Arqule hat heute einen Präsentationstag an dem auch Roche dabei ist:
ArQule, Inc., incorporated in 1993, is engaged in the research and development of small-molecule cancer therapeutics based on its novel biological approach to cancer, Activated Checkpoint Therapy (ACT), and on its expertise in small molecule chemistry and intelligent drug design.
On September 8, 2003, the Company acquired Cyclis Pharmaceuticals, Inc., an early stage cancer therapeutics company. The Cyclis acquisition provided the Company with the proprietary ACT platform, an oncology discovery pipeline, and ARQ 501, which is now in Phase I clinical trials. The ACT platform is an approach to cancer therapy that is intended to use small-molecule drugs to restore and activate cellular checkpoints that are defective in cancer cells and that, once activated, will cause the cancer cells to undergo programmed cell death. The ACT platform is based on the understanding that a therapeutic agent that reactivates the quality control, or checkpoint functions, of a cell has the potential to re-enable the cell to detect and respond to DNA damage.
Continued below
advertisement
Oncology Portfolio
The Company's oncology portfolio, based on the ACT platform, consists of four programs that it obtained through its acquisition of Cyclis. The first two seek to target and elevate E2F, a protein related to cellular checkpoint and cell death. The third and fourth involve different targets and mechanisms related to checkpoints and cell death pathways, namely Cancer Survival Proteins (CSPs) and p53.
ARQ 501 entered Phase I clinical trials in September 2003 and is the Company's first clinical-stage compound. ARQ 501 is aimed at causing rapid and sustained elevation in the checkpoint regulatory protein E2F1. In preclinical studies, ARQ 501 activated E2F-mediated checkpoints leading to selective cell death of cancer cells. The compound has demonstrated anti-cancer activity in mice when applied as both a single agent and in combination with chemotherapy. In contrast to its selectivity for tumor cells over normal cells, ARQ 501 is active against tumor cells with a broad range of genetic defects. ArQule's Phase I (monotherapy) dose-escalation study in patients with advanced solid tumors is underway at the Dana-Farber/Harvard Cancer Center in three Boston hospitals: Dana-Farber Cancer Institute, Massachusetts General Hospital and Beth Israel Deaconess Medical Center. The objectives of this study are to determine the safety profile (clinical tolerability) of ARQ 501 and a recommended dose to be used in Phase II clinical trials. Based on the results of its preclinical tests, which have shown ARQ 501 to be active against a large number of solid and hematological (bloodstream) tumors, the Company intends to investigate ARQ 501 in solid tumors both as a single agent and in combination therapy, and in hematologic tumors initially as a single agent.
Applying ArQule's platform in small molecule chemistry and intelligent drug design to its 550 series program, the Company is developing analogs and derivatives of ARQ 501. These new compounds are also aimed at modulating E2F. It has identified several such compounds, and is working to optimize these leads for further development by designing and selecting the version of a given lead compound that has the most advantageous set of drug-like characteristics possible.
In the Company's Cancer Survival Protein (CSP) program, it is developing compounds aimed at blocking cellular survival mechanisms that cancer cells possess, and thereby selectively triggering cell death in such cancer cells. CSPs are certain proteins, including cytosolic and nuclear proteins, that are inappropriately elevated to excessive levels in cancer cells. In an animal model of cancer, ArQule scientists have explored the feasibility of safely and effectively treating cancer by blocking the activity of cancer cell survival proteins with small molecule compounds.
In ArQule's p53 Modulation program, it is validating the newly discovered intracellular protein PUMA (p53-Upregulated Modulator of Apoptosis) as a target for treating cancer. p53 is a protein that controls several key cell cycle checkpoints. In normal cells, when p53 is present in sufficient amounts, the PUMA protein is produced. When PUMA is produced, it rapidly induces cell death in cancer cells. In human cancer, however, the gene that expresses the p53 protein is a commonly mutated gene. The result of this mutation is that the p53 protein is either not functional or not produced in sufficient amounts to perform its checkpoint-related functions, including the production of PUMA. In its PUMA program, the Company is researching a potential way to restore normal function to the p53/PUMA pathway by inducing the production of PUMA. ArQule is now developing cancer specific PUMA modulators. This program involves a different, but potentially equally important, checkpoint pathway to cell death, which may have application to certain types of cancer.
In the area of small molecule anti-cancer therapeutics, the Company competes with Ariad Pharmaceuticals, Genaera Corporation, Onyx Pharmaceuticals, OSI Pharmaceuticals, Oxigene, Inc., Telik Inc. and Tularik Inc.
Other Portfolio Programs
The Company has two internal drug discovery programs outside of its cancer focus, each of which was developed using its chemistry-based drug discovery technology platform. In order to focus on its cancer programs, it is exploring opportunities to out-license both of these programs.
In November 2003, the Company commenced GLP-toxicity studies with its lead compound, ARQ 101, a p38 MAP Kinase inhibitor for rheumatoid arthritis. Throughout 2003, it has progressed several compounds through advanced lead optimization demonstrating functional oral activity in a rat model of rheumatoid arthritis. In this established animal model, the data indicated that its compounds reduced joint swelling in a dose-dependent manner and were well tolerated at all doses studied.
ArQule's pain program involves the N-type Calcium channel for neuropathic pain. In the first quarter of 2003, the Company generated lead compounds with activity against the N-type Calcium channel and identified three families of chemicals. In the second half of 2003, in connection with its shift in resources to the oncology based programs, it held up this program just prior to beginning optimization work on the lead compounds.
Competitors acting both as chemistry service providers and as integrated drug discovery companies include Array BioPharma and Exelixis. Other competitors in the chemistry technology services market are Pharmacopeia, Inc., Albany Molecular Research, Inc., Evotec OAI and Discovery Partners International, Inc.
|
Thread abonnieren
