Avila Therapeutics Presents Data Demonstrating The Relevance Of Its Btk Inhibitor, AVL-292, In B Cell Malignancies Such As CLL

Avila Therapeutics™, Inc., a biotechnology company developing novel targeted covalent drugs, today announced the presentation of data on AVL-292, a clinical-stage inhibitor of Bruton's tyrosine kinase (Btk), at the 16th Congress of the European Hematology Association (EHA).


In the studies presented, AVL-292 inhibited both the growth of B cell lymphoma cell lines in vitro and the survival of primary chronic lymphocytic leukemia cells ex vivo. The data reinforce the potential of AVL-292 to treat B cell malignancies such as chronic lymphocytic leukemia (CLL) through potent and selective inhibition of Btk.


"Bruton's tyrosine kinase (Btk) 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, The University of Texas MD Anderson Cancer Center, Houston, TX, and contributing author on the presentation. "These data show that the covalent inhibition of Btk has an effect not only on B lymphoma cells, but also on the interaction of these cancer cells with their microenvironment, suggesting that Btk inhibition has the potential to mediate a robust therapeutic effect."


In a poster presentation titled "A Targeted Therapy (AVL-292) For Bruton's Tyrosine Kinase In B-Cell Malignancies", Juswinder Singh, Ph.D., Co-Founder and Chief Scientific Officer at Avila Therapeutics, presented data demonstrating that:


- 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 ≥1 mg/kg.


About AVL-292 and Bruton's Tyrosine Kinase (Btk)


AVL-292 is a novel, orally available, covalent drug that targets Bruton's tyrosine kinase (Btk). Inhibition of Btk is a promising new approach to treatment of diseases that are driven by B cells, including certain hematologic cancers (e.g. non-Hodgkin lymphoma and B cell chronic lymphocytic leukemia) and autoimmune diseases (e.g. rheumatoid arthritis).


AVL-292 selectively and covalently binds to Btk to inactivate and silence its activity. This unique mechanism of action confers greater target selectivity and a longer duration of action than is typical of conventional small molecule drugs. In preclinical studies, AVL-292 was efficacious in a variety of animal disease models. AVL-292 is in clinical development and has successfully completed two Phase 1a clinical studies to date.


Development of AVL-292 is supported in part by the Leukemia & Lymphoma Society.


Source:

Avila Therapeutics™, Inc.

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