On November 9, 2021 Biocept, Inc. (Nasdaq: BIOC), a leading provider of molecular diagnostic assays, products and services, reported the publication of a study showing that the addition of Switch-Blocker technology to common PCR-based liquid biopsy assays significantly increased sensitivity in detecting rare cancer mutations (Press release, Biocept, NOV 9, 2021, View Source [SID1234594947]). The abstract was published in the November 2021 issue of the Journal of Molecular Diagnostics.

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Biocept’s proprietary Switch-Blocker technology enriches oncogenic mutations of interest while suppressing wild-type (normal) DNA, resulting in ultra-high sensitivity, specificity and accuracy. In this study, Switch-Blockers were combined with conventional real-time PCR and droplet digital PCR (ddPCR) assays.

"Our quantitative Switch-Blocker technology demonstrates an unprecedented ability to find and distinguish extremely rare genetic events—even in blood that contains mostly DNA from normal white blood cells," said Michael Dugan, Chief Medical Officer and Medical Director of Biocept. "This can greatly enhance the clinical sensitivity of our cell-free tumor DNA assays and has broad application in the continued development of highly sensitive and quantitative molecular diagnostic assays used to evaluate cerebrospinal fluid or blood from patients with cancer. Switch-Blocker-based assays can help detect cancer biomarkers that otherwise might be missed, improving treatment selection. They can also be used to evaluate treatment-related changes, find minimal residual disease or identify early disease recurrence."

Results showed that the addition of Switch-Blockers increased the sensitivity of allele-specific primer assays by more than 200 times, from about 1% minor allele frequency (MAF) to better than 0.01%. The sensitivity of multiplex competitive allele-specific TaqMan assays, commonly used with PCR amplification, were increased greater than 1,000 times, from about 10% MAF to 0.01% or better. The ability to significantly increase the sensitivity of conventional mutation assays using Switch-Blocker technology is critical for helping to find rare genetic events in a wide range of applications, including solid tumor cancers, where a majority of biomarkers in blood occur at less than 1% MAF.

The abstract (#TT33), titled "The Use of Switch-Blocker Probes for the Ultra-High Sensitivity of Detection of Rare Genetic Events Using Conventional Real-Time and Droplet Digital PCR Assays," can be accessed here.

About Switch-Blocker Technology

Biocept’s proprietary Switch-Blocker platform is the basis for the company’s Target Selector assays and can be used with tissue, blood and cerebrospinal fluid (CSF) samples. The technology enables industry-leading sensitivity for the detection of mutations/variants from circulating tumor DNA (ctDNA). It has been validated to 0.05% minor allele frequency in blood, which provides significant advantages for identifying actionable cancer biomarkers and assessing therapeutic tumor response. Switch-Blockers enhance the performance and specificity of the PCR method, the most widely used amplification approach for clinical diagnostic applications and can be customized to aid in biopharmaceutical research for the development of targeted therapies for cancer. Switch-Blocker technology also has been validated and found to be highly sensitive, quantitative and reproducible in detecting the presence of the SARS-CoV-2 virus that causes COVID-19 infections.

On November 9, 2021 MAIA Biotechnology, Inc., a targeted therapy, immuno-oncology company focused on developing potential first-in-class oncology drugs ("MAIA"), reported that the Company will present a scientific poster at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting (SITC) (Free SITC Whitepaper) which will be held November 10-14, 2021, in Washington, DC (Press release, MAIA Biotechnology, NOV 9, 2021, View Source [SID1234594946]).

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Poster Title:

Telomerase-Driven Telomeric DNA Modification in Cancer Cells Leads to Efficient Induction of cGAS-mediated Innate and Adoptive Immune Responses

Abstract ID:

697

Category:

Immune-stimulants and immune modulators

Date:

Friday, Nov. 12, 2021

Time:

7:00 am – 8:30 pm

Location:

Poster Hall, Walter E. Washington Convention Center

Accepted abstracts can be found in the Journal for ImmunoTherapy of Cancer (JITC).

