Affimed N.V. (Nasdaq:AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, today provided an update on its NK-cell engager platform. “In 2016, we have significantly expanded our activities to optimize the elimination of malignant cells through NK-cell engagement, namely advancing our Phase 1b clinical trial of AFM13 in combination … Continued
Affimed N.V. (Nasdaq:AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, today provided an update on its NK-cell engager platform.
“In 2016, we have significantly expanded our activities to optimize the elimination of malignant cells through NK-cell engagement, namely advancing our Phase 1b clinical trial of AFM13 in combination with Merck’s Keytruda and broadening our approach to include the combination of our NK-cell engagers with adoptive transfer of activated NK-cells developed at MD Anderson,” said Adi Hoess, Ph.D., CEO of Affimed.“We further progressed our preclinical NK-cell engager pipeline with our EGFR-targeting solid tumor candidate AFM24 and BCMA-targeting multiple myeloma candidate AFM26,” added Martin Treder, Ph.D., CSO of Affimed. “Due to their high affinity and specificity to CD16A, our molecules offer a novel mechanism of action for NK-cell and macrophage engagement and avoid competition by high IgG serum levels, which currently limits the efficacy of monoclonal antibody-based treatments. In addition, we have gathered important insights into NK-cell biology in various preclinical studies which will allow us to explore further treatment options, for example combining our NK-cell engagers with cytokines such as IL-15 or IL-2.”
Leadership position in activating innate and adaptive immunity through engaging NK-cells and macrophages
Focusing its efforts on antibodies specifically binding NK-cells through CD16A, a dominant activating receptor on innate immune cells, Affimed has built a clinical and preclinical pipeline of NK-cell-engaging bispecific antibodies (TandAbs®) designed to activate both innate and adaptive immunity. Compared to a variety of T-cell-engaging technologies, Affimed’s NK-cell engagers appear to have a better safety profile and have the potential to achieve more potent and deeper immune responses through enhancing crosstalk of innate to adaptive immunity. Building on its leadership in the NK-cell space, Affimed is also developing tetravalent, bispecific alternative antibody formats (AAFs) for NK-cell engagement offering varying PK/PD profiles relevant to certain diseases.
Product candidate AFM13: The most advanced NK-cell engager in clinical development
The Company’s lead product candidate, AFM13 targeting CD16A on NK-cells and CD30 on tumor cells, is the most advanced NK-cell engager in the clinic. Its development is focused on combination therapy and supported by The Leukemia & Lymphoma Society (LLS).AFM13 is differentiated from monoclonal antibodies as it displays a 1000-fold higher binding affinity to CD16A, shows very limited competition for NK-cell binding with circulating IgG, as well as higher potency compared to full-length CD30 antibodies. Safety and clinical/pharmacodynamic activity in heavily pretreated Hodgkin lymphoma (HL) patients was established in a Phase 1 study and based on its favorable safety profile and preclinical data, AFM13 is currently under investigation as a combination therapy.
NK-cell engagers in combination therapy
Combination therapies have demonstrated improved outcomes for cancer patients and are widely pursued to maximize efficacy of immunotherapeutic approaches. Further broadening the therapeutic opportunities for its NK-cell engagers, Affimed is investigating AFM13 in several combination therapies.It is becoming increasingly clear that modulation of immune effectors or the immunosuppressive environment result in higher overall response rates and extended durability of response. In vivo studies in a patient-derived xenograft (PDX) model have shown that combining AFM13 with checkpoint inhibitors leads to synergistic efficacy of AFM13 when combined with anti-PD-1, likely attributable to the combination of both agents inducing crosstalk between innate and adaptive immunity. Consequently, AFM13 is being investigated with Merck’s anti-PD1 antibody Keytruda in a Phase 1b clinical trial.Currently in early clinical development in a number of hematological malignancies, the adoptive transfer of activated NK-cells provides a strong combination rationale with Affimed’s NK-cell platform to better exploit the therapeutic power of NK-cells. For this, the Company has entered into an exclusive strategic clinical development and commercialization collaboration with MD Anderson Cancer Center (MDACC), in which Affimed intends to investigate AFM13 preclinically and clinically in combination with MDACC’s proprietary NK-cell product in HL. Beyond HL, this approach has potential applications in further medically underserved indications such as multiple myeloma or acute myeloid leukemia.Cytokines such as IL-2 or IL-15 boost NK-cell activity and are tested clinically in a variety of cancers. In recent preclinical studies, Affimed demonstrated that AFM13 induced the upregulation of specific interleukin receptors on NK-cells and the subsequent addition of IL-2 or IL-15 had a synergistic effect on AFM13-mediated NK-cell expansion. Hence, the combination of NK-cell engagers with such cytokines may be clinically useful to deepen responses.
Ongoing Clinical Studies
AFM13 in combination with Merck’s PD-1 inhibitor Keytruda®