Eisai R&d Management Co., Ltd.

New York University

Silvia Buonamici

Peter G Smith

Lihua Yu

Ping Zhu

Ermira Pazolli

Michael W Seiler

Sudeep Prajapati

Xiang Liu

James Palacino

Kian Huat Lim

Eunice Sun Park

Dominic J Reynolds

Nathan Elliott Fishkin

Andrew Cook

Shelby Ellery

Thiwanka Samarakoon

Megan Sheehan

Zhenhua Wu

Nicholas Calandra

Yonghong Xiao

John JianShi Wang

Guo Zhu Zheng

Yoshihiko Kotake

Gregg F Keaney

Kazunobu Kira

Parcharee Tivitmahaisoon

Norio Murai

Baudouin Gerard

Yoshiharu Mizui

Satoshi Nagao

Masayuki Miyano

Michael P Thomas

Jacob D Feala

Kenzo Arai

Nicholas C Gearhart

Regina Mikie Kanada Sonobe

Betty Chan

Shouyong Peng

Marco Peter Fekkes

Atsushi Endo

Markus Warmuth

Arani Chanda

Peter Gerard Smith

Iannis Aifantis

Daniel Aird

Laura Corson

Peter Fekkes

Evan Barry

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

This disclosure relates to methods for the treatment of neoplastic disorders by administering Compound 1, or a pharmaceutically acceptably salt thereof, on its own and/or as part of a conjugate or composition, and inducing production of at least one neoantigen.

Methods of using splicing modulators

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

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

The present invention is directed to methods of preventing central nervous system leukemia, treating T-cell acute lymphoblastic leukemia, and treating immune system disorders associated with CCR7-CCL19 mediated signaling. Suitable therapeutic agents for inhibiting CCR7-CCL19 signaling and methods of identifying additional therapeutic agents useful in the methods of the present invention are also disclosed.

Leukemic cell CNS infiltration controlled by notch-induced chemotaxis

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Boston, MA, United States of America

Silvia Buonamici