Eli Lilly and Company

Isis Pharmaceuticals, Inc.

Audion Therapeutics

Bharvin Kumar Patel

Philip Arthur Hipskind

Takako Wilson (nee Takakuwa)

Hong Gao

Mark Harrath Bender

Eric E Swayze

Balkrishen Bhat

Albert Edge

Gaiying Zhao

Michele C Smith

Takako Wilson

Aaron David Wrobleski

Julia Marie Clay

Richard Paul Beckmann

Helmuth Hendrikus Gerardus Van Es

John C Gill

Aaron D Wrobleski

Helmuth Hendrikus Van Es

The present invention provides medicaments for use in treating and methods of treating T-cell acute lymphoblastic leukemia, acute lymphoblastic leukemia, chronic lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, erythroleukemia, triple negative breast cancer, breast cancer, ovarian cancer, melanoma, Sung cancer, non small-cell lung cancer, pancreatic cancer, glioblastoma, colorectal cancer, head and neck cancer, cervical cancer, prostate cancer, liver cancer, oral squamous cell carcinoma, skin cancer, medul!ob!astoma, hepatocellular carcinoma, intrahepatic and extrahepatic cholangiocarcinoma, desmoid tumor, soft tissue sarcoma, or adenoid cystic carcinoma in a patient comprising combination therapy with 4,4,4-tri-fluoro-N-[(1S)-2&#x2dc;[[(7S)-5-(2-hydroxyemyl)-6-oxo-7H-pyrido[23-d][3]benzazepin-7-yl]amino]-1-methyl-2-oxo-ethyljbutanamide, or a pharmaceutically acceptable salt or hydrate thereof, and a PD-1 or a PD-L1 inhibitor selected from pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab.

Combination therapy with notch and PD-1 or PD-L1 inhibitors

Medicaments for use in treating T-cell acute lymphoblastic leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, breast cancer, ovarian cancer, melanoma, lung cancer, pancreatic cancer, glioblastoma, sarcoma, desmoid tumors, adenoid cystic carcinoma, colorectal cancer, head and neck cancer, cervical cancer, prostate cancer, liver cancer, or skin cancer in a patient comprising combination therapy with 4,4,4-trifluoro-N-[(1S)-2-[[(7S)-5-(2-hydroxyethyl)-6-oxo-7H-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-methyl-2-oxoethyl]butanamide, or a pharmaceutically acceptable salt or hydrate thereof, and 8-[5-(1-hydroxy-1-methylethyl)pyridin-3-yl]-1-[(2S)-2-methoxypropyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one, or a pharmaceutically acceptable salt thereof.

Combination therapy with Notch and PI3K/mTOR inhibitors for use in treating cancer

Medicaments for use in treating acute myelogenous leukemia, chronic myelogenous leukemia, breast cancer, ovarian cancer, malignant melanoma, lung cancer, pancreatic cancer, glioblastoma, sarcoma, desmoid tumors, adenoid cystic carcinoma (ACC), colorectal cancer, prostate cancer, or medulloblastoma in a patient by administering simultaneously, separately, or sequentially, 4,4,4-trifluoro-N-[(IS)-2-[[(7S)-5-(2-hydroxyethyl)-6-oxo-7H-pyrido[2,3-d][3]benzazepin-7-yl]amino]-1-methyl-2-oxo-ethyl]butanamide, or a pharmaceutically acceptable salt or hydrate thereof, and N-[5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]-[5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-3H-benzoimidazol-5-yl)-pyrimidin-2-yl]-amine, or a pharmaceutically acceptable salt thereof.

Combination therapy with Notch and CDK4/6 inhibitors for the treatment of cancer

The present invention provides medicaments for use in treating and methods of treating T-cell acute lymphoblastic leukemia, acute lymphoblastic leukemia, chronic lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, erythroleukemia, triple negative breast cancer, breast cancer, ovarian cancer, melanoma, Sung cancer, non small-cell lung cancer, pancreatic cancer, glioblastoma, colorectal cancer, head and neck cancer, cervical cancer, prostate cancer, liver cancer, oral squamous cell carcinoma, skin cancer, medulloblastoma, hepatocellular carcinoma, intrahepatic and extrahepatic cholangiocarcinoma, desmoid tumor, soft tissue sarcoma, or adenoid cystic carcinoma in a patient comprising combination therapy with 4,4,4-trifluoro-N-[(1S)-2&#x2dc;[[(7S)-5-(2-hydroxyemyl)-6-oxo-7H-pyrido[23-d][3]benzazepin-7-yl]amino]-1-methyl-2-oxo-ethyljbutanamide, or a pharmaceutically acceptable salt or hydrate thereof, and a PD-1 or a PD-L1 inhibitor selected from pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab.

Combination therapy with Notch and PD-1 or PD-L1 inhibitors

The present invention provides the following compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions containing said compounds useful as a Notch pathway signaling inhibitor for the treatment of named cancers, sensorineural hearing loss caused by auditory hair cell loss, and inducing auditory hair cell generation. 

Notch pathway signaling inhibitor compounds

The present invention provides novel 1,4-disubstituted phthalazine hedgehog pathway antagonists useful in the treatment of cancer.

Disubstituted phthalazine hedgehog pathway antagonists

Compounds and compositions are provided for modulating the expression of survivin. The compounds, exemplified by those acting through an RNAi antisense mechanism of action, include double-stranded and single-stranded constructs, as well as siRNAs, canonical siRNAs, blunt-ended siRNAs and single-stranded antisense RNA compounds. Methods of using these compounds for modulation of survivin expression and for treatment of diseases associated with expression of survivin are provided.

Modulation of survivin expression

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Westfield, IN, United States of America

Bharvin Kumar Patel