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IncellDx’s Next Gen HPV/Cervical Cancer Assay (HPV OncoTect 3Dx) Receives Clinical Approval from Costa Rican Ministry of Health

On June 9, 2020 IncellDx, Inc., a global leader in single-cell diagnostics, reported approval by the Costa Rican Ministry of Health of its Next Generation HPV/cervical cancer assay, OncoTect 3Dx (Press release, IncellDx, JUN 9, 2020, View Source [SID1234560944]). This novel assay is the only test to simultaneously detect and quantify 3 molecular markers of cervical cancer—overexpression of oncogenes (E6, E7 mRNA), proliferation, and aneuploidy. Using high throughput flow cytometry, 96 cervical cytology samples can be tested and resulted in less than 4 hours, without having to examine slides.

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"We are thrilled to have received approval for the HPV OncoTect 3Dx assay, thanks to the perseverance of our team and our international collaboration with IncellDx," said Dr. Rodrigo Mora, Ph.D., Professor of Medical Virology, Faculty of Microbiology, University of Costa Rica. "We are so looking forward to start offering this test to women in Costa Rica who are currently at risk of over-treatment. Now, we will finally be able to distinguish and separate HPV infection from HPV disease to contribute to the health of our women and reduce the psychological burden associated with HPV."

Nearly 1.9 million women are at risk of cervical cancer in Costa Rica, and it is the 3rd most common female cancer in the country. Human Papillomavirus (HPV) infection has been directly linked to the development of cervical intraepithelial lesions and increased risk for cervical cancer. The HPV OncoTect 3Dx assay aids in the determination of which patients need to be further evaluated for the presence of high-grade cervical intraepithelial neoplasia.

Dr. Bruce Patterson, chief executive officer of IncellDx, added, "We appreciate the hard work done by Dr. Mora and his team in validating this assay for staging of cervical cancer using the only test in the world that combines three molecular biomarkers in a single assay in intact cells from a liquid-based cytology specimen. This assay is the next step after determining infection with a high-risk HPV genotype to determine the biological behavior of high-risk HPV infections when the overwhelming majority of these infections will not progress to cervical cancer."

C2i Genomics Raises $12 Million in Series A Funding

On June 9, 2020 C2i Genomics ("C2i"), a company dedicated to improving cancer patient lives and outcomes with a breakthrough tumor pattern recognition approach for liquid biopsy, reported that it has raised $12 million in its Series A financing (Press release, C2i Genomics, JUN 9, 2020, View Source [SID1234560943]). The financing was led by Casdin Capital and joined by additional new investors including NFX Capital, The Mark Foundation for Cancer Research and other investors. Proceeds from the financing will be used to fund the development and clinical validation of C2i Genomics’ personalized, real-time solution for monitoring recurrence and treatment response for various types of solid cancers.

"This Series A funding will allow us to take the next major step in our growth and advance our core technology into pilot and pivotal validation studies in several oncology indications," said Asaf Zviran, C2i Genomics’ co-founder, chief executive officer and chief scientific officer. "We believe that the improvement in sensitivity we’ve achieved will allow physicians to quantitatively monitor their patient treatment response and detect treatment failure or disease recurrence months and even years before they would do otherwise. We have built C2i on a solid scientific and technological foundation and are excited to work with our investors and other partners toward the deployment of our cloud-based platform for disease management. The great support of our clinical collaborators from the US, Europe and Asia highlights the global need that underlines our mission to support effective therapy decisions for millions of cancer patients around the world."

C2i Genomics’ innovative solution is based on research performed at the New York Genome Center (NYGC) and Weill Cornell Medicine (WCM) by Dr. Zviran, along with Dr. Dan Landau, core faculty member at the NYGC and assistant professor of Medicine at WCM, who serves as scientific co-founder and member of C2i’s scientific advisory board. C2i then welcomed Dr. Boris Oklander as chief technology officer, and Ezra Sofer as its general manager and chief financial officer, both of whom bring extensive executive leadership and management expertise and experience from their previous roles in the healthcare industry. The technology has been validated through longitudinal clinical cohorts in collaboration with cancer centers in New York and Boston and was recently published in Nature Medicine. This proof-of-concept research was supported by a 2017 grant from The Mark Foundation for Cancer Research.

