Acerta Pharma B.v.

Merck Sharp + Dohme B.v.

Merck Sharp + Dohme Corp.

Tjeerd Barf

Allard Kaptein

Wayne Philip Rothbaum

Brian Lannutti

Raquel Izumi

Ahmed Hamdy

Todd Covey

Arthur A Oubrie

Roger G Ulrich

Dave Johnson

Christiaan Gerardus Johannes Maria Jans

Johannes Bernardus Maria Rewinkel

Jacobus C H M Wijkmans

Fritz Blatter

Jerry B Evarts

Adrianus Petrus Antonius De Man

Edwin Aret

Cecile Krejsa

Hans C A Raaijmakers

Tim Ingallinera

Jan Gerard Sterrenburg

Niels Hoogenboom

Sander De Wilde

Eduard Willem Zwart

Jan-Gerard Sterrenburg

Dennis Demont

Saskia Verkaik

Edwin De Zwart

James Han Wang

Hao Wu

Alan B Cooper

Younong Yu

Jian Liu

Ronald M Kim

Rajan Anand

Xiaolei Gao

Chundao Yang

Shilan Liu

Sobhana Babu Boga

Hugh Y Zhu

Henry M Vaccaro

Abdul-Basit Alhassan

Carsten Schultz-Fademrecht

Xin Yao

Hans C Raaijmakers

Petrus Antonius De Adrianus Man

Carsten Schultz-Fadermrecht

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

In some embodiments, the invention relates to crystalline solid forms, including hydrates, polymorphs, and salt forms, of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention relates to amorphous solid forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention also relates to pharmaceutical compositions containing the solid forms, and methods for treating conditions or disorders by administering to a subject a pharmaceutical composition that includes the forms, including pharmaceutical compositions and methods for overcoming the effects of acid reducing agents.

Crystal forms of (s)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-n-(pyridin-2-yl)benzamide

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 relates to a BTK inhibitor or a pharmaceutically acceptable salt, cocrystal, ester, prodrug, solvate, hydrate or derivative thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to imidazopyrazine compounds, pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of a hyperproliferative disorder, an inflammatory disorder, an immune disorder, or an autoimmune disorder.

Imidazopyrazine inhibitors of Bruton's tyrosine kinase

Crystal forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide maleate

The present invention relates to 6-5 membered fused pyridine ring compounds according to Formula (I) or a pharmaceutically acceptable salt thereof or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, the present invention relates to the use of 6-5 membered fused pyridine ring compounds according to Formula (I) in the treatment of Bruton's Tyrosine Kinase (Btk) mediated disorders.

4-imidazopyridazin-1-yl-benzamides as Btk inhibitors

Pharmaceutical composition comprising a crystal form of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide for treating diffuse large B-cell lymphoma

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

4-imidazopyridazin-1-yl-benzamides as BTK inhibitors

Pharmaceutical composition comprising a crystal form of (S)-4-(8-amino-3-(1-(but-2-ynoyl) pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide

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Ravenstein, Netherlands

Tjeerd Barf