On April 14, 2021 Veracyte (Nasdaq: VCYT) reported a key milestone in its companion diagnostics program with Acerta Pharma, the hematology research and development arm of AstraZeneca (LSE/STO/NYSE: AZN) (Press release, Veracyte, APR 14, 2021, View Source [SID1234578040]). The first patient has been enrolled and randomized in Acerta Pharma’s Phase 3 ESCALADE trial, which is using Veracyte’s LymphMark lymphoma subtyping test to identify patients with untreated diffuse large B-cell lymphoma (DLBCL) who may benefit from Acerta and AstraZeneca’s acalabrutinib (Calquence) in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The randomized, double-blind, placebo-controlled ESCALADE study is designed to evaluate the efficacy and safety of acalabrutinib with R-CHOP therapy as compared to placebo plus R-CHOP in patients aged 18-65. The study is expected to enroll up to 600 participants at centers around the world. Study investigators are using the investigational LymphMark genomic test to select patients with non-germinal center B-cell (non-GCB) subtype DLBCL, an aggressive form of the disease that is associated with worse outcomes following the traditional chemoimmunotherapy regimen (R-CHOP).

"The initiation of this global study marks an important step in our multi-year companion diagnostics program with Acerta Pharma," said Bonnie Anderson, Veracyte’s chairman and chief executive officer. "By distinguishing DLBCL patients based on the genomic underpinning of their disease, we believe the LymphMark test will help identify patients early on who are more likely to respond to targeted therapies such as Calquence that may improve outcomes."

DLBCL patients respond to treatment differently based on the molecular subtype of their tumors. The LymphMark test uses gene-expression profiling of RNA extracted from surgical tissue to classify the "cell of origin" subtype of DLBCL tumors. The World Health Organization recommends gene-expression profiling for patients with DLBCL, which may potentially be mitigated by more specific treatments that are under development.i By identifying the specific subtypes in individual patients’ tumors, physicians can help ensure the right patients are included in clinical trials evaluating these therapies.

Non-Hodgkin lymphoma (NHL) ranks among the top-10 common cancers worldwide, with over 500,000 new cases estimated in 2018.ii DLBCL is the most common type of NHL, accounting for approximately 30 percent of lymphomas.iii

The LymphMark test is intended for use on the nCounter Analysis System. Veracyte acquired the LymphMark test, as well as the exclusive global diagnostic rights to the nCounter system, in December 2019.

On April 14, 2021 The National Comprehensive Cancer Network (NCCN) Oncology Research Program (ORP) reported that three projects have been selected to study oral decitabine (35 mg) and cedazuridine (100 mg) (Press release, Astex Pharmaceuticals, APR 14, 2021, View Source [SID1234578021]). The NCCN ORP convened a Scientific Review Committee to review, evaluate, and select awardees and will provide oversight for the two-year studies—which will commence later in 2021. Research funding will be provided by a grant from Taiho Oncology, who will also supply the decitabine and cedazuridine tablet.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The selected projects are:

• Michael Byrne, DO, Vanderbilt-Ingram Cancer Center, Moffitt Cancer Center
o Phase 2 Study of Decitabine and Cedazuridine in Combination with Venetoclax for AML Relapse after Allogeneic Hematopoietic Cell Transplantation

• Gurkamal Chatta, MD, Roswell Park Comprehensive Cancer Center
o A Phase 1b Clinical Trial: Improving Outcomes with Androgen Pathway inhibitors by Targeting DNA Methyltransferase Activity

• Martin McCarter, MD, University of Colorado Cancer Center
o Oral Decitabine/Cedazuridine in Combination with Nivolumab as a Strategy to Enhance the Efficacy of Immune Checkpoint Blockade in Unresectable or Metastatic Mucosal Melanoma

"Congratulations to all of the selected investigators," said Wui-Jin Koh, MD, Chief Medical Officer, NCCN. "We look forward to their work advancing our understanding of this medication combination. The potential for oral medication in place of intravenous delivery is particularly worthy of exploration, as this may provide better options for outpatient therapy with reduced office visits, which in turn improves access to care and helps underserved patient populations.

"Taiho Oncology is pleased to continue our collaboration with the National Comprehensive Cancer Network to help broaden the understanding of oral decitabine and cedazuridine for patients with solid tumors and hematologic malignancies," said Terri L. Washington, DNP, RN, Vice President, Scientific Partnerships and Medical Affairs Operations, Taiho Oncology, Inc. "These grants will help advance critical research and represent a step forward in exploring the full potential of oral decitabine and cedazuridine for patients to help improve outcomes."

