On February 17, 2022 Applied DNA Sciences, Inc. (NASDAQ: APDN) (the "Company"), a leader in Polymerase Chain Reaction (PCR)-based DNA manufacturing and nucleic acid-based technologies, and its program development partner, EvviVax, S.R.L. ("Evvivax"), reported the publication of a manuscript detailing a preclinical study (the "study") showing that LinearDNA vaccines used for cancer immunotherapy produced a strong immune and specific antitumoral response in preclinical mouse models (Press release, Applied DNA Sciences, FEB 17, 2022, View Source;id=224228&p=2220104&I=1206939-c7Z3G6f3m8 [SID1234608240]). The study investigated the use of the LinearDNA platform to produce DNA vaccines targeting either tumor-associated antigens (TAA) or tumor-specific antigens (TSA or tumor neoantigens). The manuscript, "Linear DNA Amplicons as a Novel Cancer Vaccine Strategy," is published online on the bioRxiv.org preprint server and has been submitted for peer-reviewed publication. LinearDNA is Applied DNA’s proprietary, large-scale polymerase chain reaction ("PCR")-based manufacturing platform that allows for the large-scale production of specific DNA sequences.

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DNA vaccines that target TAAs hold promise as potential pan-cancer vaccines that, when used in conjunction with existing standards of care, can increase the efficacy of cancer immunotherapies. DNA vaccines targeting TSAs, otherwise known as personalized cancer vaccines, also hold great promise in immunotherapy as they can be customized to induce an immune response only against a patient’s tumor, thereby limiting on-target, off-tumor effects.

TAA: TERT Vaccine

One aspect of the study used a DNA vaccine targeting telomerase reverse transcriptase (TERT), a TAA that holds potential as a target for a pan-cancer vaccine. The TERT DNA vaccine was designed by EvviVax and exclusively licensed by the Company for the LinearDNA platform for veterinary applications. In prior clinical trials conducted by EvviVax, a plasmid form of the TERT DNA vaccine administered along with the standard of care chemotherapy was shown to increase the survival of canines with Stage III/IV B cell lymphoma from 37 weeks to 97 weeks. B-cell lymphoma is the most common type of non-Hodgkin lymphoma in canines1, with lymphoma accounting for 15-20% of new cancer diagnoses in canines2. For the study, the TERT DNA vaccine was administered to mice in either plasmid DNA or LinearDNA form and the immune response studied and compared. The study’s results demonstrated that both the plasmid DNA and LinearDNA forms of the TERT DNA vaccine induced comparable immune responses in mouse models.

TSA/Neoantigens Vaccine

The second aspect of the study utilized a personalized DNA vaccine specifically targeting several TSAs expressed in a colon cancer mouse model. Personalized cancer vaccines hold great promise in immunotherapy as they can be customized to induce an immune response only against a specific patient’s tumor, thereby limiting off-tumor effects and increasing efficacy and therapeutic index. In the study, LinearDNA and plasmid DNA forms of the personalized cancer vaccine were administered to mice in the colon cancer model. For both forms of the DNA vaccine, several cohorts also received immune checkpoint inhibitors (ICI) based on anti-CTLA-4 and/or anti-PD1. The study demonstrated that the LinearDNA personalized vaccine produced an equal or greater immune and antitumoral response than the plasmid form of the same DNA vaccine, particularly when coupled with ICI.

Dr. James A. Hayward, president and CEO of Applied DNA, stated, "The study demonstrates that LinearDNA and plasmid DNA can elicit a comparable immune response in animal cancer models. We believe this study validates the use of LinearDNA as a more cost- and time-efficient alternative to plasmid DNA for DNA-based cancer vaccines. Cancer immunotherapy is relevant to veterinary and human markets; the latter is expected to reach $169 billion by 20283. As the exclusive licensee of the TERT DNA vaccine for veterinary applications, we believe these data support further investigation of the LinearDNA vaccine as a potential veterinary cancer immunotherapy and, beyond that, for human cancer immunotherapy."

Dr. Luigi Aurisicchio, CEO and chief scientific officer of Evvivax S.R.L., commented, "We believe that DNA vaccines for cancer hold immense promise for both human and veterinary applications. One obstacle to DNA vaccine manufacturing is their current production as plasmid DNA. We believe that the completely cell-free LinearDNA platform avoids the numerous pitfalls of plasmid DNA-based production, making it ideal for DNA vaccine manufacturing broadly, and in cancer immunotherapy, specifically."

On February 17, 2022 Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported commencement of production of its first dendritic cell cancer vaccine for a compassionate use patient at its recently licensed production facility in Sawston, UK (Press release, Northwest Biotherapeutics, FEB 17, 2022, View Source [SID1234608257]).

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This milestone follows approval by the UK Medicines and Healthcare Products Regulatory Agency (MHRA) of a license for manufacture of GMP (clinical grade) cell therapy products at its Sawston, UK facility for compassionate use cases, and approval by the Human Tissue Authority (HTA) of a license for collection and processing of human cells and tissues for medical purposes. Under this regulatory program in the UK, the vaccine is identified as ADCV ("Autologous Dendritic Cell Vaccine").

