On February 17, 2022 College of American Pathologists (CAP) reported A new evidence-based guideline published can help improve how pediatric and adult patients with the most common type of primary brain tumor, diffuse glioma, are diagnosed and managed (Press release, College of American Pathologists, FEB 17, 2022, View Source [SID1234608254]).

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"Molecular Biomarker Testing for the Diagnosis of Diffuse Gliomas," published in an early online edition of Archives of Pathology & Laboratory Medicine, sets forth 13 recommendations to guide biomarker testing of these tumors. Diffuse gliomas affect approximately 15,000 people in the US each year and present with widely variable clinical courses and treatment approaches.

"Our understanding of diffuse gliomas as discrete genetic and clinical entities has advanced markedly in the last decade, making molecular testing an established component of their integrated diagnosis," explains guideline chair Daniel Brat, MD, PhD, FCAP. "This allows for a more refined definition of disease and better prediction of both prognosis and therapeutic response."

Traditionally, diffuse gliomas have been classified by their microscopic properties as astrocytomas, oligodendrogliomas, or oligoastrocytomas ranging from World Health Organization (WHO) grades 2 to 4. And while there is some standardization around molecular-level definitions and classifications, the molecular profiles and genetic alterations of diffuse gliomas can vary widely, as can the testing methods that pathologists use to assess them.

With the new CAP guideline, clinical teams now have evidence-based guidance for diffuse glioma molecular testing more broadly, which can help improve the diagnosis, prognosis, and therapeutic care for patients.

Working across the clinical spectrum, three societies collaborated with the CAP on the guideline: the Society for Neuro-Oncology, the American Association of Neuropathologists, and the Association for Molecular Pathology.

Most notably, the guideline recommendations:

Call for IDH mutation testing for all diffuse gliomas in the appropriate clinical and radiologic setting.
Address the use of tests that assess the status of several genetic alterations that allow pathologists to classify diffuse gliomas according to the WHO classification schema.
Offers guidance specific to biomarker testing in pediatric patients with diffuse gliomas.
Under Dr. Brat’s leadership, an expert panel screened more than 4,000 titles and abstracts, reviewed 703 manuscripts, and extracted data from 188 studies to develop the recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach—a common, transparent method for grading quality (or certainty) of evidence and strength of recommendations.

Consistent with the CAP’s guideline process and principles, which follow the National Academy of Medicine’s standards, the guideline will be reviewed in four years, or earlier if evidence becomes available that could potentially alter the original guideline recommendations.

On February 17, 2022 Repertoire Immune Medicines, Inc. reported it has entered a sponsored research agreement with UMass Chan Medical School (UMass Chan) to identify the specific T cell and antigen pairs involved in causing the onset and progression of the autoimmune disease vitiligo (Press release, Repertoire, FEB 17, 2022, View Source [SID1234608253]). The potential discovery of these immunogenic drivers of vitiligo could be used to develop antigen-specific therapeutic candidates for this disease.

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The research team at UMass Chan will be led by John E. Harris, M.D., Ph.D., Chair and Professor of Dermatology and Director of the Vitiligo Clinic and Research Center.

"In autoimmune diseases, the best therapeutic options typically act broadly to suppress the immune system, which can lead to other complications for patients. One of the challenges to discovering new treatment options for vitiligo is the significant complexity of the immune system," said Dr. Harris. "We understand the role of the T cell but have not been able to identify the specific codes directing their function. The opportunity to combine our expertise in vitiligo with Repertoire’s DECODE technology means that, for the first time, we may be able to advance from translational insight to novel, antigen-specific therapies."

Vitiligo is a chronic autoimmune disease in which CD8+ T cells kill melanin-producing cells, leading to the loss of skin pigmentation. In autoimmune diseases like vitiligo, the immune system directs T cells to target and damage healthy cells. It is unknown exactly why this occurs, but it is understood that the immune system activates T cells through codes communicated by antigens that direct T cell activity. If the codes directing the CD8+ T cells can be identified, then it may be possible to develop an immunotherapy that targets these cells and prevents them from killing healthy cells.