"The C2i technology allows for the company to develop a bio-platform approach that works across cancer types and allows effective guidance of diverse treatment modalities from surgery and chemotherapy to immunotherapy and targeted therapies." said James Currier, managing partner of NFX Capital. "Such a data-based treatment management platform will produce a network effect, which will increase the value of C2i’s data and services over time. We predict that this is a unique opportunity to build a sector defining company."

Existing liquid biopsy methods focus on detecting specific mutations in targeted panels. Panel-based methods can have limited sensitivity and show only mutation-specific response which do not typically represent the full complexity of the cancer’s response due to tumor heterogeneity. C2i’s liquid biopsy analysis platform can detect and quantify very small amounts of residual disease in the patient’s blood by utilizing a personalized tumor "fingerprint" representing thousands of mutations for each individual patient. This novel genome-wide signature detection, coupled with proprietary mathematical inference models and machine learning techniques, provides ultra-sensitive quantification of the amount of circulating tumor DNA in the patient’s blood, accurately capturing the aggregate response of the heterogenic tumor.

Ultra-sensitive treatment monitoring holds promise to improve patient outcome while reducing the overall cost burden on the health system. Through effective monitoring, C2i technology also offers the opportunity to accelerate clinical trials, aiming to bring lifesaving treatments to the clinic.

"Genomic tools are bringing enormous benefit to the cancer patient treatment through more powerful and precise care and therapeutic development," said Eli Casdin, managing partner of Casdin Capital. "The C2i approach breaks through sensitivity limitations of current approaches by exploiting the team’s unique capabilities at the intersection of genomic and data sciences. The Series A financing catalyzes progress towards making an impact by supporting clinical development partnerships and collaborations with the biopharma industry."

Promega Microsatellite Instability Molecular Test, OncoMate™ MSI Dx Analysis System, CE Marked & Available in Europe

On June 9, 2020 Promega Corporation reported CE marking for the OncoMate MSI Dx Analysis System (OncoMate MSI) as a new in vitro diagnostic (IVD) medical device in Europe (Press release, Promega, JUN 9, 2020, View Source [SID1234560942]). OncoMate MSI is a PCR-based, validated gold standard for determining microsatellite instability (MSI) status in solid tumors.1,2,3 It offers analytical sensitivity and unsurpassed specificity with a short turn-around time.4,5

"European guidelines recommend MSI testing to assess deficient mismatch repair function of solid tumors for a spectrum of cancers, including colorectal cancer and endometrial cancer, in order to reduce morbidity and mortality," said Richard Hamelin, Ph.D., Research Director (Ret) at Inserm. "Data show that OncoMate MSI provides clinicians a valuable DNA-based MSI reading that is complementary to a standard MMR immunohistochemistry panel and can be used as an independent biomarker to predict response with immuno-oncology therapies."

Loss of mismatch repair (MMR) protein function results in tumor cells with DNA MSI.6 MSI testing is an important first step in the molecular characterization related to loss of MMR function, including Lynch Syndrome-related cancers.7,8 A study led by Hamelin shows accumulating evidence suggesting that MSI-High status identifies a subset of colorectal cancers with distinctive biological and clinical properties, emphasizing the importance of simple, accurate markers for detection.9 Using a pentaplex PCR system allows for accurate evaluation of tumor MSI status of DNA with high sensitivity and specificity.9

OncoMate MSI uses the most sensitive panel of markers for MSI status detection, as included in the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) guidelines. Screening cancer patients with these reliable markers can provide pathologists, oncologists, and patients with information that characterizes tumors to help guide care and treatment decisions.10

"Promega MSI technology demonstrates our commitment to developing precise and reliable tools for life scientists around the world," said Heather Tomlinson, Director of Clinical Diagnostics at Promega Corporation. "With the CE marking of OncoMate MSI, Promega aims to make MSI testing more broadly accessible to laboratories within Europe and to aid clinicians in making vital decisions in cancer patient care and treatment."

Promega MSI technology is one of the leading standard tests for MSI status detection in research laboratories and achieved innovation status and priority review by the National Medical Products Administration (NMPA) in China. It has been used extensively in clinical research for more than 15 years and is supported by more than 140 peer-reviewed publications. Promega continues to advance the promise of MSI technology globally and intends to seek regulatory clearance for OncoMate MSI in the United States and China.