As previously reported, the MHRA license was received in December of 2021, following nearly two years of preparations. This included hiring and training of technical staff, preparation of approximately 1,000 regulatory documents (including Standard Operating Procedure documents and others), validation of facilities, equipment and protocols, and practice manufacturing cycles. This was followed by a review and detailed inspection by the MHRA.

Since the issuance of the MHRA license, Advent Bioservices, NW Bio’s contract manufacturer in the UK, has been conducting the required post-approval re-validations and testing so that the facility is now ready for the manufacture of cell therapy products for clinical use. Accordingly, the first vaccine production for compassionate use treatment for a glioblastoma patient has now begun in the Sawston facility.

The Company anticipates that Phase 1A of the Sawston facility will have the capacity to produce cancer vaccines for 450-500 patients per year. The Company plans to continue developing the Sawston facility in phases, both to calibrate the capital expenditures with the capacity needed and to leave room for implementation of new technologies such as the Flaskworks system.

On February 17, 2022 At the 2022 ASCO (Free ASCO Whitepaper) GU Cancers Symposium Bayer reported that results from the Phase III ARASENS trial which demonstrated that the use of the oral androgen receptor inhibitor (ARi) darolutamide plus androgen deprivation therapy (ADT) and docetaxel significantly increased overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) compared to ADT plus docetaxel. Darolutamide plus ADT and docetaxel significantly reduced the risk of death by 32.5% compared to ADT plus docetaxel (HR=0.68, 95% CI 0.57-0.80; P<0.001) (Press release, Bayer, FEB 17, 2022, View Source;ref=irrefndcd [SID1234608324]). At the data cutoff date for the primary analysis (October 25, 2021), the median treatment duration was longer for darolutamide plus ADT and docetaxel (41.0 months) versus ADT plus docetaxel (16.7 months).

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Amid these positive results Bayer raised peak sales expectation for Nubeqa (darolutamide) to exceed €3 billion.

"Subject to regulatory approval, the team at Bayer is excited to be able to offer even more patients suffering from prostate cancer an additional treatment option backed by strong clinical data," said Stefan Oelrich, Member of the Board of Management of Bayer and President of the Pharmaceuticals Division. "With the confirmation of darolutamide’s clinical profile and expansion into the metastatic setting as well as the investments that we are making in clinical trials in other potential indications, we feel that Nubeqa has the potential to generate peak sales of more than 3 billion euros".

Darolutamide is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company. Based on results from the pivotal Phase III ARAMIS trial, the compound is already approved for the treatment of patients with nmCRPC, who are at high risk of developing metastatic disease, in more than 60 markets worldwide. Results from the second Phase III ARASENS trial evaluating darolutamide plus androgen deprivation therapy (ADT) in combination with docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC) were presented yesterday as an oral presentation at the 2022 ASCO (Free ASCO Whitepaper) GU Cancer Symposium and simultaneously published in The New England Journal of Medicine. Bayer is already in discussions with health authorities worldwide regarding the submission for marketing authorization in this additional indication.

Darolutamide is being investigated in a broad development program with additional three ongoing or planned large clinical studies, to investigate its potential across prostate cancer patients from the early- to the late-stage of this disease. This includes another Phase III trial in mHSPC (ARANOTE) as well as an ANZUP-led international co-operative group Phase III trial, evaluating darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence (DASL-HiCaP, ANZUP1801). Information about these trials can be found at www.clinicaltrials.gov. In addition, a study to explore the potential of darolutamide in the early setting for patients who have been treated with surgery or radiation and now see a rise in their prostate specific antigen (PSA) levels is also planned.

About Nubeqa (darolutamide)
Darolutamide is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. The low potential for blood-brain barrier penetration for darolutamide is supported by preclinical models and neuroimaging data in healthy humans. A low blood-brain barrier penetration would explain the overall low incidence of central nervous system (CNS)-related adverse events (AEs) compared to placebo as seen in the ARAMIS and ARASENS Phase III trials and the improved verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial.

The product is approved under the brand name Nubeqa in more than 60 markets around the world, including the U.S., EU, Japan, China, for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. The compound is also currently being investigated in further studies across various stages of prostate cancer, including another Phase III trial in mHSPC (ARANOTE) as well as an ANZUP-led international co-operative group Phase III trial, evaluating darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence (DASL-HiCaP, ANZUP1801). Information about these trials can be found at www.clinicaltrials.gov.

On February 17, 2022 Scandion Oncology (Scandion) reported its fourth quarter and year-end report for 2021 (Press release, Scandion Oncology, FEB 17, 2022, View Source,c3508355 [SID1234608203]). The following is taken from the report.

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Bo Rode Hansen, President and CEO, comments

"The fourth quarter completed a busy and successful 2021 for Scandion in which we transformed the company on substantially all accounts, increasing its fundamental value. We have prepared for the future with continued focus on fundamental value creation and are poised to enter the right partnerships for Scandion when the data are ready."

