On January 15, 2019 Oasmia Pharmaceutical AB (NASDAQ: OASM) reported that the European Medicines Agency (EMA) has validated a type II variation application to add efficacy data to the Apealea product information (Press release, Oasmia, JAN 15, 2019, View Source [SID1234556566]). Validation of the application confirms that the submission is complete and that the EMA assessment process begins. Based on the EMAs procedural timelines, Oasmia anticipates an opinion from the Committee for Medicinal Products for Human Use (CHMP) by end of Q1 or beginning of Q2 2019.

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The application is based on subpopulation data (n=599) from the OAS-07OVA study and aims to provide treating physicians with efficacy data for Apealea in combination with carboplatin for the approved indication; adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer. The current efficacy data describes the population in OAS-07OVA that also included patients with several disease relapses (n=789).

About the subpopulation analysis submitted as a type II variation:

The marketing authorisation approval for Apealea in the EEA was based on study OAS 07OVA conducted on 789 randomized patients with disease relapse. The results of the subpopulation analysis of patients experiencing their first relapse were based on 301 patients (Apealea arm) and 298 patients (Comparator arm) being part of the OAS-07OVA study. The results show that there is a statistically significant advantage for Apealea with regards to progression-free survival.

Key efficacy results in patients with their first relapse in the intention-to-treat population from the pivotal randomized clinical trial OAS-07OVA

Progression-free survival (PFS)
(N=301) Overall survival (OS)
(N=298)
Hazard ratio, HR1
(95% CI) 0.80
(0.66-0.97) 0.98
(0.79-1.21)

Apealea2 CrEL-paclitaxel2 Apealea2 CrEL-paclitaxel2
Median, months
(95% CI) 10.3
(10.1-11.1) 10.0
(9.6-10.2) 24.7
(21.9-28.0) 23.4
(20.5-26.7)
1A longer PFS or OS for Apealea compared to Cremophor-EL (CrEL)-formulated paclitaxel is indicated by a HR less than 1.0.
2In combination with carboplatin.

About epithelial ovarian cancer

Ovarian cancer is the seventh most common cancer in women. Approximately 239,000 women are annually diagnosed with ovarian cancer globally and 152,000 dies from the disease. Epithelial ovarian cancer is the most common form and accounts for about 90% of ovarian cancers. The disease is often diagnosed at an advanced staged since it has no symptoms at early stages. The five-year survival rate (i.e. survival of patients with ovarian cancer compared to survival in the general population at the same age) for ovarian cancer has been estimated to 38% in Europe. During 2018, approximately 68,000 women will be diagnosed with ovarian cancer in Europe and 45,000 are predicted to die from the disease. Carboplatin and paclitaxel are common chemotherapy drugs for treatment of ovarian cancer and are often used in combination.

About Apealea

Apealea is a Cremophor- and albumin-free formulation of the well-known cytostatic paclitaxel combined with Oasmia’s excipient technology XR17. Paclitaxel is one of the most widely used anticancer substances and is included in the standard treatment of a variety of cancers such as lung cancer, breast cancer and ovarian cancer. Apealea consists of a freeze-dried powder, which is dissolved in conventional solutions for infusion.

On January 15, 2019 Marker Therapeutics, Inc. (Nasdaq:MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported that data from four abstracts—including three oral presentations—were accepted for presentation at the Transplantation & Cellular Therapy (TCT) Meetings of the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research (ASBMT and CIBMTR) (Press release, TapImmune, JAN 15, 2019, View Source [SID1234532667]). The studies summarize data achieved using multi-tumor antigen specific T cells that were developed at Baylor College of Medicine in the laboratories of Dr. Swati Naik, Dr. Ann Leen, and Dr. Premal Lulla, and exclusively licensed to Marker.

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The TCT meetings of ASBMT and CIBMTR 2019 will take place in Houston, TX from February 20-24.

Oral Presentation Details

Presentation Title: "Targeting Lymphomas Using Non-Engineered, Multi-Antigen-Specific T Cells" (Abstract #24)

Session Title: Session C – Lymphoma and Myeloma

Session Date/Time: Wednesday, February 20, 2019, 5:00 p.m. CST

Presentation Title: "Administering Leukemia-Directed Donor Lymphocytes to Patients with AML or MDS to Prevent or Treat Post-Allogeneic HSCT Relapse" (Abstract #11)

Session Title: Session A – Acute and Chronic Leukemia

Session Date/Time: Wednesday, February 20, 2019, 5:45 p.m. CST

Presentation Title: "Adoptive T-Cell Therapy for Acute Lymphoblastic Leukemia Targeting Multiple Tumor-Associated Antigens" (Abstract #78)

Session Title: Session K – Immune and Gene Therapy

Session Date/Time: Saturday, February 23, 2019, 5:00 p.m. CST

Poster Presentation Details

Presentation Title: "Safety and Efficacy of Multiantigen-Targeted T Cells for Multiple Myeloma" (Abstract #621)

Presentation Date/Time: Saturday, February 23, 6:45 p.m. CST

On January 15, 2019 Kitov Pharma (NASDAQ/TASE: KTOV), an innovative pharmaceutical company, reported new findings from its ongoing collaboration with researchers from the Hebrew University of Jerusalem (Press release, Kitov Pharmaceuticals , JAN 15, 2019, View Source [SID1234532669]). The data reveal NT219’s high affinity and selective binding to its target proteins.

