Newly Published American Gastroenterological Association Clinical Practice Update Supports Esophageal Precancer Screening Using Lucid Diagnostics’ EsoGuard® and EsoCheck® Technologies

On August 4, 2022 Lucid Diagnostics Inc. (Nasdaq: LUCD) ("Lucid"), a commercial-stage, cancer prevention medical diagnostics company, and majority-owned subsidiary of PAVmed Inc. (Nasdaq: PAVM, PAVMZ) ("PAVmed"), reported that a recently published American Gastroenterological Association ("AGA") clinical practice update supports esophageal precancer ("Barrett’s Esophagus," "BE") screening to prevent highly lethal esophageal cancer ("EAC") utilizing its EsoGuard Esophageal DNA Test ("EsoGuard") on samples collected with its EsoCheck Cell Collection Device ("EsoCheck") (Press release, Lucid Diagnostics, AUG 4, 2022, View Source [SID1234617607]).

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The clinical practice update entitled "AGA Clinical Practice Update on New Technology and Innovation for Surveillance," the first such update since 2011, was recently published online in the journal, Clinical Gastroenterology and Hepatology. The expert review was commissioned by the AGA’s Clinical Practice Update Committee, its Center for GI Innovation and Technology, and Governing Board to "provide timely guidance on a topic of high clinical importance…" Senior author Srinadh Komanduri M.D., M.S., Professor of Medicine and Surgery, Associate Chief, Division of Gastroenterology and Hepatology and Director of Endoscopy at the Feinberg School of Medicine, Northwestern University, is a member of Lucid’s Medical Advisory Board.

The AGA update mirrors the recently updated American College of Gastroenterology ("ACG") clinical guideline on the same topic, by acknowledging the "significant need for noninvasive screening tools that are easy to administer, patient friendly, and cost-effective for the detection of BE," and endorsing, for the first time, such tools as an acceptable alternative to endoscopy to directly address this need.

Best Practice Advice 2: Non-Endoscopic Cell Collection Devices may be considered as an option to screen for BE.

The clinical practice update specifically mentions EsoCheck, along with Lucid’s EsophaCap device, as such "Non-endoscopic Cell Collection Devices" – the only such devices commercially available in the United States – indicating that they "have demonstrated excellent tolerability, safety, and sensitivity for the diagnosis of BE." The authors cite the seminal NIH-funded multicenter, case-control study published in 2018 in Science Translational Medicine, which demonstrated that EsoGuard is highly accurate at detecting esophageal precancer and cancer, including on samples collected with EsoCheck.

"We are gratified that the AGA has joined the ACG in updating their clinical practice guidelines to recognize the role that groundbreaking technologies, such as EsoGuard and EsoCheck, can play in driving widespread esophageal precancer screening to prevent esophageal cancer deaths," said Lishan Aklog M.D., Lucid’s Chairman and Chief Executive Officer. "We now have a consensus. The two leading gastroenterology professional associations support the use of our nonendoscopic tools as an acceptable alternative to endoscopy – which has unequivocally failed as a screening tool despite over a decade of clinical guidelines recommending screening of at-risk patients. This ongoing failure to screen makes the thousands of esophageal deaths in the U.S. each year a profound and preventable tragedy, which we are determined to eliminate."

The clinical practice update also significantly expands the target population for esophageal precancer screening, including for EsoGuard and EsoCheck, by recommending, for the first time, screening in at-risk patients without symptoms of reflux. The AGA does so by adding a history of chronic gastroesophageal disease ("GERD," commonly known as chronic heartburn) as merely an additional, seventh, risk factor to the six risk factors for BE and EAC that have traditionally identified at-risk symptomatic patients recommended for screening. As a result, chronic symptomatic GERD is no longer a mandatory prerequisite and asymptomatic patients with three other risk factors are now considered appropriate for screening.

Best Practice Advice 1: Screening with standard upper endoscopy may be considered in individuals with at least 3 established risk factors for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC), including individuals who are male, non-Hispanic White, age >50 years, have a history of smoking, chronic GERD, obesity or a family history of BE or EAC.

