On March 20, 2019 The National Comprehensive Cancer Network (NCCN) Oncology Research Program (ORP) and Eli Lilly and Company (NYSE: LLY) reported six projects that aim to improve the delivery of gastric and gastroesophageal junction (GEJ) cancer care in the United States (Press release, Eli Lilly, MAR 20, 2019, View Source [SID1234554022]). The quality improvement studies will focus on methods of intervention that can be implemented across a variety of different oncology practice settings. These projects are eligible to receiving funding from Lilly Oncology after completing contract negotiations. Forty-nine letters of intent were submitted in response to the RFP and subsequently 19 full proposals were requested for review.

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!

"As part of our mission to facilitate care that helps patients live better lives, we’re honored to support research that enhances outcomes and experiences for people with gastric and gastroesophageal junction cancers," said Wui-Jin Koh, MD, Chief Medical Officer, NCCN. "This project is intended to identify disparities in care between the community and academic setting, and define scalable, shareable solutions that will rapidly improve adherence to guidelines and quality of care."

The following studies were selected by the NCCN ORP:

Dan G. Blazer III, MD; Daniel P. Nussbaum, MD; Linda M. Sutton, MD; Duke University Health System and Duke Cancer Network Affiliates; The DCN Passport: A Novel, Patient-Centered Approach to Improve Care for Gastric/Gastroesophageal Junction Cancer Across an Academic-Community Oncology Network
Efrat Dotan, MD; Fox Chase Cancer Center; Improving the Approach to and Management of the Older Patient with Metastatic Gastric Cancer
Jae Kim, MD; City of Hope National Medical Center; Telehealth Intervention for Self-Management of Dietary Quality of Life After Gastric Cancer Surgery
Veena Shankaran MD, MS; University of Washington/Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center; Randomized Pragmatic Trial of a Proactive Financial Navigation Intervention in Patients with Newly Diagnosed Gastric and Gastroesophageal Junction Adenocarcinoma
Qiuling Shi, PhD; Loretta A. Williams, PhD; The University of Texas MD Anderson Cancer Center; Symptom Management Through an Automated Alert System to Improve Adherence During Systemic Therapy for Patients with Gastric/Gastroesophageal Junction (GEJ) Cancer
Kuang-Yi Wen, PhD; Sidney Kimmel Cancer Center (SKCC) at Jefferson; mChemoCoping – GC: A Text Messaging System Enabling Real-Time Monitoring and Management of Chemotherapy Side Effects Among Patients with Gastric Cancer (GC)
"NCCN ORP congratulates all of the collaborators, and looks forward to their contributions to the future of gastric and GEJ cancer care," said Dr. Koh.

"Lilly is proud to work with the NCCN ORP to research better ways for delivering high-quality cancer care to patients with this aggressive disease," said Maura Dickler, MD, Vice President of Late Phase Development, Lilly Oncology. "By utilizing novel approaches and advancing technology, these studies will help us to address some of the largest disparities in care that exist for patients undergoing treatment for gastric and GEJ cancers."

The NCCN ORP was responsible for the Request-for-Proposals (RFP) process, application review and evaluation. A committee led by NCCN and including a medical representative from Lilly determined which proposals would be eligible to receive funding. Project funding will be provided directly by Lilly upon mutual agreement of project terms and conditions.

The studies will be conducted over a period of two years.

The NCCN ORP fosters innovation and knowledge discovery that improves the lives of people with cancer by supporting investigator-initiated trials at NCCN Member Institutions and their affiliates. To date, it has supported more than 140 studies, with numerous publications in peer-reviewed journals. To learn more about the NCCN ORP and ongoing clinical trials, visit NCCN.org/ORP.

