Affimed Presents Data on Immune Cell Engager Pipeline at the AACR Annual Meeting 2017
- Category: Antibodies
- Published on Thursday, 06 April 2017 09:45
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HEIDELBERG, Germany I April 5, 2017 I Affimed N.V. (Nasdaq: AFMD), a clinical stage biopharmaceutical company focused on discovering and developing highly targeted cancer immunotherapies, announced today the presentation of preclinical data for the Company's lead candidate AFM13, its preclinical programs AFM24 and AFM26, as well as its MHC-peptide-targeting discovery program at the American Association for Cancer Research (AACR) 2017 Annual Meeting being held April 1 - 5, 2017 in Washington, D.C.
"We continue to evolve and advance our leadership position in the NK-cell engager field and our unique portfolio of tetravalent, bispecific immune cell engagers," said Dr. Martin Treder, CSO of Affimed. "At AACR, we presented differentiating data on our two novel NK-cell engagers targeting EGFR and BCMA and we introduced a platform for the specific targeting of MHC-peptide complexes, which opens up the therapeutic target space of tumor-specific antigens for T-cell engagement."
In a presentation on Monday, April 3, 2017, Affimed provided insights into the molecular characteristics and function of its NK-cell engagers and their potential to therapeutically reactivate NK-cells that are dysregulated in cancer. The Company's CD16A-specific tetravalent, bispecific antibodies are well-differentiated from native and Fc-engineered monoclonal antibodies by their high affinity and ability to overcome interference from serum IgG, leading to highly potent NK-cell activation. Furthermore, Affimed's lead product candidate AFM13, targeting CD30/CD16A, induced upregulation of specific interleukin receptors on NK-cells in a target-dependent manner. The Company presented further evidence of AFM13 modulating NK-cells by sensitizing them to IL-2 and IL-15 stimulation. After exposure to AFM13, the NK-cells showed improved IL-2- and IL-15-mediated proliferation and cytotoxicity. In summary, these data support the strategy of combining Affimed's NK-cell engagers with cytokines to potentially achieve deeper clinical responses.
In a poster session on Tuesday, April 4, 2017, Affimed presented data for its first-in-class tetravalent, bispecific EGFR/CD16A-targeting NK-cell engager AFM24. Designed to address the critical unmet need in recurrent or metastatic EGFR-positive tumors, AFM24 possesses a novel mechanism of action offering higher efficacy and an improved safety profile as compared to current EGFR-targeting marketed agents. In vitro and in vivo, AFM24 shows high potency and its NK-cell killing is virtually unaffected by polyclonal serum IgG interference. Importantly, AFM24 showed an excellent safety profile in toxicity studies in cynomolgus monkeys, with single intravenous administration being well-tolerated up to the highest dose level of 93.75 mg/kg. In summary, AFM24 lead candidates have the potential to exhibit a favorable side effect profile and reduced toxicity and to address the resistance to other targeted anti-EGFR therapeutic agents.
In a poster session on Wednesday, April 5, 2017, Affimed presented data for AFM26, a first-in-class BCMA/CD16A-targeted tetravalent bispecific antibody designed to redirect NK-cell cytotoxicity to multiple myeloma (MM). In vitro, AFM26 potently induced NK-cell-mediated lysis of BCMA-positive myeloma cell lines and exhibited both greater efficacy and potency than anti-CS1 IgG1 (elotuzumab). Notably, AFM26 had a much higher affinity to primary human NK-cells than native or Fc-enhanced mAbs in both the presence and absence of competing serum IgG, suggesting that AFM26 can activate NK-cells despite the high M-protein levels characteristic for MM. Furthermore, AFM26 showed significantly longer NK-cell surface retention than native and Fc-enhanced IgG formats. In summary, AFM26 alone or in combination with ex vivo-expanded NK-cells appears to be a highly promising approach to eliminate minimal residual disease (MRD) in the post-transplantation period. These data suggest that AFM26 is uniquely suited to engage NK-cells in MM. Furthermore, the long-lasting NK-cell surface retention and inability to induce NK-cell depletion may allow premixing of NK-cells ex vivo prior to infusion.
MHC-peptide targeting (#3753/9)
In a poster session on Tuesday, April 4, 2017, Affimed presented data on its MHC-peptide-targeting discovery program. Addressing the need to open up the therapeutic target space of tumor-specific antigens for effective and safe T-cell engagement, the Company, together with its collaboration partner Immatics, identified a novel tumor-associated MHC/peptide complex, the HLA-A*02-binding peptide MMP1-003. MMP1-003 originates from matrix metalloproteinase 1 (MMP1), a protein overexpressed in several solid tumors and associated with advanced stage, metastasis and poor prognosis. The Company's subsidiary AbCheck identified highly specific antibody domains (scFvs) directed against the MMP1 peptide in an MHC-complex. Using these scFvs, Affimed generated and characterized specific and potent T-cell-engaging tetravalent bispecific antibodies. The lead antibody demonstrated excellent specificity and potent cytotoxicity of endogenously target-expressing cancer cell lines and no lysis of control cell lines. In summary, Affimed has developed novel tumor-targeting antibodies with the potential to open up the therapeutic space to T-cell-engagement by providing access to intracellular proteins that are presented as disease-specific MHC/peptide complexes.
Affimed's presentation and posters can be downloaded on Affimed's corporate website at http://www.affimed.com/events-aacr-2017.php.
About Affimed N.V.
Affimed (Nasdaq: AFMD) engineers targeted immunotherapies, seeking to cure patients by harnessing the power of innate and adaptive immunity (NK- and T-cells). We are developing single and combination therapies to treat cancers and other life-threatening diseases. For more information, please visit www.affimed.com.