It is estimated that approximately 40% of GERD patients have "silent GERD" without classic symptoms of heartburn, representing an estimated thirty million persons in addition to the estimated fifty million U.S. adults with weekly symptoms of GERD. The AGA experts based their expansion of the target screening population on a growing consensus, driven by data indicating that over 50% of U.S. patients diagnosed with esophageal cancer would not have qualified for screening per traditional clinical practice guidelines – nearly all because they lacked symptoms of GERD. A recently launched NIH-funded and Lucid-supported study, Detection of Barrett s Esophagus in Patients Without GERD Symptoms, seeks to directly demonstrate that EsoGuard performed by Lucid on samples collected with EsoCheck can detect esophageal precancer in such asymptomatic patients.

"We applaud this bold move by the AGA, which represents a profound paradigm shift in how we view screening for esophageal precancer," said Dr. Aklog. "Based on data its experts cite, removing symptomatic GERD as a mandatory prerequisite for screening has the potential to dramatically increase our ability to prevent esophageal cancer deaths through esophageal precancer screening. We believe that ongoing studies, including the NIH-funded ‘non-GERD’ study we are supporting, will provide additional clinical evidence to support the use of EsoGuard and EsoCheck in asymptomatic at-risk patients."

About EsoGuard and EsoCheck

Millions of patients with GERD are at risk of developing esophageal precancer and a highly lethal form of esophageal cancer ("EAC"). Over 80% of EAC patients die within five years of diagnosis, making it the second most lethal cancer in the U.S. The mortality rate is high even in those diagnosed with early stage EAC. The U.S. incidence of EAC has increased 500% over the past four decades, while the incidences of other common cancers have declined or remained flat. In nearly all cases, EAC silently progresses until it manifests itself with new symptoms of advanced disease. All EAC is believed to arise from esophageal precancer, which occurs in approximately 5% to 15% of at-risk GERD patients. Early esophageal precancer can be monitored for progression to late esophageal precancer which can be cured with endoscopic esophageal ablation, reliably halting progression to cancer.

Esophageal precancer screening is already recommended by clinical practice guidelines in millions of GERD patients with multiple risk factors, including age over 50 years, male gender, White race, obesity, smoking history, and a family history of esophageal precancer or cancer. Unfortunately, fewer than 10% of those recommended for screening undergo traditional invasive endoscopic screening. The profound tragedy of an EAC diagnosis is that likely death could have been prevented if the at-risk GERD patient had been screened and then undergone surveillance and curative treatment.

The only missing element for a viable esophageal cancer prevention program has been the lack of a widespread screening tool that can detect esophageal precancer. Lucid believes EsoGuard, performed on samples collected with EsoCheck, is the missing element – the first and only commercially available test capable of serving as a widespread screening tool to prevent esophageal cancer deaths through the early detection of esophageal precancer in at-risk GERD patients. An updated American College of Gastroenterology clinical practice guideline and an American Gastroenterological Association clinical practice update both endorse nonendoscopic biomarker tests as an acceptable alternative to costly and invasive endoscopy for esophageal precancer screening. EsoGuard is the only such test currently available in the United States.

EsoGuard is a bisulfite-converted NGS DNA assay performed on surface esophageal cells collected with EsoCheck, which quantifies methylation at 31 sites on two genes, Vimentin (VIM) and Cyclin A1 (CCNA1). The assay was evaluated in a 408-patient, multicenter, case-control study published in Science Translational Medicine and showed greater than 90% sensitivity and specificity at detecting esophageal precancer and cancer.

