On January 6, 2023 2seventy bio, Inc. (Nasdaq: TSVT) reported an amendment to its collaboration with Regeneron that will facilitate an expanded and accelerated development plan for novel cell therapy-based combinations for solid tumors (Press release, 2seventy bio, JAN 6, 2023, View Source [SID1234625952]). The collaboration will leverage 2seventy bio’s unique cell therapy engineering and early-stage development capabilities, including the newly built in-house clinical cell therapy manufacturing facility, with Regeneron’s differentiated antibodies and bispecifics.

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"We’re excited to continue our collaboration with Regeneron which is now delivering several interesting CAR / TCR programs for potential clinical development. The deepened collaboration is a testament to the mutual desire to drive these programs and promising combinations forward faster and in more sophisticated ways," said Philip Gregory, D.Phil., chief scientific officer, 2seventy bio. "As an industry, we’ve experienced the challenges of developing transformative new therapies for solid tumors. Multi-layered approaches are needed to realize the potential of cell-based immunotherapy. The power of our renewed collaboration is the ability to leverage our end-to-end scientific and manufacturing cell therapy platform to test CAR-Ts, including enhanced CAR-Ts, in combination with innovative biologics in multi-arm proof of concept clinical studies. We believe this approach will be the most efficient way to accelerate the identification and development of the most transformative therapies possible."

"We look forward to building upon the strength of our existing collaboration to accelerate progress in the clinic," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron. "We have several exciting targets already identified and this opportunity to more rapidly explore 2seventy’s engineered T cell platform, in combination with our proprietary antibodies and bispecifics, will help us learn and move faster toward our goal of delivering the best possible therapeutic options for patients."

To support this expanded clinical development plan Regeneron will make a $20 million equity investment in 2seventy bio at a 50% premium and another approximately $20 million in near-term pre-clinical and clinical milestones. The parties will continue sharing costs for these activities in a manner largely consistent with the existing agreement, with Regeneron covering 75% of certain preclinical costs necessary to study combinations and 100% of the costs for the arms of clinical studies that include Regeneron agents through regulatory approval. For other programs, cost-sharing will follow the existing 50/50 cost sharing agreement.

On January 5, 2023 BroadenBio reported the first patient enrollment and dosed in the Phase 1 clinical trial of the independently developed, highly-selective small molecule inhibitor BB102 in Henan Cancer Hospital, marking the substantive progress of the clinical trial for this program (Press release, BroadenBio, JAN 5, 2023, View Source [SID1234640202]). The Phase 1 clinical trial of BB102 is led by renowned medical expert Professor Luo Suxia as the principal investigator.

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The Phase 1 clinical trial will assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of the oral small molecule Fibroblast Growth Factor Receptor 4 (FGFR4) BB102 in adults with advanced solid tumors. Currently, no drug with the same target has been approved for marketing globally.

BB102 is an innovative, highly-selective, reversible covalent FGFR4 inhibitor, which has shown significant anti-tumor efficacy in a variety of mice tumor models in preclinical studies. Based on the novel mechanism and extensive translational medicine studies, BB102 will be investigated for the treatment of advanced solid tumors with FGFR4/FGF19 high expression or FGFR4 mutation. Besides, BB102 is expected to have lesser adverse effects in clinical trials, since no obvious off-target toxicity has been observed in animal studies.

"The successful administration of BB102 for the first patient is another milestone for BroadenBio. I would like to express my heartfelt thanks to the team of Professor Luo Suxia from Henan Cancer Hospital, the team of Professor Guo Yabing from Nanfang Hospital of Southern Medical University, The company’s shareholders and other people for their full support, and I am also grateful to the company’s team for their hard work," said Xingmin Zhang, M.D., Ph.D., founder and Chief Executive Officer of BroadenBio. "In the New Year, we look forward to proceeding the clinical research of BB102 efficiently with the joint efforts of everyone, accelerating the progress of the other two preclinical projects into the clinic, and benefiting more cancer patients."

