SYDNEY, Australia I August 19, 2020 I Pharmaceutical research company Pharmaxis Ltd (ASX: PXS) announced that the Food and Drug Administration (FDA) has completed a safety review of the company’s Investigational New Drug (IND) application for the pan‐LOX inhibitor PXS‐5505 and given Pharmaxis permission to proceed with a phase 1/2 clinical trial for the treatment of myelofibrosis in adults.
The study will incorporate a one‐month dose escalation phase followed by 6 months’ treatment in an open label study of patients with intermediate or high‐risk myelofibrosis, including primary myelofibrosis, post‐polycythemia vera myelofibrosis and post‐essential thrombocythemia myelofibrosis patients. The study is planned to commence in Q4 2020 and expected to conclude in 2022.
Chief Executive Officer of Pharmaxis, Mr Gary Phillips, said, “The positive FDA feedback on our IND is a crucial step forward for Pharmaxis in advancing its pan‐LOX anti‐cancer program which has already shown compelling evidence of efficacy in a number of pre‐clinical cancer models. The company is well advanced in its preparations to start this study including production of the drug product, assigning a contract research organisation to manage the study and completing feasibility in a number of countries. We can therefore progress to initiate patient recruitment in Q4 2020 and respond as needed to the rapidly changing availability of trial sites caused by Covid‐19 outbreaks.”
PXS‐5505 works by inhibiting all of the lysyl oxidase family members that are involved in the bone marrow fibrosis that characterises myelofibrosis. It is hoped that this will have beneficial effects on blood cell production and consequently other aspects of this fatal disease which has a very high unmet medical need. Pharmaxis strategy for PXS‐5505 is to follow this first phase 1/2 study as a monotherapy with further studies to include myelofibrosis patients being treated with JAK inhibitors which are the existing standard of care for many patients.
Mr Phillips added, “The IND application was a significant body of work containing over 20,000 pages of reports on the phase 1 studies in healthy volunteers, numerous individual pre‐clinical studies and manufacture of the drug substance and drug product to be used in human clinical trials. We have been very encouraged by the support of clinicians who treat myelofibrosis and the researchers who have conducted many of the pre‐clinical studies. We will announce further details of the upcoming trial after completing discussions with our partners and collaborators.”
About Pharmaxis
Pharmaxis Limited is an Australian pharmaceutical research company and a global leader in drug development for inflammation and fibrotic diseases. The company has a highly productive drug discovery engine, drug candidates in clinical trials and significant future cash flows from partnering deals.
Leveraging its small‐molecule expertise and proprietary amine oxidase chemistry platform, Pharmaxis has taken four in‐ house compounds to Phase 1 trials in just five years. Boehringer Ingelheim acquired the Pharmaxis anti‐inflammatory AOC3 inhibitor in 2015 to develop it (BI 1467335) for two diseases: the liver condition Non‐alcoholic Steatohepatitis (NASH) and diabetic retinopathy (DR).
The company’s successor amine oxidase program has developed an oral anti‐fibrotic LOXL2 inhibitor, aimed at NASH, pulmonary fibrosis (IPF) and other high‐value fibrotic heart and kidney diseases, with a commercial partnering process underway, a systemic pan‐LOX inhibitor for acute fibrosis and cancer that will enter a phase 2 study in 2020 and a topical pan‐LOX inhibitor for scarring that is expected to commence phase 1 studies in 2H 2020. Pharmaxis’ Mannitol platform has yielded the products Bronchitol® for cystic fibrosis, which is marketed in Europe, Russia and Australia, with United States FDA approval pending; and Aridol® for the assessment of asthma, which is sold in the United States, Europe, Australia and Asia.
Pharmaxis is listed on the Australian Securities Exchange (PXS). Its head office, manufacturing and research facilities are in Sydney, Australia. http://www.pharmaxis.com.au/
What is myelofibrosis?
Myelofibrosis is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar‐like material. Over time, this leads to progressive bone marrow failure. Under normal conditions, the bone marrow provides a fine network of fibres on which the stem cells can divide and grow. Specialised cells in the bone marrow known as fibroblasts make these fibres.
In myelofibrosis, chemicals released by high numbers of platelets and abnormal megakaryocytes (platelet forming cells) over‐stimulate the fibroblasts. This results in the overgrowth of thick coarse fibres in the bone marrow, which gradually replace normal bone marrow tissue. Over time this destroys the normal bone marrow environment, preventing the production of adequate numbers of red cells, white cells and platelets. This results in anaemia, low platelet counts and the production of blood cells in areas outside the bone marrow for example in the spleen and liver, which become enlarged as a result.
Myelofibrosis can occur at any age but is usually diagnosed later in life, between the ages of 60 and 70 years. The cause of myelofibrosis remains largely unknown. It can be classified as either JAK2 mutation positive (having the JAK2 mutation) or negative (not having the JAK2 mutation).
