ANTIBODY BIOTHERAPEUTICS

For the next several decades, antibodies are poised to remain the most attractive modality for the development of high value-added therapeutics. According to IMS Midas, biologics drug sales should exceed US$250Bn in 2020 and comprise 20% of total sales of pharmaceutical products. Therapeutic antibodies will represent the majority of these sales, including engineered antibodies, and fusion proteins. Within the next decade, three main platforms will dominate antibody R&D:

Bispecific antibodies (hyperlink to Biomunex platform)

  • Antibody drug conjugates
  • Fc engineered mAb

Cancer and Bispecific Antibody Therapies

Cancer is a complex disease that is usually associated with multiple redundant ligand-receptor interactions, which signal through different, often overlapping, cellular pathways. It has been demonstrated that cancer therapy with mAbs solely targeting a single antigen has limitations. Blockade of multiple targets, or different epitopes on a single target, should result in improved therapeutic efficacy. However combination therapy requires substantial investment of resources for manufacturing, clinical studies, and regulatory review.

The main alternative to combination therapy, dual targeting with bispecific antibodies, has recently emerged in oncology and has proven to be synergistic. This synergistic activity, deriving from targeting two antigens with a bispecific antibody, should lead to higher efficacy, broader therapeutic window, and thus safety, and may result in advantageous new biological effects unattainable by monospecific targeting.

The discovery that immune system can potently destroy cancer cells, if inhibitory signals from cancer cells are blocked, revolutionized the treatment of cancer. Currently 6 different “checkpoint” inhibitors are approved for the treatment of various cancer diseases such as melanoma, lung, kidney, bladder, head-and-neck cancers, as well as Hodgkin Lymphoma. All these antibodies target specific signaling pathways that tumors exploit preventing immune system to kill cancer cells. Such approaches dramatically changed the course of many cancers and achieved cures of some previously incurable diseases while extending lives of other patients.
Biomunex is capitalizing on all these novel advancements in the treatment of cancer and is building a portfolio of innovative therapeutics combining the power of checkpoint inhibitor mechanism of action with the power of bispecific antibodies.

Biomunex Platform

The BIOMUNEX platform possesses numerous advantages over most competitors’ formats, and BIOMUNEX continues to further advance this innovative platform. One of the key advantages of the unique BIOMUNEX bispecific antibody format is its modularity: it enables the incorporation of existing antibodies in a Plug-and-Play fashion, without a lengthy and costly antibody engineering process.

The BIOMUNEX bispecific antibodies possess excellent manufacturability: they express similarly to other clinically validated mAbs in the industry-favored CHO expression system and are efficiently purified using standard techniques. Importantly, these antibodies do not have propensity to form aggregates or display any degraded species in the course of biomanufacturing.

The BIOMUNEX bispecific antibodies demonstrate a similar to parental monospecific antibodies stability profile, re-affirming that our antibody format produces optimal molecules and does not in the degradation of the good drug-like properties of parental antibodies.

The BIOMUNEX bispecific antibodies display excellent biding characteristics towards both of its antigenic targets, with binding affinities similar to its parental monospecific mAbs; these antibodies efficiently bind soluble and cell-membrane attached targets.

The BIOMUNEX bispecific antibodies are tetravalent, and thus maintain the symmetry and bivalency of natural mAbs for each target; such bispecific antibodies possess avidity and therefore exhibit high affinity to both targets. Depending on the requirements of a specific application, the BIOMUNEX bispecific antibody can be produced with or without the Fc domain;

  • the Fc-containing antibodies possess long half-life typical of mAbs and display all effector functions, which may be selectively enhanced or eliminated based on the requirements of the specific application.
  • the antibodies lacking the Fc-domain are beneficial for applications in which mono-valent targeting, smaller size, and short half life are beneficial.

The BIOMUNEX bispecific antibodies are amenable to all standard mAb derivatizations.

Pipeline

BIOMUNEX is developing a pipeline of innovative bispecific antibodies for oncology by applying the unique BIOMUNEX bispecific antibody platform to a broad range of clinically validated therapeutic targets. The lead program of this group of immunotherapeutics is BMX-002.

BMX-002.

This experimental therapeutic is targeting 2 receptors of the EGFR family of onco-genes, namely EGFR and HER2. Both of these receptors are validated cancer targets through the decades of use of their inhibitors in the clinical practice There are several clinically approved tyrosine kinase inhibitors and monoclonal antibodies that target these receptors for the treatment of colon, breast, head-and-neck, gastric, pancreatic and other cancers. HERE YOU CAN ADD BACKGROUND INFO ON THE CANCERS THAT YOU WANT TO SPECIFICALLY PROFILE, E.G.PANCREATIC, HNSCC, GASTRIC ETC.

However, many patients do not respond to theses treatments and those that do frequently exhibit fast relapse. Therefore, additional treatments are urgently needed. By targeting both of these receptors simultaneously, BMX-002 will block most of signaling pathways associated with proliferation of cancer cells and may facilitate substantially stronger clinical responses and prevent the relapse. In addition, BMX-002 will recruit immune cells to directly kill cancer cells and will increase the potency of such a therapeutic. We have already demonstrated excellent killing properties of this experimental therapeutic in vitro and in vivo. In the mouse model of pancreatic cancer BMX-002 was significantly more potent and efficacious dramatically extending lives of animals compared to those that received the combination of two monospecific antibodies approved for clinical use that separately target either EGFR or HER2. We have also demonstrated that the growth of tumors in animals receiving BMX-002 was completely abrogated during the period of time the animals received that therapy, whereas the tumors continued to grow under treatment in animals that received that combination of 2 monospecific antibodies. This demonstrates remarkable potential of BMX-002 for treating of various cancers and we are rapidly moving this program forward to initiate human clinical trials.

