Acerta Pharma B.v.

Raquel Izumi

Ahmed Hamdy

Wayne Philip Rothbaum

Tjeerd Barf

Brian Lannutti

Allard Kaptein

Todd Covey

Roger G Ulrich

Dave Johnson

Francisco Salva

David M Johnson

Roger Ulrich

Therapeutic methods of treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a combination of a BTK inhibitor and an anti-CD20 antibody.

Methods of treating chronic lymphocytic leukemia and small lymphocytic leukemia using a BTK inhibitor

Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the &#x3b3;- and &#x3b4;-isoforms and selective for both &#x3b3;- and &#x3b4;-isoforms (PI3K-&#x3b3;,&#x3b4;, PI3K-&#x3b3;, and PI3K-&#x3b4;), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-&#x3b4; inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.

Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor, a JAK-2 inhibitor, and/or a BCL-2 inhibitor

In some embodiments, the invention includes a therapeutic combination of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the &#x3b3;- and &#x3b4;-isoforms and selective for both &#x3b3;- and &#x3b4;-isoforms, and a Bruton's tyrosine kinase (BTK) inhibitor. In some embodiments, the invention includes therapeutic methods of using a BTK inhibitor and a PI3K-&#x3b4; inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.

Therapeutic combination of PI3K inhibitor and a BTK inhibitor

Therapeutic combinations of a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the &#x3b3;- and &#x3b4;-isoforms and selective for both &#x3b3;- and &#x3b4;-isoforms, are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of (1) a PI3K-&#x3b4; inhibitor and a BTK inhibitor, (2) a JAK-2 inhibitor and a BTK inhibitor, or (3) a JAK-2 inhibitor, PI3K-&#x3b4; inhibitor, and BTK inhibitor, and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.

Therapeutic combinations of a BTK inhibitor, a PI3K inhibitor and/or a JAK-2 inhibitor

In some embodiments, the present invention relates to novel small molecule inhibitors that block the CXCR4-SDF-1 signaling pathway by directly inhibiting members of the Tec family of kinases, namely Bruton's tyrosine kinase (BTK), and their use in treating diseases in which pathogenesis is mediated by the CXCR4/SDF-1 signaling pathway.

Methods of blocking the CXCR-4/SDF-1 signaling pathway with inhibitors of bruton's tyrosine kinase

Methods to improve hematopoiesis and increase white blood cell counts in subjects and patients using pyrimidine-based inhibitors of Bruton's tyrosine kinase (Btk) are disclosed.

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San Carlos, CA, United States of America

Raquel Izumi