On December 16, 2021 Menarini Silicon Biosystems (MSB), a pioneer of single cell technologies, reported its new FFPE Rescue Application, to enable molecular testing on formalin-fixed, paraffin-embedded (FFPE) samples with low tumor cell contents (Press release, Menarini Silicon Biosystems, DEC 16, 2021, View Source [SID1234597345]). Thanks to the sorting capabilities of the recently launched DEPArray PLUS instrument, it is possible to isolate a sufficient number of tumor cells to generate relevant molecular data, even from FFPE tissues that were previously discarded from conventional Next Generation Sequencing (NGS) processing. Thus, the DEPArray PLUS workflow can reduce the failure rates of FFPE molecular analyses and provide clinical researchers with valuable information about actionable mutations, potentially improving clinical trial recruitment and allowing more patients to access new targeted therapies.

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Formalin fixation and paraffin embedding remains the gold standard preservation method of human tissue for molecular diagnostics. NGS of FFPE tissue is becoming increasingly important to identify targetable mutations and has greatly enhanced the ability of physicians to optimize treatment strategies.

However, not all FFPE samples are suitable for molecular analyses. The failure rate for molecular testing of FFPE tissues ranges between 5 and 15%, with the primary driver being low tumor content. The precise digital sorting capability of DEPArray PLUS allows for the isolation of small pools of only a few hundred tumor cells that are then suitable for NGS library preparation and sequencing.

According to Dr Javier Hernández Losa, Director of the Molecular Biology Laboratory within the Pathology Department at the Vall d´Hebron University Hospital in Barcelona, Spain "the DEPArray platform allows us to conduct unambiguous genetic analyses on FFPE samples that failed the standard NGS procedure and identify potentially targetable mutations". MSB and the Vall d’Hebron University Hospital have recently engaged in a research collaboration to expand the types of complex samples that can be analyzed by DEPArray, such as cytologic samples. The Vall d’Hebron University Hospital Pathology lab provides molecular testing for many hospitals throughout Catalonia. It aims to establish a NGS testing service across the entire region to provide the information that will help physicians improve their decision-making and patient care.

Prof Lorenzo Leoncini, MD, Head of the Department of Medical Biotechnology and Director of the Pathological Anatomy Division at the University of Siena, Italy adds that: "the DEPArray technology helped to rescue tissue samples with less than a 5% tumor cell content to generate robust data on cancer mutations. We are now planning to use this technology in different new research projects. For example, we will use DEPArray to study tumor cells in classical Hodgkin Lymphoma tissue biopsies, a setting in which isolation of these rare cells is extremely challenging, as they are present in a very low percentage compared to normal cells".

"We are excited to be able to deliver such a unique technology for the analysis of FFPE biopsies with low tumor cellularity," said Fabio Piazzalunga, President and CEO of MSB. "Our DEPArray platform could help pathology labs reduce the significant burden, caused by FFPE biopsies that are rejected from molecular analysis and support pharma companies involved in clinical trials to expedite recruitment".

On December 16, 2021 Debiopharm (www.debiopharm.com), a Swiss biopharmaceutical company, reported the first patient treated in the newly launched open-label, phase I study evaluating Debio 0123, an oral, potent and highly selective WEE1 inhibitor, as monotherapy in patients with advanced solid tumors (NCT05109975). Part of an emerging new class of drugs working within the DNA damage response (DDR) pathway, the compound’s anti-tumor capacity has been evaluated in several preclinical studies along with the ongoing phase I study in combination with carboplatin-based chemotherapy (Press release, Debiopharm, DEC 16, 2021, View Source [SID1234597344]). This new trial’s primary objective is to identify the maximum tolerated dose and/or recommended phase II dose in adults with advanced solid tumors that have recurred or progressed after prior therapy and/or for whom no standard therapy of proven benefit is available.

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The development of the Debio 0123 program is rooted in the growing understanding of the DNA damage response of cancer cells. Research reveals that cancer cell survival relies on the tightly regulated cell cycle that pauses at certain points to allow the repair of damaged DNA so that tumor cells can continue to divide and grow. WEE1 is a catalyzing enzyme implicated in these "DNA repair stops" helping cancer to thrive. By inhibiting WEE1, the cell cycle checkpoints are compromised, driving cancer cells to start their replicating prematurely, or before the repair of detrimental DNA damage, ultimately leading to cell death. Furthermore, WEE1 inhibitors are suspected to selectively target tumor cells, inducing synthetic lethality without impacting survival of normal cells. The potential best-in class status of Debio 0123 relies on its highly selective inhibition against WEE1.