Highlights during Q4 2021

On November 8, Scandion Oncology announced that the timeline for read-out of the dose-finding clinical Phase Ib study PANTAX will be extended, and read-out is expected in Q2-Q3 2022. The reasons are challenging patient recruitment and a staggered study design, as requested by the German authorities. Disregarding this postponement, the study is performing as well as the Company could have hoped for.
Highlights after the end of the period

On January 12, Scandion Oncology announced that Mads Kronborg, bringing more than a decade of corporate communication and investor relations experience in the global life-science industry, will now help plan and drive its external communication as Head of External Communication.
On January 18, Scandion Oncology announced that data with the Company’s lead compound SCO-101 as combination therapy in patients with metastatic colorectal cancer was accepted for poster presentation at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium.
On February 2, Scandion Oncology announced approval from the German and Spanish regulatory authorities to expand part 2 of the CORIST Phase II study to Germany and Spain.
The Q4 and year-end report 2021 is available on the Company’s website: www.scandiononcology.com.

Audiocast today, February 17 at 08:30 am CET

Today at 08:30, Scandion Oncology’s executive management will host a webcast and conference call presenting the results and a company update.

At the end of the presentation there will be a Q&A session.

Access to the event can be obtained as follows:

View Source

REPLAY access:

Webcast replay will be available at www.scandiononcology.com in the Investors section and at www.financialhearings.com

The information was provided by the contact person above for publication on February 17, 2022, at 07.30 CET.

On February 17, 2022 Celsion Corporation (NASDAQ: CLSN), a clinical-stage company focused on DNA-based immunotherapy and next-generation vaccines, reported that following a pre-planned interim safety review of 81 as treated patients randomized in the Phase I/II OVATION 2 Study with GEN-1 in advanced (Stage III/IV) ovarian cancer, the Data Safety Monitoring Board (DSMB) has unanimously recommended that the OVATION 2 Study continue treating patients with the dose of 100 mg/m2 (Press release, Celsion, FEB 17, 2022, View Source [SID1234608224]). The DSMB also determined that safety is satisfactory with an acceptable risk/benefit, and that patients tolerate up to 17 doses of GEN-1 during a course of treatment that lasts up to six months. No dose-limiting toxicities were reported.

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The OVATION 2 Study combines GEN-1, the Company’s IL-12 gene-mediated immunotherapy, with standard-of-care neoadjuvant chemotherapy (NACT) in patients newly diagnosed with Stage III/IV ovarian cancer. NACT is designed to shrink the cancer as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of chemotherapy to treat any residual tumor.

The OVATION 2 Study is designed with an 80% confidence interval for an observed Progression Free Survival (PFS) Hazard Ratio of 0.75, which would mean an approximate 33% improvement in risk for cancer progression when comparing the treatment arm (NACT + GEN-1) with the control arm (NACT only). GEN-1 is an immunotherapy that produces safe and durable local levels of IL-12, a pluripotent cytokine associated with the stimulation of innate and adaptive immune response against cancer. The GEN-1 nanoparticle comprises a DNA plasmid encoding IL-12 gene and a synthetic polymer facilitating plasmid delivery vector. Cell transfection is followed by persistent, local secretion of the IL-12 protein at therapeutic levels.

The Company also announced that more than 75% of the projected 110 patients have been enrolled in the OVATION 2 Study. Interim clinical data from the first 39 patients who have undergone interval debulking surgery showed that the GEN-1 treatment arm is showing a 27% improvement in R0 surgical resection rate over the control arm. A complete tumor resection (R0) is a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed.

"Findings from our OVATION I and OVATION 2 studies show a consistent dose-dependent clinical response in both surgical outcome and tumor response, which is further supported by translational data of the tumor microenvironment," noted Nicholas Borys, M.D., Celsion’s executive vice president and chief medical officer. "We are encouraged by the current rate of patient recruitment and expect to complete enrollment by mid-2022. The primary endpoint for the study is progression-free survival (PFS) which we expect to report approximately 12 months after patient enrollment is completed."

In February 2021, the Company announced that GEN-1 received FDA Fast Track Designation in advanced ovarian cancer. Celsion plans to request FDA Breakthrough Therapy Designation for GEN-1 based on the encouraging clinical data.

"We thank the DSMB members for their work and advice," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "FDA Fast Track and Orphan Drug Designations for GEN-1 in advanced ovarian cancer are important for our future commercialization efforts. In addition, under the Biologics Price Competition and Innovation Act of 2009, sponsors of new, licensed biological products like GEN-1 that are approved through a Biologics License Application receive 12 years of market exclusivity. The FDA cannot license any 351(k) application for a biosimilar or interchangeable product that relies on the previously approved product as a reference for biosimilarity during this 12-year period."

About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy or a combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer, and recently completed a Phase Ib dose-escalation trial (OVATION 1 Study) of GEN-1 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the fifth deadliest malignancy among women in the United States. There are approximately 22,000 new cases of ovarian cancer every year and the majority (approximately 70%) are diagnosed in advanced stages III and IV. EOC is characterized by dissemination of tumor in the peritoneal cavity with a high risk of recurrence (75%, stage III and IV) after surgery and chemotherapy. Since the five-year survival rates of patients with stages III and IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for regional approach to immune modulation.