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.

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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).

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"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.

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"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.

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"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.

On April 14, 2021 Boehringer Ingelheim and The University of Texas MD Anderson Cancer Center reported the extension and expansion of their joint Virtual Research and Development Center (VRDC) to explore new molecules from Boehringer Ingelheim’s KRAS (Kirsten rat sarcoma) and TRAILR2 (TNF-related apoptosis-inducing ligand receptor 2) portfolios for the potential treatment of lung cancer, particularly non-small cell lung cancer (Press release, Boehringer Ingelheim, APR 14, 2021, View Source [SID1234578023]).

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The collaboration, launched in 2019, has successfully combined MD Anderson’s innovative clinical research infrastructure and the patient-driven drug development capabilities of the Therapeutics Discovery division with Boehringer Ingelheim’s pipeline of innovative cancer medicines and expertise in advancing breakthrough therapies. Under the new agreement, joint research will continue for five additional years.

"Our collaboration with MD Anderson strengthens our determination to find solutions for the most difficult-to-treat cancers, and this latest commitment marks an important step forward, especially in our holistic KRAS program," said Norbert Kraut, Ph.D., Head of Global Cancer Research at Boehringer Ingelheim. "We are delighted to extend our collaboration with MD Anderson. With our shared dedication to patients and like-minded approach to innovation, we have the potential to bring the medicines to lung and gastrointestinal cancer patients that they so much need."

The flexible nature of the VRDC agreement allows the teams to expand their lung cancer indication programs targeting KRAS and TRAILR2, including Boehringer Ingelheim’s first-in-class SOS1::pan-KRAS inhibitor (BI 1701963), inhibitors of KRAS G12C (BI 1823911) and MEK (BI 3011441), as well as a novel undisclosed bi-specific TRAILR2 agonist.

The collaboration already has resulted in a number of joint publications1, conference presentations (including at the 2021 AACR (Free AACR Whitepaper) Annual Meeting2) and clinical trial activities. Boehringer Ingelheim is pursuing a comprehensive mutant KRAS-directed effort with multiple programs expected to enter the VRDC with MD Anderson.

"We are proud to expand our work with Boehringer Ingelheim in a very exciting drug-development space – advancing novel targeted therapies against KRAS and TRAILR2," said Timothy Heffernan, Ph.D., Head of Oncology Research in Therapeutics Discovery at MD Anderson. "Our collaboration is built upon a strong working relationship and complementary expertise, highlighting how an academic center and a pharmaceutical company can strategically work together to advance innovative therapies for patients with cancer."
MD Anderson’s Therapeutics Discovery division is anchored by an experienced team of drug development experts working to advance the next generation of cancer therapies. The Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION) platform, led by Heffernan, performs cutting-edge translational research to rapidly advance new therapies to the patients most likely to benefit.

KRAS is the most frequently mutated cancer-causing oncogene. One in seven of all human metastatic cancers expresses KRAS mutations, with mutation rates of more than 30 percent in lung adenocarcinomas, more than 40 percent in colorectal cancers and more than 90 percent in pancreatic cancers. No approved treatments for KRAS-driven cancers exist currently, further underscoring the need for continued investment in research and development. Tumor cell-selective activation of TRAILR2 can trigger cancer cell death in indications of high medical need, including lung and gastrointestinal malignancies.

Intended Audiences
This press release is issued from our corporate headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.

Disclosures
MD Anderson has an institutional financial conflict of interest with Boehringer Ingelheim related to this research and has therefore implemented an Institutional Conflict of Interest Management and Monitoring Plan.