Source: Australian Leukemia Foundation: https://www.leukaemia.org.au/disease‐information/myeloproliferative‐disorders/types‐of‐mpn/primary‐myelofibrosis/
SOURCE: Pharmaxis
Post Views: 247
SYDNEY, Australia I August 19, 2020 I Pharmaceutical research company Pharmaxis Ltd (ASX: PXS) announced that the Food and Drug Administration (FDA) has completed a safety review of the company’s Investigational New Drug (IND) application for the pan‐LOX inhibitor PXS‐5505 and given Pharmaxis permission to proceed with a phase 1/2 clinical trial for the treatment of myelofibrosis in adults.
The study will incorporate a one‐month dose escalation phase followed by 6 months’ treatment in an open label study of patients with intermediate or high‐risk myelofibrosis, including primary myelofibrosis, post‐polycythemia vera myelofibrosis and post‐essential thrombocythemia myelofibrosis patients. The study is planned to commence in Q4 2020 and expected to conclude in 2022.
Chief Executive Officer of Pharmaxis, Mr Gary Phillips, said, “The positive FDA feedback on our IND is a crucial step forward for Pharmaxis in advancing its pan‐LOX anti‐cancer program which has already shown compelling evidence of efficacy in a number of pre‐clinical cancer models. The company is well advanced in its preparations to start this study including production of the drug product, assigning a contract research organisation to manage the study and completing feasibility in a number of countries. We can therefore progress to initiate patient recruitment in Q4 2020 and respond as needed to the rapidly changing availability of trial sites caused by Covid‐19 outbreaks.”
PXS‐5505 works by inhibiting all of the lysyl oxidase family members that are involved in the bone marrow fibrosis that characterises myelofibrosis. It is hoped that this will have beneficial effects on blood cell production and consequently other aspects of this fatal disease which has a very high unmet medical need. Pharmaxis strategy for PXS‐5505 is to follow this first phase 1/2 study as a monotherapy with further studies to include myelofibrosis patients being treated with JAK inhibitors which are the existing standard of care for many patients.
Mr Phillips added, “The IND application was a significant body of work containing over 20,000 pages of reports on the phase 1 studies in healthy volunteers, numerous individual pre‐clinical studies and manufacture of the drug substance and drug product to be used in human clinical trials. We have been very encouraged by the support of clinicians who treat myelofibrosis and the researchers who have conducted many of the pre‐clinical studies. We will announce further details of the upcoming trial after completing discussions with our partners and collaborators.”
About Pharmaxis
Pharmaxis Limited is an Australian pharmaceutical research company and a global leader in drug development for inflammation and fibrotic diseases. The company has a highly productive drug discovery engine, drug candidates in clinical trials and significant future cash flows from partnering deals.
Leveraging its small‐molecule expertise and proprietary amine oxidase chemistry platform, Pharmaxis has taken four in‐ house compounds to Phase 1 trials in just five years. Boehringer Ingelheim acquired the Pharmaxis anti‐inflammatory AOC3 inhibitor in 2015 to develop it (BI 1467335) for two diseases: the liver condition Non‐alcoholic Steatohepatitis (NASH) and diabetic retinopathy (DR).
The company’s successor amine oxidase program has developed an oral anti‐fibrotic LOXL2 inhibitor, aimed at NASH, pulmonary fibrosis (IPF) and other high‐value fibrotic heart and kidney diseases, with a commercial partnering process underway, a systemic pan‐LOX inhibitor for acute fibrosis and cancer that will enter a phase 2 study in 2020 and a topical pan‐LOX inhibitor for scarring that is expected to commence phase 1 studies in 2H 2020. Pharmaxis’ Mannitol platform has yielded the products Bronchitol® for cystic fibrosis, which is marketed in Europe, Russia and Australia, with United States FDA approval pending; and Aridol® for the assessment of asthma, which is sold in the United States, Europe, Australia and Asia.
Pharmaxis is listed on the Australian Securities Exchange (PXS). Its head office, manufacturing and research facilities are in Sydney, Australia. http://www.pharmaxis.com.au/
What is myelofibrosis?
Myelofibrosis is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar‐like material. Over time, this leads to progressive bone marrow failure. Under normal conditions, the bone marrow provides a fine network of fibres on which the stem cells can divide and grow. Specialised cells in the bone marrow known as fibroblasts make these fibres.
In myelofibrosis, chemicals released by high numbers of platelets and abnormal megakaryocytes (platelet forming cells) over‐stimulate the fibroblasts. This results in the overgrowth of thick coarse fibres in the bone marrow, which gradually replace normal bone marrow tissue. Over time this destroys the normal bone marrow environment, preventing the production of adequate numbers of red cells, white cells and platelets. This results in anaemia, low platelet counts and the production of blood cells in areas outside the bone marrow for example in the spleen and liver, which become enlarged as a result.
Myelofibrosis can occur at any age but is usually diagnosed later in life, between the ages of 60 and 70 years. The cause of myelofibrosis remains largely unknown. It can be classified as either JAK2 mutation positive (having the JAK2 mutation) or negative (not having the JAK2 mutation).
Source: Australian Leukemia Foundation: https://www.leukaemia.org.au/disease‐information/myeloproliferative‐disorders/types‐of‐mpn/primary‐myelofibrosis/
SOURCE: Pharmaxis
Post Views: 247