On November 5, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a company applying innovative diagnostics to inform disease management and improve patient outcomes, reported the publication of a study validating performance of a novel algorithm designed to integrate the DecisionDx-Melanoma gene expression profile (GEP) test with clinicopathologic features (i31-GEP SLNB) to determine sentinel lymph node biopsy (SLNB) positivity risk in patients with cutaneous melanoma (Press release, Castle Biosciences, NOV 5, 2021, View Source [SID1234594614]).

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DecisionDx-Melanoma is Castle’s risk-stratification GEP test that is designed to predict 5-year risk of metastasis as well as metastasis to the SLN. The test’s Integrated Test Result (ITR) includes the traditional class designation of lowest risk (Class 1A), increased risk (Class 1B/2A) or highest risk (Class 2B), as well as a more precise risk prediction for both SLNB positivity and risk of recurrence, distant metastasis and melanoma survival in patients with stage I, II or III melanoma through the i31- GEP algorithms (SLNB and Risk of Recurrence). The i31-GEP SLNB and ROR are distinct independently validated algorithms that integrate clinicopathologic features with the DecisionDx-Melanoma score.

"The majority of patients who undergo the SLNB surgical procedure receive a negative result," said Robert Cook, Ph.D., senior vice president of research and development of Castle Biosciences and study author. "The i31-GEP SLNB clinical validation data showed that integrating clinicopathologic risk factors with the DecisionDx-Melanoma test provided very high correlation between the predicted and the actual, or observed, rates and a high sensitivity in identifying patients at low risk for SLN metastasis who may be able to safely avoid the SLNB procedure. Importantly, the study demonstrated that the DecisionDx-Melanoma test result was the most important variable in predicting SLN positivity."

The article, titled "Integrating 31-Gene Expression Profiling with Clinicopathologic Features to Optimize Cutaneous Melanoma Sentinel Lymph Node Metastasis Prediction," was published in the peer-reviewed journal JCO Precision Oncology and can be accessed here. The study highlights the development and validation of the i31-GEP SLNB algorithm.

Study background:

National guidelines recommend that an SLNB be offered to patients with >10% likelihood of SLN positivity (typically thought to encompass T2-T4 tumors), but do not recommend SLNB for patients who are thought to have <5% likelihood of a positive SLN (typically thought to encompass T1a tumors without high-risk features).
The decision to perform SLNB is less certain for patients with higher-risk T1 melanomas (T1a tumors with high-risk features or T1b tumors) in which a positive node is expected 5%-10% of the time.
The integrated DecisionDx-Melanoma test result for SLNB (i31-GEP SLNB) was designed to combine DecisionDx-Melanoma’s output, a risk assignment based on GEP analysis, with clinicopathologic risk factors.
The study describes the development and validation of the i31-GEP SLNB, which utilizes a neural network algorithm to integrate the continuous DecisionDx-Melanoma result with patient histologic and clinical features.
The i31-GEP SLNB algorithm was developed in a cohort of 1,398 patients and independently validated on a cohort of 1,674 patients.
Study findings:

In comparison to all clinicopathologic features considered, the DecisionDx-Melanoma continuous score was the most important variable for prediction of a positive SLN, with a P value of less than 0.001.
The i31-GEP SLNB algorithm demonstrated a very high correlation comparing predicted versus observed SLN positivity rates of 0.999 (1.0 is complete correlation).
The i31-GEP SLNB algorithm demonstrated a highly sensitive prediction of SLN positivity rates (95.1%) compared to observed rates.
In patients with T1-T4 tumors, the i31-GEP SLNB increased the percentage of patients predicted to have <5% SLN positivity risk from 8.5%, using current staging guidelines, to 27.7%.
Specifically, for patients predicted to have 5%-10% risk by current guidelines, the i31-GEP SLNB restratified 63% of cases to an SLN positivity risk of <5% or >10%.
The i31-GEP SLNB identified patients with <5% SLN positivity risk, who might forego SLNB, or those with >10% SLN positivity risk, who might be offered SLNB, according to current guidelines.
These data demonstrated that the i31-GEP SLNB could provide personalized risk estimates for SLN positivity, potentially reducing the number of SLNBs and provide additional information to appropriately identify patients at the highest risk of having a positive SLN.
This personalized information may help clinicians and their patients make more informed decisions about the SLNB surgical procedure.
About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. To predict risk of recurrence and likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithms, i31-ROR and i31-SLNB, to produce an integrated DecisionDx-Melanoma test result. Through June 30, 2021, DecisionDx-Melanoma has been ordered 78,277 times for use in patients with cutaneous melanoma.