The NCCN ORP fosters innovation and knowledge discovery that improves the lives of people with cancer and supports preclinical, translational, clinical research and quality improvement projects in oncology at NCCN Member Institutions. In an effort to improve collaboration in cancer research, the NCCN ORP also maintains a shared resources website and an informed consent database. For more information, visit NCCN.org/orp.

On April 14, 2021 OncoSec Medical Incorporated (NASDAQ:ONCS) (the "Company" or "OncoSec"), a biotechnology company focused on cytokine-based intratumoral immunotherapies, reported that it has received authorization to CE mark its proprietary next generation go-to-market gene delivery device, GenPulse, a part of the OncoSec Medical System (OMS) electroporation device platform for use in solid tumors (Press release, OncoSec Medical, APR 14, 2021, View Source [SID1234578041]). The CE mark certification augments the Notified Body certification to the International Organization for Standardization’s (ISO) 13485 standard for the design, development, manufacture and distribution of electroporation devices, which is renewed annually, subject to a successful audit. The GenPulse is the gene electrotransfer device which OncoSec plans to deploy commercially, both in the U.S. and the European Union (EU).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This CE certification is an essential regulatory milestone on OncoSec’s road to commercialization in Europe," said Robert Ashworth, Senior Vice President, Regulatory Quality and CMC at OncoSec. "The CE mark on our proprietary GenPulse generator represents the culmination of years of work and demonstrates that OncoSec has the capability to manufacture and develop a device that meets performance, quality and safety requirements in the EU."

A CE mark indicates the OMS electroporation device complies with Directives of the European Commission (EC) and therefore can be marketed within the 31-nation European Economic Area (EEA) and Switzerland. This OMS electroporation device applies short electric impulses to a tumor, causing pores to open in the membrane of cancer cells, significantly increasing the uptake of anti-cancer agents into these cells. The CE mark certification involved a comprehensive audit of the company’s quality system, as well as thorough evaluation and testing of the OMS electroporation device to assure it performs safely and as designed.

On April 14, 2021 Celularity Inc. ("Celularity"), a clinical-stage biotechnology company, leading the next evolution in cellular medicine with the development of off-the-shelf allogeneic therapies derived from the postpartum human placenta, reported the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to the company’s non-genetically modified cryopreserved human placental hematopoietic stem cell-derived natural killer (NK) cell therapy, CYNK-001, for the treatment of patients with malignant gliomas (Press release, Celularity, APR 14, 2021, View Source [SID1234578060]). CYNK-001 is currently being investigated in a phase 1 clinical trial (NCT04489420) for the treatment of patients with glioblastoma multiforme (GBM), an indication within the scope of this orphan designation.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are very pleased the FDA has granted Orphan Designation in malignant gliomas to continue to develop off-the-shelf therapies for serious unmet clinical needs," said Robert J. Hariri, M.D., Ph.D., founder, Chairperson and Chief Executive Officer of Celularity. "Building on the FDA’s recent decision to grant Fast Track status to CYNK-001, we view the Orphan Drug Designation as yet another milestone on our journey to deliver patients a potentially novel treatment. To date, we have observed the potential of CYNK-001 in multiple preclinical models as well as early evidence of activity in the clinic and believe this approach may shift the paradigm in augmenting the body’s natural immune response to diseases such as glioblastoma, other cancer indications and infectious diseases. We are very excited to continue working with the FDA on the development of this exciting therapy."

About Orphan Drug Designation

The Orphan Drug Act (ODA) encourages biotechnology and pharmaceutical companies to develop drugs for conditions which affect fewer than 200,000 people in the United States by providing economic incentives. To qualify for orphan designation, both the drug and the condition must meet criteria specified in the ODA and FDA’s implementing regulations 21 CFR Part 316. Orphan designation qualifies the drug sponsor for development incentives including tax credits for qualified expenses, reduction in the FDA user fee, and seven years of exclusivity for a drug that obtains approval.

About Malignant Gliomas

Glioma is a type of tumor that occurs in the brain and spinal cord. Malignant gliomas consist of glioblastoma multiforme (GBM), anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, anaplastic ependymoma, and anaplastic ganglioglioma. Malignant gliomas are associated with high morbidity and mortality. GBM accounts for the majority of malignant gliomas. Currently there are no effective long-term treatments for the disease. Patients with GBM usually survive less than 15 months following diagnosis. In most patients, the rapidly growing malignant tumor tends to recur within 6-8 months following treatment. Patients with recurrent GBM have even poorer prognosis. Therefore, malignant gliomas, such as GBM, are serious diseases with high unmet medical needs.