On March 20, 2019 Trizell Ltd (Trizell) reported that it has opened a Phase 3 Study of its novel gene therapy TR002, an adenovirus-mediated interferon alfa 2b, in patients with malignant pleural mesothelioma (MPM) who have failed first-line standard of care chemotherapy (Press release, Trizell, MAR 20, 2019, View Source [SID1234561809]). TR002 is given to trigger the pleiotropic anti-tumour effects of interferon, a naturally occurring protein the body uses to fight cancer, and is followed by gemcitabine chemotherapy. This study will include sites in the United States, Europe, Australia, and Russia.

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!

Malignant pleural mesothelioma is an aggressive and devastating form of cancer affecting the outer (pleural) membrane of the lungs. The disease is usually triggered by inhalation of asbestos fibres that slowly make their way from the alveoli to the outer surface of the lung in the pleural cavity. The fibres then induce a cancer which grows on the outside of the lung into the pleural space, eventually invading surrounding thoracic tissues leading to death. There is a clear association between occupational or environmental asbestos and mineral fibre exposure and MPM development.
A previous Phase 2 study of TR002 at the Abramson Cancer Center included 40 MPM patients who were newly diagnosed or failed standard chemotherapy (Pemetrexed/ Platin) showed an overall disease control rate of 87.5%. The second line treatment cohort showed an almost doubling of median survival time compared to historical study controls (17 months vs. 9 months) with approximately 25% of patients living at least 2 years and approximately 20% at least 3 years.

MPM prognosis is poor and following failure of standard of care first line treatment, median life expectancy is around 9 months, with very few cases surviving past 18 months. With a prevalence of around 200,000 cases worldwide, there are around 3000 and 5000 new cases diagnosed every year in the EU and US alone. Dust from the September 11th attacks in New York is predicted to cause a rise in the number of future cases in the US, although the extent of the future rise is currently unclear.
"This is an exciting trial. The results that we noted in our previous study showed significant prolongation of life expectancy and particularly so for about 25 percent of these refractory patients who have gone on to live two and in some cases three years and more," said Daniel H. Sterman, MD, Director of the Multidisciplinary Pulmonary Oncology Program at NYU Langone Health. "We will work hard to get this potentially ground-breaking clinical trial completed."

The Phase 3 study is an open-label, randomized, parallel group study in up to approximately 300 patients who have failed chemotherapy. TR002 is given by catheter directly into the pleural cavity as a single dose of 3 x 1011 viral particles. Gemcitabine chemotherapy commences 14 days later and continues until disease progression.

"It is very exciting to see a therapeutic approach developed at the University of Pennsylvania being moved to an international, randomized trial, as it is a career milestone for any academic researcher to see their work tested in this way," said Steven M. Albelda, MD, William Maul Measey Professor of Medicine, Perelman School of Medicine, University of Pennsylvania.

TR002 was pioneered by Drs. Albelda and Sterman, and by Dr. Evan W. Alley, MD, PhD, whose current appointment is at Cleveland Clinic Florida but who was involved in the trial during his time at Penn.

About TR002
TR002 (nadofaragene firadenovec) is an investigational gene therapy consisting of an adenovirus containing the gene interferon alfa-2b. It is administered by catheter into the pleural cavity, where the virus enters the cells lining the pleural cavity. Inside the cells, the virus breaks down leaving the active gene to do its work. The internal gene/DNA machinery of the cells picks up the gene and translates its DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This novel gene therapy approach turns the patient’s own pleural cavity cells into multiple interferon microfactories, enhancing the body’s natural defences against the cancer.

About Malignant Pleural Mesothelioma
Malignant pleural mesothelioma is usually triggered by inhalation of asbestos fibres. These slowly make their way from the alveoli to the outer surface of the lung in the pleural cavity where they induce a cancer which grows on the outside of the lung into the pleural space, eventually invading surrounding thoracic tissues leading to death. Prognosis is poor and following failure of standard of care first-line treatment, median life expectancy is around 9 months, with very few cases surviving past 18 months.

