On October 15, 2020 bioAffinity Technologies, a privately held biotech company, and Smiths Medical, a leading global medical device manufacturer, reported a partnership to improve patient care with at-home collection of sputum to be analyzed by CyPath Lung, a non-invasive flow cytometry diagnostic test for lung cancer that is being developed as a Laboratory Developed Test (LDT) by Precision Pathology Services (Press release, BioAffinity Technologies, OCT 15, 2020, View Source [SID1234568529]).

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"The partnership enables the use of the acapella vibratory PEP therapy system made by Smiths Medical for at-home collection of samples that are analyzed by bioAffinity’s CyPath Lung, a patient-friendly test shown to have high sensitivity and specificity in detecting lung cancer in people at high risk for the disease," said bioAffinity Technologies President and CEO Maria Zannes. "One of the hallmarks of CyPath Lung is the ease by which patients collect their sputum samples at home using the acapella device."

"Innovation is a cornerstone of Smiths Medical. As a leader in airway management solutions, we are proud that our acapella device can facilitate the use of this non-invasive breakthrough test that can detect lung cancer at its earliest stages when treatment can be most effective and lives can be saved," said JehanZeb Noor, Chief Executive Officer, Smiths Medical. "Smiths Medical and bioAffinity Technologies share a commitment to putting patients first and making quality healthcare accessible and affordable."

CyPath Lung is a flow cytometric test to aid in the diagnosis of lung cancer. Patients collect sputum samples non-invasively at home using the acapella device. The sample is shipped overnight to the laboratory for processing. Sample data is acquired by flow cytometry, a technique that can count, sort and profile individual cells quickly. Using an automated analysis with pre-set parameters, CyPath Lung profiles the lung micro-environment including the presence of cancer-associated cells. Test results can be provided to the physician in minutes.

A test validation trial conducted by bioAffinity Technologies comparing people at high risk for lung cancer to high-risk patients with the disease resulted in CyPath Lung specificity of 88% and sensitivity of 82%, similar to far more invasive procedures currently used to diagnose lung cancer. CyPath Lung performed even better, with 92% sensitivity and 87% specificity, in the group of cancer and cancer-free high-risk participants who had no nodules or small nodules less than 2 cm in diameter. Results of the test validation trial have been submitted for presentation at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer.

Precision Pathology Services has licensed and is developing CyPath Lung as a Laboratory Developed Test (LDT) in accordance with the College of American Pathologists (CAP) and the Clinical Laboratory Improvement Amendment (CLIA) guidelines and regulations. Precision Pathology Services is an accredited CAP/CLIA laboratory in San Antonio, Texas. Following completion of development of CyPath Lung as an LDT, physicians may order the test for their patients who are smokers and former smokers at high risk for lung cancer and who receive a positive screening result or otherwise are suspected of having the disease.

People who have smoked the equivalent of one pack of cigarettes a day for 30 years or more, have not quit smoking in the past 15 years and are 55-80 years of age are recommended for annual screening by low dose computed tomography (LDCT). Screening by LDCT has been proven to detect lung cancer at earlier stages when it can be successfully treated, but screening has a low Positive Predictive Value (PPV) that can lead to unnecessary and risky procedures.

On October 15, 2020 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for cancer, reported the company’s participation at the Immuno Series US Virtual meeting which will be held online, October 15-16, 2020 (Press release, Personalis, OCT 15, 2020, View Source [SID1234568528]).

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Personalis will present "Maximizing immunotherapy biomarker discovery with a multidimensional tumor immunogenomics platform," featuring the Personalis universal cancer immunogenomics approach, ImmunoID NeXT. Kedar Hastak, PhD, will present for Personalis. His presentation will focus on the current challenges facing investigators in immuno-oncological translational research including maximizing data generation from a single sample and the analysis of complex data.

Dr. Hastak will discuss how more accurate, predictive biomarker analysis may assist in the selection of effective combinatorial immunotherapy treatments for patients. Additionally, the complexity of both the tumor and tumor microenvironment suggests a comprehensive approach is needed for robust characterization of the cancer ecosystem. By combining highly sensitive, exome-scale DNA and RNA sequencing with advanced analytics, the ImmunoID NeXT Platform provides a multidimensional view of the tumor and the tumor microenvironment (TME) from a single sample preparation. Dr. Hastak will feature a case study demonstrating the ability of this immunogenomics profiling platform to uncover tumor escape mechanisms and to identify composite biomarkers of potentially greater predictive capacity from patients treated with immune checkpoint blockade. Additionally, the presentation will highlight NeXT Liquid Biopsy, an exome-wide liquid biopsy approach combined with ImmunoID NeXT, to further explore critical areas of tumor biology.