EsoCheck is an FDA 510(k) and CE Mark cleared noninvasive swallowable balloon capsule catheter device capable of sampling surface esophageal cells in a less than five-minute office procedure. It consists of a vitamin pill-sized rigid plastic capsule tethered to a thin silicone catheter from which a soft silicone balloon with textured ridges emerges to gently swab surface esophageal cells. When vacuum suction is applied, the balloon and sampled cells are pulled into the capsule, protecting them from contamination and dilution by cells outside of the targeted region during device withdrawal. Lucid believes this proprietary Collect+Protect technology makes EsoCheck the only noninvasive esophageal cell collection device capable of such anatomically targeted and protected sampling. The sample is sent by overnight express mail to Lucid’s CLIA-certified, CAP-accredited laboratory, LucidDx Labs, for EsoGuard testing.

Thermo Fisher Scientific Introduces Highly Sensitive Research Assays for Measurable Residual Disease Detection in Myeloid Malignancies

On August 4, 2022 Thermo Fisher Scientific reported a next-generation sequencing (NGS)-based assay for research in myeloid measurable residual disease (MRD) (Press release, Thermo Fisher Scientific, AUG 4, 2022, View Source [SID1234617606]). As the first NGS-based tests to support both DNA and RNA input, the Ion Torrent Oncomine Myeloid MRD Assays (RUO)* provide a comprehensive and highly sensitive MRD assessment from blood and bone marrow samples.

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Acute myeloid leukemia (AML) is characterized by rapid disease progression and can be fatal if not treated promptly. Depending on their interventions, the number of AML patients who experience relapsed disease can be as high 78%1. Detecting remaining mutations after treatment can help identify the presence of residual disease and guide patient prognosis and further treatment decisions. This is driving a growing need for an MRD detection methods that can simultaneously track mutations across multiple genes with high sensitivity.

Current MRD detection methods do not evaluate individual mutations or can only track a very limited number at once. Thermo Fisher’s Myeloid MRD Assay has been designed to enable simultaneous testing and identification of more than 90% of common AML mutations and fusions, providing insights to guide the future of clinical applications, standards and drug development.

"MRD can help predict potential relapse in cancer patients but is not widely used for patients with AML due to lack of accurate, reproducible tests," said Luca Quagliata, global head of medical affairs at Thermo Fisher Scientific. "With the Myeloid MRD Assay, laboratories may perform comprehensive MRD analysis of mutations in myeloid samples to inform future clinical options. We are also working with the Foundation for the National Institutes of Health Biomarkers Consortium as they assess future requirements for validation and standardization of MRD as a biomarker, with the goal of improving care and advancing treatment development for patients with AML."

The Myeloid MRD Assay enables sensitive variant detection as low as 0.05% allele frequency for key DNA mutations in 33 genes and evaluation of more than 900 isoforms in 43 RNA fusion driver genes – including many targets for which there are no established assays to-date. The end-to-end workflow delivers results in as little as two days with an integrated informatics pipeline and reporting tool that can help to minimize user hands-on time and speed up time to results.

"There is a critical need for more effective disease monitoring and treatment for patients with AML who are at high risk of relapse. The MRD biomarker will be used to better understand disease progression and guide therapy decisions in the future, and as such MRD assessment is becoming an important part of cancer research today," said Bevan Tandon, MD, director of hematopathology and molecular pathology at Pathline, a leading provider of specialized pathology services. "By introducing an assay that can be evaluated as a more accurate and comprehensive way to measure residual disease, we can begin to make strides to realize the true clinical potential of MRD to improve patient outcomes."

To learn more about the Ion Torrent Oncomine Myeloid MRD Assay (RUO), please visit: www.oncomine.com/myeloid-mrd-ngs-assay

The Real-World Incidence of Relapse in Acute Myeloid Leukemia (AML): A Systematic Literature Review (SLR); Blood, Nov. 29, 2018.
*For research use only. Not for use in diagnostic procedures.

AnHeart Therapeutics to Present Poster and Host Investigator Meeting at WCLC 2022

On August 4, 2022 AnHeart Therapeutics reported it will host an investigator meeting in addition to a e-poster presentation at the World Conference on Lung Cancer (WCLC) in Vienna, Austria at 11:00 am ET on Sunday, Aug. 7, 2022 (Press release, AnHeart Therapeutics, AUG 4, 2022, View Source [SID1234617605]).

