AVL-292 from 16th EHA

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AVL-292 is a Bruton's tyrosine kinase (Btk) (like PCI-32765)

" plays a crucial role in promoting proliferation and

survival of B cell malignancies, representing a promising

new drug target for novel therapies such as AVL-292, " said

Jan A. Burger, M.D., Ph.D., Assistant Professor, Department

of Leukemia, MD .

In a Phase I trial:

AVL-292 is a potent, selective, covalent inhibitor of Btk.

AVL-292 completely abrogates anti-IgM induced viability of

primary CLL cells, and completely blocks B cell receptor

activation.

AVL-292 reduces expression of the chemokines, CCL3 and CCL4,

in primary CLL cells cultured with Nurse-like Cells (NLCs).

AVL-292 reduces migration of CLL cells towards CXCL12 and

CXCL13

In a Phase 1a clinical trial in healthy volunteers, AVL-292

was safe and well-tolerated with dose-proportional exposure

to drug at doses from 0.5 mg/kg to 7.0 mg/kg.

Further, Btk target occupancy was detected at all dose

levels tested, and complete target engagement was

demonstrated at dose levels & #8805;1 mg/kg.

Development of AVL-292 is supported in part by the Leukemia

& Lymphoma Society.

Source: http://www.avilatx.com/news/2011_0610_Avila-EHA.pdf