On April 22, 2021 Novocure (NASDAQ: NVCR) reported that the U.S. Food and Drug Administration (FDA) has approved its investigational device exemption (IDE) application to initiate the KEYNOTE-B36 trial, conducted in collaboration with MSD (Merck & Co., Inc., Kenilworth, NJ, USA) (Press release, NovoCure, APR 22, 2021, View Source [SID1234578377]). Novocure also announced the members of its scientific steering committee who will provide expert opinions and recommendations regarding enrollment strategies, country distribution, study timelines and other scientific topics. The KEYNOTE-B36 trial will evaluate Tumor Treating Fields (TTFields) together with pembrolizumab for first-line treatment of locally advanced or metastatic intrathoracic, PD-L1 positive non-small cell lung cancer (NSCLC).

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KEYNOTE-B36 steering committee members include:

Corey Langer, M.D., director of thoracic oncology and professor of medicine at the Hospital of the University of Pennsylvania
Anne S. Tsao, M.D., professor and section chief of thoracic medical oncology and director of the mesothelioma program at The University of Texas MD Anderson Cancer Center
Vinicius Ernani, M.D., Senior Associate Consultant at Mayo Clinic
Rupesh Kotecha, M.D., radiation oncologist and chief of radiosurgery at Miami Cancer Institute
"In vivo data suggest that using TTFields together with anti-PD-1 therapy results in increased tumor response versus either therapy alone," said Asaf Danziger, Novocure’s Chief Executive Officer. "We are honored to have such an esteemed group of key opinion leaders join the KEYNOTE-B36 steering committee as we look to translate our preclinical knowledge into clinical data demonstrating the effect of TTFields together with pembrolizumab in first-line NSCLC. With the FDA IDE approval, we are now working closely with trial sites, investigators and institutional review boards to open sites and enroll patients as quickly as possible."

About KEYNOTE-B36

KEYNOTE-B36 is a phase 2 pilot trial conducted in collaboration with MSD (Merck & Co., Inc., Kenilworth, NJ, USA). KEYNOTE-B36 will evaluate the effectiveness of TTFields together with pembrolizumab for first-line treatment of locally advanced or metastatic intrathoracic, PD-L1 positive NSCLC. Objective response rate (ORR) is the primary endpoint of the study. Secondary endpoints include overall survival, progression free survival (PFS), PFS at six months, one-year survival rate, duration of response, disease control rate at 18 weeks and safety. The study is designed to enroll approximately 66 patients in the United States.

About Non-small Cell Lung Cancer

Lung cancer is the most common cause of cancer-related death worldwide, and NSCLC accounts for approximately 85% of all lung cancers. It is estimated that approximately 193,000 patients are diagnosed with NSCLC each year in the U.S.

Physicians use different combinations of surgery, radiation therapy and systemic therapies to treat NSCLC, depending on the stage of the disease. Surgery, which may be curative in a subset of patients, is usually used in early stages of the disease. Since 1991, radiation with a combination of platinum-based chemotherapy has been the first-line standard of care for locally advanced NSCLC and systemic therapy alone for those with metastatic disease. Certain immune checkpoint inhibitors have recently been approved for the first-line treatment of NSCLC and the standard of care in this setting appears to be evolving rapidly. The standard of care for second-line treatment is also evolving and may include platinum-based chemotherapy for patients who received immune checkpoint inhibitors as their first line regimen, pemetrexed, docetaxel or immune checkpoint inhibitors.

Use of Tumor Treating Fields for the treatment of NSCLC is investigational only.

About Tumor Treating Fields

Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division.

When cancer develops, rapid and uncontrolled division of unhealthy cells occurs. Electrically charged proteins within the cell are critical for cell division, making the rapidly dividing cancer cells vulnerable to electrical interference. All cells are surrounded by a bilipid membrane, which separates the interior of the cell, or cytoplasm, from the space around it. This membrane prevents low frequency electric fields from entering the cell. TTFields, however, have a unique frequency range, between 100 to 500 kHz, enabling the electric fields to penetrate the cancer cell membrane. As healthy cells differ from cancer cells in their division rate, geometry and electric properties, the frequency of TTFields can be tuned to specifically affect the cancer cells while leaving healthy cells mostly unaffected.

