MOR202

MOR202 is a human monoclonal HuCAL antibody directed against CD38 in clinical development for the treatment of multiple myeloma (MM) and potentially autoimmune diseases.

MOR202 is currently under clinical investigation in patients with relapsed or refractory multiple myeloma. We believe MOR202 offers a potentially differentiated safety and administration profile relative to infusion site reaction and infusion time of other agents targeting CD38. End of 2017, MorphoSys entered into an exclusive regional licensing agreement with I-Mab Biopharma to develop and commercialize MOR202 in Greater China.

 

Mode of action

CD38 is one of the most strongly and uniformly expressed antigens on the surface of malignant plasma cells, and is an established diagnostic marker for multiple myeloma. Key activities of MOR202 are antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) mediated killing of cancer cells. The antibody does not involve complement dependent cytotoxicity, or CDC, an additional immune mechanism involved in tumor cell killing. In addition, pre-clinical data point to a low NK-cell depletion.

 

The figure depicts the suggested mechanism of action of MOR202

The therapeutic field: Multiple Myeloma and potential other indications

Multiple myeloma causes cancer cells to accumulate in the bone marrow, where they displace and suppress healthy blood progenitor cell populations. Multiple myeloma is also characterized by destructive lytic bone lesions (rounded, punched-out areas of bone), diffuse osteoporosis, bone pain, and the production of abnormal proteins, which accumulate in the urine. Anemia is also present in most multiple myeloma patients at the time of diagnosis and during follow-up. Anemia in multiple myeloma is multifactorial, and is secondary to bone marrow replacement by malignant plasma cells, chronic inflammation, relative erythropoietin deficiency, and vitamin deficiency.

There is currently no standard multiple myeloma treatment. A patient’s individual treatment plan is based on such factors as age and general health, results of laboratory and cytogenetic (genomic) tests, symptoms and disease complications, prior myeloma treatment, patient’s lifestyle, goals, views on quality of life, and personal preferences. In addition, many cancer centers have developed their own guidelines for treating myeloma.

The introduction of CD38 monoclonal antibodies to the treatment landscape of multiple myeloma, highlighted by the approval of daratumumab, might be transformative. Based on their distinct mechanisms of action, generally favorable toxicity profile, and single agent activity, CD38 antibodies are considered attractive partners in combination regimens.
Beyond multiple myeloma, scientific research suggests that an anti-CD38 antibody such as potentially MOR202 may have therapeutic activity in other indications, among those certain autoimmune diseases.

 

Phase 1/2a dose escalation study in relapsed/refractory multiple myeloma (MorphoSys)

MOR202 is currently under clinical investigation in a phase 1/2a, open-label, multi-center, dose-escalation study conducted in several sites in Germany and Austria. The study is evaluating the safety and preliminary efficacy of MOR202 alone and in combination with the immunomodulatory drugs pomalidomide (Pom) and lenalidomide (Len) plus dexamethasone (Dex) in patients with relapsed/refractory multiple myeloma. The primary endpoints of the trial are the safety, tolerability and recommended dose of MOR202 alone and in combination with the IMiDs. Secondary outcome measures are pharmacokinetics and preliminary efficacy based on overall response rate, duration of response, time-to-progression, and progression-free survival.

Phase 2 study to evaluate the efficacy and safety of MOR202/TJ202 combined with dexamethasone in relapsed/refractory multiple myeloma (I-Mab)

The multi-center, single-arm phase 2 study to evaluate the efficacy and safety of MOR202/TJ202 combined with dexamethasone in patients with relapsed or refractory multiple myeloma is conducted by I-Mab Biopharma. The trial will enroll patients in mainland China and Taiwan who received at least 2 prior lines of treatment of which one treatment must include a proteasome inhibitor (PI) and an immunomodulator (IMiD). All patients will receive MOR202/TJ202 and dexamethasone (Dex) in the study. The primary endpoint of the study is overall response rate, secondary outcome measures are amongst others duration of response, time-to-progression, and progression-free survival. The treatment will continue until endpoint events such as intolerance or progressive disease. The study has been designed as a pivotal trial, which, if successful, could lead to a biologics license application (BLA) in Greater China.

Phase 3 study to evaluate the efficacy and safety of MOR202/TJ202 combined with lenalidomide in relapsed/refractory multiple myeloma (I-Mab) 

The randomized, open-label, parallel-controlled, multicenter phase 3 study will be conducted by I-Mab in mainland China and Taiwan to evaluate the efficacy and safety of the combination of MOR202/TJ202 plus lenalidomide (LEN) and dexamethasone (DEX) versus the combination of LEN and DEX in patients with relapsed or refractory multiple myeloma who received at least one prior line of treatment. The primary endpoint is to evaluate the progression-free survival (PFS) comparing the efficacy of MOR202/TJ202 plus LEN/DEX versus LEN/DEX. The study has been designed as a pivotal trial, which, if successful, could lead to a biologics license application (BLA) in Greater China.

 

Partnering

In November 2017, MorphoSys and I-Mab entered into an exclusive regional licensing agreement to develop and commercialize MOR202 in Greater China (China, Taiwan, Hong Kong and Macao). I-Mab Biopharma has assumed exclusive responsibility for all subsequent development and commercialization of MOR202 in the agreed territory. I-Mab Biopharma started the pivotal clinical development of MOR202 in patients with multiple myeloma in China in the first quarter of 2019.