Bispecific Cancer Antibody Pipeline Optimized by GlymaxX® Manufacturing Technology
Berlin, Germany and Utrecht, The Netherlands, June 1, 2016 / B3C newswire / -- ProBioGen AG and Merus N.V. today jointly announced that Merus has signed a commercial multi-product license agreement for ProBioGen's GlymaxX® ADCC (Antibody-Dependent Cell-Mediated Cytotoxicity) enhancement technology. Under the terms of the agreement, Merus has obtained non-exclusive use of GlymaxX® technology for Merus' Biclonics® pipeline of bispecific cancer antibodies to enhance their ADCC activity. Financial details of the license agreement were not disclosed.
MCLA-158 is the first GlymaxX®-modified ADCC-enhanced bispecific antibody being developed under this commercial license. MCLA-158 is being developed as a potential treatment for colorectal cancer and other types of solid tumors. The compound is designed to bind to cancer stem cells that express EGFRs (epidermal growth factor receptors) and Lgr5 (leucine-rich repeat-containing G protein-coupled receptor 5).
Merus had previously utilized the GlymaxX® Technology for its lead candidate, MCLA-128, which is designed to bind to HER2 and HER3-expressing solid tumors. Merus reported interim clinical data from an ongoing phase 1/2 clinical trial for MCLA-128 in April 2016. These data included a favorable safety profile and early signs of anti-tumor activity in patients with advanced solid tumors.
"We are pleased that Merus is again collaborating with ProBioGen for development of their promising antibody cancer therapy, MCLA-158," said Dr. Wieland Wolf, CEO of ProBioGen. "Merus' Biclonics® platform represents an encouraging approach to the killing of cancer cells, and we believe that Biclonics® utilizing our enhanced ADCC technology hold great promise in potentially transforming the cancer treatment paradigm."
"ProBioGen's GlymaxX® technology is proven to increase an antibody's ability to bind to cellular targets, resulting in greater cell-killing proficiency," said Ton Logtenberg, PhD, Chief Executive Officer of Merus. "We are eager to advance development of MCLA-158 utilizing this exciting technology, and we plan to file an IND with the FDA by the end of next year. At the same time, we are continuing to advance our other GlymaxX®-enabled candidate, MCLA-128 for HER-expressing solid tumors, and we expect to report topline results from our ongoing Phase 1/2 trial in the second half of 2017."
ProBioGen's GlymaxX® technology is based on the heterologous, cytosolic expression of a bacterial enzyme that redirects the de-novo fucose synthesis pathway towards a sugar-nucleotide that cannot be metabolized by the cell. The enzyme mediates the secretion of antibodies with minimized fucose content. The resulting modification of the glycostructure of IgG1 antibodies enhances their binding to natural killer, or NK, cells and thus the ADCC response in potency assays. Consequently, the potency of the modified antibodies, directed against tumor or infected cells, is substantially increased.
ADCC (Antibody-Dependent Cell-Mediated Cytotoxicity) activity is an important antibody function, leading to the selective killing of target cells, i.e. cancerous cells or pathogen-infected cells. Several therapeutic antibody drugs on the market rely on ADCC as a mechanism of action. ADCC enhancement has the potential to increase the therapeutic effect and/or to greatly reduce antibody dosage requirements, resulting in fewer side-effects and treatment costs.
About GlymaxX® The GlymaxX® technology, developed by ProBioGen, prevents the synthesis of the sugar "fucose" and hence, in antibody-producing cells, its addition to the N-linked carbohydrate part of the antibody. The absence of fucose is known to greatly enhance ADCC. The GlymaxX® technology is based on the stable introduction of a gene for an enzyme which literally eliminates the producer cells' fucose biosynthesis pathway. As a unique feature, differentiating it from other approaches, GlymaxX® can be applied to both novel and already existing antibody producer cell lines and entire antibody expression and discovery platforms, without negatively affecting their productivity or product characteristics. Moreover, it is simple, rapid, potent, and universally applicable to different Chinese hamster ovary, or CHO, hosts and all other eukaryotic cell species. GlymaxX® can be rapidly applied in a few weeks to any existing antibody producer cell line, can be used in the context of ProBioGen's pre-engineered GlymaxX® host cells, or can be introduced into entire animal cell expression platforms by modifying the host cell line. ProBioGen offers its GlymaxX® technology royalty-free as a service or as an individual license.