More information about the test and disease can be found at www.CastleTestInfo.com.

On November 5, 2021 Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’ with its lead drug candidate, lenzilumab, reported two abstracts pertaining to the potential use of lenzilumab in CAR-T will be presented at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) taking place December 11-14, 2021 (Press release, Humanigen, NOV 5, 2021, View Source [SID1234594613]). The society counts more than 18,000 hematologists among its membership from more than 100 countries, and its annual meeting attracts over 30,000 professional attendees.

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"After completing a Phase 3 trial of lenzilumab, in 2021, for the treatment of patients hospitalized with COVID-19 pneumonia, we look forward to advancing our efforts to develop lenzilumab as a complementary therapy to potentially reduce CAR-T associated toxicities and to potentially improve outcomes for non-Hodgkin lymphoma patients," said Adrian Kilcoyne, Chief Medical Officer, Humanigen. "My experience working in the development of CAR-T therapies, which are now currently commercially available, suggests preventing toxicity and optimizing durable response rates remain challenges. Our plans include initiating the Phase 3 SHIELD study of lenzilumab in the first half of 2022 and we may be able to announce interim data at ASH (Free ASH Whitepaper) 2022."

Abstract #2777

Optimized Inhibition of GM-CSF in Preclinical Models of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy

Summary: The abstract describes the evaluation of differential targeting of the GM-CSF ligand using lenzilumab compared to targeting the GM-CSFα receptor using a different antibody in pre-clinical models. The research demonstrated significant differences on CAR-T cell functions and CAR-T cell-monocyte interactions when GM-CSF is neutralized with lenzilumab compared to blocking its receptor with other agents. A key finding is that lenzilumab neutralization of GM-CSF improved CAR-T cell proliferation, but the GM-CSFRα receptor blocking antibody may significantly inhibit CAR-T cell proliferation in a dose-dependent manner. This may have efficacy implications.

Presenter: Evandro Bezerra, MD, Mayo Clinic in Rochester, MN.
Session: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Date: December 12, 2021; 6:00-8:00 PM EST

Abstract #175

A Phase 3 Randomized, Placebo-Controlled, Open-Label, Multi-Center Trial of Lenzilumab to Improve the Safety and Efficacy of CAR-T Cell Therapy in Adults with Relapsed or Refractory Large B-Cell Lymphoma* (The SHIELD Study)

Summary: The abstract describes a planned Phase 3 study of prophylactic lenzilumab administration in sequenced therapy with commercially available CAR-Ts to treat non-Hodgkin lymphoma. The study aim is to determine if lenzilumab can break the efficacy/toxicity linkage associated with CAR-T therapy thereby improving the toxicity and tolerance of CAR-T while maintaining or improving efficacy by neutralizing GM-CSF.

Presenter: Saad Kenderian, MD, principal investigator in the T Cell Engineering Lab at Mayo Clinic in Rochester, MN.
Session: 704. Cellular Immunotherapies: Clinical: Poster I
Date: December 11, 2021; 5:30 PM-7:30 PM EST

* The SHIELD study protocol has been adapted since submission of the abstract to include a broader patient population

On November 5, 2021 Calidi Biotherapeutics, Inc., a clinical-stage biotechnology company at the forefront of stem cell-based delivery of oncolytic viruses, reported that its physician advisor, Maciej S. Lesniak, MD, Department Chair of Neurological Surgery, Feinberg School of Medicine, Northwestern University, will present at the upcoming International Oncolytic Virotherapy Conference (IOVC), which will be held in hybrid format November 5 through November 7, 2021, as both a virtual event and an in-person meeting in Sedona, AZ (Press release, Calidi Biotherapeutics, NOV 5, 2021, View Source [SID1234594612]).

