Eisai R&d Management Co., Ltd.

Millennium Pharmaceuticals Limited

The General Hospital Corporation

Massachusetts General Hospital Corporation

Peter G Smith

Frederick M Schwarz

Ping Zhu

Silvia Buonamici

Lihua Yu

Sudeep Prajapati

Xiang Liu

Ermira Pazolli

Michael W Seiler

John JianShi Wang

Guo Zhu Zheng

Dominic J Reynolds

Nathan Elliott Fishkin

Andrew Cook

James Palacino

Shelby Ellery

Thiwanka Samarakoon

Mark G Bock

Ming-Hong Hao

Yoshihiko Kotake

Gregg F Keaney

Kazunobu Kira

Parcharee Tivitmahaisoon

Norio Murai

Yoshiharu Mizui

Anand Selvaraj

George J Mulligan

Satoshi Nagao

Masayuki Miyano

Atsushi Endo

Markus Warmuth

Jeffrey E Settleman

Arani Chanda

Baudouin Gerard

Kian Huat Lim

Eunice Sun Park

Manav Korpal

Megan Sheehan

Zhenhua Wu

Nicholas Calandra

Yonghong Xiao

Michael P Thomas

Regina Mikie Kanada Sonobe

Nicholas C Gearhart

Jacob D Feala

Kenzo Arai

Stephen J Blakemore

Xiaoling Puyang

Shouyong Peng

Vijay Kumar Nyavanandi

Betty Chan

Marco Peter Fekkes

Matthew C Schu

Eric S Lightcap

Bin Li

Cyril H Benes

Jonathan L Blank

Peter Fekkes

Laura Corson

Daniel Aird

Craig D Karr

Nathalie Rioux

Regina Mikie Kanada Sonabe

Regina Kanada Sonobe

Sundeep Prajapati

Linker-drug compounds and antibody-drug conjugates that bind to human oncology targets are disclosed. The linker-drug compounds and antibody-drug conjugates comprise a splicing modulator drug moiety. The disclosure further relates to methods and compositions for use in the treatment of neoplastic disorders by administering the antibody-drug conjugates provided herein. In an embodiment, the splicing modulator comprises a pladienolide or a pladienolide derivative.

Splicing modulator antibody-drug conjugates and methods of use

Provided herein is a combination therapy useful for the treatment hepatocellular carcinoma. The combination comprises an FGFR4 inhibitor and lenvatinib.

Combination therapies for the treatment of hepatocellular carcinoma

Splice variants associated with neomorphic SF3B1 mutations are described herein. This application also relates to methods of detecting the described splice variants, and uses for diagnosing cancer, evaluating modulators of SF3B1, and methods of treating cancer associated with mutations in SF3B1.

Splice variants associated with neomorphic SF3B1 mutants

The present disclosure provides pharmaceutical combinations comprising at least one spliceosome modulator and at least one inhibitor chosen from BCL2, BCL2/BCLxL, and BCLxL inhibitors. Also provided are methods of treating cancer comprising administering a therapeutically effective amount of at least one spliceosome modulator and a therapeutically effective amount of at least one inhibitor chosen from BCL2, BCL2/BCLxL, and BCLxL inhibitors.

Combination comprising at least one spliceosome modulator and at least one inhibitor chosen from BCL2 inhibitors, BCL2/BCLxL inhibitors, and BCLxL inhibitors and methods of use

Provided herein is a combination of agents for reducing cell viability and/or cell proliferation. The combination comprises an FGFR4 inhibitor and an EGFR inhibitor.

Drug combinations for reducing cell viability and/or cell proliferation

Provided herein is a combination therapy useful for the treatment breast cancer. The combination comprises an ER-alpha inhibitor and a CDK 4/6 inhibitor.

Combination therapies for the treatment of breast cancer

Disclosed herein are markers whose mutational status is associated with sensitivity to treatment with NAE inhibitors. Mutational status is determined by measurement of characteristics of markers associated with the marker genes. Compositions and methods are provided to assess markers of marker genes to predict response to NAE inhibition treatment.

Biomarkers of response to NAE inhibitors

Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-&#x3b1; protein.

Tetrasubstituted alkene compounds and their use

The present disclosure provides a novel solid state form of pladienolide pyridine compounds having Formula I, compositions comprising at least one such solid state form, and methods of preparation and use and the same. The novel solid state form of pladienolide pyridine compounds may be useful in the treatment of cancer, such as, for example, cancers in which agents that target the spliceosome and mutations therein are known to be useful. 

Crystalline form of (2S,3S,6S,7R,10R,E)-7,10-dihydroxy-3,7-dimethyl-12-oxo-2-((R,2E,4E)-6-(piridin-2-yl)hepta-2,4-dien-2-yl)oxacyclododec-4-en-6-yl-4-methylpiperazine-1-carboxylate and methods of use thereof

The present invention provides novel pladienolide pyridine compounds, pharmaceutical compositions containing such compounds, and methods for using the compounds as therapeutic agents. These compounds may be useful in the treatment of cancer, particularly cancers in which agents that target the spliceosome and mutations therein are known to be useful.

Pladienolide pyridine compounds and methods of use

Growing community of inventors

Arlington, MA, United States of America

Peter G Smith