Clinical Trial Investor

The Science Rucaparib or Rubraca® is a PARP inhibitor currently being investigated for use as an anti-cancer agent by Clovis Oncology. It has been approved for the maintenance of Ovarian cancer, however it is also currently being investigated in three Phase III trials for the treatment of Ovarian, Prostate and Bladder cancers. Exploratory studies in other tumour types are also underway. Rucaparib is a potent inhibitor of PARPs or Poly (ADP-Ribose) Polymerase proteins, PARPs play a pivotal role in repairing DNA damage and maintaining genomic stability in cells. Cells can have certain genomic mutations such as BRCA1/2 or mutations in genes used for repairing DNA double strand breaks which would otherwise cause cell death. Tumours with these mutations must rely on alternative methods to repair DNA damage. PARP enzymes (particularly PARP1/2) play a critical role in repairing the DNA in cells that have these mutations. Inhibition of these PARP enzymes causes a build up of sing

The Science Intravenous andexanet alfa, coagulation factor Xa (recombinant), inactivated-zhzo or Andexxa® is a first-in-class modified factor Xa protein that has been developed by Portola Pharmaceuticals as an antidote to reverse anticoagulant effects of direct or indirect factor Xa inhibitors.  In May 2018, Andexxa received FDA approval in the USA for use in patients that have been treated with rivaroxaban and apixaban, two factor Xa inhibitors. It is currently undergoing regulatory review for use in the EU, approval is expected in February 2019. Direct or Indirect factor Xa inhibitors are powerful anticoagulants for the prevention and treatment of thromboembolism and stroke prevention in atrial fibrillation. These agents have been shown to be more effective than vitamin K antagonists such as warfarin but nonetheless the risk of complications is still high and a reversing agent would be beneficial.  Andexxa is a first in class therapy for reversing the anticoagulat

The Science Tab Cel, Tabelecleucel or allogeneic EBV-specific cytotoxic T lymphocytes ATL129 is a therapy that is currently being investigated by Atara Biotherapeutics for patients with EBV+ PTLD After Failure of Rituximab.  EBV or Epstein-Barr Virus is a human gamma herpes virus, more commonly know as the virus to cause Glandular Fever. This virus asymptomatically infects over 95% of adults by age 30. Infection typically occurs in childhood and is often difficult to distinguish from a cold or flu. The virus establishes a latent infection with B-memory cells and lies dormant in the body in very low numbers.  Patients with malignant bone marrow disorders and other disorders of the immune system often are treated by allogenic stem cell transplantation. This involves high doses of chemo/radiotherapy to destroy the patients immune system followed by a replacement of bone marrow stem cells. As the patients immune system is compromised during the procedure, latent EBV infection

In my previous post about BB2121, I noted that AMG 420 seemed more effective scientifically, and more practical from a cost point of view as compared to BB2121. I decided to explore that a bit further. The Science AMG 420 is an anti-BCMA x anti-CD3 BiTE (Bi-specific T cell engager) antibody construct currently being investigated as a treatment for multiple myeloma by Amgen.  Multiple myeloma is a cancer that originates in plasma cells, a type of white blood cell. It can impact much of the body but especially target the bone marrow where plasma cells are made. Multiple myeloma cells produce a protein called B-cell maturation antigen (BCMA) in excess. The immune system usually can recognise abnormal cells, such as cancer cells, and uses specific immune cells, such as T-cells, to destroy them. However, some tumour cells develop mechanisms to evade detection by the immune system. AMG 420 is an immunotherapy, meaning that it does not directly target the tumour but aims

Liso-Cel The Science JCAR017, Lisocabtagen maraleucel or Liso-Cel for short is a CAR T-cell therapy currently being developed by Juno Therapeutics, in collaboration with Celgene. The therapy has been granted blockbuster drug status to possibly treat certain patients with aggressive B-cell non-Hodgkin’s lymphoma (NHL). NHL is a collective name for a group of closely related blood cancers that develop in the lymphatic system. Clear fluid called lymph flows through the lymphatic vessels and contains infection-fighting white blood cells known as lymphocytes. In non-Hodgkin lymphoma, the affected lymphocytes start to multiply in an abnormal way and begin to collect in certain parts of the lymphatic system, such as the lymph nodes (glands). In B-cell lymphomas, it is B-cells that multiply uncontrollably and loss normal function. B-cells function in the humoral immunity component of the adaptive immune system by secreting antibodies, presenting antigens and secreting cytokines.

Ozanimod The Science Ozanimod is an immunomodulatory drug developed by Celgene that is currently in Phase III clinical trials for the conditions of relapsing Multiple Sclerosis (RMS) and Ulcerative Colitis (UC). Multiple Sclerosis is a condition in which the bodies immune system attacks myelin, a substance designed to protect neurons and help nerve signals travel quickly around the nervous system. This strips the myelin from the neurons and leaves scars known as lesions or plaques. This damage disrupts messages travelling along nerve fibres – they can slow down, become distorted, or not get through at all. Immune cells (Lymphocytes) contain a receptor called a sphingosine-1-phosphate (S1P) receptor. When S1P interacts with this receptor, it causes the egress of Lymphocytes from the thymus and Lymph nodes into lymphatic vessels, from there it can reach the CNS. The drug acts as a S1P receptor agonist, meaning it binds to the receptor and produces a biological response. In

BB2121 The Science BB2121 is an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy currently being investigated by Celgene and Bluebird Bio to primarily treat Multiple Myeloma patients. Multiple Myeloma cells express B-Cell Maturation Antigen (BCMA) on their surface, BB2121 is a T cell that has been engineered to add the chimeric antigen receptor protein that is specific to BCMA. BCMA is a cell surface protein that is involved in the differentiation and maturation of B-cells into plasma cells. BCMA is very common on Myeloma and plasma cells but is under expressed on B Lymphocytes, meaning it is a promising target for investigational treatments. The receptor is chimeric as it combines antigen-binding and T-cell activating functions into a single receptor. BB2121 has two intracellular domains, one involved in signalling and one to increase the proliferation, persistence and activation of the T cell. T-cells (or Lymphocytes) are produced by the immune system and are

CAVATAK The Science CAVATAK or Coxsackievirus A21 (CVA21) is an immuno-oncolytic therapy manufactured by Viralytics Ltd currently being investigated in a number of Phase I and II trials.  The idea of infecting cancer cells with viruses is not new, infact it originated over a century ago. Viruses have been found to show certain affinities which predispose them to infect certain cell types. Their main mode of action is through infiltration and replication within the tumour mass leading to oncolysis or bursting of the cancer cells. CAVATAK's mechanism of action is through the required binding of intercellular adhesion molecule-1 (ICAM-1) and optional binding of decay accelerating factor (DAF) on the cancer cells surface.  ICAM-1 and DAF receptors are over expressed on malignant cells surfaces in comparison to normal cells. This has been demonstrated in melanoma, breast, colon, endometrial, head and neck, pancreatic, and lung cancers so far. After attaching to ICAM-1 or DAF