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Dr. Lesniak’s presentation: "Neural Stem Cell Delivery of Oncolytic Virotherapy for Glioma," will focus on the use of stem cells for virotherapy of cancer, featuring clinical findings from a first-in-human, open-label, Phase 1, dose-escalation trial demonstrating strong safety and efficacy signals for the NSC-CRAd-S-pk7 product, which Calidi refers to as NeuroNova (NNV), in patients with newly diagnosed high-grade glioma. Results from the clinical trial are published in The Lancet Oncology (June 29, 2021).

"Malignant glioma has been historically associated with dismal survival rates due to a lack of effective treatment," said Maciej S. Lesniak, MD, Department Chair of Neurological Surgery, Feinberg School of Medicine, Northwestern University. "I’m eager to share the promising results of our recently completed Phase 1 trial examining the safety and activity of NeuroNova in patients with advanced glioma."

In June 2021, Calidi reached an exclusive license agreement with Dr. Lesniak’s team at Feinberg School of Medicine, Northwestern University—designating exclusive commercialization rights to Northwestern’s investigational new drug (IND) application and data generated from the clinical trial, as well as commercial development rights for stem-cell based products loaded with adenovirus. NNV is composed of an immortalized neural stem cell (NSC) line loaded with an engineered oncolytic adenovirus.

"Calidi’s continued collaboration with Dr. Lesniak has been critical to the development and clinical success of our NeuroNova platform," said Allan J. Camaisa, Chairman and CEO of Calidi Biotherapeutics.

Scheduled for Sunday, November 7, Dr. Lesniak’s presentation will occur during Scientific Session 9: Clinical Trials 3 of the IOVC. Hosted by the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper), the conference spans three days, with presentations from credentialed professionals in the following categories: Novel Payloads and Mechanisms of Action, Novel Combinations and Mechanisms of Action, Novel Platforms, and Clinical Trials. A full program schedule and complete list of invited speakers are available at asgct.org/events/iovc.

On November 5, 2021 Reven Holdings, Inc. ("Reven") is a privately held clinical stage biotechnology and pharmaceutical company dedicated to the discovery and development of novel treatment platforms for cancer, viral illnesses, including COVID-19 – and inflammatory disorders (Press release, Reven Holdings, NOV 5, 2021, View Source [SID1234594611]).

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Reven reported the publication of a peer-reviewed article in the prestigious medical journal Frontiers in Oncology. The article reports a systematic analysis of the antibody responses to COVID-19 vaccination in cancer patients. This analysis was completed in collaboration with the Hacettepe University Cancer Institute team in Ankara/Turkey and Ares Pharmaceuticals, LLC in St. Paul, MN. COVID-19 vaccine seroconversion rates (i.e., antibody development success) were substantially lower in patients with hematologic malignancies (example: leukemias and lymphomas) and cancer patients receiving chemotherapy or immunosuppressive treatments than controls who did not have cancer.