On January 5, 2023 Frontier Medicines Corporation, a precision medicine company seeking to unlock the proteome to advance breakthroughs against otherwise undruggable disease-causing targets, reported the second and third programs under the company’s global partnership with AbbVie have advanced into lead generation (Press release, Frontier Medicines, JAN 5, 2023, View Source [SID1234630855]). These programs harness novel E3 Ligases for targeted protein degradation, through the discovery of small molecules from The FrontierTM Platform.

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"Our collaboration with Frontier is continuing to make progress against difficult-to-drug protein targets" said Jonathon Sedgwick, Ph.D., vice president and global head, Discovery Research, AbbVie. "Two years into our partnership, Frontier’s technology is showing important advances in the drugging of previously inaccessible biology, this time towards enabling binders for novel E3 ligases, with the potential to be applied to the discovery and development of new and better therapeutic options for patients."

Started in 2020, the objective of the global partnership is to discover, develop, and commercialize a pipeline of innovative small molecule therapeutics against certain high-interest, difficult-to-drug protein targets.

"We are excited that our team’s work, with support from AbbVie, has resulted in accessing two previously undruggable E3 Ligases for targeted protein degradation, and each program has the potential to drive new therapeutic opportunities for patients," said Chris Varma, Ph.D., Frontier’s co-founder, chairman, and CEO. "Our delivery of three programs into lead generation further validates The Frontier Platform’s ability to systematically discover and deliver small molecules to drug undruggable targets. We look forward to progressing these novel breakthrough discoveries to help advance transformative care for patients."

About Frontier and AbbVie Partnership

Under the partnership, the companies will collaborate on the research and pre-clinical development of programs directed to novel E3 ligases, and certain immunology and oncology targets. AbbVie will reimburse Frontier’s R&D costs through defined stages of pre-clinical development. Upon successful completion, AbbVie will assume full responsibility for global development and commercialization activities and costs for the programs. Frontier will retain an option to share development activities and expenses for certain oncology programs through the completion of Phase 2. Frontier will be eligible to receive success-based development and commercial milestone payments that could potentially exceed $1 billion, in addition to royalty payments on commercialized products. AbbVie retains the right to expand the collaboration in the future by exercising options to a defined number of additional targets. The collaboration excludes all of Frontier’s internal programs for which Frontier retains exclusive global rights.

On January 5, 2023 ErVaccine Technologies, a biotech company and spin-off from the Centre Léon Bérard-Centre de Recherche en Cancérologie de Lyon, which develops next-generation therapeutic vaccines and cellular immunotherapies targeting "unconventional" tumor antigens, such as those derived from human endogenous retroviruses (HERVs), reported the closing of a €4.5 million seed round, including dilutive and non-dilutive funds, with Seventure and Bpifrance as part of the Aide au Développement de l’Innovation (ADI) program (Press release, ErVaccine, JAN 5, 2023, View Source [SID1234629611]).

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These funds are dedicated to financing Ervaccine’s work with its development portfolio, which currently includes nine projects, two of which are in late pre-clinical development.

To prepare for the next stages of development, including the start of a clinical trial with a first vaccine candidate in 2023, Ervaccine is currently preparing a A-round of financing.

Nathalie Donne, CEO of Ervaccine, declares: "The work of Ervaccine’s teams, led by Prof. Stéphane Depil, and the support of our strategic investors, Seventure and Bpifrance, have enabled us to decisively advance our preclinical programs and bring us to the doorstep of the first clinical trials. Meanwhile, throughout the year, we published numerous non-clinical data of high scientific quality, confirming the immense potential of our technology. These publications have enabled us to make progress in our discussions with several international investors specialized in life sciences, with a view to our next stage of financing, as well as with potential industrial partners."

During the year 2022, Ervaccine obtained the publication of 3 major scientific articles in high impact factor journals.

The first article, published in January 2022 in the journal Science Advances and entitled "Identification of shared tumor epitopes from endogenous retroviruses inducing high avidity cytotoxic T cells for cancer immunotherapy", demonstrates the value of using antigens derived from endogenous human retroviruses (HERV) specifically overexpressed by tumor cells as therapeutic targets for developing new immunotherapies in cancer.