WHO estimates that 43,000 people die of MPM each year; annually in North America, Western Europe, Japan, and Australia, there are 10,000 cases each year1. With the passage of the Clean Air Act, asbestos use was banned in the US in 19702, and the incidence of mesothelioma in the US was predicted to steadily decline. However, dust from the September 11th attacks in New York is predicted to cause a rise in the number of future cases although the extent of the future rise is currently unclear3. In contrast, asbestos use continued in Australia until 2003 and in Europe until 2005. As a result, the incidence of mesothelioma in European countries continues to rise and is projected to peak in 2020 and may account for as many as 250,000 European deaths in the next 35 years. In 2020, it is estimated over 18,000 Australian cases will be diagnosed4.

On March 20, 2019 4SC AG (4SC, FSE Prime Standard: VSC) reported the financial results for the financial year ended 31 December 2018, presenting all material reporting period developments and provides an outlook for 2019. The full report is available at 4SC’s website (Press release, 4SC, MAR 20, 2019, View Source [SID1234534507]).

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!

Key highlights of 2018 and 2019 YTD

4SC continued to make solid progress on clinical development of both resminostat and domatinostat (4SC-202)
More than two thirds of patients recruited for pivotal RESMAIN study of resminostat in advanced-stage cutaneous T-cell lymphoma (CTCL); positive safety outcomes to date
Phase II study of resminostat plus S-1 chemotherapy versus S-1 chemotherapy plus placebo as second-line treatment in Japanese patients with biliary tract cancer initiated by Yakult Honsha Co., Ltd. (Yakult Honsha), 4SC’s development partner for resminostat in Japan
Completed second dose cohort of Phase Ib/II study SENSITIZE of domatinostat in combination with pembrolizumab in advanced-stage melanoma; positive safety outcomes to date; third dose cohort started
Initiated investigator-initiated Phase II study EMERGE of domatinostat in combination with avelumab in microsatellite-stable gastrointestinal tumors
Published preclinical data on combination of domatinostat with either chemotherapy or several immunotherapeutic agents leading to evaluation of further clinical combination trials
Strengthened patent protection for Hedgehog/GLI signaling inhibitor 4SC-208 in the U.S., China, Japan, Singapore, Australia and New Zealand.
Received milestone payments from several partnered programs.
Jason Loveridge, Ph.D., CEO of 4SC, said: "4SC continues to make excellent progress with the development of our portfolio of drug candidates.

We expect that the two ongoing clinical trials of domatinostat will provide clinical evidence to further support the efficacy of domatinostat in patients that do not benefit from immunotherapeutic treatment with checkpoint inhibitors (SENSITIZE study, melanoma) or in a historically checkpoint inhibitor non-responsive indication (EMERGE study, microsatellite-stable gastrointestinal cancer). Taken together, we expect these studies to drive initiation of a pivotal clinical study of domatinostat in the aggressive rare skin cancer Merkel-cell carcinoma.

For resminostat, we expect to enroll sufficient patients in the pivotal RESMAIN study in 2019 to observe the required 125 events to unblind the study. Should the trial prove positive, we plan to submit applications for marketing approval of resminostat in CTCL in Europe, and potentially the U.S., and Yakult Honsha will submit in Japan. If approved, resminostat would be the first histone deacetylase inhibitor approved for CTCL in Europe and the first and only drug approved for maintenance therapy in this indication in either Europe, Japan or the U.S.

The main goal of all our activities is to create significant benefit for patients and value for our shareholders by bringing resminostat and domatinostat to market as soon as possible."

Business outlook

Top-line data of the pivotal RESMAIN study expected in H1 2020.
Results of Yakult Honsha’s Phase II study of resminostat in biliary tract cancer to be available by mid-2020.
SENSITIZE study expected to complete in H1 2019.
Safety data of EMERGE expected in Q2 2019 and early efficacy data in H2 2019
Expand clinical development for domatinostat and initiate potentially pivotal study in Merkel-cell carcinoma
Cash balance development in full year 2018 and financial forecast

As of 31 December 2018, 4SC holds cash balance/funds of €25.0 million, as compared to €41.3 million as of 31 December 2017. The average monthly use of cash from operations in 2018 was €1.357 million (2017: €0.723 million), which is within the €1.3 million to €1.5 million forecast in the previous Q3 announcement. The increase of the monthly use of cash and the decrease in cash balance/funds in 2018 was mainly driven by investments in the ongoing clinical studies RESMAIN and SENSITIZE.