On November 9, 2021 EdiGene, Inc., a global biotechnology company focused on translating gene-editing technologies into transformative therapies for patients with serious genetic diseases and cancer, reported that it has entered into a research collaboration with the University of Wisconsin–Madison as part of the company’s effort of translating proprietary LEAPER RNA editing technology into in vivo therapies (Press release, EdiGene, NOV 9, 2021, View Source [SID1234594945]).

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Under the partnership, EdiGene’s U.S.-based R&D Center will work with the David Gamm Laboratory at the University of Wisconsin-Madison to evaluate the pharmacological property of LEAPER RNA base editing candidates targeting specific genetic diseases.

"EdiGene’s U.S. R&D Center has built up its capabilities with an exceptional team of talented scientists who are advancing the company’s pipeline both within our own labs and through external partnerships," said Bo Zhang, Ph.D., Head of EdiGene’s U.S. subsidiary. "Dr. Gamm’s knowledge and insights are a tremendous asset in this effort."

"This collaboration allows us to leverage our expertise and experience to help translate EdiGene’s RNA base editing technology into transformative medicines that can benefit patients with genetic diseases who today have limited or no therapeutic options," said David Gamm, MD, Ph.D., Principal Investigator of the research, Professor of Ophthalmology and Visual Sciences, and Director of the McPherson Eye Research Institute at the University of Wisconsin–Madison.

LEAPER (Leveraging endogenous ADAR for programmable editing of RNA) employs short engineered ADAR-recruiting RNAs (arRNAs) to recruit native ADAR enzymes to change specific adenosine to inosine. LEAPER is a robust, precise, and efficient RNA editing technology uniquely suited for in vivo therapies with broad therapeutic applicability. It is developed by Professor Wensheng Wei’s lab at Peking University. Professor Wensheng Wei is the Scientific Founder of EdiGene.

"Earlier this year, we announced the first patient enrolled in multicenter Phase I clinical study of our investigational ex vivo gene-editing hematopoietic stem cell therapy ET-01. This collaboration furthers our efforts in RNA editing and in vivo gene-editing therapies," said Dong Wei, Ph.D., CEO of EdiGene. "Along with the expansion of our U.S. R&D Center, such effort will help accelerate the translation of our proprietary gene-editing technology for patients in need worldwide."

About the David Gamm Laboratory

The Gamm laboratory was established at the University of Wisconsin-Madison in 2003 to advance the use of human pluripotent stem cells (hPSCs) in the study and treatment of retinal degenerative diseases. To facilitate these efforts, the Gamm lab developed the first hPSC-based 3D retinal organoid culture method, which has since yielded key insights into mechanisms of early human retinal development. Moreover, their studies have established the authenticity of hPSC-derived retinal progeny, including photoreceptor cells (rods and cones), retinal pigmented epithelium (RPE) cells, and neural retinal tissue. Lastly, they were pioneers in the use of patient-specific and gene-modified iPSCs to model retinal disorders and to test therapeutic strategies, and have advanced efforts to adapt this technology for human use.

On November 9, 2021 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, and BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported preclinical data supporting the mode of action of BT-001, their novel dual mechanism-of-action oncolytic Vaccinia virus. The data demonstrate high intratumoral expression of an immune checkpoint-inhibiting antibody and robust anti-tumoral activity in several tumor models (Press release, Transgene, NOV 9, 2021, View Source [SID1234594944]).

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BT-001, developed by BioInvent and Transgene, is a clinical phase oncolytic virus engineered to deliver an anti-CTLA-4 antibody and human GM-CSF in a tumor-specific vehicle (the VVcopTK-RR- virus backbone) for the treatment of solid tumors.

The companies’ poster at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2021) shows that BT-001 selectively replicates in tumor cells. The murine surrogate of BT-001 delivered sustained and high intratumoral levels of antibody accompanied by low systemic exposure. These differential expression levels were associated with high depletion of intratumoral regulatory T cells (Treg) but the absence of systemic Treg depletion. Similar effects in humans would allow BT-001 to deliver powerful antitumor immunity.

Patient inclusion into the ongoing Phase I/IIa clinical study of BT-001 (NCT04725331) is progressing well. The multicenter trial, authorized in Europe and in the U.S., is assessing BT-001 as single agent and in combination with the PD-1 checkpoint inhibitor pembrolizumab for the treatment of solid tumors. Initial Phase I data are expected in the first half of 2022.

