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HEIDELBERG, Germany—Clinical-stage biopharmaceutical company Affimed N.V., which focuses on the discovery and development of targeted cancer immunotherapies, has begun a clinical research collaboration with Merck & Co. (known as MSD outside the United States and Canada) in the field of immuno-oncology, specifically for the combination of their respective therapies.
Per the terms of the collaboration, Affimed will fund and conduct a Phase 1b clinical trial to evaluate the combination of Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), with Affimed’s proprietary drug candidate AFM13 in patients with Hodgkin lymphoma whose disease has relapsed or is refractory to chemotherapy, including treatment with Adcetris (brentuximab vedotin). The study, which is expected to begin in the first half of 2016, will seek to establish a dosing regimen for the combination and determine its safety and efficacy.
The agreement is between Affimed and Merck, through a subsidiary, and includes a provision for a potential expansion of the deal to include a Phase 3 clinical trial. Financial details were not released.
“Evaluating the potential for innovative combination therapies through strategic collaborations in difficult-to-treat tumor types continues to be an important part of our clinical development program for KEYTRUDA,” Dr. Eric Rubin, vice president and therapeutic area head, oncology early-stage development at Merck Research Laboratories, said in a press release. “In partnering with companies such as Affimed, we continue our efforts to bring forward new scientific breakthroughs for patients with Hodgkin lymphoma and the field of immuno-oncology overall.”
AFM13 is a first-in-class bispecific NK-cell TandAb. Affimed's NK-cell TandAbs are “tetravalent, bifunctional proteins that recognize a specific biologic target and, utilizing their second functionality, bind with high affinity to NK cells and thereby direct the NK-cells to eliminate the target cell,” as described on the company's website. In the case of AFM13, it binds NK cells specifically through CD16A, which is expressed on NK cells, with a second binding domain for CD30, a cancer-specific target expressed in a variety of T cell and B-cell lymphomas.
AFM13 redirects the NK cells to CD30-expressing cancer cells and binds both targets with high affinity. The compound is designed to treat CD30-positive malignancies, including Hodgkin lymphoma and T cell lymphoma, and it is currently in Phase 2 studies in Hodgkin lymphoma patients.
Merck's KEYTRUDA is a humanized monoclonal antibody that increases the ability of the body’s immune system to help detect and fight tumor cells by blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
In patient-derived xenograft models, combining AFM13 with an anti-PD-1 antibody resulted in impressive synergy, with up to 90 percent of the tumor eradicated. In this preclinical work, which was conducted at Stanford University, NK and T cells infiltrated the tumors and cytokine levels, including interferon-gamma, were elevated.
“Our development strategy is to combine our NK-cell engagers with other immunotherapies that could enhance their efficacy through the uptake of both NK-cells and T-cells, and the collaboration with Merck is an important step in executing this strategy,” Dr. Adi Hoess, CEO of Affimed, explained in a statement. “AFM13, a first-in-class NK-cell engager, has shown an acceptable safety profile and preliminary antitumor activity in the first-in-human Phase 1 study. Additionally, preclinical studies indicate that a combination with an anti PD-1 therapy could act synergistically and represent an additional future treatment option for patients.”
Affimed is also advancing AFM13 with the help of the Leukemia and Lymphoma Society (LLS). In August 2013, the organizations signed a deal under which LLS committed to co-fund up to $4.4 million over two years for the Phase 2a development of AFM13.