Taking into account the current financial planning and the intended operating activities, the Management Board estimates that current funds should be sufficient to finance 4SC for the next twelve months. For 2019, 4SC is expecting an average monthly use of cash from operations of between €1.4 million and €1.6 million. For 2019, 4SC expects the net loss to be similar to 2018. 4SC is expecting to report similar annual net losses, with almost identical functional cost allocations in the short to medium term future as well.

Conference call

Investors, financial analysts, and journalists interested in participating in the conference call on the annual results 2018 can access via the telephone numbers stated below. Please join the event conference 5-10 minutes prior to the start time. You will be asked to provide your name, company and location as well as the access code.

Date: 20 March 2019
Time: 3 pm CET (10 am ET)
Phone Numbers: +49 (0)32 22109 8334 (Germany)
+44 (0)20 3936 2999 (United Kingdom)
+1 845 709 8568 (USA)
Joining by web (free of charge): www.incommuk.com/customers/online
Access Code: 802724

A presentation document supporting the conference call will be available earlier on the same day at 4SC’s website. After the event, a replay can be accessed from there as well.

On March 20, 2019 Oncorus, Inc., an oncolytic virus therapeutics company focused on driving innovation to transform outcomes for cancer patients, reported that four abstracts have been accepted for presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019, which will be held from March 29 through April 3, 2019 at the Georgia World Congress Center in Atlanta, GA (Press release, Oncorus, MAR 20, 2019, View Source [SID1234534509]).

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!

Oncorus will give an oral presentation highlighting preclinical data supporting the advancement of its lead pipeline candidate, ONCR-177, a locally administered oncolytic virus therapy armed with five immunomodulatory payloads for the treatment of multiple solid tumor indications. ONCR-177 is built on Oncorus’ proprietary, next-generation oncolytic herpes simplex virus (oHSV) platform. The company’s three poster presentations will detail proprietary innovations in potency and safety engineered by Oncorus into both its oHSV platform as well as its novel synthetic oncolytic virus platform that enable best-in-class potential for the company’s portfolio programs and the opportunity to pursue multiple tumor indications

"Our research team under the leadership of our CSO, Dr. Christophe Quéva, continues to make rapid progress advancing both our oncolytic herpes simplex virus and synthetic oncolytic virus platforms to enable intratumoral and intravenous administration of oncolytic virus therapies, respectively, that have the potential to address a spectrum of critical, unmet cancer treatment needs," said Ted Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. "We look forward to sharing our proprietary innovations on both platforms at this year’s AACR (Free AACR Whitepaper) Annual Meeting, in particular preclinical data supporting the clinical advancement of our lead candidate ONCR-177."

The schedule and details for Oncorus’ oral and poster presentations are as follows:

Oral Presentation

Abstract #: 940
Title: Development of ONCR-177, a miR-attenuated oncolytic HSV-1 designed to potently activate systemic antitumor immunity
Session: MS.IM02.03 – Cancer Vaccines and Intratumoral Immunomodulation
Date and Time: Sunday, March 31, 2019 / 3:05 – 3:20 pm EDT
Location: Georgia Ballroom 3 – Building C
Abstract Link: View Source!/6812/presentation/2236

Poster Presentations

Abstract #: 1455
Title: Design of ONCR-177 base vector, a next generation oncolytic herpes simplex virus type-1, optimized for robust oncolysis, transgene expression and tumor-selective replication
Session: PO.IM02.08 — Cancer Vaccines and Intratumoral Immunomodulation
Date and Time: Monday, April 1, 2019 / 8:00 am – 12:00 pm EDT
Location: Poster Section 22
Abstract Link: View Source!/6812/presentation/2749