To learn more about OncoMate MSI Dx Analysis System, visit: www.promega.com/OncoMateCEIVD

About OncoMate MSI Dx Analysis System

OncoMateTM MSI Dx Analysis System encompasses a complete workflow for MSI determination from DNA extraction to data analysis, offering an easy to use and standardized system. It includes the same validated and endorsed loci as the Promega Research Use Only MSI Analysis System Version 1.2 with the new advantages of a shorter turn-around time and GoTaq MDx DNA polymerase. OncoMate MSI is a fluorescent, multiplex PCR-based test to detect DNA sequence length changes in microsatellite regions of tumor cell DNA relative to the same regions from the patient’s normal cells thereby indicating microsatellite instability. OncoMate MSI targets seven microsatellite markers: five mononucleotide-repeat markers (BAT-25, BAT-26, NR-21, NR-24 and MONO-27) and two pentanucleotide-repeat markers (Penta C and Penta D). These mononucleotide-repeat markers are analyzed to determine MSI status and were selected for high sensitivity and specificity to alterations in repeat lengths in samples containing mismatch repair defects. MSI is a form of genomic instability caused by insertion or deletion of additional bases into DNA microsatellites, regions of repeating bases distributed throughout the human genome. During DNA replication, failure of the mismatch repair system to correct these errors causes MSI.

Press Release Oncology Venture calls first investment tranche of SEK 10 million under its share subscription agreement with Global Corporate Finance

On June 9, 2020 Oncology Venture A/S (Nasdaq First North Stockholm: OV.ST) ("OV" or the "Company") reported that it has called upon Global Corporate Finance (GCF) to invest SEK 10 million in a directed shared issue in accordance with the Company’s share subscription agreement with GCF (Press release, Oncology Venture, JUN 9, 2020, View Source [SID1234560941]). The draw-down notice was issued to GCF on June 9, and the share subscription price shall be calculated as 95% of the daily volume weighted average price (VWAP) of the Company’s shares for the five consecutive trading days following the date of the draw down notice.

The investment is the first investment tranche of up to a total of five such tranches Oncology Venture may request from Global Corporate Finance (New York City, NY, U.S.). Each investment tranche can total up to SEK 10 million.

Provectus Biopharmaceuticals Expands Global Patent Portfolio to India for Cancer Combination Therapy

On June 9, 2020 Provectus (OTCQB: PVCT) reported that the Indian Patent Office (IPO) has granted the Company’s patent application for the combination of investigational autolytic cancer immunotherapy PV-10 and systemic immunomodulatory therapy, such as immune checkpoint blockade (CB) (Press release, Provectus Biopharmaceuticals, JUN 9, 2020, View Source [SID1234560940]). Pfizer, Inc. is a co-assignee on this award. The Company’s cancer combination therapy patent estate provides intellectual property (IP) protection in a number of countries in Asia, Europe, and North America into the 2030s.

New IPO patent 337563 is associated with a family of US patents, including 9,107,887, which is entitled "Combination of local and systemic immunomodulative therapies for enhanced treatment of cancer" and was awarded by the United States Patent and Trademark Office (USPTO) in 2015, and 9,808,524, 9,839,688, and 10,471,144, which were awarded by the USPTO from 2017 to 2019.

The new 2020 IPO patent award for cancer combination therapy follows the Company’s IPO patent 297453, which was awarded in 2018 and protects Provectus’ proprietary manufacturing process used to produce the active pharmaceutical ingredient (API) in the Company’s current and prospective investigational drug products. IPO patent 297453 is associated with a family of US composition of matter and process patents, including 8,530,675, which is entitled "Process for the Synthesis of 4,5,6,7-tetrachloro-3′,6′-dihydroxy-2′,4′,5′,7′-tetraiodo-3H-spiro[isobenzofuran-1,9-xanthen]-3-one (Rose Bengal) and Related Xanthenes" and was awarded by the USPTO in 2013, and 9,273,022 and 9,422,260, which were awarded by the USPTO in 2016.