Other data highlighted in the SITC (Free SITC Whitepaper) poster show improved survival in several syngeneic tumor models following treatment with a murine version of BT-001. There is also evidence of a positive synergistic effect between the murine ‘BT-001’ oncolytic virus expressing the CTLA-4 antibody and a systemic PD-1 checkpoint inhibitor.

"These impressive data, demonstrating the multiple mechanisms of action and anti-cancer properties of BT-001, played a key role in our decision to take this unique oncolytic virus into the clinic. We are pleased to be able to share them with our scientific and clinical peers at SITC (Free SITC Whitepaper)" said Martin Welschof, CEO of BioInvent and Hedi Ben Brahim, Chairman and CEO of Transgene.

SITC 2021 will take place on November 10–14, 2021, at the Walter E. Washington Convention Center in Washington, D.C. and virtually. The poster, entitled "Vectorized Treg-depleting aCTLA-4 elicits antigen cross-presentation and CD8+ T cell immunity to reject "cold" tumors", will be presented on the Virtual ePoster Hall and presented in the Poster Hall (Hall E) on Saturday, November 13, 2021.

Authors: Monika Semmrich, Jean-Baptiste Marchand, Matilda Rehn, Laetitia Fend, Christelle Remy, Petra Holmkvist, Nathalie Silvestre, Carolin Svensson, Patricia Kleinpeter, Jules Deforges, Fred Junghus, Linda Mårtensson, Johann Foloppe, Ingrid Teige, Eric Quéméneur and Björn Frendéus.

Abstract and poster number: 746

About BT-001
BT-001 is an oncolytic virus generated using Transgene’s Invir.IO platform and its patented large-capacity VVcopTK-RR- oncolytic virus, which has been engineered to encode both a Treg-depleting human recombinant anti-CTLA-4 antibody generated by BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms, and the human GM-CSF cytokine. By selectively targeting the tumor microenvironment, BT-001 is expected to elicit a much stronger and more effective antitumoral response. As a consequence, by reducing systemic exposure, the safety and tolerability profile of the anti-CTLA-4 antibody will be greatly improved.

BT-001 is being co-developed as part of a 50/50 collaboration on oncolytic viruses between Transgene and BioInvent. To know more on BT-001, watch our video here.

On November 9, 2021 Palleon Pharmaceuticals, a company pioneering the field of glyco-immunology to treat cancer and inflammatory diseases, reported data on a novel mechanism of action of the company’s EAGLE sialoglycan degradation therapeutic platform (Press release, Palleon Pharmaceuticals, NOV 9, 2021, View Source [SID1234594943]). Preclinical studies, presented in a poster at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), show that EAGLE therapeutic candidates’ desialylation of T cells enhances T cell anti-tumor immunity, and that lead candidate E-602 (Bi-Sialidase) is efficacious and safe in animal models.

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"The exciting package of data we are presenting at SITC (Free SITC Whitepaper) demonstrates for the first time that Palleon’s EAGLE platform could offer a novel immunomodulatory approach to enhancing T-cell immunity for cancer treatment," said Li Peng, Ph.D., Chief Scientific Officer of Palleon and the poster’s principal author. "These findings will bolster our upcoming IND filing for E-602 and continue to deepen our understanding of the therapeutic potential of the EAGLE platform."

Upregulation of sialoglycans on tumors has been observed for decades and correlates with poor clinical outcomes across many tumor types. Recent findings made possible by advances in the tools used to study glycobiology have shown that these sialoglycans are immunosuppressive. In addition to tumor cells, most immune cells present substantially more abundant sialoglycans than non-hematological healthy cells, which may also contribute to immunosuppression. Palleon utilized various assays to study the effect of E-602 on naïve, exhausted, and effector T cells. These studies found that desialylation by E-602 enhanced naïve T cell priming/activation, restored exhausted-like T cell functions, and enhanced effector T cell function.

Further studies evaluated the single-agent antitumor activity of E-602 in multiple syngeneic mouse tumor models, and its safety profile in rat and non-human primate models. These studies found that E-602 demonstrated single-agent antitumor activity and a wide safety margin.