Monoclonal Antibodies

Monoclonal antibodies (mAbs) have two antigen binding regions and one constant region that other immune cells, such as natural killer (NK) cells, can attach to and kill the cancer cell that the antibody is bound to. When our mAbs are infused into a person, the two antigen binding regions attach to specific antigens on the target cells (the cancer cells) in the body. Once this binding occurs, a natural killer (NK) cell from the immune system binds to the constant region of the antibody. This binding activates the NK cell, which results in killing of the cancer cell.

HaemaLogiX's monoclonal antibodies do not bind to normal, healthy immune cells called plasma cells, thus leaving them unharmed and able to function normally.

To kill myeloma cells, HaemaLogiX is developing proprietary monoclonal antibodies KappaMab (for patients with kappa-type multiple myeloma) and LambdaMab (for patients with lambda-type multiple myeloma).

Several drugs that are currently in use to help treat multiple myeloma can be used in combination with KappaMab and LambdaMab to help make them more effective at killing the cancer cells. Giving a patient an immunomodulatory drug (IMiD), such as lenalidomide or pomalidomide will make the cancer cell express more of our target antigen (either KMA or LMA) on its cell surface.

Hence, when our antibodies are infused into the patient, the cancer cell now has a much greater number of target antigens for our antibodies to bind to. This makes our antibodies much more effective at attaching to the cancer cell and recruiting the NK cells to kill the cancer cells. This increase in antigen number following pre-treatment with an IMiD is a mechanism that should increase the efficacy of our antibodies in the treatment of myeloma.

HaemaLogix’s pre-clinical studies showed that KappaMab binds to malignant plasma cells but not to normal plasma cells.

The Phase 1 and 2a studies were conducted in patients who had received two or more lines of treatment and had persistent, stable disease. A Phase 2b clinical trial was conducted in combination with Revlimid® and dexamethasone in relapsed and refractory myeloma (RRMM) patients with progressive disease. Together, the studies have demonstrated KappaMab’s specificity, efficacy and safety.

Recent Phase 2b clinical trial outcomes

HaemaLogiX recently completed a Phase 2b trial of KappaMab in multiple myeloma patients which was led by Professor Andrew Spencer at the Alfred Hospital in Melbourne.

• Phase 2b results show that KappaMab in combination with Revlimid® and dexamethasone (KM-RD) demonstrated significantly improved efficacy with an overall response rate (ORR) of 83% versus 45% ORR in the Revlimid^® and dexamethasone (RD) matched case controls. The patient population had failed one to three lines of prior treatment and had progressive disease.
• KappaMab demonstrated an excellent safety profile at multiple doses at the 10mg/kg level and there were no antibody related immune cell toxicities. Compared to the control group there were no increases in infection.
• There was a 46% reduction in the risk of death, versus matched case controls.
• A dramatic increase in depth of response was observed, with three times the number of combined complete responses (CR) and very good partial responses (VGPR), versus matched controls.
• Two patients in the KappaMab combination with Revlimid® and dexamethasone group had CRs and remained on this combination therapy three to five years post-study.

Next Phase 2b trial – start-up underway

The Company has initiated the start-up activities for a further Phase 2b clinical trial for KappaMab in combination with pomalidomide and dexamethasone at an increased KappaMab dose, in patients who have failed three classes of standard-of-care drugs.