On October 15, 2020 Cellaria, Inc. (Wakefield, MA, USA), a scientific innovator with breakthrough tools for cancer research, reported that it has introduced three next generation Pancreatic Cancer cell lines, substantially boosting the value of in vitro methods in the development of more effective therapies (Press release, Cellaria, OCT 15, 2020, View Source [SID1234568527]). Difficult to detect and with a poor survival rate, Pancreatic Cancer remains a primary and illusive therapeutic target for researchers. The new cell models are scalable and stable, securely linked to specific patient tumor samples and supported by Cellaria quality control certifications, which include full cell line authentication. They directly facilitate more clinically relevant, translatable research and represent a major step forward for academic and industrial researchers working to advance more effective, personalized medicine and lead drug candidates.

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"Legacy cell lines are a crucial tool for cost-effective in vitro studies, but most do not securely represent the heterogeneity of the original patient tumor," said David Deems, CEO, Cellaria, Inc. "Genetic drift, selective overgrowth and/or contamination are recognized issues that erode the relevance of commercial lines, thereby compromising progress. In contrast, our novel cell models are extremely stable and have a strong, robustly authenticated connection to specific patient tumors. They offer breakthrough reproducibility, rigor and relevance in both clinical studies and drug discovery."

Pancreatic cancer tumors are elusive in conforming to standard definitions and tend to morph and metastasize into different cancers following treatment. Cellaria’s three new cell models – "Stew", "Chocolate", and "Basket" – are derived from patients diagnosed with pancreatic adenocarcinoma (the most common form of Pancreatic Cancer), and vary with respect to factors such as gender, ethnicity, age, treatment history, and diagnosis. As a result, they enable researchers to closely align their studies with a specific patient cohort, with defined molecular targets and biomarkers. All are provided with protocols for preserved biomarker expression and a Certificate of Analysis (COA) attesting their growth characteristics. Beyond supporting optimal application of the cell line, the COA meets growing requirements within the research community for demonstrable cell line authentication.

"In-depth scientific know-how is a hallmark of the Cellaria approach," said David Deems. "All our cell models are subject to extensive characterization assays including genomic and biomarker analysis, gene expression and protein profiling. Furthermore, we have data showing response to at least three approved drug therapies for each line. This information is a powerful aid to gathering useful, actionable data from the outset for new or established research groups. We’re delighted to add these new products to our established portfolio for breast, lung, colon, and ovarian cancers, to accelerate the progress of therapeutic and basic science towards a treatment for this challenging condition."

Cellaria cell models for a range of cancers have already demonstrated proven value in in vitro studies. Find out more about the potential impact of the Stew, Chocolate and Basket at: www.cellariabio.com or call 978-720-8051.

On October 15, 2020 TAE Life Sciences (TLS), a biologically-targeted radiation therapy company developing a breakthrough, accelerator-based boron neutron capture therapy (BNCT) system, reported that Bruce Bauer, Chief Executive Officer, will present at the 22nd Annual Southern California Biomedical Council (SoCalBio) Conference (Press release, TAE Life Sciences, OCT 15, 2020, View Source [SID1234568526]).

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Date: Friday, October 23, 2020
Time: 11:15 – 11:27 AM PST

TLS’ presentation is part of the Nurturing Innovators track that showcases emerging biosciences companies. Mr. Bauer will provide an overview of the company and its recent business milestones.

On October 15, 2020 Provectus (OTCQB: PVCT) reported that H. Lee Moffitt Cancer Center will present non-clinical data from ongoing research on investigational autolytic cancer immunotherapy PV-10, an injectable formulation of Provectus’ proprietary rose bengal disodium (RBD), as a single-agent and in combination with chemotherapy for the treatment of pancreatic cancer at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020), to be held online from November 9-14, 2020 (Press release, Provectus Biopharmaceuticals, OCT 15, 2020, View Source [SID1234568525]).

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RBD selectively accumulates in the lysosomes of cancer cells upon contact, disrupts these lysosomes, and causes the cells to die. Intralesional (IL) (aka intratumoral) administration of PV-10 for the treatment of solid tumors can yield immunogenic cell death and induce tumor-specific reactivity in circulating T cells.1-3

The abstract accepted for poster presentation at SITC (Free SITC Whitepaper) 2020 is entitled "Intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors" (Abstract ID: 585; Category: Immune-stimulants and immune modulators). Moffitt co-authors include Patrick Innamarato, PhD, Jennifer Morse, MS, Amy Mackay, Sarah Asby, Matthew Beatty, PhD, Jaime Blauvelt, Scott Kidd, John Mullinax, MD, Amod Sarnaik, MD, and Shari Pilon-Thomas, PhD.

This pancreatic cancer work was led by Dr. Pilon-Thomas and members of the Pilon-Thomas Lab, whose previous peer-reviewed published work on RBD includes:

"Intralesional injection of rose bengal induces a systemic tumor-specific immune response in murine models of melanoma and breast cancer" (Toomey et al., PLoS One 2013),
"Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1" (Liu et al., Oncotarget 2016), and
"T cell mediated immunity after combination therapy with intralesional PV-10 and blockade of the PD-1/PD-L1 pathway in a murine melanoma model" (Liu et al., PLoS One 2018).
About Rose Bengal Disodium

RBD is 4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein disodium, a halogenated xanthene and Provectus’ proprietary lead molecule. The Company manufactures cGMP RBD using a patented process designed to meet stringent modern global quality requirements for pharmaceuticals and pharmaceutical ingredients.

