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Cyclacel Pharmaceuticals Reports Fourth Quarter and Full Year 2015 Financial Results

On March 24, 2016 Cyclacel Pharmaceuticals, Inc. (NASDAQ:CYCC) (NASDAQ:CYCCP); "Cyclacel" or the "Company"), a biopharmaceutical company developing oral therapies that target the various phases of cell cycle control for the treatment of cancer and other serious disorders, reported its financial results and business highlights for the fourth quarter and full year ended December 31, 2015 (Press release, Cyclacel, MAR 24, 2016, View Source [SID:1234509935]).

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The Company’s net loss applicable to common shareholders for the fourth quarter ended December 31, 2015 was $3.4 million, or $0.10 per basic and diluted share, compared to net loss applicable to common shareholders of $4.8 million, or $0.21 per basic and diluted share for the fourth quarter ended December 31, 2014. As of December 31, 2015, cash and cash equivalents totaled $20.4 million.

"In SEAMLESS, our Phase 3 pivotal study in acute myeloid leukemia (AML), approximately 4% of required events remain to be observed before mature data become available, expected around the first half of 2016 or approximately 18 months after completion of enrollment," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. "The primary endpoint of the study is overall survival. After top-line data readout, the mature data will be evaluated for submissibility to regulatory authorities. In parallel, we have been progressing our CDK inhibitor programs. We have reported encouraging interim data from the ongoing Phase 1/2 combination trial of seliciclib and sapacitabine in solid tumor patients, including durable partial responses and stable disease in patients with BRCA positive breast, ovarian and pancreatic cancers. In particular, two ongoing patients with BRCA positive breast cancer have achieved over 1 and 4.5 years of treatment, respectively. In light of these data and investigator interest, we have started an extension cohort in a BRCA-enriched population of breast cancer patients. Last fall we initiated a first-in-human, Phase 1 study of CYC065, our second-generation CDK2/9 inhibitor, in patients with solid tumors and lymphomas following extensive preclinical data in the literature suggesting broad activity of CYC065 in both liquid and solid tumor models. The Cyclacel team continues to pursue the vision of our founders, as appreciation of the importance of CDK inhibitors is increasing among the medical community."

Recent Business Highlights

SEAMLESS Study

Continued follow up of patients enrolled in SEAMLESS, a Phase 3 study of orally-administered sapacitabine alternating with intravenous decitabine compared to decitabine alone, as first-line treatment in patients aged 70 years or older with AML.
Approximately 4% of the pre-specified events remain to be observed until mature data become available for analysis.
Submitted to the European Medicines Agency (EMA) a Paediatric Investigation Plan application for sapacitabine.
Cyclin Dependent Kinase 2/9 (CDK2/9) Inhibitor Programs

Dosed first patients in an extension cohort of the Phase 1/2 combination study of seliciclib and sapacitabine in a population of BRCA-positive breast cancer patients. In the first part of the study, several patients with BRCA positive breast, ovarian and pancreatic cancers achieved durable partial responses and stable disease.
Continued patient recruitment in the first-in-human trial of CYC065, a second-generation CDK2/9 inhibitor, to evaluate the safety, tolerability and pharmacokinetic profile of CYC065 in patients with solid tumors and lymphomas.
Presented preclinical data on the molecular rationale and therapeutic potential in both hematologic and solid tumors of CYC065 at several medical conferences during the fourth quarter, including the Society of Hematologic Oncology (SOHO) 2015 Annual Meeting, the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference, the San Antonio Breast Cancer Symposium (SABCS) and the Neuroblastoma UK Annual Meeting.
Cyclacel’s Key Milestones for 2016

Sapacitabine in SEAMLESS

Continue follow-up of patients until the requisite number of events occur, which is anticipated around the end of the first half of 2016.
Report top-line results.
Determine submissibility to regulatory authorities for marketing approval following analysis of the mature data set.
Progress a Paediatric Investigation Plan for sapacitabine with the EMA.
Sapacitabine in myelodysplastic syndromes (MDS):

Initiate a Phase 1/2 trial of sapacitabine in combination with other agents to determine safety and tolerability.
Plan a Phase 2 randomized controlled trial (RCT) of sapacitabine in combination with other agents following review of all relevant clinical data with mature follow-up.
CDK Inhibitor Programs

Progress the seliciclib and sapacitabine Phase 1/2 study in an extension cohort of breast cancer patients enriched for BRCA mutations.
Report updated Phase 1 seliciclib and sapacitabine combination data in approximately 60 patients with advanced solid tumors.
Report top-line results of the CYC065 Phase 1 trial in patients with solid tumors and lymphomas.
Present additional preclinical data on CYC065 at the upcoming AACR (Free AACR Whitepaper) conference in April.
Report data when available from on-going investigator sponsored trials (ISTs) evaluating seliciclib in patients with Cushing’s disease and rheumatoid arthritis. Seliciclib is also being evaluated in cystic fibrosis through a license and supply agreement with ManRos Therapeutics.
Fourth Quarter 2015 Financial Results

Grant Revenue

Revenue for the three months ended December 31, 2015 was $0.4 million compared to $0.2 million for the same period of the previous year. The revenue is related to previously awarded grants from the UK government being recognized over the period to progress CYC065 to IND and complete IND-directed preclinical development of CYC140, a novel, orally available, Polo-Like Kinase 1 (PLK 1) inhibitor.