The second article was published in June 2022 in the European Journal of Cancer and entitled: "Tumor burden and antigen-specific T cell magnitude represent major parameters for clinical response to cancer vaccine and TCR-engineered T cell therapy". It shows the interest of TCR-T cell therapy approaches (T lymphocytes modified to express a T cell receptor specific to a tumour antigen) in cancers with a large tumour mass. This cell therapy could be combined with a vaccine approach to provide long-term tumour control, which would be a major advance in cancer treatment.

The third paper, published in June 2022 in the American Journal of Hematology and entitled "HERVs characterise normal and leukemia stem cells and represent a source of shared epitopes for cancer immunotherapy", shows that HERVs represent an important source of genetic information that can help improve cancer stratification and the identification of new targets and biomarkers.

Prof. Stéphane Depil, MD, PhD, founder and Executive Chairman of ErVaccine, declares: "Human endogenous retroviruses (HERVs) are fossils of viruses that were integrated into the genome of our ancestors millions of years ago and represent about 8% of our genetic make-up. These genes are silent in normal cells but become active when cells become tumorous. ErVaccine has demonstrated that cancer cells present antigens from HERV to the immune system and has built on this discovery to develop a unique, potentially universal therapeutic vaccine technology platform. Our most advanced preclinical assets are targeting triple-negative breast cancer as the first indication. We are also considering other low mutational burden tumours such as ovarian cancer, sarcoma, glioblastoma and acute myeloid leukemia. In these indications, current checkpoint inhibitor immunotherapies are proving to be of little or no benefit, and there remains a major unmet medical need. We are putting everything in place to enter the clinic next year."

On January 5, 2023 Crown Bioscience reported that its study aligns well with the recent Senate Bill 5002, titled FDA Modernization Act 2.0, introduced in the United States Senate, which authorizes the use of alternatives to animal testing, including cell-based assays for the purposes of drug and biological product applications (Press release, Crown Bioscience, JAN 5, 2023, View Source [SID1234627461]).

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"This invaluable publication demonstrates our ongoing commitment to develop innovative preclinical models for our customers by including the provision of robust and clinically relevant in vitro solutions as early as possible in the drug development process followed with matched translational models downstream," commented Rajendra Kumari, PhD, Executive Director of Integrated Solutions at Crown Bioscience. "Organoids maintain a high degree of clinical relevance that cannot be achieved with traditional 2D cell lines and other 3D systems. As a result, in vitro drug screening with PDXOs represents a highly physiologically relevant platform that better predicts patient response making these ideal alternatives to animal testing."

This new study reports on the largest living, commercially available PDXO biobank—with approximately 550 tumor organoid models derived from a collection of matched PDXs representing 17 different types of carcinomas. The main findings of the study include:

Crown Bioscience, a global contract research organization (CRO), and JSR Life Sciences company, announced today their newly published study in PLOS ONE, a journal of the Public Library of Science (PLOS), demonstrating the establishment and application of a highly clinically relevant 3D in vitro PDX-derived organoid (PDXO) biobank for higher-throughput screening for cancer drug discovery.

The biological equivalence and interchangeability between PDXOs and parental PDXs were confirmed based on genomics, histopathology, and pharmacology.
PDXOs in 384-well format assays are reliable, robust, and suitable for higher-throughput screening for rapid identification of drug sensitivity and drug combination strategies, including for matrix screening, encompassing both lead compounds and indications.
PDXOs are amenable to engineering, such as gene editing to significantly broaden large-scale research applications, including in vitro/in vivo imaging analysis.
The successful co-culture of PDXOs with PBMCs and CAR-T cells to investigate immune modulation and tumor killing.
This large biobank provides a unique collection of matched in vitro and in vivo preclinical patient-derived models which can be accessed via Crown Bioscience’s online databases OrganoidBase and HuBase. This powerful translational tool has distinct advantages over other systems such as providing higher throughput with faster results as compared to in vivo models alone, with robust and renewable assay performance that reflects reproducibility of other in vitro systems. In vitro drug screening with PDXOs can rapidly be integrated into early drug development and interchangeably with translational studies and improved predictions of clinical outcome.

To read the full publication entitled "A living biobank of matched pairs of patient-derived xenografts and organoids for cancer pharmacology", follow this link.