An IL formulation (i.e., by direct injection) of cGMP RBD drug substance, cGMP PV-10, is being developed as an autolytic immunotherapy drug product for solid tumor cancers. By targeting tumor cell lysosomes, RBD treatment may yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells, including a T cell mediated immune response against treatment refractory and immunologically cold tumors.1-3 Adaptive immunity can be enhanced by combining immune checkpoint blockade (CB) with RBD.4 IL PV-10 is undergoing clinical study for relapsed and refractory adult solid tumor cancers, such skin and liver cancers.

IL PV-10 is also undergoing preclinical study for relapsed and refractory pediatric solid tumor cancers, such as neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.5,6

A topical formulation of cGMP RBD drug substance, PH-10, is being developed as a clinical-stage immuno-dermatology drug product for inflammatory dermatoses, such as atopic dermatitis and psoriasis. RBD can modulate multiple interleukin and interferon pathways and key cytokine disease drivers.7

Oral formulations of cGMP RBD are undergoing preclinical study for relapsed and refractory pediatric blood cancers, such as acute lymphocytic leukemia and acute myelomonocytic leukemia.8,9

Oral formulations of cGMP RBD are also undergoing preclinical study as prophylactic and therapeutic treatments for high-risk adult solid tumor cancers, such as head and neck, breast, pancreatic, liver, and colorectal cancers.

Different formulations of cGMP RBD are also undergoing preclinical study as potential treatments for multi-drug resistant (MDR) bacteria, such as Gram-negative bacteria.

Tumor Cell Lysosomes as the Seminal Cancer Drug Target

Lysosomes are the central organelles for intracellular degradation of biological materials, and nearly all types of eukaryotic cells have them. Discovered by Christian de Duve, MD in 1955, lysosomes are linked to several biological processes, including cell death and immune response. In 1959, de Duve described them as ‘suicide bags’ because their rupture causes cell death and tissue autolysis. He was awarded the Nobel Prize in 1974 for discovering and characterizing lysosomes, which are also linked to each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Building on the Discovery, Exploration, and Characterization of Lysosomes

Cancer cells, particularly advanced cancer cells, are very dependent on effective lysosomal functioning.10 Cancer progression and metastasis are associated with lysosomal compartment changes11,12, which are closely correlated (among other things) with invasive growth, angiogenesis, and drug resistance13.

RBD selectively accumulates in the lysosomes of cancer cells upon contact, disrupting the lysosomes and causing the cells to die. Provectus1,14, external collaborators5, and other researchers15,16,17 have independently shown that RBD triggers each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Cancer Cell Autolytic Death via RBD: RBD-induced autolytic cell death, or death by self-digestion, in Hepa1-6 murine hepatocellular carcinoma (HCC) cells can be viewed in this Provectus video of the process (ethidium homodimer 1 [ED-1] stains DNA, but is excluded from intact nuclei; lysosensor green [LSG] stains intact lysosomes; the video is provided in 30-second frames, with a duration of approximately one hour). Exposure to RBD triggers the disruption of lysosomes, followed by nucleus failure and autolytic cell death. Identical responses have been shown by the Company in HTB-133 human breast carcinoma (which can be viewed in this Provectus video of the process, with a duration of approximately two hours) and H69Ar human multidrug-resistant small cell lung carcinoma. Cancer cell autolytic cell death was reproduced by research collaborators in neuroblastoma cells to show that lysosomes are disrupted upon exposure to RBD.5

Tumor Autolytic Death via RBD: RBD causes acute autolytic destruction of injected tumors (via autolytic cell death), mediating the release of danger-associated molecular pattern molecules (DAMPs) and tumor antigens; release of these signaling factors may initiate an immunologic cascade where local response by the innate immune system may facilitate systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. Mediated immune signaling pathways may include an effect on STING, which plays an important role in innate immunity.9

Orphan Drug Designations (ODDs)

ODD status has been granted to RBD by the U.S. Food and Drug Administration for metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

Intellectual Property (IP)

Provectus’ IP includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the process by which cGMP RBD and related halogenated xanthenes are produced, avoiding the formation of previously unknown impurities that exist in commercial-grade rose bengal in uncontrolled amounts. The requirement to control these impurities is in accordance with International Council on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.

The Company’s IP also includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the combination of RBD and CB (e.g., anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents) for the treatment of a range of solid tumor cancers. US patent numbers are 9,107,887, 9,808,524, 9,839,688, and 10,471,144, with expirations ranging from 2032 to 2035; US patent application numbers include 20200138942.