases, including aurora A and B, and JAK2. Initial clinical trials have demonstrated early signals of efficacy in patients with hematological malignancies. AT9283 has been investigated as monotherapy in patients with advanced solid tumors in two Phase I, open-label, dose-escalation trials at centers in the United Kingdom, United States and Canada.
AT9283 has been investigated in a United States Phase I/II open-label, dose-escalation trial to assess the initial safety, tolerability and preliminary efficacy of AT9283 as monotherapy in patients with acute leukemia. AT9283 is also being investigated in a Phase II study in a chemotherapy refractory, multiple myeloma patient population sponsored by the NCIC Clinical Trials Group in Canada.
AT13148 ACG Kinase Inhibitor
AT13148 is an orally active small molecule inhibitor of PKB/Akt and p70S6 kinase, key enzymes in the PI3K/PKB/mTOR tumor cell survival pathway. PKB inhibitors, such as AT13148 have potential for use as both single agents and in combination with cytotoxics and other molecularly targeted agents in the treatment of a range of solid tumors.
LEE011 is a selective inhibitor of the key cell cycle enzyme CDK4. It is focusing on developing cancer therapies targeting the cell cycle.
AZD5363 PKB/Akt Inhibitor (Oncology)
AZD5363 is an orally active, selective protein kinase B (PKB, also known as Akt) inhibitor derived from a collaborative drug discovery program with AstraZeneca, ICR, and CRT. In April 2011, AstraZeneca announced that it had commenced a Phase I study of AZD5363 in patients with advanced solid tumors.
FGFr Inhibitor (Oncology)
The Company has entered into a research alliance with Janssen, a Johnson and Johnson company (Janssen), focused on the research, development, and commercialization of drugs for the treatment of cancer. The agreement grants Janssen a worldwide license to compounds arising from its Fibroblast Growth Factor Receptor (FGFr) inhibitor program, and calls for the application of Pyramid to other targets of interest to Janssen.
AZD3839 Beta-Secretase Inhibitor (Alzheimer's)
AstraZeneca has commenced a Phase I study of AZD3839, a clinical candidate and derived from the collaborative program on beta-secretasea key enzyme implicated in the progression of Alzheimer's disease. Beta-secretase, which is also called BACE1 (beta-site of amyloid precursor protein cleaving enzyme) or memapsin-2, is an aspartic-acid protease important in the formation of myelin sheaths in peripheral nerve cells and in the pathogenesis of Alzheimer's disease.
Multiple Targets (Multiple Therapeutic Areas)
The Company has entered into a collaboration agreement with GlaxoSmithKline (GSK) to discover, develop and commercialize compounds directed against multiple therapeutic targets of interest to GSK. Under the collaboration, it will apply its fragment chemistry platform, Pyramid, to multiple targets identified by GSK, with the objective of identifying and developing new candidate drugs.
The Company competes with ArQule, Inc., Array BioPharma, Crystal Genomics, Exelixis, Infinity Pharmaceuticals, Daiichi Sankyo Group, Vertex Pharmaceuticals, Sanofi, Bristol-Myers Squibb Company, Celgene Corporation, Eli Lilly & Co., GSK, Novartis AG, Pfizer and Synta Pharmaceuticals.
Astex Pharmaceuticals Inc
Suite 200, 4140 Dublin Blvd.
DUBLIN CA 94568