Decided not to wait for today's presentation, and profitably covered my small short at an average of about $10.50.
Looks like there may actually have been some cancer patients treated already, according to this late breaker abstract:
Proceedings of the 1999 AACR NCI EORTC International Conference
#0741 Preclinical efficacy, clinical safety and pharmacokinetics of ANGIOZYME, an antiangiogenic ribozyme targeting the flt-1 VEGF receptor. Usman, N., Braeckman, R., Pavco, P., Sandberg, J., Tressler, Radka, S., R., Smith, J., Parker, V. Ribozyme Pharmaceuticals, Inc. 2950 Wilderness Place, Boulder, CO 80301. Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608.
A significant number of antiangiogenic compounds are being developed for the treatment of cancer. One strategy involves abrogation of the VEGF pathway. This may be achieved by blocking the receptor-ligand interaction, or by interfering directly with the signal transduction pathway. Another approach is to down-regulate the expression of the molecules in the pathway. Ribozymes are enzymatic RNA molecules that can be engineered to specifically cleave a target RNA sequence and are thus applicable to the expression down regulation approach. One type of ribozyme, the Hammerhead, can be chemically modified to yield a molecule that retains its catalytic cleavage activity but is stabilized to nuclease degradation. We have designed such ribozymes to target and cleave the mRNAs for the VEGF receptors Flt-1 and KDR. One of these, ANGIOZYME, is a 35 nucleotide stabilized Hammerhead ribozyme that specifically targets site 4229 of the flt-1 mRNA. We have demonstrated significant inhibition of both primary tumor growth and metastases in two rodent models. Preclinical toxicology studies indicate that the drug is well tolerated at single doses up to 6000 mg/m2 and multiple doses up to 300 mg/m2. Pharmacokinetic results from rodent and primate studies have shown good subcutaneous bioavailability. Based on positive preclinical efficacy results and an excellent safety profile, ANGIOZYME has advanced into clinical trials. In addition to preclinical studies, recent results from single-dose Phase Ia and Ib trials in normal volunteers and cancer patients and data from 28 day toxicology studies will be presented. In general, ANGIOZYME was safe and well tolerated. Human plasma concentrations following sc dosing of 100 mg/m2 were in excess of the level required to achieve efficacy in a rodent tumor model and sc bioavailability was 75-95%.
Peter
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