Research and Development Expenses

Research and development expenses decreased to $2.6 million for the three months ended December 31, 2015 compared to $4.4 million for the same period in the previous year. The decrease was primarily due to reduced study and clinical supply costs associated with the SEAMLESS Phase 3 trial, which completed enrollment in December 2014, offset by increased expenditures primarily related to the first-in-human, Phase 1 study of CYC065 and grant supported research and development.

General and Administrative Expenses

General and administrative expenses for the three months ended December 31, 2015 increased to $1.7 million, compared to $1.6 million for the same period in 2014.

Based on current plans, the Company estimates that it has capital resources to reach beyond the final analysis of SEAMLESS and continue existing programs through the end of 2017.

Varian Honors Commitment to Algeria by Opening New Office in Country

On March 24, 2016 Varian Medical Systems (NYSE: VAR), leader in radiotherapy systems and software for the treatment of cancer, reported the official opening of a new strategic operating entity in Algeria, providing support to customers across North Africa (Press release, Varian Medical Systems, MAR 24, 2016, View Source [SID:1234509932]). The Algerian Minister of Health’s chief of staff and the U.S. Chief of Mission in Algeria joined with local dignitaries and senior Varian personnel at an inauguration ceremony today to mark the launch of Varian Medical Systems Algeria SPA.

"Varian is proud to meet our commitment to the Algerian Ministry of Health and the country’s clinical community by creating a strategic hub here in Algiers," said Fouad Rahal, managing director of VMS Algeria SPA. "Since we created the new entity nearly a year ago, we have established a facility and hired highly trained Algerian technical service, clinical applications, logistics and other experts to support cancer clinics here."

The new Varian facility in the Hydra district of Algiers employs 16 people and houses a training and education center, a parts depot and a service center. "This entity will provide clinics with a high level of service as well as offering educational programs to train clinicians on the use of Varian technology to deliver advanced radiotherapy for the benefit of Algerian cancer patients," added Rahal.

At today’s inauguration ceremony, former Minister of Health and head of the Algeria National Cancer Plan Professor Messaoud Zitouni presented on global and regional cancer trends and discussed the importance of collaboration with Varian in helping to address a growing cancer burden.

Burt Lang, Varian’s senior managing director in Africa, said, "The incidence of cancer is unfortunately growing rapidly in Africa and has become one of the continent’s top healthcare concerns. Radiotherapy plays a vital and cost effective role in treating cancer and we are committed to making it available to more patients across the continent."

The first Varian linear accelerator was installed in Algeria over 20 years ago and the company now has 21 systems operating across the country. Eighteen months ago, Varian announced that it had entered into an agreement with the Algerian Ministry of Health to equip six cancer treatment centers with advanced technology for radiotherapy and radiosurgery. The first six of these systems, including advanced TrueBeam treatment devices, are due to be installed by the end of this year.

FUJIFILM AND NATIONAL BREAST CANCER FOUNDATION CELEBRATE INSTALL OF MAMMOGRAPHY SYSTEM AT WHITE MEMORIAL MEDICAL CENTER

On March 24, 2016 White Memorial Medical Center, a member of the Adventist Health System and a 353-bed hospital in downtown Los Angeles, reported the installation of a new mammography system donated by FUJIFILM Medical Systems U.S.A., Inc. and National Breast Cancer Foundation (NBCF) on March 23, 2016 (Press release, Fujifilm, MAR 24, 2016, View Source [SID:1234509930]). A ceremony unveiled Fujifilm’s Aspire Cristalle at White Memorial Medical Center that will help meet the screening needs of women and assist medical professionals in the early detection and diagnosis of breast cancer.

"We are pleased to be working with National Breast Cancer Foundation and White Memorial Medical Center to make a contribution that will have both immediate and long-term impacts on improving breast health care in the community," said Johann Fernando, Chief Operating Officer, FUJIFILM Medical Systems U.S.A., Inc.

According to the National Cancer Institute, 1 in 8 women will be diagnosed with breast cancer in their lifetime. Early detection and treatment are among the most effective ways to overcome cancer. The latest technology at White Memorial Medical Center will assist radiologists in screening and diagnosis of breast cancer.

