In Oncology, many new developments of the last decade have made it possible to treat cancers in ways that are better-targeted, more potent, and less harmful than traditional chemotherapies.

One way this has been done is by utilizing the body’s own immune system to help fight cancer, called immuno-oncology. This research area uses several methods to treat cancer, including the use of bispecific antibodies, which can target both cancer cells and the body’s immune system cells, in order to “train” the immune cells to recognize and attack the cancer.

Recently, Merus Therapuetics, a clinical stage immune-oncology company, has submitted an Investigational New Drug Indication or IND application for MCLA-117, a bispecific antibody therapeutic called a Biclonic®, for the treatment of acute myleloid leukemia (AML). Additionally, Merus has received approval of a clinical trial application in Belgium for the Biclonic® MCLA-158, for its potential use in metastatic colorectal cancer. [1]

Biclonics® are bispecific, full length monoclonal antibodies that are generated in hopes of producing better tumor killing activity than conventional monoclonal antibodies have been able to do.

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Image 1.0  Biclonics MOA diagram (accessed from January 6, 2017.)  Courtesy: © 2018 Merus BV. The Netherlands. Used with permission.

Biclonics are based on the IgG format, but with a modified CH3 region of the IgG antibody isotype, which drives heterodimerisation and production of the Biclonics by eukaryotic cells. This allows Bioclonics to be able to have the predictable in vivo behavior associated with conventional antibodies, as well as a long half-life and immunogenicity. [2]

The Biclonics technology platform allows scientists to  functionally evaluated a (novel) drug) in the relevant therapeutic format, in order to discover therapeutic candidates with differentiated properties.

MCLA-177 and MCLA-158
MCLA-117, a T-Cell Engager Biclonic developed for patients with Acute Myeloid Leukemia, has been submitted for an IND to the U.S. Federal Drug Association (FDA). AML is, when refractory, very difficult to treat, and an estimated 10,670 deaths from AML will occur in the United States this year.

MCLA-117 binds to both CD3, a cell surface molecule present on T-Cell, as well as CLEC12A, which is a cell surface molecule present on AML cells and stem cells. By targeting molecules present on tumor cells, the drug is able to minimize damage to normal tissue, and by targeting T-Cells, it is able to activating the the body’s own immune system to target and kill tumor cells. [3]

This drug is currently being studies in an ongoing phase I first-in-human, dose escalation clinical trial. It is currently being studied in Europe for patients with relapsed or refractory AML, and Merus plans to start trials in the US upon acceptance of the IND by the U.S. FDA.

Additionally, MCLA-158, an ADCC-enhanced Biclonic, was approved for trial in Belgium, one of the several European countries where Merus has filed a Clinical Trial Application (CTA). MCLA-158 binds to cancer stem cells that espress l eucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and epidermal growth factor receptors (EGFR). The trial will focus initially on patinets with metastatic colorectal cancer, and is expected to start in the first quarter of 2018.

“The filing of an IND for MCLA-117 and the first CTA approval for MCLA-158 represent key steps forward for both programs as we continue to progress our robust pipeline of proprietary bispecific antibodies in the clinic with the goal of addressing significant unmet medical needs,” stated Ton Logtenberg, Ph.D., Chief Executive Officer of Merus.

Earlier this week, Merus announced that the company will grant Simere Pharmacuetical Group an exclusive license to use their immune-oncology technology to develop and commercialize three bispecific antibodies in China.

Based on this collaboration, Merus will lead research and development, while Simcere will be responsible for several other components, such as clinical development, regulatory filings, commercialization, and importantly, including IND enabling studies and the manufacturing of clinical materials in China, which Merus intends to use in order to assist their regulatory filing and early stage clinical development in the rest of the world.

“We believe this collaboration leverages Merus’ unique platform and Biclonics® suite of technologies with Simcere’s drug development experience and strong commercial presence in China,” stated Ton Logtenberg, “There is a clear strategic fit between the two companies and we believe that by combining our collective expertise and resources, we will be able to develop innovative therapeutics in the China market and globally.”

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