MorphoSys is a German biopharmaceutical company dedicated to developing innovative and differentiated therapies for critically ill patients. Recently, the company announced that it has signed a global cooperation and licensing agreement with Incyte to further develop and commercialize MorphoSys' proprietary anti-CD19 antibody tafasitamab (MOR208), a new humanized Fc targeting CD19 Domain-optimized immune-enhancing monoclonal antibodies, CD19 is a clear biomarker for a variety of B-cell malignancies.
Tafasitamab is currently in clinical development for the treatment of a variety of B-cell malignancies. At the end of December 2019, MorphoSys submitted a biologics approval application (BLA) to the US FDA seeking approval for tafasitamab in combination with lenalidomide for patients with relapsed or refractory diffuse large B-cell lymphoma (r / r DLBCL) . The FDA expects to make a decision in mid-2020. In the European Union, a marketing authorization application (MAA) for tafasitamab for the above indications is expected to be submitted to the European Medicines Agency (EMA) in mid-2020.
Under the agreement, MorphoSys will receive an advance payment of $ 750 million. In addition, Incyte will invest $ 150 million in MorphoSys to purchase MorphoSys' American Depositary Shares (ADS) at a premium to the stock price when the agreement was signed. MorphoSys will also be eligible for milestone payments of up to $ 1.1 billion based on the achievement of specific development, regulatory and commercialization milestones. MorphoSys will also receive tiered royalties ranging from ten to 20 percent based on tafasitamab's net sales outside the United States.
In the United States, MorphoSys and Incyte will jointly commercialize tafasitamab. MorphoSys will lead the commercialization strategy and will record all sales revenue of tafasitamab. The two parties will share profits and losses at 50:50. Outside the United States, Incyte will have exclusive commercialization rights and will lead the commercialization strategy, record all sales revenue for tafasitamab, and pay royalties for MorphoSys' net sales outside the United States. In addition, the two parties will share development costs related to specific global and US-based trials at a ratio of 55 (Incyte): 45 (MorphoSys). Incyte will pay 100% of future development costs for specific trials outside the United States.
The two sides have agreed to extensively develop tafasitamab in r / r DLBCL, first-line DLBCL, and other indications such as follicular lymphoma [FL], marginal zone lymphoma [MZL], and chronic lymphocytic leukemia [CLL]. Incyte will lead a joint study of the PI3Kδ inhibitors parsaclisib and tafasitamab in r / r B-cell malignancies. In addition, Incyte will lead a potential registration study for CLL and a phase III study for r / r FL / MZL. MorphoSys will continue to be responsible for the ongoing clinical trials of tafasitamab for non-Hodgkin's lymphoma (NHL), CLL, r / r DLBCL and first-line DLBCL. The two parties will share the responsibility for launching more global trials. Incyte plans to promote the development of tafasitamab in more countries, including China and Japan.
The agreement between MorphoSys and Incyte, including equity investments, is subject to approval by US antitrust authorities and German and Austrian antitrust authorities, and will take effect immediately after regulatory requirements are met.
CD19 expression at various developmental stages of B cells and the mechanism of tafasitamab
tafasitamab is a humanized Fc-enhanced monoclonal antibody targeting CD19. The Fc domain has been modified (including 2 amino acid substitutions S239D and I332E). It significantly enhances the antibody by increasing its affinity for activated FcγRIIIa on effector cells. Key mechanisms for tumor-dependent cell killing by cell-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell phagocytosis (ADCP). In preclinical model studies, tafasitamab has been shown to induce direct apoptosis of cancer cells by binding to CD19.
Tafasitamab is currently being developed for two types of B-cell malignancies, including DLBCL and chronic lymphocytic leukemia (CLL). Globally, DLBCL is the most common type of non-Hodgkin's lymphoma (NHL) in adults, accounting for 40% of all cases; CLL is the most common type of leukemia in adults. Regarding regulation, the FDA granted tafasitama breakthrough drug qualification (BTD) in October 2017 in combination with lenalidomide for patients with r / r DLBCL who are not suitable for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). In 2014, the FDA granted fast-track qualification (FTD) for tafasitamab to treat r / r DLBCL. Also in 2014, the FDA and EMA granted tafasitamab orphan drug eligibility to treat DLBCL and CLL / SLL (small cell lymphoma).
tafasitamab for B-cell malignancies-DLBCL shows strong efficacy.
