Project: Development of a Bispecific therapeutic antibody for the treatment of metastatic breast cancer

Breast cancer is among the most common cancers globally (1 million new cases and ~500,000 deaths / year). The prognosis for advanced breast cancer although poor has improved with the introduction of drugs, particularly antibodies (mAbs), targeting receptor tyrosine kinases – surface proteins whose overexpression is linked to the uncontrolled growth of many cancers. However, clinical experience has highlighted two key limitations: _x000D_1) Resistance - Prolonged treatment can lead to target down-regulation and up-regulation of other receptors to compensate_x000D_2) Unwanted Toxicity - serious side effects such as cardiotoxicity restrict dose and duration of treatments reducing their potential effectiveness._x000D__x000D_ReBAT brings together a consortium with expertise in the discovery and process development of antibody therapeutics that aims to validate a novel mAb therapeutic format (BiClonics™) a fully human bispecific IgG1 mAb that is capable of binding two targets simultaneously. Merus will apply its unique technologies to generate the bispecific molecule and Chromacon will apply its cutting edge process technologies to isolate the molecule at purities demanded for therapeutic application. As a direct result of this program pre-clinical candidates will be generated for further development to address key unmet needs in advanced breast cancer therapy: overcoming resistance (by blocking multiple cancer cell growth and survival pathways simultaneously) and unwanted toxicity (by better tumor to normal tissue targeting and greater selective potency). Successful implementation of this project could result in early stage licensing of products or technologies or product candidates poised to compete in billion $ markets. A further consequence of the program will be validation of the BiClonics™ platform for the generation of fully human bispecific therapeutic mAbs. These agents could be applied against other combinations of targets to address unmet needs in therapeutic areas such as oncology and chronic inflammation. Moreover new process technologies will result from this project that in addition to their direct application to the BiClonics platform could also be more broadly applied for the generation of cheaper and safer antibody therapeutics._x000D_A BiClonic™ therapeutic for breast cancer could form the basis of breakthrough treatments allowing clinicians to focus on managing cancer and it symptoms as a chronic disease rather than prolonging a terminal disease. Like the treatment revolution heralded by cytokine neutralizing antibodies, this would allow breast cancer patients to live longer and fuller lives._x000D_

Acronym	ReBAT (Reference Number: 6121)
Duration	01/10/2010 - 30/09/2013
Project Topic	Develop a fully human bispecific antibody (Biclonic™) production technology platform and apply it to generate a therapeutic candidate for breast cancer that:_x000D_ 1) limits the appearance of treatment resistant tumors_x000D_ 2) reduces treatment toxicity_x000D_ 3) is effective in a broader patient population
Project Results (after finalisation)	1. Generation and preclinical development of a human therapeutic bispecific antibody targeting HER2 and HER3 (MCLA-128)._x000D_2. Improvement of the Merus Biclonics® platform and patent filings._x000D_3. Further validation of the ChromaCon MCSGP process and publications
Network	Eurostars
Call	Eurostars Cut-Off 5

Project partner

Number	Name	Role	Country
2	ChromaCon Ltd.	Partner	Switzerland
2	MERUS BV	Coordinator	Netherlands