"We’re intrigued to learn more about the clinical benefits that WEE1 inhibition with Debio 0123 alone could offer cancer patients. We believe that this new modality can effectively exploit the genomic instability and malfunctioning of the DNA repair process in cancer cells in hopes that ultimately tumor progression is halted and patient survival is improved," Dr. Esteban Rodrigo Imedio, Senior Medical Director, Oncology Research & Development, Debiopharm. "As Debio 0123 is highly selective against WEE1, in time, ongoing clinical research could confirm Debio 0123’s potential best-in-class status."

Initially discovered by Almac Discovery before being in-licensed by Debiopharm in 2017, the evaluation of Debio 0123 as monotherapy could help to better characterize the safety and efficacy profile of the compound in a clinical setting and define the parameters for eventual phase II research. Pre-clinical research suggests potential activity for cancer patients, particularly in combination with DNA damaging agents such as chemo- and radiotherapy. WEE1 inhibitors are promising drug candidates as they inhibit DDR, offering the possibility to enhance the efficacy of these agents, frequently part of the standard-of-care of various cancer types. Debiopharm plans to advance the clinical program while simultaneously negotiating potential partnerships, such as during the upcoming JP Morgan 2022 conference, with larger pharmaceutical companies for eventual commercialization.

Dr. Stephen Barr, Managing Director & President, Almac Discovery commented, "Since the discovery of our highly selective WEE1 inhibitor, now known as Debio 0123, we have looked forward with anticipation to understanding its potential therapeutic benefit for cancer patients across the globe. We are therefore delighted that, in addition to the ongoing combination clinical study, Debio 0123 is also being evaluated as a monotherapy in the treatment of advanced solid tumors. We look forward to seeing further progress from this ongoing clinical research."

About Debio 0123

Debio 0123 is a WEE1 kinase inhibitor, a key regulator of the G2/M and S phase checkpoints, activated in response to DNA damage, allowing cells to repair their DNA before resuming their cell cycle. WEE1 inhibition, particularly in combination with DNA damaging agents, induces an overload of DNA breaks. In conjunction with abrogation of other checkpoints such as G1, the compound pushes the cells through cycle without DNA repair, promoting mitotic catastrophe and inducing apoptosis of cancer cells.

On December 16, 2021 Inceptor Bio, a Research Triangle Park-based next-generation cell and gene therapy biotechnology company, reported that it has executed an in-licensing agreement with the University of California, Santa Barbara (UCSB) for an investigational Chimeric Antigen Receptor Macrophage (CAR-M) therapy targeting difficult-to-treat tumors (Press release, Inceptor Bio, DEC 16, 2021, View Source [SID1234597343]).

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"This strategic alliance is an important step in advancing Inceptor Bio’s next-generation cell therapy platform focused on multiple novel mechanisms to address solid tumors," said Shailesh Maingi, Founder and CEO of Inceptor Bio. "Our aim for this cutting-edge technology is to transform how solid tumors are treated."

"CAR-M is a new frontier for harnessing immune cells to treat and cure cancer. We’re thrilled to partner with Dr. Denise Montell and UCSB on a potentially groundbreaking technology in the fight against difficult-to-treat cancers," added Mike Nicholson, Ph.D., Chief Scientific Officer at Inceptor Bio.

Macrophage cells naturally engulf viruses and bacteria through a process called phagocytosis, and when combined with a CAR construct to form a CAR-M, they can selectively target and engulf cancer cells and generate an immune response via modulation of the tumor microenvironment. Inceptor’s CAR-M technology builds upon this foundation and plans to optimize the effectiveness of this therapeutic approach.

This technology was invented by Dr. Denise Montell’s research lab at UCSB. Dr. Montell earned her B.S. in biochemistry and cell biology at the University of California, San Diego, and her Ph.D. in neuroscience at Stanford University. She joined the faculty at UCSB in 2012. Dr. Montell serves on the Board of Scientific Counselors of the National Cancer Institute and was elected into the National Academy of Sciences in 2021.

"I am excited to work with Inceptor to transform our fundamental cell biological discoveries into cancer immunotherapies," said Denise Montell, Ph.D., Duggan Professor, UCSB. "It is gratifying to see decades of our basic science research coming to fruition to help cancer patients. The partnership with Inceptor is making it possible."

On December 16, 2021 Epic Sciences, Inc. reported DefineMBC, a novel metastatic breast cancer (MBC) test that includes both cell-based and cell-free analysis from a single blood draw (Press release, Epic Sciences, DEC 16, 2021, View Source [SID1234597341]). DefineMBC provides comprehensive MBC profiling when a tissue biopsy result is not available.

