HaemaLogiX is engaged in three broad phases of research and development. First, the Research & Discovery phase of our pipeline involves discovering and developing new antibodies and CAR T cells. Second, the Preclinical phase includes testing antibody candidates in the lab to show that, for example, they bind to the intended target(s). Third, Phases 1-3 are clinical trials, where safety and effectiveness (efficacy) are tested in stages in humans.
Phase IIb trial in 40 patients, KMab + Rev/Dex 1-3 lines of therapy
Indication: Multiple Myeloma
Research & Discovery
Our lead antibody, KappaMab, is in clinical trials to treat patients with kappa-type myeloma cells (i.e., kappa-restricted myeloma). In a first-in-human Phase I clinical trial, multiple myeloma patients were given a single intravenous infusion of the KappaMab antibody to assess safety. Following administration of KappaMab, there were no dose-limiting toxicities and the maximum tolerated dose was not reached. Based on these findings and the observed activity of the antibody on myeloma disease, a dose level of 10 mg/kg of KappaMab was then explored in a multiple dose Phase IIa clinical trial. The antibody was shown to be well tolerated and had a good safety profile when given to patients as a weekly dose for 8 weeks.
As the antibody was well tolerated and Revlimid was shown to enhance the activity of KappaMab in vitro, a Phase IIb clinical trial in relapsed-refractory myeloma patients was initiated. This two-stage study evaluated the effects of the antibody alone in stage 1 and then, in the stage 2, in combination with Revlimid and dexamethasone. This clinical trial is fully recruited and is ongoing. An interim analysis of the results was presented at the American Hematology Society (ASH) meeting in 2019. A further analysis of this study will be conducted in the latter half of 2020 to be presented late in the year at a scientific congress.
LambdaMab candidate selection is ongoing
Lambda Myeloma Antigen (LMA) is another unique target that is found on lambda-type myeloma cells but not on normal cells in the human body. We have proven the existence of LMA on myeloma cells and we have two human LambdaMab antibody candidates with different binding characteristics in development.
We will explore if the two antibody candidates are useful in different diseases such as multiple myeloma and AL amyloidosis (a form of myeloma which is predominantly lambda type). In AL Amyloidosis, deposits of amyloid are laid down most frequently in the heart and kidneys, which cause irreparable organ damage. Currently, these antibodies are being tested in vitro (in the lab) against human myeloma cell lines and myeloma and amyloidosis tissues.
We are transitioning to a viral vector and mouse model to be initiated
CAR T cell technology is truly a form of personalised medicine. To make CAR T cells, a cancer patient’s own T cells are collected, genetically modified in the laboratory, multiplied many times in culture to create billions of cells that are then infused back into the same patient. The cell surfaces of these modified T cells contain the special receptor (the Chimeric Antigen Receptor, or CAR), which recognises Kappa Myeloma Antigen (KMA) on the surface of myeloma cells.
In in vitro studies, we have shown that these KMA.CAR T cells recognise and specifically kill only cells with the surface antigen--that is, only the myeloma cells. The manufacturing process for producing an individual myeloma patient’s CAR T cells is currently under evaluation.
constructs, purification & affinity testing is the next step
Bispecific antibodies are genetically engineered to combine 2 different antibodies, one that binds an antigen on the myeloma cell and the other that binds to and stimulates a T cell that will attack the myeloma cell. HaemaLogiX is in the early phase of developing a bispecific antibody using the KappaMab antibody to target KMA on myeloma cells and an immune cell engager to bind to a T cell, bringing the myeloma cell and the T cell together to kill the myeloma cell.
*LMA.CAR-T and LMA Bispecific are potential future additions to our pipeline
Indication: AL Amyloidosis
Preclinical evaluation of KMab use in AL amyloidosis is ongoing
Patients with Amyloid Light-chain (AL) Amyloidosis can suffer from congestive heart failure, kidney failure and nerve damage due to the amyloid deposits in these organs and tissues. Amyloid is an aggregate of fibrils that can be arranged in bundles or in felt-like mesh in stacked sheets. These fibrils, called light chains are either of a kappa or lambda type. The light chains are produced by the malignant plasma cells, B cells in the bone marrow.
Our antibodies may bind to both the light chains and the KMA and LMA targets on the surface of the malignant B cells and have the potential to block the light chains from depositing and causing organ damage. At the same time both antibodies have the ability to bind to KMA and LMA and kill the amyloid-producing cells.