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Rounding the oncology bases
SAN DIEGO—Crown Bioscience, a global drug discovery and development services company providing translational platforms to advance oncology, inflammation, cardiovascular and metabolic disease research, has announced several oncology deals and breakthroughs this spring, beginning with a new humanized drug target model. CrownBio also announced a new strategic partnership with Phanes Therapeutics, and presented posters at AACR 2018 which describe innovations in CrownBio’s Internal R&D focusing on preclinical oncology research.
In April, CrownBio enhanced its existing portfolio of humanized drug target models (HuGEMM) by launching a new transgenic CD3E model to advance development of immuno-oncology (IO) drugs. Novel therapeutic T cell redirecting antibodies, including bispecific T cell engagers, show great promise in effectively treating cancer. However, development of these drugs is hampered by a lack of in-vivo models that can accurately recapitulate human specific responses. CrownBio says it is addressing this need with its new CD3E transgenic model, which was validated in collaboration with and developed by NBRI of Nanjing University in China. NBRI is a leading company that provides high-quality human disease related animal models for the biomedical community, as well as pharmaceutical companies.
The CD3E model expresses the human form of CD3E and is phenotypically normal, with levels of T, B and NK cells comparable to control. These features are said to make it an ideal model for determining the efficacy of CD3-targeted T cell redirecting therapies through direct assessment of T cell activation, antigen recognition and related intracellular signal transduction pathways.
According to CrownBio’s website, “The HuGEMM CD3E mouse is a transgenic model where the CD3E chain of the CD3 co-receptor has been humanized for a more translational immune response. The CD3E model was developed via insertion of an engineered BAC chromosome in a BALB/c background to express the human CD3ε gene, which allows the CD3E chain to be recognized by human-specific immunotherapies. This enables the testing of therapeutic efficacy directly in the mouse model. CD3E is one of four subunits of the CD3 co-receptor, which plays an important role in the immune response, associating with the T cell receptor (TCR) to couple antigen recognition to intracellular signal transduction, leading to T cell activation.”
The CD3E model, the website notes, “enables the in-vivo evaluation of CD3E targeted, human-specific T cell engagers; provides an efficient model to study a range of human origin bispecific antibodies; transgene expression does not affect normal T cell development, unlike other previously developed models; [and] displays strong T cell activation post anti-CD3E stimulation, with consistent IL-2 and IFNγ secretion.”
“Data generated from our new CD3E models demonstrate their unique ability to guide development of bispecific T cell engagers and other T cell redirecting therapies,” explained Dr. Davy Ouyang, director of translational oncology at CrownBio. “We are very excited about the potential these innovative models have to uncover new insights in the discovery and development of cutting-edge IO agents.”
In addition, CrownBio announced in March that it had been selected by Phanes Therapeutics as a strategic partner to advance their oncology drug discovery pipeline. Phanes Therapeutics is a biotech company with drug discovery and development programs in metabolic complications and oncology areas; it focuses exclusively on biologics drug discovery with multiple first-in-class and best-in-class molecules in its pipeline.
“We are very pleased that Phanes Therapeutics has selected us as a trusted partner to advance their leading-edge oncology compounds,” said Laurie Heilmann, CrownBio’s chief business officer. “Our unique capabilities will help Phanes efficiently and thoroughly assess drugs in their pipeline to identify and advance candidates showing the most promise for improved treatment of cancer.”
CrownBio provides the world’s largest collection of patient-derived xenograft (PDX) models and is a leading provider of integrated oncology solutions that enable development of cutting-edge cancer treatments. Phanes Therapeutics will gain access to CrownBio’s clinically relevant cell line-derived xenograft models, exclusive PDX models and robust in-vitro assays to propel their innovative drug discovery pipeline.
Dr. Ming Wang, president and CEO of Phanes Therapeutics, expressed enthusiasm about this partnership. “We are an innovative drug discovery company with a robust pipeline and need access to top-notch in-vivo pharmacology efficacy models to quickly evaluate and advance our lead molecules. We are very glad to partner with CrownBio. They have very unique MuPrime models, as well as humanized GEMMs and patient-derived xenograft models for our oncology programs. We look forward to a productive partnership.”
And in a final bit of CrownBio news, the company in May presented more than a dozen posters at the American Association of Cancer Research’s 2018 meeting. A library of narrated posters is now available to watch and download at https://www.crownbio.com/posters. These scientific posters describe innovations in CrownBio’s internal R&D focusing on preclinical oncology research.
“CrownBio is providing unfettered access to CrownBio’s innovative research with scientific colleagues worldwide,” opined Dr. Henry Li, CrownBio’s vice president of translational oncology. “We are committed to sharing with scientists globally the cutting-edge tools that are available to accelerate, inform and enlighten contemporary evaluation of cancer therapies and immunotherapies.”
The most compelling work is now available on-demand and narrated by CrownBio scientists, according to the company. The library of poster presentations includes details on the development and application of several innovative humanized models, a new large-scale ex-vivo PDX drug screening service and a novel IDO1 inhibition assay platform. Collectively, the data are said to demonstrate CrownBio’s unique capacity to enhance knowledge, guide development decisions and advance immunotherapy programs.
“Crown Bioscience is committed to making valuable contributions to the scientific community,” said Dr. Jean Pierre Wery, Crown Bioscience’s CEO. “By providing these posters, narrated by the experts behind the science, we hope to deliver insights researchers can use to advance their preclinical drug development programs.”