The Company is also pleased to announce that it received application number 20200138942 from the USPTO for a fifth cancer combination therapy patent application filing, which is based on the abovementioned patent family and includes the combination of PV-10 and two systemic immunomodulatory therapies, such as an anti-CTLA-4 agent (e.g., Yervoy) and an anti-PD-1 agent (e.g., Opdivo). The Company is the sole assignee for this new cancer combination therapy patent application.

The triplet immunotherapy combination of PV-10, Yervoy, and Opdivo for the treatment of uveal melanoma metastatic to the liver (mUM) in patients naïve to CB and refractory to single-agent and combination therapy CB was the subject of the Company’s poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program, held online May 29-31, 2020, entitled "Percutaneous hepatic injection of rose bengal disodium (PV-10) in metastatic uveal melanoma." This study, led by Sapna Patel, MD, Associate Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine of The University of Texas MD Anderson Cancer Center (MDACC), is enrolling patients into a single-center cohort at MDACC of up to 25 mUM patients.

Small molecule-based PV-10 is administered either by cutaneous intratumoral (IT) injection to superficial melanoma and non-melanoma skin cancer tumors (such as basal cell carcinoma, Merkel cell carcinoma, and squamous cell carcinoma) or by percutaneous IT injection to visceral primary and metastatic tumors of the liver (such as hepatocellular carcinoma, metastatic colorectal cancer, metastatic neuroendocrine tumors, and mUM). By targeting tumor cell lysosomes, PV-10 treatment may yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells and a T cell mediated immune response against treatment refractory and immunologically cold tumors.1-3 Adaptive immunity can be enhanced by combining CB with PV-10.4

About PV-10

PV-10 is an investigational new drug undergoing clinical study for adult solid tumor cancers, such as relapsed and refractory cancers metastatic to the liver and metastatic melanoma. PV-10 is also undergoing preclinical study for relapsed and refractory pediatric solid tumor cancers (e.g., neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma)5,6 and relapsed and refractory pediatric blood cancers (such as acute lymphocytic leukemia and acute myelocytic leukemia)7,16.

Tumor Cell Lysosomes as the Seminal 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.8 Cancer progression and metastasis are associated with lysosomal compartment changes9,10, which are closely correlated with (among other things) invasive growth, angiogenesis, and drug resistance11.

PV-10 selectively accumulates in the lysosomes of cancer cells upon contact, disrupting the lysosomes and causing the cells to die. Provectus1,12, external collaborators6, and other researchers14,15,17 have independently shown that PV-10 (RB) triggers each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Cancer Cell Autolytic Death via PV-10: PV-10 induced autolytic cell death, or death by self-digestion, in Hepa1-6 murine HCC cells can be viewed in this Provectus video of the event (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; the event has a duration of approximately one hour). Exposure to PV-10 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; this event has 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 from POETIC using relapsed and refractory human pediatric neuroblastoma cells to show that lysosomes are disrupted upon exposure to PV-10.5

Immune Signaling Pathways: PV-10 causes acute autolytic destruction of injected tumors (i.e., cell death), mediating several identified immune signaling pathways studied to date, such as the release of danger-associated molecular pattern molecules (DAMPs) and tumor antigens that initiate an immunologic cascade where local response by the innate immune system facilitates 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. Other mediated immune signaling pathways that have been identified include PARP cleavage5 and, now, stimulator of interferon genes (STING), which plays an important role in innate immunity16. PV-10 is the first cancer drug that may facilitate multiple, complementary, immune system signaling pathways.17

Orphan Drug Designations (ODDs)

ODD status has been granted to PV-10 by the U.S. Food and Drug Administration for the treatments of metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

Drug Product

Rose bengal disodium (RB) (4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein disodium salt) is a small molecule halogenated xanthene and PV-10’s active pharmaceutical ingredient. The Company manufactures RB using a patented process designed to meet strict modern global quality requirements for pharmaceuticals and pharmaceutical ingredients (Good Manufacturing Practice, or GMP). PV-10 drug product is an injectable formulation of 10% w/v GMP RB in 0.9% saline, supplied in single-use glass vials containing 5 mL (to deliver) of solution, and administered without dilution to solid tumors via IT injection.

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 GMP RB and related halogenated xanthenes are produced, avoiding the formation of previously unknown impurities that exist in commercial grade RB 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 PV-10 and systemic immunomodulatory therapy (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.