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Hadas Reuveni, Ph.D., Chief Technology Officer at Kitov’s subsidiary, TyrNovo Ltd., in collaboration with Dr. Galia Blum and Dr. Ofra Moshel from the Hebrew University demonstrated that NT219 binds directly to Insulin Receptor Substrates (IRS) 1/2 and to the Signal Transducer and Activator of Transcription 3 (STAT3), both known modulators of tumor survival, metastasis and drug resistance. Data showed that a short exposure of cancerous cells to NT219 was sufficient to trigger irreversible shutdown of these pathways, resulting in a long-term anti-cancer effect.

Based on these latest findings, Kitov and Yissum, the Technology Transfer company of the Hebrew University of Jerusalem, have extended their collaboration agreement in order to deepen the understanding of NT219’s efficacy in overcoming tumors’ resistance to immunotherapy.

As previously reported (Reuveni et al, Cancer Research, 2013) upon binding to IRS1/2 a three-step mechanism is activated. IRS1/2 dissociates from the cell membrane, undergoes serine phosphorylation which prevents rebinding to the receptor, and is finally degraded by the proteasome. This sequence of events leads to the blockage of AKT – a major cancer cell survival pathway.

"We are excited about the new data which demonstrate NT219’s unique mechanism of action. NT219, a new and promising concept in cancer therapy, is designed to prevent, reverse, and delay resistance to anti-cancer drugs. We are developing NT219 as a drug to be used in combination with other therapies that has a potential to overcome cancer drug resistance and to boost the efficacy of numerous oncology drugs on the market today," stated Kitov CEO, Isaac Israel.

About NT219

NT219 is a small molecule that presents a new concept in cancer therapy by promoting the degradation and inhibiting the phosphorylation of two oncology-related signal transducers, Insulin Receptor Substrates (IRS) 1/2 and signal transducer and activator of transcription 3 (STAT3), respectively. While targeted anti-cancer drugs inhibit the "ON" signal, NT219 activates the "OFF" switch, extensively blocking major oncogenic pathways. In pre-clinical trials, NT219, in combination with several approved cancer drugs, displayed potent anti-tumor effects and increased survival in various cancers, including sarcoma, melanoma, pancreatic, lung, head & neck, prostate and colon cancers, by preventing the tumors from developing drug resistance and reversing resistance after it had been acquired. NT219 is licensed from Yissum, the technology transfer company of the Hebrew University of Jerusalem

On January 15, 2019 Inovio Pharmaceuticals, Inc. (NASDAQ: INO) reported the successful development of optimized DNA-encoded monoclonal antibodies (dMAbs) targeting the immune checkpoint molecule PD-1 (Press release, Inovio, JAN 15, 2019, View Source [SID1234532653]). The breakthrough preclinical data demonstrated that a single injection of synthetic designer dMAb versions of pembrolizumab (KEYTRUDA) or nivolumab (OPDIVO) sequences targeting PD-1 protein can be robustly redeveloped to be expressed directly in vivo in mice for up to several months. Furthermore, Inovio’s proprietary sequence optimization of the molecular design of these therapeutics resulted in significantly improved expression compared to the original KEYTRUDA and OPDIVO native sequences while maintaining identical binding capabilities.

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These published dMAb results demonstrate the potential of advancing of a new generation of checkpoint inhibitors with multiple benefits including: 1) simplifying the patient regimen for checkpoint blockade therapy – converting 90-minute intravenous infusions administered every three weeks with currently marketed protein-based mAbs into a single local injection of dMAbs, 2) possibly resulting in more consistency of expression in vivo providing improved benefits for the patient, and 3) through simple additional modifications and simplified dMAb combination formulations, engender further improved functions rapidly providing additional clinical benefit. The PD-1 dMAb results were published in the recent edition of Oncotarget in an article entitled, "Simplifying checkpoint inhibitor delivery through in vivo generation of synthetic DNA-encoded monoclonal antibodies (dMAbs)," by Inovio’s collaborators at The Wistar Institute.