Whether cells are healthy or cancerous, cell division, or mitosis, is the same. When mitosis starts, charged proteins within the cell, or microtubules, form the mitotic spindle. The spindle is built on electric interaction between its building blocks. During division, the mitotic spindle segregates the chromosomes, pulling them in opposite directions. As the daughter cells begin to form, electrically polarized molecules migrate towards the midline to make up the mitotic cleavage furrow. The furrow contracts and the two daughter cells separate. TTFields can interfere with these conditions. When TTFields are present in a dividing cancer cell, they cause the electrically charged proteins to align with the directional forces applied by the field, thus preventing the mitotic spindle from forming. Electrical forces also interrupt the migration of key proteins to the cell midline, disrupting the formation of the mitotic cleavage furrow. Interfering with these key processes disrupts mitosis and can lead to cell death.

TTFields is intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect.

Fundamental scientific research extends across two decades and, in all preclinical research to date, TTFields has demonstrated a consistent anti-mitotic effect. The TTFields global development program includes a broad range of clinical trials across all phases, included four phase 3 pivotal trials in a variety of tumor types. To date, more than 18,000 patients have been treated with TTFields.

On April 22, 2021 Virpax Pharmaceuticals, Inc. ("Virpax" or the "Company") (NASDAQ:VRPX), reported that the Company has engaged Torreya Capital, LLC (Torreya) to serve as the exclusive financial advisor for the Company’s partnering and licensing efforts in strategic global markets (Press release, Virpax Pharmaceuticals, APR 22, 2021, View Source [SID1234578376]).

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Torreya is a global investment bank that has facilitated more than $100 billion worth of transactions in the life sciences industry since its inception in 2007.

"We are excited to be working with Torreya to expand our partnerships in key markets," stated Anthony Mack, Chairman and CEO of Virpax Pharmaceuticals. "There is a growing global demand for non-opoid, non-addictive pain treatments and we believe that our product candidates, Epoladerm, Probudur, and Envelta can offer a competitive advantage in their addressable markets," concluded Mr. Mack.

"We look forward to helping Virpax Pharmaceuticals find strong regional partners for their innovative acute and chronic pain product candidate pipeline," said Tom Bird, Partner of Torreya. "Virpax’s product candidates incorporate its proprietary technologies that may enable the product candidates to deliver enhanced benefits with non-addictive pain relief."

On April 22, 2021 Synthekine Inc., an engineered cytokine therapeutics company, reported a new agreement with Stanford University to license cytokine partial agonist programs for IL-10, IL-12 and IL-22 (Press release, Synthekine, APR 22, 2021, View Source [SID1234578375]). These programs augment a growing pipeline of selective cytokine partial agonists at Synthekine that is maturing toward clinical development.

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Most cytokines are pleiotropic and drive a range of signaling responses across multiple cell types, which limits their potential as therapeutics. Research conducted in the laboratory of Chris Garcia, PhD, a Howard Hughes Medical Institute Investigator and professor of structural biology at Stanford, has shown that IL-10, IL-12, and IL-22 can be tuned to achieve specific signaling. Modifying these cytokines enables selective activity to be directed to specific cell types for therapeutic benefit, often by decoupling efficacy from toxic effects driven by non-specific immune system activation. Synthekine plans to leverage discoveries in IL-12, recently published in the journal Cell, to develop potential treatments for cancer, and the discoveries in IL-10, recently published in the journal Science, and IL-22, recently published in the journal Immunity, to develop potential treatments for autoimmune disease.

"Synthekine was founded two years ago with several cytokine partial agonist programs based on the work from the Garcia Laboratory, and we have already moved two of those programs into IND enabling development," said Debanjan Ray, CEO of Synthekine. "Extending our license with Stanford allows us to bring in three new promising cytokine partial agonist programs that we believe have considerable potential in treating cancer and autoimmune disease."

On April 22, 2021 Candel Therapeutics, Inc., a late clinical stage biopharmaceutical company developing novel oncolytic viral immunotherapies, reported it has completed enrollment for its Phase 1 clinical trial in patients with newly diagnosed high-grade glioma to evaluate the safety and efficacy of CAN-2409 in combination with immune checkpoint inhibitor Opdivo (nivolumab) and standard of care radiation therapy, as well as temozolomide for patients with methylated MGMT promoters (Press release, Candel Therapeutics, APR 22, 2021, View Source [SID1234578374]). The trial enrolled 35 evaluable patients and is being conducted in collaboration with Bristol Myers Squibb Company, manufacturer of Opdivo, and separately the Adult Brain Tumor Consortium at Johns Hopkins University.