The article, "Antibody Responses to COVID-19 Vaccination in Cancer: A Systematic Review," has been published in Frontiers in Oncology, and it is available online. To view the online publication, click here: http://journal.frontiersin.org/article/10.3389/fonc.2021.759108/full?&utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Oncology&id=759108

Citation: Guven DC, Sahin TK, Kilickap S and Uckun FM (2021) Antibody Responses to COVID-19 Vaccination in Cancer: A Systematic Review. Front. Oncol. 11:759108. doi: 10.3389/fonc.2021.759108

The corresponding author, Executive Vice-President for Global Medical Affairs and Chief Medical Officer of Reven, Dr. Fatih Uckun MD PhD, explained: "We are reporting the challenges for oncology patients in achieving adaptive immunity against COVID-19. This report illustrates the importance of developing effective treatments against high-risk COVID-19 and COVID-19-associated cytokine release syndrome (CRS) considering the poor performance of vaccinations in cancer patients. Reven’s clinical development efforts for our lead COVID-19 drug candidate RJX are aimed at reducing the risk of life-threatening complications of COVID-19 and accelerating the full recovery of high-risk patients, such as those with cancer."

"This paper illustrates the importance of our randomized trial to address unmet needs in COVID-19 therapy," added Peter Lange, the CEO of Reven.

Reven had recently announced the successful completion of Part 1 of the Two-Part, Two Cohort Multi-Center Phase I/II trial of RJX in hospitalized high-risk COVID-19 patients. 12 hospitalized adult patients with symptomatic high-risk COVID-19 pneumonia and abnormally elevated inflammation markers in the blood were treated with daily intravenous infusions of RJX in combination with standard of care. Nine (9) of the 12 patients, including 3 patients with hypoxemic respiratory failure, had shown rapid clinical recovery with normalization of the abnormally elevated inflammation markers in the blood and were discharged from hospital at a median of 5 days. All patients tolerated their RJX infusions without any side effects. An Independent Data and Safety Monitoring Board (DSMB) that oversees and acts independently from the Reven project team had reviewed the clinical data in all 12 patients, and approved the initiation of the randomized, double-blind Part 2 portion of the Phase 2 study.

10 patients have already been enrolled and dosed in the randomized, double-blind, placebo-controlled Part 2 portion of the Phase 2 study (ClinicalTrials.gov Identifier: NCT04708340; View Source). This FDA-approved controlled clinical trial is aimed at evaluating the efficacy and safety of RJX in side-by-side comparison with a placebo as an adjunct to standard of care in hospitalized COVID-19 patients. Michael Volk, Director and Chief Strategy Officer of Reven, stated, "We are excited about the rapid progress in our clinical program against COVID-19."

"We are expecting topline data from this very important study by end of 2021," said Brian Denomme, Reven’s President.

"We are diligently advancing the clinical development of RJX," said Fatih Uckun, MD PhD.

RJX is an intravenous (IV) formulation of a patented first-in-class pharmaceutical composition containing a specific mixture of antioxidant and anti-inflammatory ingredients that is being developed for more effective treatment of patients with inflammatory disorders, including COVID-19 patients with viral sepsis, multi-system inflammation, cytokine release syndrome (CRS), shock, ARDS, and multi-organ failure. The FDA-approved clinical trial is aimed at evaluating the efficacy and safety of RJX as an adjunct to standard of care in hospitalized COVID-19 patients, who have high-risk features for progression to severe disease and ARDS and patients with hypoxemic respiratory failure receiving either non-invasive positive pressure ventilation (NIPPV) or high flow oxygen, who have not yet developed ARDS to require mechanical ventilation. Since RJX is a potent anti-oxidant and anti-inflammatory agent that has been shown to reduce the tissue-level oxidative stress in multiple organs in animal models of severe systemic inflammation, shock, cytokine storm, and multiorgan failure, Reven hopes that it will contribute to prevention of progression of COVID-19 and its faster resolution in high-risk patients.

About Rejuveinix (RJX)

RJX is an intravenous (IV) formulation of physiologically compatible compounds that is being developed for more effective treatment of patients with sepsis, including COVID-19 patients with viral sepsis and acute respiratory distress syndrome (ARDS).

On November 5, 2021 Bluestar Genomics, an innovative company leading the development of next-generation liquid biopsy approaches to early cancer detection, reported the presentation of new analytical performance data on its proprietary non-invasive pancreatic cancer test at the American Pancreatic Association (APA) annual meeting (Press release, Bluestar Genomics, NOV 5, 2021, View Source [SID1234594610]). Data from the study showed that the company’s test detected a pancreatic cancer signal in people across various age groups, including patients with new-onset diabetes, occurring in 25% of new pancreatic cancer cases.