"The deep expertise and clinical experience that the UMass Chan team has in the field of vitiligo makes this an ideal partnership for Repertoire. We will be able to apply the proprietary technology in our DECODE platform to assess and potentially identify the key drivers of the dysregulated immune response underlying this autoimmune disease, specifically the T cells and the antigens that activate them," said Anthony Coyle, Ph.D., President, Research and Development, Repertoire Immune Medicines. "Repertoire’s DECODE technology also provides us with the potential to design targeted immunotherapies for vitiligo."

About the DECODE Platform

The DECODE platform is a powerful discovery engine that characterizes essential elements of the immune synapse. In particular, the platform identifies T cell receptor-antigen pairs in the context of other important features of the immune synapse, such as T cell function and how these antigens are presented by molecules on antigen-presenting cells, known as major human leukocyte antigen, or HLA, molecules. Repertoire intends to utilize these insights into key drivers that govern immune function to design and develop novel immune product candidates.

On February 17, 2022 REVEAL GENOMICS, S.L., a Barcelona-based biotechnology start-up that is seeking to revolutionize precision oncology through diagnostic innovation, reported that has launched its first genomic test (Press release, REVEAL GENOMICS, FEB 17, 2022, View Source [SID1234608252]). The HER2DX test predicts the risk of HER2+ breast cancer recurrence in newly diagnosed patients and the likelihood that they will respond to pharmacological treatment. This innovative tool, which combines a patient’s clinical data and the tumor’s genomic profile, is the world’s first specialized genomic test for HER2+ breast cancer.

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"This is our first product launch. It encapsulates our vision, which is to help patients and physicians improve outcomes and quality of life by using more accurate information," says Dr. Patricia Villagrasa-Gonzalez, CEO of REVEAL GENOMICS.

HER2DX is a 27-gene plus clinical feature-based classifier that provides accurate estimates of the risk of recurrence and the probability of achieving a response to anti-HER2 drugs in early-stage HER2+ breast cancer. HER2DX is currently provided as a Laboratory Developed Test (LDT) whose quality system is based on the UNE-EN-ISO 9001:2015 standard for collecting, receiving, and processing biological samples. It is also undergoing ISO 15189 accreditation. The reliability of the test has been described in a study1 published in The Lancet’s EBioMedicine.

HER2DX uses smart analytical software to stratify patients into low- and high-risk groups. The HER2DX algorithm was derived from a dataset of 434 patients and was validated in an external dataset of 268 patients. The algorithm was also validated using the data of more than 1,000 patients available from public datasets.

HER2DX is performed on RNA isolated from FFPE breast cancer tissues where only one sample is necessary. The results are obtained in 7-10 working days. The current assay measures the expression level of 27-genes by digital multiplex technology, and then REVEAL GENOMICS proprietary software, weighted together with clinical variables, outputs an individual patient-level risk score and a pCR likelihood score.

An excellent debut on the diagnostic test market
As a result of the launch of the HER2DX test in Spain in January of this year, the company has already signed deals with Spanish private hospitals, which now include the test in their treatment portfolio. "Based on our stepwise reimbursement approach, we are initially targeting hospitals in Spain and Italy and will subsequently be expanding to other E.U. countries and the U.S., where we are exploring marketing strategic partners," Dr. Villagrasa-Gonzalez explains.

Another goal of the company for upcoming years is to see HER2DX become the routine test option in public and private hospitals. Consequently, it is currently conducting the required clinical studies so that the test is recommended in national and international clinical guidelines and so that it can be covered by health reimbursement arrangements in the short term.

Dr. Villagrasa-Gonzalez adds that "over the past few months, we have put a lot of effort into bringing HER2DX to market. Considering that the company has only been in existence for 18 months, to have developed and brought our first product to market is definitive proof that we have a solid project."

REVEAL GENOMICS was incorporated in September 2020 with private funding. This year, the company plans to increase its capital with injections from additional private sources. Moreover, it is preparing a round of Series A funding for 2023 to provide the initial boost for its international expansion.