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"The addition of CAN-2409 to immune checkpoint inhibitor treatment has the potential to train lymphocytes to specifically recognize tumor neoantigens and to change the ‘cold’, immunosuppressive tumor microenvironment, thereby synergizing with lymphocyte activation induced by nivolumab resulting in tumor cell destruction," said Paul Peter Tak, M.D., Ph.D., President and Chief Executive Officer of Candel Therapeutics. "With a significant number of patients affected each year and limited treatment options available, there remains a critical need for effective therapies in high-grade glioma. It is our hope that CAN-2409 can create new, more effective options for this patient population, and we look forward to the readout from this study next year."

The primary endpoints of the study are safety and tolerability of this combined treatment regimen. Secondary endpoints include overall survival, progression free survival and immunological biomarkers. For more information about this study, please visit: www.clinicaltrials.gov (NCT03576612).

Opdivo is a registered trademark of Bristol Myers Squibb.

About CAN-2409

CAN-2409, previously known as gene-mediated cytotoxic immunotherapy (GMCI), Candel’s most advanced oncolytic viral immunotherapy candidate, is a replication-deficient adenovirus that delivers the herpes simplex virus thymidine kinase (HSV-tk) gene to cancer cells. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. The intra-tumoral administration results in the release of tumor-specific neoantigens in the microenvironment, thereby training the immune system to recognize these antigens. The activated effector T cells have the potential to migrate to distant, uninjected metastases for broad anti-tumor activity. At the same time, the adenoviral capsid protein elicits a strong pro-inflammatory signal in the tumor microenvironment. This adjuvant effect helps create a better immune response against the tumor neoantigens released locally. This dual mechanism of antigen unmasking and immune activation may enable CAN-2409 to generate a powerful and lasting attack against a variety of the patient’s tumor-associated neoantigens, minimizing the possibility for antigen escape and tolerance development.

Because of its versatility, CAN-2409 may have the potential to treat a broad range of solid tumors. Combination activity with standard of care radiation therapy, surgery, immune checkpoint inhibitors

(ICI) and chemotherapy has already been shown in several preclinical and clinical settings. Candel has previously published preclinical data that supports combination of CAN-2409 with ICI. In a mouse model of glioblastoma unresponsive to ICI, addition of CAN-2409 was shown to modulate the immunosuppressive, unresponsive tumor microenvironment, resulting in a synergistic effect in vivo, with significantly improved survival in mice treated with CAN-2409 and ICI combination. Furthermore, CAN-2409 presents a favorable tolerability profile. More than 700 patients have been dosed to date, supporting the potential for combination with other therapeutic strategies without inordinate concern of overlapping adverse events. Currently, Candel is evaluating the effects of treatment with CAN-2409 for brain, prostate, lung, and pancreatic cancers in clinical trials.

On April 22, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported participation in the Dermatology Nurses’ Association 2021 Annual Convention (Press release, Castle Biosciences, APR 22, 2021, View Source [SID1234578373]). Castle presented posters highlighting each of the company’s three skin cancer gene expression profile (GEP) tests.

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Poster information is as follows:

DecisionDx-Melanoma:

The poster is entitled, "31-gene expression profiling improves risk stratification in patients with T1 cutaneous melanoma."

DecisionDx-Melanoma is Castle’s 31-gene expression profile test that uses an individual patient’s tumor biology to predict risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node (SLN) positivity, independent of traditional staging factors.

Study methods and findings:

Nearly 70% of melanomas are diagnosed with tumor thickness that is less than or equal to 1.0 mm (T1 tumors), and recurrence-free survival (RFS) is generally good among these patients. However, up to 15% of patients with T1 tumors may experience a recurrence. Moreover, due to the large number of patients with T1 tumors, 27-30% of melanoma-related deaths occur in patients originally diagnosed with a T1 tumor, suggesting better identification of T1 patients at high risk of recurrence or metastasis is needed.
DecisionDx-Melanoma is designed to classify a patient’s recurrence risk as low (Class 1: Class 1A lowest) or high (Class 2: Class 2B highest) and has been validated in multiple prospective and retrospective studies.
Univariate analysis of the study data shows DecisionDx-Melanoma to be a stronger predictor of RFS than SLN status.
Multivariable analysis shows DecisionDx-Melanoma to be a strong, independent predictor of RFS.
With Class 2B RFS status similar to SLN positive status, Class 2B patients warrant follow-up strategies similar to SLN positive patients.
DecisionDx-SCC:

The poster is entitled, "Clinical utility of the 40-gene expression profile (40-GEP) for improved patient management decisions and disease related outcomes when combined with current clinicopathological risk factors for cutaneous squamous cell carcinoma (cSCC): Case Series."

