Innate Immune Cell Engagers

The immune system is our body’s defense mechanism. With its two components, innate and adaptive immunity, it recognizes and fights thousands of foreign and abnormally altered cells every day. In the initial stages of cancer, there is a balance between abnormally dividing tumor cells and the immune response. But tumor cells learn how to disguise themselves from the immune system. This tips the balance and allows the tumor to grow. A tremendous amount of research has been done to fight cancer and several treatments have been developed. Unfortunately these often fail to provide a long-term benefit or cure and can come with severe side effects.

At Affimed, we aim to overcome these limitations by reactivating the immune system. Leveraging our ROCK® platform, we teach it to recognize and fight the disguised tumor cells.

Innate Immune Cell Engager Mode of Action

Redirecting innate immune cells to fight cancer

AFM13

Targets CD30 on tumor cells and CD16A on innate immune cells

AFM13 is a first-in-class tetravalent, bispecific innate immune cell engager that is being developed in Hodgkin lymphoma (HL) and in other CD30-positive lymphomas. AFM13 has shown a favorable safety profile and signs of therapeutic efficacy in a monotherapy setting in studies in HL and CD30+ lymphoma with cutaneous manifestation. In addition, data from a combination study of AFM13 with Merck’s anti-PD-1 antibody Keytruda® (pembrolizumab) supports proof of principle for the combination of NK cell engagement with checkpoint inhibition.

AFM24

Targets EGFR on tumor cells and CD16A on innate immune cells

The Epidermal Growth Factor Receptor (EGFR) is ubiquitously expressed in healthy epithelial tissues, but, when constitutively activated through binding by growth factors or mutations, plays an important role in the pathophysiology of numerous solid cancers such as colorectal, lung or head and neck cancer. A number of EGFR-targeting drugs have been approved to treat solid tumors including tyrosine kinase inhibitors and monoclonal antibodies, but despite demonstrated clinical activity, intrinsic or acquired resistance is frequently observed. Displaying significant advances over IgG-based antibodies in recruiting innate immune cells, AFM24 is a tetravalent, bispecific innate immune cell engager that has the potential to overcome these limitations. AFM24 is being developed in a variety of solid tumor indications.

AFM26 (partnered)

Targets BCMA on tumor cells and CD16A on innate immune cells

While new treatments of multiple myeloma have been developed recently, an unmet need remains as most patients eventually relapse and/or become refractory to currently available treatments. AFM26 specifically binds both B cell maturation antigen (BCMA) and CD16A with high affinity, resulting in high avidity, prolonged cell surface retention and potent induction of innate immune cell-mediated in vitro lysis of target cells. NK cell engagement via CD16A is largely unimpaired at high levels of polyclonal IgG, suggesting an advantage over classical mAbs for AFM26 in the treatment of multiple myeloma patients.

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