On February 17, 2022 Gracell Biotechnologies Inc. ("Gracell" or the "Company",NASDAQ: GRCL), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, reported that it has dosed multiple patients in a clinical trial evaluating GC012F, the Company’s autologous CAR-T therapeutic candidate dual-targeting B cell maturation antigen (BCMA) and CD19 in B-cell non-Hodgkin’s lymphoma (B-NHL) (Press release, Gracell Biotechnologies, FEB 17, 2022, View Source [SID1234608251]). NHL is the fifth most common cancer in the U.S.[1]

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The Phase 1 investigator-initiated trial (IIT), being conducted in China, is a first-in-human study evaluating FasTCAR-enabled BCMA/CD19 dual-targeting GC012F for the treatment of relapsed or refractory (r/r) B-NHL. GC012F is the first BCMA/CD19 dual-targeting CAR-T in human trials for B-NHL. Most B-NHL cells express CD19, and data also suggest that 39% to 97% clinical samples of NHL cells also express BCMA. [2] [3] [4] By simultaneously targeting BCMA and CD19, GC012F is designed to improve efficacy outcome in r/r B-NHL patients.

GC012F, developed using Gracell’s proprietary FasTCAR platform which enables next-day manufacturing, GC012F is currently also being evaluated in IIT studies in China including relapsed/refractory multiple myeloma. In November 2021, GC012F was granted Orphan Drug Designation by the U.S. Food and Drug Administration.

"Dual-targeting CD19 and BCMA represents an innovative approach for the treatment of B-NHL. This study of GC012F for r/r B-NHL marks an important step in the product candidate’s development to expand to additional indications and we look forward to confirming its potential to treat B-NHL, an indication for which patients are in need of additional treatment options," said Dr. Martina A. Sersch, Chief Medical Officer of Gracell. "We are confident that this study will further validate GC012F, our FasTCAR platform and our dual-CAR technology."

[1] View Source

[2] Blood Cancer Journal (2020) 10:73

[3] Blood. 2017;130:2755.

[4] Hum Gene Ther. 2018; 29(5): 585.

About GC012F

GC012F is a FasTCAR-enabled dual-targeting CAR-T product candidate that is currently being evaluated in IIT studies in China for the treatment of multiple myeloma and B-cell non-Hodgkin’s lymphoma. GC012F simultaneously targets CD19 and BCMA to drive fast, deep and durable responses, which can improve efficacy and reduce relapse in multiple myeloma and B-NHL patients.

About B-NHL

Non-Hodgkin’s lymphoma (NHL) is a group of blood cancers that developed from lymphocytes, most commonly derived from B cells (B-NHL). Globally, approximately 510,000 patients are diagnosed with NHL every year with over 77,000 patients diagnosed in the United States, and approximately 68,000 diagnosed in China in 2020. B-NHL accounts for approximately 85% of NHL diagnoses.

About FasTCAR

CAR-T cells manufactured on Gracell’s proprietary FasTCAR platform appear younger, less exhausted and show enhanced proliferation, persistence, bone marrow migration and tumor cell clearance activities as demonstrated in preclinical studies. With next day manufacturing, FasTCAR is able to significantly improve cell production efficiency which may result in meaningful cost savings, increasing the accessibility of cell therapies for cancer patients.

On February 17, 2022 Edison Oncology Holding Corp. ("Edison Oncology"), a company established to develop and commercialize novel therapies targeting the fight against cancer reported that the first patient has received treatment with Orotecan (irinotecan HCI oral solution) in a Phase I/IIa clinical trial for patients with recurrent pediatric solid tumors (Press release, Edison Oncology, FEB 17, 2022, View Source [SID1234608250]).

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The clinical trial will enroll up to 20 patients with recurrent pediatric and solid tumors, including but not limited to neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, hepatoblastoma and medulloblastoma. The trial endpoints will characterize the pharmacokinetics of Orotecan vs. unformulated irinotecan in an already established oral treatment regimen, document safety and tolerability, and assess tumor response. The trial is currently enrolling patients at Duke University Children’s Hospital and Cincinnati Children’s Hospital Medical Center, with opening of additional sites anticipated in the near future.

"We are excited to have treated the first patient treated with Orotecan, our novel oral formulation of irinotecan, which we believe has the potential to improve the quality of life for pediatric and adult cancer patients, improve patient compliance and reduce costs" said Jeffrey Bacha, Edison Oncology’s chief executive officer.

Further details of the trial can be found on clinicaltrials.gov (NCT04337177).

About Orotecan

Orotecan is a patented, novel formulation of irinotecan that was developed to improve palatability and

clinical utility of an established oral delivery regimen for numerous pediatric cancers.