Biomunex is also developing bispecific antibodies for immunooncology by targeting clinically validated pairs of immune checkpoint inhibitors and tumor associated antigens, which will enable novel mechanisms of action. The lead program of this group of immunotherapeutics is BMX-101.

BMX-001.

This program is being developed for the treatment of Multiple Myeloma (MM). MM is the second most common blood cancer after non-Hodgkin lymphoma. The American Cancer Society’s estimates that in 2017 in the United States about 30,280 new cases will be diagnosed and about 12,590 deaths are expected to occur. According to Cancer UK since the early 1990s MM incidence rates increased 29%.

MM is a cancer of plasma cells in the bone marrow. The mechanisms of MM causation are not only limited to genetic mutations in the plasma cells but also include alterations in the bone marrow (BM) microenvironment and loss of immune surveillance. Thus, it is is associated with severe dysregulation of immune cells and the resultant immune deficiency. Despite advances in treatment options, including autologous stem cell transplantation (ASCT), MM remains an incurable malignancy since relapse is inevitable in MM patients. The median age at diagnosis is 70 years old and patients have a median 5-year survival rate of 49%. In spite of formidable progress in treatment options, including proteasome inhibitors, such as bortesomib and carfilzomib, immunomodulatory drugs, such as lenalidomide and pomalidomide, ASCT for younger patients under 65 years old, and monoclonal antibodies, MM remains one of the few hematological malignancies with an unmet medical need.

Biomunex is developing a bispecific antibody, which is targeting a Tumor Associated Antigen (TAA) and an Immune Checkpoint Inhibitor (ICI) pathway, BMX-101 as a novel immunotherapeutic treatment for relapsed and refractory MM. This therapeutic was designed to possess multiple mechanisms of action:

  • Local inhibition for enhanced tumor cell killing. BMX-101 mediates local inhibition of an ICI pathway via a TAA targeting of MM inhibitory tumor microenvironment in order to facilitate enhanced tumor cell killing. A combination of monospecific antibodies is incapable of facilitating such a MOA since bispecific targeting by the anti-TAA moiety of BMX-101 is required for the tumor-specific ICI pathway inhibition.
  • Reversal of disease-mediated “immune paralysis” via immune modulatory activities of anti-ICI and anti-TAA. BMX-101 is designed to reverse disease mediated “immune paralysis” via targeting of MM inhibitory microenvironment cells and thus enhance direct targeting of tumor cells by de-repressed immune cells. This is a synergistic effect resulting from the combination of the immune modulatory activities of the anti-ICI and anti-TAA moieties of BMX-101.

We designed BMX-101 to greatly enhance the MOA described above by the employ of a bispecific BMX-101 since a combination of monospecific mAbs targeting this TAA and the ICI are incapable of facilitating such a MOA. Thus, we anticipate that BMX-101 will greatly increase treatment efficacy in relapsed/refractor MM patients and will enhance treatment safety and the Quality of Life of patients.

BIOMUNEX is also evaluating additional novel pairs of antigen targets, identified by BIOMUNEX and its academic partners, for the development of oncology bispecific antibody therapeutics employing the BIOMUNEX bispecific antibody platform.

BIOMUNEX is exploring the expansion of the platform to development of a robust trispecific antibody technology. Using such technologies Biomunex plans to develop molecules with much increased potency and decreased side effects, i.e. immunotherapeutics that possess a substantially broader Therapeutic Index (TI). Since BiXAbs possess four binding domains we are advancing the BiXAb technology to efficiently bind 3 targets simultaneously. Initial work is aimed at targeting two ICI pathways in a tumor-targeted fashion, by adding the TAA-binding properties to such a BiXAb. Another expansion of trispecific technology is into the areas of highly potent immune cells retargeting, e.g. T cell retargeting. This MOA has previously been demonstrated to be extremely potent and efficacious in killing of cancer cells but due to a low therapeutic window this promising MOA could be applied only to a very limited number of TAA. In order to expand this approach to the treatment of diverse cancers that are targeted by redirected T cells, we are developing BiXAb molecules containing the anti-CD3 moiety that also simultaneously targets two TAAs, allowing for greater selectivity/targeting of cancer cells; simultaneously such a BiXAb will spare healthy tissues expressing only one or the two TAAs. Such approach is expected to substantially broaden the TI.

Intellectual Property

BIOMUNEX bispecific antibody platform is based on the granted license from European academic partners.

BIOMUNEX is actively developing new patentable intellectual property from its own R&D efforts and in collaboration with academic groups and industrial partners.

BIOMUNEX has filed two patent applications on the BiXAb® technology optimization.

BIOMUNEX has also filed two patent applications for lead products (BMX-002 and BMX-101).

Partnering

BIOMUNEX is actively seeking partnerships and collaborations with pharma and biotech companies that are interested in either licensing its unique and innovative technology to create unique BiXAb antibodies that target antigens of interest for industrial partners or licensing innovative molecules that currently being developed by BIOMUNEX.