DecisionDx-SCC is Castle’s prognostic 40-gene expression profile test for patients diagnosed with high-risk cutaneous squamous cell carcinoma (SCC) designed to use a patient’s tumor biology to predict individual risk of metastasis for patients with SCC and one or more risk factors.

Study methods and findings:

Two SCC cases were presented that highlight DecisionDx-SCC’s utility in stratifying risk in SCC.
The cases were very similar at diagnosis, both presenting with a history of immunosuppression along with identical staging (T2a per Brigham and Women’s Hospital staging; T1 per American Joint Committee on Cancer staging), but had divergent outcomes:
Case 1 did not recur, despite incomplete resection.
Case 2 developed local recurrence and regional metastasis, and died from SCC, despite clear surgical margins, radiation and chemotherapy treatments.
Subsequent DecisionDx-SCC test results yielded risk level assignments that correlated with the two patients’ outcomes:
Case 1 had a retrospective low-risk (Class 1) DecisionDx-SCC result.
Case 2 had a highest-risk (Class 2B) DecisionDx-SCC result.
The authors concluded that incorporating DecisionDx-SCC as a prognostic factor with traditional clinicopathological risk factors can improve stratification of high-risk SCC patients with at least one risk factor, thereby informing risk-appropriate management strategies.
DecisionDx DiffDx-Melanoma:

The poster is entitled, "Development, validation, and clinical utility of the 35-gene expression profile test for use as an adjunctive melanoma diagnostic tool."

DecisionDx DiffDx-Melanoma is designed to aid dermatopathologists in characterizing difficult-to-diagnose melanocytic lesions.

Study methods and findings:

DecisionDx DiffDx-Melanoma was developed using artificial intelligence methods trained on 200 benign nevi and 216 melanomas to select a panel of 32 discriminant and 3 control genes.
The test’s ability to differentiate accurately between benign and malignant pigmented skin lesions was characterized.
The test provides a high technical success rate at 96.6% with a modest intermediate-risk zone of 3.6%.
The analytical validity data of the DecisionDx DiffDx-Melanoma test demonstrates high precision as an indication of technical success.
Dermatopathologists utilized the DecisionDx DiffDx-Melanoma result to refine their diagnoses and their diagnostic confidence increased by 51%.
Dermatologists utilized the DecisionDx DiffDx-Melanoma result, which in the majority of responses, led to altered treatment plans in agreement with the DecisionDx DiffDx-Melanoma result.
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. To predict likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithm, i31-GEP, to produce an integrated test result. i31-GEP is an artificial intelligence-based neural network algorithm (independently validated in a cohort of 1,674 prospective, consecutively tested patients with T1-T4 cutaneous melanoma) that integrates the DecisionDx-Melanoma test result with the patient’s traditional clinicopathologic features. 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. Through December 31, 2020, DecisionDx-Melanoma has been ordered more than 68,920 times for use in patients with cutaneous melanoma.

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

About DecisionDx DiffDx-Melanoma

DecisionDx DiffDx-Melanoma is designed to aid dermatopathologists in characterizing difficult-to-diagnose melanocytic lesions. Of the approximately 2 million suspicious pigmented lesions biopsied annually in the U.S., Castle estimates that approximately 300,000 of those cannot be confidently classified as either benign or malignant through traditional histopathology methods. DecisionDx DiffDx-Melanoma classifies these lesions as: benign (gene expression profile suggestive of benign neoplasm); intermediate-risk (gene expression profile cannot exclude malignancy); or malignant (gene expression profile suggestive of melanoma). Interpreted in the context of other clinical, laboratory and histopathologic information, DecisionDx DiffDx-Melanoma is designed to add diagnostic clarity and confidence for dermatopathologists while helping dermatologists deliver more informed patient management plans.

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

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1, 2A or 2B risk category, predicts individual metastatic risk to inform risk-appropriate management.

Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

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