MOR106

a new antibody in development
for atopic dermatitis

MOR208

an investigational antibody
for blood cancer

Anetumab
ravtansine

A drug candidate for mesothelioma

Guselkumab

An antibody developed by
Janssen Research & Development, LLC
based on MorphoSys’s HuCAL
antibody library

Annual Report 2016

Engineering the Medicines
of Tomorrow

MOR106
MOR208
ANETUMAB RAVTANSINE
GUSELKUMAB

Phase 2

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The compound:
MOR208 – an investigational potency-enhanced antibody targeting CD19

MOR208 (previously Xmab®5574) is an investigational Fc-enhanced antibody targeting CD19 that is currently in clinical development for the treatment of patients with blood cancer.

MOR208 binds to CD19. This antigen is broadly and homogeneously expressed across different B cell-derived blood cancers including diffuse large B cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). According to preclinical findings, 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.

The constant Fc region of the antibody has been engineered to enhance the response of the body’s immune system against cancer cells. This Fc-enhancement of MOR208 has been shown to lead to a substantial potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

MorphoSys is currently investigating MOR208 in a number of phase 2 studies in combination with other cancer drugs in the blood cancer indications of DLBCL and CLL/SLL. In 2017, MorphoSys intends to transition one of these trials into a phase 3 trial. This study, which is evaluating MOR208 plus the chemotherapeutic agent bendamustine in comparison to the CD20 antibody rituximab plus bendamustine, could become the first compound from MorphoSys’s proprietary antibody pipeline to progress to a pivotal trial.

  1. Mode of action MOR208
  1. MACROPHAGE NATURAL KILLER CELL ENGINEERED FC-PORTION MOR208 CD19 TUMOR CELL ADCP ADCC DIRECT CYTOTOXICITY
    Like a key fitting into the right lock, the Fc-enhanced antibody MOR208 specifically binds to the CD19 molecule on the surface of blood cancer cells. The binding of the antibody leads to a labeling of the cancer cells. This attracts the immune system’s natural killer cells, and/or macrophages, which attach themselves to the cancer cells via the antibody and kill them. In scientific terms these processes are called antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP). Due to the Fc-enhancement of the antibody’s constant Fc region, a significant potentiation of the body’s immune reaction to the cancer cells is intended to be achieved. In addition, the binding of MOR208 to CD19 may lead to the direct killing of the tumor cells (direct cytotoxicity).

The therapeutic field: Targeting B cell malignancies

MOR208 is currently in clinical development in various B cell-derived blood cancers.

These diseases malignantly affect B lymphocytes (or B cells) from 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. As a consequence of B cells turning malignant, the healthy and functional white blood cells are displaced and/or no longer function properly leading to a heavily weakened immune system.

MorphoSys is currently investigating MOR208 in two types of B-cell malignancies:

Diffuse large B cell lymphoma (DLBCL). DLBCL is the most common type of non-Hodgkin’s lymphoma in adults, comprising about 30% of all 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. There is a high unmet medical need for novel treatments for these patients, especially for those who relapse or are refractory to current treatment options.

Chronic lymphocytic leukemia (CLL). CLL is the most common form of leukemia in adults. In CLL, B cells become malignant and multiply uncontrollably 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 BTK inhibitors. However, for those patients who do not respond or no longer respond to this treatment, options are limited. This results in a high medical need for this patient group after discontinuation of a prior BTK inhibitor therapy.

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Interview

Dr. Gudrun Gatz-MackMorphoSys AG

Dr. Gatz-Mack, in 2016 you started a phase 2 program with MOR208 in various blood cancer indications. What are you investigating?
We investigate MOR208 in combination with other cancer agents in B cell malignancies. The general idea is to attack tumor cells from multiple sides to significantly increase the therapeutic benefit we can achieve. We are currently developing MOR208 in three combination studies in two indications. In the L-MIND trial we test MOR208 in combination with the immunomodulatory agent lenalidomide in patients with relapsed/refractory DLBCL. In the B-MIND study, we compare MOR208 together with the chemotherapy bendamustine with rituximab plus bendamustine in relapsed/refractory DLBCL. Finally, in our third trial, named COSMOS, we study MOR208 in combination with idelalisib in patients with CLL or SLL after discontinuation of a BTK inhibitor therapy. We are currently evaluating options to add another combination arm to this trial.
Why have you chosen those indications?
In the patient populations we are focusing on, we see a high unmet medical need. There are currently only a few therapies available for patients suffering from relapsed and refractory DLBCL. In CLL, patients who discontinue BTK inhibitor therapy have limited treatment options. CD19 is clearly implicated in DLBCL and CLL and MOR208 has already shown great promise in these indications.
You announced plans to start the first pivotal study with MOR208 in 2017. What will be the rationale of this trial?
You’re referring to our B-MIND trial in DLBCL. This would be the first pivotal study with a candidate from our proprietary pipeline – and certainly a major milestone for MorphoSys. In this study we enroll patients with DLBCL who relapsed or are refractory to at least one prior therapy comprising a chemotherapy regimen combined with rituximab. Our goal is to investigate whether the combination of MOR208/bendamustine is superior to the rituximab/bendamustine combination. If we can prove this, it could ultimately lead to a regulatory filing and eventual approval of MOR208.
Are you on track with your plans? Where do you stand now?
We are well on track here. We are currently testing the safety of the MOR208/bendamustine combination in the phase 2 part of the trial. If that is successful, we will kick off phase 3 in 2017. This is a big project for MorphoSys: Altogether we are planning to enroll about 330 patients in the trial in up to 180 different sites in North America, Europe and Asia-Pacific.

as of March 2017

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