Tafasitamab - Model MOR208 - Humanized FC-Modified CD19 Targeting Immunotherapy

Following accelerated approval by the U.S. Food and Drug Administration in July 2020, Tafasitamab is being co-commercialized by MorphoSys and Incyte in the United States. Incyte has exclusive commercialization rights outside the United States. Tafasitamab, combined with Lenalidomide, has been approved, under accelerated approval, in US for adult patients with relapsed/refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplantation (ASCT). In August 2021, Health Canada and the European Commission and in October 2021, MHRA granted conditional Marketing Authorization for Minjuvi® (tafasitamab) in combination with Lenalidomide for the same indication (for details see Regulatory Highlights). There is a high-unmet medical need for this patient group.

Tafasitamab (MOR208) is a therapeutical Fc-modified antibody targeting CD19 and is currently in clinical development for the treatment of patients with B cell malignancies.

Tafasitamab (MOR208) binds to CD19. This antigen is broadly and homogeneously expressed across different B cell malignancies including diffuse large B cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). CD19 is able to enhance B cell receptor (BCR) signaling, which is important for B cell survival. Therefore, CD19 is considered a potential therapeutic target for drugs aimed at treating B cell-related lymphomas and leukemias.

CD19 is expressed very broadly and early on B cells. Therefore, it provides potential target for the treatment of B cell malignancies.

Tafasitamab (MOR208) is currently in clinical development in various B cell malignancies. Focus of development is on patient populations with a high unmet medical need.

These diseases arise from B lymphocytes (or B cells) that are normally part of the body’s immune system which, in a healthy organism, play an important role as they produce antibodies against invaders such as viruses and bacteria. When B cells turn malignant, they displace the healthy and functional white blood cells leading to an impaired and heavily weakened immune system.

MorphoSys is currently investigating tafasitamab (MOR208) in four types of B-cell malignancies:

Diffuse large B cell lymphoma (DLBCL): DLBCL is the most common type of non-Hodgkin’s lymphoma in adults worldwide, accounting for ~40% of NHL cases . Although this disease is prevalent mainly in the elderly, it can occur at any age. It is a very aggressive disease that affects the B cells of the immune system and 30-40% of all patients do not respond to initial therapy or relapse thereafter. There is a high unmet medical need for novel treatments for these patients, since current options are limited and the prognosis for these patients is poor. In particular, patients who have failed initial therapies and who are ineligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT), are in need for more therapeutic options.

Chronic lymphocytic leukemia (CLL): CLL is the most common form of leukemia in adults. In CLL, B cells have become malignant and multiply uncontrolled in the blood. These leukemia cells displace functional B lymphocytes and other blood cells, resulting in a weakening of the immune system and a significantly higher susceptibility to infections. Today, patients are increasingly being treated with a new class of drugs called Bruton‘s Tyrosine Kinase (BTK) inhibitors and B-cell leukemia/lymphoma-2 (BCL-2) inhibitors. However, for those patients who do not respond or no longer respond to this treatment, options are limited. This results in a high unmet medical need for this patient group after discontinuation of a prior BTK/bcl-2 inhibitor therapy.

Follicular lymphoma (FL)  and Marginal Zone Lymphoma (MZL): FL and MZL are the most common indolent NHL subtypes and account for approximately 20% to 25% and 7% of adult NHL cases, respectively (Swerdlow et al 2016). Both subtypes are considered incurable and have a variable clinical course, with options for management ranging from active surveillance for asymptomatic patients to chemo-immunotherapy, immunotherapy, or treatment with targeted agents for those with symptomatic disease. Patients usually respond to initial therapy but typically relapse over time. There is no standard treatment approach for patients with relapsed indolent NHLs such as FL or MZL and these patients are treated similarly despite being distinct entities (Dreyling et al 2016, Zucca et al 2020). However, despite improvements in treatment options for R/R FL and MZL, there is a high medical need for additional treatment options with improved outcomes and better safety profiles.