Clinical Pipeline

KappaMab is at an advanced stage of clinical development, having completed Phase 1, 2a and 2b clinical trials with positive results.

A Phase 1 clinical trial to determine the safety, tolerability and maximum tolerated dose of KappaMab was conducted. The trial was a single dose escalation study in kappa type multiple myeloma patients who had received two or more prior lines of treatment but had persistent, stable disease.¹⁴ The trial included assessing any serious adverse events, the maximum tolerated dose and any dose-limiting toxicities at doses of 0.3, 1, 3 and 10 mg/kg when given intravenously.

KappaMab was shown to be safe and well tolerated at all doses tested and the recommended Phase 2a dose for the subsequent clinical trial was established.

A Phase 2a clinical trial evaluated the safety and efficacy of KappaMab as a monotherapy (single agent) in multiple myeloma patients who had previously received several prior treatments with standard of care drugs.¹⁵ Patients received weekly intravenous infusions of KappaMab (10 mg/kg) for eight weeks, followed by monthly monitoring. KappaMab was well tolerated, with no dose-limiting toxicities or serious antibody-related side effects.

As KappaMab was well tolerated and Revlimid^® was shown to enhance the activity of KappaMab in vitro, a Phase 2b 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 stage 2, in combination with Revlimid and dexamethasone. The results of this clinical trial have been published in the British Journal of Haematology.¹⁶

Key findings included:

• Significant improvement in Overall Response Rate (83%) compared with matched case control group (45%).
• Significant overall survival advantage, with a 46% reduction in the risk of death.
• Excellent safety profile and significant efficacy bolster HaemaLogiX's plan to progress further KappaMab / standard of care combination studies.

HaemaLogiX has initiated the start-up activities for a further Phase 2b clinical trial to further evaluate KappaMab's efficacy and safety in multiple myeloma patients who have received 1-3 prior lines of therapy. The previous clinical trials were conducted with a KappaMab dose of 10 mg/kg. Given the excellent safety profile for KappaMab in these trials, the Phase 2b trial will use a higher dose of 30 mg/kg in combination with pomalidomide and dexamethasone. In addition, other monoclonal antibodies used to treat multiple myeloma are given at doses higher than 10 mg/kg.

This Phase 2b study has been designed to enable a roll over to a registration Phase 3 clinical trial in multiple myeloma patients who have failed three classes of drug and therefore have a significant unmet medical need with few treatment options available. Successful efficacy, as determined by Minimal Residual Disease (MRD) analysis, overall response rates, progression free survival and safety outcomes could also enable fast track regulatory approval with the FDA.

14. Spencer A, Walker P, Asvadi P, Campbell D, Dunn R et al. A preliminary study of the anti-k myeloma antigen monoclonal antibody KappaMab (MDX-1097) in pretreated patients with K-restricted multiple myeloma. Blood Cancer J, 2019; (9): 58.
15. Dunn R, Spencer A, Augustson B, et al. Phase 2a, open-label, multi-dose study of the anti-kappa monoclonal antibody, MDX-1097, in relapsed kappa-chain restricted multiple myeloma with stable measurable disease. Haematologica. 2013; 98(s1):776.
16. Spencer A, Kalff A, Shortt J, Harrison SJ, Dunn R, Wellard C. et al. A sequential cohort study evaluating single-agent KappaMab and KappaMab combined with lenalidomide and low-dose dexamethasone in relapsed and/or refractory kappa light chain-restricted multiple myeloma (AMaRC 01-16). Br J Haematol. 2023 Aug;202(4):801-811.

In vitro studies have shown that KMA.CAR-T cells recognised and specifically killed only myeloma cells that expressed KMA and did not kill myeloma cells that expressed LMA thus demonstrating the unique specificity for KMA. An in vivo study showed that in mice with human myeloma tumour cells, the KMA expressing myeloma tumours were completely eradicated 15 days after infusion with 5 million KMA.CAR-T cells.

The results of the in vitro and in vivo pre-clinical studies have proven that the KMA.CAR-T cells specifically and effectively kill KMA expressing myeloma cells. They can survive as a living drug in vivo and prevent tumour growth in the long term (the mice were monitored and measured on survival out to 100 days).

HaemaLogiX, in collaboration with the Peter MacCallum Cancer Centre, is set to initiate its first-in-human Phase 1 clinical trial of KMA.CAR-T therapy for kappa-type multiple myeloma patients, once TGA approval is received. This dose finding KMA.CAR-T cell study represents an opportunity to assess this cell therapy approach in patients who have failed multiple standard-of-care treatments and have few therapeutic options available. Patients will only be enrolled in this study if they have evidence of KMA on the surface of their myeloma plasma cells.

The trial is fully funded by Peter MacCallum Cancer Centre and will assess the safety and effectiveness of HaemaLogiX's KMA.CAR-T cell therapy.

The LMA.CAR-T cell is in pre-clinical development. Similar to the KMA.CAR-T cell pre-clinical studies, in vitro (laboratory) experiments will be conducted to show that LMA.CAR-T cells are functional, bind specifically to LMA and are able to directly kill LMA-positive myeloma cells. Once their activity is proven in laboratory experiments, they will be tested in vivo in a mouse model of lambda-type multiple myeloma to show that they are effective at killing LMA-positive tumours.

If pre-clinical specificity and in vivo efficacy is established, the LMA.CAR-T cell will be developed for a Phase 1 clinical trial to treat patients whose myeloma plasma cells express LMA.

HaemaLogiX is committed to the discovery and development of bispecific antibodies as next-generation immunotherapies. Bispecifics are designed to attach to multiple myeloma plasma cells expressing either KMA or LMA and to simultaneously engage a T cell through its specific cell surface target called CD3. This dual action brings the patient’s own T cells into direct contact with the myeloma cancer cells, enabling targeted T cell mediated cell killing.

The key advantage of bispecific antibodies lies in their dual-targeting mechanism, which enhances immune activation by engaging two critical immune pathways.