L.e.a.f. Holdings Group LLC

Merrimack Pharmaceuticals, Inc.

Ipsen Biopharm Limited

Clet Niyikiza

Victor Mandla Moyo

Jonathan Basil Fitzgerald

Eliel Bayever

Navreet Dhindsa

Peter Laivins

Jaeyeon Kim

Zhenghong Xu

Kaniz Khalifa

Bolin Geng

Gwangseong Kim

Jose Varghese

Victor Moyo

Provided herein are pharmaceutical compositions comprising carotenoids, including liposomes that encapsulate carotenoids including ionizable carotenoids such as trans-crocetin. The provided compositions have uses in treating diseases, disorders and conditions associated with, but not limited to, infection, endotoxemia, inflammation, sepsis, ischemia, hypoxia, shock, stroke, lung injury, wound healing, traumatic injury, reperfusion injury, cardiovascular disease, kidney disease, liver disease, inflammatory disease, metabolic disease, pulmonary disorders, blood related disorders and hyperproliferative diseases such as cancer. Methods of making, delivering, and using the pharmaceutical compositions are also provided.

Carotenoid compositions and uses thereof

The disclosure relates generally to alpha polyglutamated pemetrexed, formulations containing liposomes filled with alpha polyglutamated pemetrexed, methods of making the alpha polyglutamated pemetrexed and liposome containing formulations, and methods of using polyglutamated alpha polyglutamated pemetrexed and liposome containing formulations to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

Alpha polyglutamated pemetrexed and uses thereof

Provided are methods for treating pancreatic cancer in a patient by administering liposomal irinotecan (MM-398) alone or in combination with additional therapeutic agents. In one embodiment, the liposomal irinotecan (MM-398) is co-administered with 5-fluorouracil and leucovorin.

Methods for treating pancreatic cancer using combination therapies

The disclosure relates generally to gamma polyglutamated aminopterin compositions, including delivery vehicles such as liposomes containing the gamma polyglutamated aminopterin, and methods of making and using the gamma polyglutamated aminopterin compositions to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., inflammation and autoimmune diseases such as rheumatoid arthritis).

Gamma polyglutamated aminopterin and uses thereof

The disclosure relates generally to polyglutamated alpha tetrahydrofolate compositions, including delivery vehicles such as liposomes containing the polyglutamated alpha tetrahydrofolate, and methods of making and using the polyglutamated alpha tetrahydrofolate compositions to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., inflammation and autoimmune diseases such as rheumatoid arthritis). The disclosed compositions also have uses in combination therapy with one or more therapeutic agents to enhance the effectiveness or to reduce the toxicities associated with the therapeutic agent(s).

Alpha polyglutamated tetrahydrofolates and uses thereof

The disclosure relates generally to alpha polyglutamated aminopterin, formulations containing liposomes filled with alpha polyglutamated aminopterin, methods of making the alpha polyglutamated aminopterin and liposome containing formulations, and methods of using polyglutamated alpha polyglutamated aminopterin and liposome containing formulations to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

Alpha polyglutamated aminopterin and uses thereof

The disclosure relates generally to polyglutamated antifolates, formulations containing liposomes filled with alpha or D-gamma polyglutamated antifolates, methods of making the polyglutamated antifolates and liposome containing formulations, and methods of using polyglutamated antifolates and liposome containing formulations to treat hyerproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

D glutamate polyglutamated antifolates and uses thereof

The disclosure relates generally to gamma polyglutamated methotrexate compositions, including delivery vehicles such as liposomes containing the gamma polyglutamated methotrexate, and methods of making and using the gamma polyglutamated methotrexate compositions to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., inflammation and autoimmune diseases such as rheumatoid arthritis).

Gamma polyglutamated methotrexate and uses thereof

The disclosure relates generally to alpha polyglutamated lometrexol, formulations containing liposomes filled with alpha polyglutamated lometrexol, methods of making the alpha polyglutamated lometrexol and liposome containing formulations, and methods of using polyglutamated alpha polyglutamated lometrexol and liposome containing formulations to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

Alpha polyglutamated lometrexol and uses thereof

The disclosure relates generally to alpha polyglutamated raltitrexed, formulations containing liposomes filled with alpha polyglutamated raltitrexed, methods of making the alpha polyglutamated raltitrexed and liposome containing formulations, and methods of using polyglutamated alpha polyglutamated raltitrexed and liposome containing formulations to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

Alpha polyglutamated raltitrexed and uses thereof

The disclosure relates generally to gamma polyglutamated pemetrexed compositions, including delivery vehicles such as liposomes containing the gamma polyglutamated pemetrexed, and methods of making and using the gamma polyglutamated pemetrexed compositions to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., inflammation and autoimmune diseases such as rheumatoid arthritis).

Gamma polyglutamated pemetrexed and uses thereof

The disclosure relates generally to gamma polyglutamated raltitrexed compositions, including delivery vehicles such as liposomes containing the gamma polyglutamated raltitrexed, and methods of making and using the gamma polyglutamated raltitrexed compositions to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., inflammation and autoimmune diseases such as rheumatoid arthritis).

Gamma polyglutamated raltitrexed and uses thereof

The disclosure relates generally to gamma polyglutamated Antifolate, formulations containing liposomes filled with gamma polyglutamated Antifolate, methods of making the gamma polyglutamated Antifolate and liposome containing formulations, and methods of using polyglutamated gamma polyglutamated Antifolate and liposome containing formulations to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., inflammation and an autoimmune disease such as rheumatoid arthritis).

Gamma polyglutamated antifolates and uses thereof

The disclosure relates generally to alpha polyglutamated pralatrexate, formulations containing liposomes filled with alpha polyglutamated pralatrexate, methods of making the alpha polyglutamated pralatrexate and liposome containing formulations, and methods of using polyglutamated alpha polyglutamated pralatrexate and liposome containing formulations to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

Alpha polyglutamated pralatrexate and uses thereof

The disclosure relates generally to polyglutamated antifolates, formulations containing liposomes filled with the polyglutamated antifolates, methods of making the polyglutamated antifolates and liposome containing formulations, and methods of using the polyglutamated antifolates and liposome containing formulations to treat hyerproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

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Gulph Mills, PA, United States of America

Clet Niyikiza