SRI and Sareum are working to complete the lead optimisation phase of discovery, prior to moving into formal preclinical development. In the course of this research we have discovered advanced lead molecules such as SAR-20347, which leads to a striking decrease in symptoms in preclinical disease standard models of psoriasis, rheumatoid arthritis and colitis.
Seeking to build on the insights gained from this research, we are synthesising new molecules with improved potency and other properties.
We intend to progress active compounds into other disease models including inflammatory bowel disease, lupus and multiple sclerosis.
My simplistic taking on tomorrow is I am expecting a little more than just results ...Wether it's a little paragraph of positive wording regarding the future ..or a breakdown of what's happened so far and what is expected etc almost like a rundown.
I think some people/institutions maybe just awaiting the results and rns before committing...so if that's the case we could see alot of volume tomorrow.
AZD1480: a phase I study of a novel JAK2 inhibitor in solid tumors.
Randomized controlled trial
Plimack ER, et al. Oncologist. 2013. Show full citation Abstract
BACKGROUND: AZD1480 is a novel agent that inhibits Janus-associated kinases 1 and 2 (JAK1 and JAK2). The primary objective of this phase I study was to investigate the safety and tolerability of AZD1480 when administered as monotherapy to patients with solid tumors.
METHODS: Thirty-eight patients with advanced malignancies were treated at doses of 10-70 mg once daily (QD) and 20-45 mg b.i.d.
RESULTS: Pharmacokinetic (PK) analysis revealed rapid absorption and elimination with minimal accumulation after repeated QD or b.i.d. dosing. Exposure increased in a dose-dependent manner from 10-50 mg. Maximum plasma concentration (Cmax) was attained ∼1 hour after dose, and t1/2 was ∼5 hours. Pharmacodynamic analysis of circulating granulocytes demonstrated maximum phosphorylated STAT3 (pSTAT3) inhibition 1-2 hours after dose, coincident with Cmax, and greater pSTAT3 inhibition at higher doses. The average pSTAT3 inhibition in granulocytes at the highest dose tested, 70 mg QD, was 56% (standard deviation: ±21%) at steady-state drug levels. Dose-limiting toxicities (DLTs) consisted of pleiotropic neurologic adverse events (AEs), including dizziness, anxiety, ataxia, memory loss, hallucinations, and behavior changes. These AEs were generally reversible with dose reduction or treatment cessation.
CONCLUSIONS: Whether the DLTs were due to inhibition of JAK-1/2 or to off-target effects is unknown. The unusual DLTs and the lack of clinical activity led to discontinuation of development.
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