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Ignatius Ou, M.D., Ph.D., Professor of Medical Oncology, University of California Irvine School of Medicine, along with members of AnHeart’s clinical development team and study investigators, will discuss the most recent clinical data of taletrectinib and the current status of the TRUST-II clinical trial for its ROS-1 inhibitor taletrectinib in ROS1-positive non-small cell lung cancer (NSCLC).

Taletrectinib received FDA granted Breakthrough Therapy Designation (BTD) for the treatment of adult patients with advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who are ROS1 tyrosine kinase inhibitor (TKI) treatment naïve or previously treated with crizotinib.

Details of the e-poster presentation at WCLC 2022:

Abstract Title: TRUST-II: A Global Phase II Study for Taletrectinib in ROS1-fusion Positive Lung Cancer and Other Solid Tumors
Session: EP08.02 – Metastatic Non-small Cell Lung Cancer – Molecular Targeted Treatments
Final Program #: EP08.02-118
Author: Misako Nagasaka, M.D. Ph.D., University of California Irvine, School of Medicine

E-posters will be displayed on both days of the conference from August 7-8, 2022, 09:45 – 18:00. For more information, visit: View Source

The e-poster, as with other selected presentations regarding developments in AnHeart’s business given by management at certain investor and medical conferences, can be found on the company’s website, www.anhearttherapeutics.com, under Publications.

American Gastroenterological Association (AGA) Clinical Practice Update States That TissueCypher® May Be Beneficial for Risk-Stratification of Patients with Non-Dysplastic Barrett’s Esophagus

On August 4, 2022 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported that the American Gastroenterological Association (AGA) recently published a best practice advice article stating that the TissueCypher Barrett’s Esophagus test may be beneficial for risk-stratification of patients with non-dysplastic Barrett’s esophagus (BE) (Press release, Castle Biosciences, AUG 4, 2022, View Source [SID1234617604]). TissueCypher is Castle’s test for patients with BE that is designed to predict progression to high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC), a form of esophageal cancer. The best practice advice article from the AGA, titled "AGA Clinical Practice Update on New Technology and Innovation for Surveillance and Screening in Barrett’s Esophagus: Expert Review," was recently published online in Clinical Gastroenterology and Hepatology and can be viewed here.

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"TissueCypher uses artificial intelligence to provide clinicians with critical information about a patient’s risk of developing HGD or EAC beyond what is possible through traditional pathology review," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "TissueCypher is designed to identify patients diagnosed with Barrett’s esophagus who may progress to HGD or EAC at a rate five to ten times higher than the current standard of care.1 This type of personalized risk-stratification information can potentially save lives when patients at high-risk of progression are identified early and provided with risk-appropriate treatments."

"Current approaches for risk stratification of patients with BE, both in community practice and academic clinical settings, are limited to subjective systems that have failed to stem the rapid rise in the incidence of EAC over the last few decades," said Robert Cook, Ph.D., senior vice president of research and development at Castle Biosciences. "TissueCypher can be a game-changing innovation in this clinical area through its ability to identify patients at risk of progression to HGD and EAC, who are often missed due to reliance on traditional histopathology and clinical variables, and also predict future progression to esophageal cancer, two, three or even five years post endoscopy. Based on the published clinical data, the AGA agreed that TissueCypher may be beneficial as part of an improved care pathway for managing patients with BE."

AGA Clinical Practice Update

AGA’s clinical practice updates present the current state-of-the-art guidance and include a combination of evidence-based information, and when not available, best consensus opinion concerning the management of gastrointestinal (GI) diseases.2 AGA’s latest update on BE was an expert review commissioned jointly by the AGA Institute Clinical Practice Updates Committee, the AGA Center for GI Innovation and Technology and the AGA Governing Board. It includes a number of Best Practice Advice statements (BPAs) intended to provide practical advice on the management of BE based on expert opinion and a review of existing literature.