About ProBioGen AGProBioGen is a specialist for the development and manufacturing of complex therapeutic glyco-proteins. Combining both state-of-the-art development platforms together with intelligent product-specific technologies yields biologics with optimized properties.
Rapid and integrated cell line and process development, comprehensive analytical development and following reliable GMP manufacturing is performed by a highly skilled and experienced team. All services and technologies are embedded in a total quality management system to assure compliance with international ISO and GMP standards (EMA/FDA).
ProBioGen is operational since more than 20 years and is located in Berlin, Germany.
About Merus N.V.Merus is a fully-integrated biotechnology company developing cancer therapeutics that combine the benefits of monoclonal antibodies with the ability to simultaneously bind to multiple targets. Merus has two lead programs in development: MCLA-128 for the treatment of solid tumors and MCLA-117 for the treatment of acute myeloid leukemia. Merus is also developing a broad pipeline of preclinical programs. Merus' technologies encompass the proprietary MeMo® transgenic mouse for the production of common light-chain human antibodies and the CH3 heterodimerization technology for the production of full-length IgG Biclonics®. These Biclonics® are robustly produced from a single clonal manufacturing cell line, using industry-standard systems. Merus' Biclonics® are designed to bind to multiple disease-associated targets, thereby eliminating tumor cells more efficiently and preventing tumor cells from escaping treatment. In Merus' Biclonics®-ENGAGE approach used in the MCLA-117 program, bispecific antibodies are used to induce the cytotoxic activity of T-cells to kill cancer cells.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the impact our Biclonics® platform can have on cancer, MCLA-158's potential to treat colorectal cancer and other types of solid tumors, the potential benefits ProBioGen's GlymaxX® technology may have on our Biclonics® pipeline, the timing of FDA filings and the timing and anticipated results from our clinical trials.
These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have incurred significant losses, are not currently profitable and may never become profitable; our need for additional funding, which may not be available and which may require us to restrict out operations or require us to relinquish rights to our technologies or bispecific antibody candidates; potential delays in regulatory approval, which would impact the ability to commercialize our product candidates and affect our ability to generate revenue; the unproven approach to therapeutic intervention of our Biclonics® technology; potential difficulties in validating and developing companion diagnostics, which could harm our development strategy; our limited operating history; economic, political, regulatory and other risks involved with international operations; exchange rate fluctuations or abandonment of the euro currency; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential adverse public reaction to the use of cancer immunotherapies; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; our potential exposure to costly and damaging liability claims; post-marketing restrictions or withdrawal from the market; failure to obtain marketing approval internationally; compliance with environmental, health, and safety laws and regulations; anti-kickback, fraud, abuse, and other healthcare laws and regulations exposing us to potential criminal sanctions; recently enacted or future legislation; failure to compete successfully against other drug companies; potential competition from other drug companies if we fail to obtain orphan drug designation or maintain orphan drug exclusivity for our products; the possibility that governmental authorities and health insurers may not establish adequate reimbursement levels and pricing policies to support our products; the potential failure of our product candidates to be accepted on the market by the medical community; our lack of experience selling, marketing and distributing products and our lack of internal capability to do so; potential competition from biosimilars; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents being found invalid or unenforceable; potential lawsuits for infringement of third-party intellectual property; adequate protection of our trademarks; our potential failure to obtain extensions of the terms of patents covering our products; potential difficulties protecting our intellectual property rights in certain jurisdictions; changes in United States patent law; protection of the confidentiality of our trade secrets; claims asserting that we or our employees misappropriated a third-party's intellectual property or otherwise claiming ownership of what we regard as our intellectual property; compliance with patent regulations; potential system failures; our ability to attract and retain key personnel; managing our growth could result in difficulties; the price of our common stock may fluctuate substantially; certain of our shareholders and members of our management board own a majority of our outstanding shares and exercise significant control over us; a significant portion of our total outstanding shares are eligible to be sold into the market; provisions of our Articles of Association or Dutch corporate law might deter favorable acquisition bids for us or prevent a beneficial change of control; we may lose our foreign private issuer status and incur significant expenses as a result; and unfavorable or lacking analyst research or reports might cause the price of our common shares to decline.
These and other important factors discussed under the caption "Risk Factors" in our final prospectus filed with the Securities and Exchange Commission, or SEC, on May 20, 2016 relating to our Registration Statement on Form F-1, and our other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.
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