Abstract #: 1452
Title: Development of ONCR-148, a miR-attenuated oncolytic HSV-1 designed to potently activate antitumor T cell response
Session: PO.IM02.08 — Cancer Vaccines and Intratumoral Immunomodulation
Date and Time: Monday, April 1, 2019 / 8:00 am – 12:00 pm EDT
Location: Poster Section 22
Abstract Link: View Source!/6812/presentation/2746

Abstract #: 4773
Title: Development of ONCR-NEP, a lipid nanoparticle delivered oncolytic virus capable of robust in situ amplification resulting in tumor lysis and regression
Session: PO.ET08.01 — Gene- and Vector-based Therapy
Date and Time: Wednesday, April 3, 2019 / 8:00 am – 12:00 pm EDT
Location: Poster Section 12
Abstract Link: View Source!/6812/presentation/1354

On March 20, 2019 Genzada Pharmaceuticals USA Inc. (Genzada), a subsidiary of Ionics Life Sciences Limited, reported that the first patient enrolled in its Phase 1 clinical trial for the oral therapeutic GZ17-6.02 received the first dose this week at HonorHealth Research Institute in Scottsdale, Ariz (Press release, Genzada Pharmaceuticals, MAR 20, 2019, View Source [SID1234534510]). Genzada’s GZ17-6.02 will be administered to patients with advanced solid cancers and lymphoma.

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 drug is derived in part from the black calla lily (arum palaestinum), a native plant found in several regions of the Middle East. Traditional Middle Eastern medicine has used the lily for more than 1,000 years as an herbal remedy for multiple maladies, including inflammation, viral infection and cancer.

"We’re excited to have reached the clinical stage of development of GZ17-6.02. Through the rigorous preclinical developmental path, we have discovered a unique mechanism of action via super-enhancer inhibition. We’re confident that this agent will be both safe and effective in cancer patients and are thrilled to bring this into the clinic," said Genzada Chief Operating Officer Cameron West, MD. "Additionally, as GZ17-6.02 is composed of three active pharmaceutical ingredients—originally derived from medicinal plants—we’re hopeful that 6.02 will tackle various malignancies on multiple fronts."

Genzada chose TD2, a contract research organization (CRO), to manage the operational aspects of the trial, including trial design, project management, data management, monitoring, clinical site management, safety and statistics.

"Reaching the clinical stage is a huge milestone for the companies we work with, as it takes a lot of hard work and preparation to get to this point," said Stephen Gately, president and CEO of TD2. "This particular drug is quite interesting in its composition, and we’re honored to be part of this trial that could potentially improve the lives of cancer patients."

With enrollment for the study projected to reach 30-40 patients nationally, Genzada expects continued treatments among trial patients throughout the remainder of 2019. Currently, patients enrolled in this clinical trial will receive the GZ17-6.02 (6.02), an investigational compound, at HonorHealth Research Institute in Scottsdale. In the future, additional trial sites may be included as the study progresses.

"GZ17-6.02 is truly a novel therapy with the potential to transform cancer care. With the support of Genzada and TD2, we are pleased to make this treatment available at HonorHealth Research Institute," said Frank Tsai, MD, medical oncologist, principal investigator at HonorHealth Research Institute.

In November 2018, the project’s Investigational New Drug (IND) application received clearance from the U.S. Food and Drug Administration (FDA) to proceed with the Phase 1 human trial of 6.02 in patients with advanced solid cancers and lymphoma.

The 6.02 compound acts as an inhibitor to super-enhancers, the areas of the genome bound by transcription factors that are uniquely susceptible to repair signal disruption. It previously showed success in many therapeutic settings, including patients with pancreatic cancer and those with head and neck squamous cell carcinoma.