Chemocentryx, Inc.

Other

University of California

James J Campbell

Rajinder Paul Singh

Thomas J Schall

Penglie Zhang

Israel Charo

Karen Ebsworth

Yibin Zeng

Venkat Reddy Mali

Ju Yang

Antoni Krasinski

Chao Yu

Xuesong Wu

Samuel Hwang

Jeffrey P McMahon

Eugene C Butcher

Zhenhua Miao

Lijun Wu

Shijie Li

Noriko Gotoh

James B Rottman

Jeffrey Mcmahon

Christine Marie Janson

Rajinder Singh

The present disclosure provides, inter alia, methods of treating a solid-tumor by administering an effective amount of a Chemokine Receptor 2 (CCR2) antagonist. Also provided herein are methods of reducing the number of macrophages in a solid tumor microenvironment, said method comprising administering effective amount of a Chemokine Receptor 2 (CCR2) antagonist. In an additional aspect, the current disclosure further provides methods of increasing the number CD8+ T cells in a solid tumor microenvironment, said method comprising administering effective amount of a Chemokine Receptor 2 (CCR2) antagonist. In some embodiments, the CCR2 antagonist has the formula I or Formula III:

Methods of treating solid tumors with CCR2 antagonists

Provided herein are compositions, methods and kits for treating inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis in a mammal in need thereof. The method include administering to a subject with IBD a combination therapy containing a therapeutically effective amount of a chemokine receptor 9 (CCR9) inhibitor compound and a therapeutically effective amount of an anti-IL-23 antibody. Also provided herein is a kit containing the CCR9 inhibitor compound and anti-IL-23 antibody.

Compositions and methods for treating inflammatory bowel disease using CCR9 inhibitor and anti-IL-23 blocking antibodies

The present disclosure provides, inter alia, methods of treating generalized pustular psoriasis (GPP) by administering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C-X-C motif chemokine receptor 2 (CXCR2) antagonist. Also provided herein are methods of modulating dysregulated IL-36 signaling in a subject in need thereof and methods of reducing neutrophil, inflammatory dendritic cell (iDC), and/or CD4 T cell accumulation in a subject in need thereof, said methods, include dministering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C-X-C motif chemokine receptor 2 (CXCR2) antagonist. In some embodiments, the CCR6 and/or CXCR2 antagonist has the formula:

Methods of treating generalized pustular psoriasis with an antagonist of CCR6 or CXCR2

Provided herein are methods of treating cancer in an individual in need thereof, the methods comprising administering to the individual a CXCR7 inhibitor. In some embodiments, additional therapeutic agents are used. Also provided herein are methods of preventing precancerous cells expressing FRS2&#x3b2; from developing into cancer, the method comprising administering to an individual having precancerous cells expressing FRS2&#x3b2; a CXCR7 inhibitor. In some embodiments, additional therapeutic agents are used.

CXCR7 inhibitors for the treatment of cancer

The present disclosure is drawn to the combination therapy of a Chemokine Receptor 2 (CCR2) antagonist and a PD-1 and/or PD-L1 inhibitor in the treatment of cancer.

Combination therapy using a chemokine receptor 2 (CCR2) antagonist and a PD-1/PD-L1 inhibitor

The present disclosure provides, inter alia, methods of treating generalized pustular psoriasis (GPP) by administering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C&#x2014;X&#x2014;C motif chemokine receptor 2 (CXCR2) antagonist. Also provided herein are methods of modulating dysregulated IL-36 signaling in a subject in need thereof and methods of reducing neutrophil, inflammatory dendritic cell (iDC), and/or CD4 T cell accumulation in a subject in need thereof, said methods, include administering an effective amount of a Chemokine Receptor 6 (CCR6) antagonist and/or a C&#x2014;X&#x2014;C motif chemokine receptor 2 (CXCR2) antagonist. In some embodiments, the CCR6 and/or CXCR2 antagonist has the formula: 

The present disclosure provides, inter alia, methods of treating a solid-tumor by administering an effective amount of a Chemokine Receptor 2 (CCR2) antagonist. Also provided herein are methods of reducing the number of macrophages in a solid tumor microenvironment, said method comprising administering effective amount of a Chemokine Receptor 2 (CCR2) antagonist. In an additional aspect, the current disclosure further provides methods of increasing the number CD8+ T cells in a solid tumor microenvironment, said method comprising administering effective amount of a Chemokine Receptor 2 (CCR2) antagonist. In some embodiments, the CCR2 antagonist has the formula I: 

Provided herein are compositions, methods and kits for treating inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis in a mammal in need thereof. The method include administering to a subject with IBD a combination therapy containing a therapeutically effective amount of a chemokine receptor 9 (CCR9) inhibitor compound and a therapeutically effective amount of an anti-&#x3b1;4&#x3b2;7 integrin antibody such as vedolizumab. Also provided herein is a kit containing the CCR9 inhibitor compound and anti-&#x3b1;4&#x3b2;7 integrin antibody.

Compositions and methods for treating inflammatory bowel disease using a combination therapy of small molecule inhibitors of C-C chemokine receptor type 9 (CCR9) and anti-&#x3b1;4&#x3b2;7 integrin blocking antibodies

Compositions and methods for treating inflammatory bowel disease using a combination therapy of small molecule inhibitors of C&#x2014;C chemokine receptor type 9 (CCR9) and anti-&#x3b1;4&#x3b2;7 integrin blocking antibodies

Provided herein are compositions, methods and kits for treating inflammatory bowel disease (IBD) such as Crohn's disease and ulcerative colitis in a mammal in need thereof. The method include administering to a subject with IBD a combination therapy containing a therapeutically effective amount of a chemokine receptor 9 (CCR9) inhibitor compound and a therapeutically effective amount of an anti-TNF&#x3b1; antibody. Also provided herein is a kit containing the CCR9 inhibitor compound and anti-TNF&#x3b1; antibody.

Compositions and methods for treating inflammatory bowel disease using CCR9 inhibitor and anti-TNF-alpha blocking antibodies

Methods are provided to specifically modulate the trafficking of systemic memory T cells, particularly CD4&plus; T cells, without affecting naive T cells or intestinal memory T cells. It is shown that systemic memory T cells, which are characterized as CD45Ra,, and integrin &agr;4&bgr;7,, express high levels of CCR4. Ligands of CCR4, such as TARC or MDC, act as an adhesion trigger, wherein upon CCR4 binding, these cells undergo integrin-dependent arrest to the appropriate vascular receptor(s). This arrest acts to localize the cells at the target site. The methods of the invention manipulate this triggering, and CCR4 mediated chemotaxis, to affect the localization of T cells in targeted tissues. In one embodiment of the invention, the active agent is a CCR4 agonist, that acts to enhance T cell localization. In an alternative embodiment, the agent is an antagonist that blocks CCR4 biological activity. An advantage of the invention is the selectivity for systemic memory T cells, without affecting native T cells or intestinal memory T cells.

Growing community of inventors

San Jose, CA, United States of America

James J Campbell