In the United States, the submission of BLA is based on the main analysis results of the L-MIND study from tafasitamab combined with lenalidomide in the treatment of r / r DLBCL patients and a retrospective observation of the efficacy of lenalidomide in the treatment of r / r DLBCL patients Results of a matched control cohort in the sex study Re-MIND.
-L-MIND: This is a single-arm, open-label Phase II study that is evaluating tafasitamab in combination with lenalidomide, which has previously received at least one but no more than three therapies (including an anti-CD20 targeted therapy, such as Rituximab), R / R DLBCL patients who are not eligible for high-dose chemotherapy (HDC) and subsequent autologous stem cell transplantation (ASCT).
In May this year, the L-MIND study reached its primary endpoint: the total response rate (ORR) of tafasitamab + lenalidomide was 60%, and the complete response rate (CR) was 43%. At a median follow-up of 17.3 months, the median Progression-free survival (PFS) was 12.1 months; remission was durable with a median duration of response (DOR) of 21.7 months. At a median follow-up of 19.6 months, the median overall survival (OS) had not yet reached (95% CI: 18.3 months-NR), and the 12-month survival rate was 73.3%.
-Re-MIND: An observational, retrospective study of real-world data designed to isolate the contribution of tafasitamab in a combination regimen with lenalidomide and demonstrate the effectiveness of the combination therapy. The study compared real-world response data for patients receiving r / r DLBCL with lenalidomide monotherapy and the efficacy outcomes of tafasitamab and lenalidomide in patients with r / r DLBCL in the L-MIND study. The study collected data from 490 patients in the U.S. and European real-world who received lenalidomide monotherapy for R / R DLBCL who were not eligible for transplantation. Of these, 76 were compared with 76 patients in the L-MIND study in terms of important baseline characteristics. Has a 1: 1 match.
The analysis showed that the study reached the primary endpoint: tafasitamab + lenalidomide combination therapy has clinical advantages over lenalidomide monotherapy. The specific data is: compared with lenalidomide monotherapy, tafasitamab + lenalidomide combination therapy has a statistically significant superiority in the main endpoint ORR (ORR: 67.1% vs 34.2%, p <0.0001), in Consistent superiority was also observed in all secondary endpoints, including: complete response rate (CR: 39.5% vs 11.8%, p <0.0001), overall survival (median OS: not reaching vs 9.3 months, p <0.0008 ).
"CAR-T Killer": tafasitamab will challenge two CD19 CAR-T therapies that have been on the market
Some analysts pointed out that after tafasitamab is listed, it will directly challenge the two anti-CD19 CAR-T therapies on the market that treat R / R DLBCL-Novartis Kymriah and Gilead Yescarta. CAR-T therapy is different from conventional small molecule or biotherapies, which is a living T-cell therapy product. Both Kymriah and Yescarta treatment procedures require patient T cells to be isolated and genetically modified in vitro to allow T cells to express a chimeric antigen receptor (CAR) designed to target CD19, and then return the modified T cells to the patient. Find cancer cells that express CD19 and play a therapeutic role.
In terms of efficacy, tafasitamab is comparable to Kymriah and Yescarta. In terms of medication, both Kymriah and Yescarta need to be prepared separately for each patient, which takes a certain amount of time, and tafasitamab is an industrially produced ready-to-use monoclonal antibody, which is available on demand. In terms of treatment costs, Kymriah and Yescarta both cost hundreds of thousands of dollars, while tafasitamab can be controlled very low. Some analysts have compared tafasitamab as a "CAR-T cell therapy killer". If the drug is successfully marketed, it will inevitably have a huge impact on Kymriah and Yescarta.
Original source: MorphoSys and Incyte Sign Global Collaboration and License Agreement for Tafasitamab (news with additional features)