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Bluestar Genomics’ pancreatic cancer test uses a standard blood draw to assess whether an individual has an abnormal DNA signal associated with pancreatic cancer. This one-of-its-kind test would allow for early diagnosis of pancreatic cancer, one of the deadliest cancers in part because there are no existing screening methods to enable early detection. When found early, accurate detection of pancreatic cancer enables more timely, potentially curative surgical and therapeutic options for patients. People with new-onset diabetes are at high-risk of pancreatic cancer. Out of an estimated 60,000 patients diagnosed each year with pancreatic cancer in the U.S. alone, nearly 25% are found to have new-onset diabetes before a pancreatic cancer diagnosis.

"Along with our test’s recent designation by the FDA as a breakthrough device, the findings from this study presented at APA underscore the opportunity we have to make a positive difference for patients by bringing this pancreatic cancer test to market," said Samuel Levy, Ph.D., chief executive and chief scientific officer at Bluestar Genomics and lead author of the study. "Based on these results, we are moving forward with completing the analytical validation in the coming months and making a CLIA laboratory developed test available next year."

Unlike other liquid biopsy cancer tests, this pancreatic cancer-focused test is performed with Bluestar Genomics’ groundbreaking epigenomics technology platform that uses state-of-the-art machine learning coupled with a DNA-based 5-hydroxymethylcytosine (5hmC) biomarker as a precise screening method for detecting cancer at earlier stages. By combining a novel 5-hydroxymethylation enrichment assay with high-throughput sequencing, it is possible to generate powerful predictive models using machine learning to enable the detection of pancreatic cancer in patients with high accuracy.

Pancreatic cancer is the third-leading cause of cancer death in the U.S., surpassing common cancers such as breast and prostate. Bluestar Genomics’ test has the potential to screen an estimated one million adults diagnosed annually with new-onset diabetes in the U.S. for the early detection and treatment of pancreatic cancer, which could enable better patient outcomes.

The study presented at APA included 917 patients, examining whole blood samples from 117 patients with pancreatic cancer and 800 non-cancer control patients, with and without new-onset diabetes. The predictive model was trained on samples using 5hmC signals from cell-free DNA. When applied to the validation set, 50% of which were early stage (stages I and II) disease, this model showed a median of 51.5% sensitivity and 98% specificity. Results from the study demonstrated pancreatic cancer signal detection in plasma-derived cell-free DNA using 5hmC profiles. Overall, these findings showed that the model performed consistently well between the training and independent validation datasets.

In addition to completing the analytical validation, Bluestar Genomics is planning a large clinical study to further validate the use of this test to detect pancreatic cancer in patients with new-onset diabetes.

With the commercialization efforts for the test focused on pancreatic cancer as well as a growing pipeline of other epigenomic assays, the company also announced that Jim Vaughn, R. Ph., has joined the company as its chief commercial officer. Vaughn brings more than 20 years of strategic leadership experience in commercializing molecular tests in oncology, including a breadth of expertise in sales, marketing, and reimbursement strategy. Most recently, Vaughn led efforts to successfully commercialize the Oncotype DX portfolio at Genomic Health/Exact Sciences, where he was the global chief commercial officer.

"Liquid biopsy continues to show great promise in improving cancer patient survival," said Vaughn. "Our epigenomics approach is to focus on the highest-risk cancers with the greatest needs, starting with pancreatic and certain women’s cancers. I look forward to leading our efforts to bring new-generation liquid biopsy tests to physicians and patients to enable curative therapies."

"The positive data at APA along with Jim’s appointment as CCO provide confidence for the company to move forward with commercial planning for our first product, with the goal of developing a pipeline of tests employing our unique type of epigenomics analysis," said Levy.