Dr. J. Joseph Kim, Inovio’s President and CEO, said, "We are rapidly pioneering a potentially breakthrough class of medicines – dMAbs – produced directly in the human body. PD-1/PD-L1 targeting checkpoint inhibitor mAb products represent some of the most important advancements in immuno-oncology today. We look forward to advancing our PD-1 targeting dMAb products as potentially better versions of blockbusters KEYTRUDA and OPDIVO – with whole new sets of IP behind them – through corporate partnerships, external funding and collaborations."

Inovio recently initiated the first human study of its dMAb technology. In addition to demonstrating safety and tolerability, the Phase 1 dose-escalation study of INO-A002 (for preventing or treating Zika virus infection) will assess initially the level of the body’s production of the Zika dMAb over several doses. Using direct delivery into the body, the genetic instructions provided by the designed synthetic dMAbs delivered locally by the CELLECTRA platform, instruct the body’s cells to become a customized patient specific factory which manufactures their own therapeutic antibody products, enabling a major leap in antibody technology.

Traditional monoclonal antibodies represent the largest segment of pharmaceutical markets today, accounting for more than $100 billion in pharmaceutical sales each year, with treatments spanning cancer, infectious diseases, inflammation and cardiovascular diseases. With its synthetic design and in-patient production, dMAb products represent a disruptive entrant to this important class of pharmaceuticals. Inovio and its collaborators have already received over $60 million in non-dilutive grant funding to advance its dMAb platform in the last few years. There is a significant interest in dMAb’s as a disruptive entrant to a highly profitable overall mAb market as well as its unique applicability for rapid responses against emerging global infectious disease threats and for addressing critical vaccine limitations.

In the past few years Inovio and collaborators have published multiple impactful papers consistently demonstrating potent preclinical data from the dMAb platform, with therapeutic displays spanning protection against deadly infections to eliminating cancers and lowering life-threatening levels of cholesterol. In this regard dMAbs offer unique features for rapid production, deployment and advancement of new mAb-like biologics, with much increased efficiency. In addition, the dMAb’s constructed in vivo likely have additional advantages such as expression profiles, as well as patient specific glycosylation, and unlike traditional mAb approaches, there is no reliance on in vivo tissue culture and costly or time consuming production systems. Inovio has previously published successful animal testing of dMAbs targeting the immune checkpoint molecule CTLA-4 (Duperret et al. Cancer Res. 2018). The preclinical study demonstrated that highly optimized dMAbs targeting mouse CTLA-4 protein can be robustly expressed in vivo, and can drive therapeutic anti-tumor immune responses in established disease models. Importantly, Inovio’s dMAb constructs for anti-human CTLA-4 antibodies ipilimumab and tremelimumab, achieved high levels and prolonged expression for months from a single delivery. Inovio has multiple patents awarded in this space including the first two patents from the U.S. patent office covering this specific dMAb technology granted last quarter.

KEYTRUDA is a registered trademark of Merck & Co. (MRK); OPDIVO is a registered trademark of Bristol-Myers Squibb Company (BMY).

About Inovio’s DNA-based Monoclonal Antibody Platform

Traditional monoclonal antibodies are manufactured outside the body in bioreactors, typically requiring costly large-scale manufacturing facility development and laborious production. Inovio’s disruptive dMAb technology has the potential to overcome these limitations by virtue of their simplified design using novel plasmid vectors and unique formulations allowing for rapidity of development, product stability, ease of manufacturing and deployability, ultimately all resulting in increases in cost effectiveness, providing potential new avenues for treating a range of diseases. These dMAbs are delivered directly into cells of the body using CELLECTRA and the encoded monoclonal antibody is then produced by the locally transfected cells. Previously published studies show that a single administration of a highly optimized DNA-encoded monoclonal antibody targeting Ebola virus produced a high level of expression of the antibody in the bloodstream of mice that was protective against lethal animal challenge; Additional studies similarly reported data showing that dMAb products against flu, chikungunya and dengue protected animals against lethal challenge. In addition the team has reported delivery of dMAbs that impact prostate as well as breast and ovarian cancers in animals.

On January 15, 2019 Neurocrine Biosciences, Inc. (NASDAQ: NBIX) reported that it will report fourth quarter and year-end 2018 financial results after the Nasdaq market closes on Tuesday, Feb. 5, 2019 (Press release, Neurocrine Biosciences, JAN 15, 2019, View Source;p=RssLanding&cat=news&id=2383457 [SID1234532654]). Neurocrine will then host a conference call and webcast to discuss its financial results and provide a Company update that day at 1:30 p.m. Pacific Time (4:30 p.m. Eastern Time).

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Participants can access the live conference call by dialing 877-876-9174 (US) or 785-424-1669 (International) using the conference ID: NBIX. The webcast can also be accessed on Neurocrine’s website under Investors at www.neurocrine.com. A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month.