About CYNK-001

Celularity’s lead therapeutic program based on its placental-derived unmodified NK cell type is CYNK-001, an allogeneic unmodified NK cell being developed as a treatment for hematologic malignancies, solid tumors, and infectious diseases.

On April 14, 2021 Aura Biosciences, a clinical-stage oncology company developing a novel class of virus-like drug conjugate (VDC) therapies for multiple oncology indications, reported the online publication of data in the peer-reviewed medical journal Cancer Immunology Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), that supports the broad application of the Company’s proprietary VDC technology platform for treating cancer (Press release, Aura Biosciences, APR 14, 2021, View Source [SID1234578022]). The manuscript, titled, "Virus-like Particle-drug Conjugates Induce Protective, Long-lasting Adaptive Anti-Tumor Immunity in the Absence of Specifically Targeted Tumor Antigens," describes promising long term anti-tumor activity of AU-011, the Company’s lead VDC candidate, as a monotherapy and in combination with checkpoint inhibitor antibodies in preclinical studies conducted in collaboration with the Center for Cancer Research at the National Cancer Institute of the National Institutes of Health.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Collectively, these promising results confirm treatment of AU-011 resulted in targeted tumor cytotoxicity with hallmarks of immunogenic cell death that may promote a durable anti-tumor immune response," said Cadmus C. Rich, MD, MBA, Chief Medical Officer and Head of R&D for Aura. "Additionally, the additive activity of AU-011 in combination with checkpoint inhibitors has shown a high level of durable complete responses and prevention of tumor recurrence, warranting continued research into its potential clinical utility to effectively treat multiple types of tumors like non-muscle invasive bladder cancer as a primary treatment and further prevent metastatic disease."

Key findings from the manuscript include:

In vitro and in vivo studies in immunocompetent murine tumor models demonstrated a dose-dependent cytotoxic response of AU-011 with an upregulation of the markers of immunogenic cell death like caspase-1 and calreticulin surface expression demonstrating that AU-011 mediated cell death was able to generate potent immune stimulatory conditions within the tumor microenvironment.

A single in vivo dose administration of AU-011 caused rapid cell death leading to long term complete responses in 50% of all animals. Combination with immune checkpoint inhibitor antibodies improved therapeutic efficacy resulting in 70-100% complete response rate that was durable 100 days post-treatment with 50-80% of those animals displaying protection from secondary tumor re-challenge.

Depletion studies of CD4+ or CD8+ T-cells at the time of AU-011 treatment or tumor re-challenge confirmed the involvement of both cell populations in the mechanism of action of AU-011 and the promotion of long-lasting anti-tumor protection.

"These promising findings further reinforce the therapeutic advantages of VDCs in treating cancer compared to other available treatments, which include the broad tumor selectivity and multivalent binding of the virus-like particles compared to antibodies, the ability to deliver hundreds of cytotoxic molecules and the generation of long-lasting anti-tumor immunity," said Elisabet de los Pinos, Ph.D., Chief Executive Officer of Aura. "While our initial clinical focus has been in ocular oncology, our VDC approach has wide application as a single agent and as a combination therapy in a variety of solid tumors, including non-muscle invasive bladder cancer, which is expected to enter the clinic in 2022 We remain focused on advancing our novel VDC approach to transform the treatment of tumors and improve outcomes for patients with cancer."

About AU-011 (belzupacap sarotalocan)

AU-011 is a first-in-class virus-like drug conjugate (VDC) therapy in development for the first line treatment of choroidal melanoma. The virus-like component of the VDC selectively binds unique heparan sulphate proteoglycans (HSPGs) that are modified and overexpressed on the tumor cell surface of choroidal melanoma (and other tumor types) and delivers a potent cytotoxic drug that is activated with infrared light. Upon activation with an ophthalmic laser, the cytotoxic drug rapidly and specifically disrupts the cell membrane of malignant melanoma cells with a pro-immunogenic cell death that can activate the immune system generating long term anti-tumor immunity. The unique specificity of tumor binding by the VDC enables the preservation of key eye structures, which may allow for the potential of preserving patients’ vision and reducing other long-term complications of radiation treatment. The possibility of early treatment intervention and the activation of the immune system could lead to a reduction in the metastases rate for patients with this life-threatening disease. AU-011 can be delivered using equipment commonly found in an ophthalmologist’s office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma has been granted Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration and is currently in Phase 2 clinical development.