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"Tissue biopsy to confirm metastatic breast cancer diagnosis and to subtype the cancer is the established standard of care, but can be highly invasive, expensive to payers, and due to sampling and access limitations, tissue biopsy may not provide physicians with the information needed to guide therapy. DefineMBC uses both cell-based and cell-free analysis from a simple blood draw and provides information for optimal treatment decision making," says Rick Wenstrup MD, Chief Medical Officer, Epic Sciences. DefineMBC also enables better therapeutic decision making in more advanced MBC where tissue biopsy is not routinely performed but patients’ cancers often evolve due to the impact of targeted therapies, ongoing clonal variations, and other known cancer dynamics."

DefineMBC combines several multi-analyte assay methods to perform comprehensive cancer profiling and has demonstrated impressive sensitivity, specificity, accuracy, and precision. The features of DefineMBC are described below:

Detection of circulating tumor cells (CTCs), and quantification of ER and HER2 protein expression on those cells, through immunofluorescent staining combined with image analysis by an algorithm developed through advanced machine learning.
Whole-genome sequencing of individual CTCs (called single-cell sequencing) to detect presence of amplified cancer-related genes through analysis of copy number variation provide Isolation and characterization of the copy number variation (CNV).
Analysis of cell-free DNA (cfDNA) by next-generation sequencing (NGS) of 56 genes, the detection of genomic alterations [single nucleotide variants (SNVs), fusions, CNVs, microsatellite instability (MSI), and tumor mutational burden (TMB)]. Expanded coverage of up to 500 genes is available for research and biopharma trials.
"DefineMBC delivers on the full potential of liquid biopsy, ensuring no information is left behind." says Lloyd Sanders, CEO and President at Epic Sciences. "We are excited about the positive impact this product can have on patient care as well as the opportunity to provide critical data to drug development efforts. We are now enrolling several community cancer centers into our Early Access Program for DefineMBC and expanding the menu of assays we offer to our pharmaceutical and research partners.

On December 16, 2021 Aqemia, the next-gen pharmatech company leveraging artificial intelligence and quantum physics, and Servier, a global pharmaceutical group, reported that they have entered into a collaboration agreement that will use Aqemia’s technology to accelerate the discovery of small molecule therapeutic drug candidates on an undisclosed target in immuno-oncology (Press release, Servier, DEC 16, 2021, View Source [SID1234597340]). The agreement includes upfront payments and payments for potential milestones from the early-stage discovery and the clinical trials in developing the drug candidates resulting from this collaboration.

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This collaboration builds upon a successful pilot initiated in early 2021 by Servier to blind test the unique AI, quantum, and statistical physics technologies of Aqemia.

Aqemia will take responsibility for the AI-based design to deliver optimized molecules that fulfill several small molecule design goals. Unlike most AI-based technologies that need experimental data to train their algorithms prior to starting the design, Aqemia will tackle the project from the earliest stage of the drug discovery by generating its own data with quantum and statistical physics-based calculations.

Maximilien Levesque, CEO and co-founder of Aqemia, commented, "We are thrilled to initiate this new collaboration with Servier, following a successful pilot phase that demonstrated the value brought by Aqemia’s team and technology to the rapid discovery of innovative therapeutic molecules.". He added, "Our goal is to find innovative new drugs for many, many diseases at a massive scale, thanks to our unique platform, to change the lives of patients, and this collaboration with Servier is an important step in this direction."

"We are delighted to collaborate with Aqemia to accelerate the identification of novel bioactive compounds, combining Aqemia’s unique AI-driven technology and Servier’s expertise in medicinal chemistry and computer-aided drug design (CADD)," added Christophe Meyer, Head of Molecular Modeling and Chemoinformatics at Servier. "Both teams will work together in a collaborative mindset to leverage Aqemia’s generative technology and physics-based evaluation of binding free energy to design molecules optimized according to multi-criteria design objectives."

Olivier Nosjean, Head of Open Innovation and Scientific Affairs at Servier R&D concluded, "This collaboration with Aqemia is a concrete example of Servier working side by side with a start-up to create value for both parties, working jointly to accelerate therapeutic innovation for patients. This collaboration is the result of the Start-up @ Servier program, where an initial phase of joint work allows us to carry out a key study or pilot application of a technology, before entering into a classic collaboration. This is our first application of this Start-up @ Servier model, and we are very happy to see it take shape with Aqemia, which is such a promising collaboration."