The potential risk-stratification benefit of TissueCypher in the management of patients with BE is included in BPA 9 in the recent update: "Tissue systems pathology-based prediction assay may be utilized for risk-stratification of patients with non-dysplastic BE."

Several clinical studies were cited as evidence in the BPA.3-6 These studies provide further support for the overall accuracy and strong, independent predictive ability of TissueCypher in risk-stratifying patients for progression to esophageal cancer, by identifying both high-risk patients who may be missed by the current standard of care as well as low risk patients who may be able to avoid unnecessary treatments.

About TissueCypher Barrett’s Esophagus Test

The TissueCypher Barrett’s Esophagus test is Castle’s precision medicine test designed to predict future development of high-grade dysplasia (HGD) and/or esophageal cancer in patients with Barrett’s esophagus (BE). The TissueCypher Barrett’s Esophagus test is indicated for use in patients with endoscopic biopsy confirmed BE that is graded non-dysplastic (NDBE), indefinite for dysplasia (IND) or low-grade dysplasia (LGD); its clinical performance has been supported by nine peer-reviewed publications of BE progressor patients with leading clinical centers around the world. The test received Advanced Diagnostic Laboratory Test (ADLT) status from the Centers for Medicare & Medicaid Services (CMS) in March 2022.

invoX Pharma Extends Tender Offer to Acquire F-star Therapeutics, Inc.

On August 4, 2022 invoX Pharma Limited ("invoX"), a wholly owned subsidiary of Sino Biopharmaceutical Limited ("Sino Biopharm") (HKEX 1177 HK), focused on research and development (R&D) and business development activities outside of China, and F-star Therapeutics, Inc. ("F-star") (NASDAQ:FSTX), a clinical-stage biopharmaceutical company pioneering bispecifics in immunotherapy so more people with cancer can live longer and improved lives, reported that invoX has extended the expiration of its previously announced tender offer for all of the issued and outstanding shares of F-star common stock for a price of $7.12 per share (Press release, InvoX Pharma, AUG 4, 2022, View Source [SID1234617603]). The tender offer is now scheduled to expire at 05:00 p.m., Eastern Time, on September 19, 2022, unless it is further extended. The tender offer was previously scheduled to expire at one minute after 11:59 P.M., Eastern time, on August 3, 2022.

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The tender offer is being extended in order to allow additional time for the satisfaction of the regulatory conditions to the offer. The depositary for the tender offer has advised invoX that as of the previous expiration time there were validly tendered and not withdrawn a total of approximately 13,026,582 shares of F-star common stock, and approximately 2,704,867 shares of F-star common stock tendered pursuant to a notice of guaranteed delivery.

All terms and conditions of the tender offer remain unchanged during the extension period. F-star shareholders who have already tendered their shares do not have to re-tender their shares or take any other action as a result of the extension. Complete terms and conditions of the tender offer are set forth in the Offer to Purchase, Letter of Transmittal and other related materials, which have been filed by invoX with the Securities and Exchange Commission ("SEC") on July 7, 2022, as amended. In addition, F-star filed a Solicitation/Recommendation Statement on Schedule 14D-9 with the SEC on July 7, 2022, as amended, which includes, among other things, the recommendation of F-star’s board of directors that F-star stockholders tender all of their shares in the tender offer.

The Information Agent for the tender offer is Innisfree M&A Incorporated. The Depositary and Paying Agent for the tender offer is Computershare Trust Company, N.A. For all questions relating to the tender offer, please call the Information Agent, Innisfree M&A Incorporated toll-free at (888) 750-5830; banks and brokers may call collect at (212) 750-5833.

Advisors

PJT Partners is acting as financial advisor to invoX, and Morgan Stanley & Co. LLC is acting as financial advisor to F-star. Shearman & Sterling LLP is serving as legal counsel to invoX and Sino Biopharm and Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. is serving as legal counsel to F-star.