"The incredible support we receive from National Breast Cancer Foundation makes a big difference at White Memorial Medical Center," said John Raffoul, President and CEO, White Memorial Medical Center. "This year alone, thanks to support from NBCF and other generous donors, we will be able to provide more than 2,300 free clinical breast exams/mammograms to underserved women of our community, of whom 45 will unfortunately test positive for cancer. This state-of-the-art equipment from Fujifilm will literally allow us to save the lives of women when we can diagnose them at an early stage of breast cancer. We are blessed to have these incredible partners supporting our hospital."

Since 2006, Fujifilm has donated $1.6 million to NBCF. The support has allowed NBCF to provide thousands of mammograms and early detection services to women in all 50 states and helped ensure that those facing breast cancer have access to quality healthcare.

"Through the donation of the Aspire Cristalle mammography system, Fujifilm will provide life-saving mammograms to women throughout the Los Angeles area," said Janelle Hail, NBCF Co-Founder & CEO. "We thank them for their partnership and support of our mission of Helping Women Now to those affected by breast cancer."

Over 9,000 worldwide facilities trust Fujifilm’s full-field digital mammography solutions, making Fujifilm the most popular digital mammography system provider in the world. To learn more about Fujifilm’s women’s health care products, please visit www.fujifilmhealthcare.com

DelMar Pharmaceuticals Announces Abstract Presentations for the American Association Cancer Research (AACR) Annual Meeting in April 2016

On March 24, 2016 DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that it will present three abstracts at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting based on pre-clinical research conducted with its lead anti-cancer product candidate, VAL-083 (dianhydrogalactitol), a "first-in-class" small-molecule chemotherapeutic agent (Press release, DelMar Pharmaceuticals, MAR 24, 2016, View Source [SID:1234509928]).

The Company’s first two abstracts have been published and can be viewed on the AACR (Free AACR Whitepaper) Annual Meeting website.

DelMar will present abstract (#2157): "Enhanced in vitro activity of dianhydrogalactitol (VAL-083) in combination with platinum drugs: Impact of p53 and platinum-resistance," during the session entitled "New Drugs, Therapeutic Targets, and Treatment Approaches being held on Monday, April 18, 2016, from 1:00 p.m.-5:00 p.m. CDT. In this abstract, the Company will present new in vitro data in cell-lines representing difficult to treat subsets of non-small cell lung and ovarian cancer that may be targeted by VAL-083’s unique anti-cancer mechanism.

A second abstract (#2985): "Molecular mechanisms of dianhydrogalactitol (VAL-083) in cancer treatment," will be presented during the session entitled New Mechanisms of Anticancer Drug Action being held on Tuesday, April 19, 2016, from 8:00 a.m.-12:00 p.m. CDT. In this abstract, DelMar will present new data related to VAL-083’s mechanism of action, which may lead to opportunities to treat resistant cancer phenotypes and to beneficial combination therapy approaches in the treatment of cancer.

DelMar will also present an update on its ongoing "Phase I/II study of VAL-083 in patients with recurrent glioblastoma," as a late-breaking abstraction during the Phase II/III Clinical Trials in Progress session on Tuesday, April 19. Details of this abstract (#CT074) will be published during the session beginning at 8:00 a.m. CDT.

About VAL-083
VAL-083 is a "first-in-class," small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia (CML) and lung cancer, and has received orphan drug designation in Europe and the U.S. for the treatment of malignant gliomas. DelMar recently announced that the FDA’s Office of Orphan Products had also granted an orphan designation to VAL-083 for the treatment of medulloblastoma.

DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by the expression of MGMT, a DNA repair enzyme that is implicated in chemotherapy resistance and poor outcomes in GBM patients following standard front-line treatment with Temodar (temozolomide).

DelMar has been conducting a Phase I/II clinical trial in GBM patients whose tumors have progressed following standard treatment with temozolomide, radiotherapy, bevacizumab and a range of salvage therapies.

Sub-group analysis of data from the Phase I dose-escalation portion of the study suggests a dose-dependent and clinically meaningful survival benefit following treatment with VAL-083. Patients in a low dose (≤5mg/m2) sub-group had a median survival of approximately five (5) months versus median survival of approximately nine (9) months for patients in the therapeutic dose (30mg/m2 & 40mg/m2) sub-group following initiation of VAL-083 treatment. DelMar also reported increased survival at 6, 9 and 12 months following initiation of treatment with VAL-083 in the therapeutic dose sub-group compared to the low dose sub-group.

VAL-083 is well tolerated using a regimen of 40mg/m2 daily x 3 every 21 days. Dose limiting toxicity (DLT) defined by thrombocytopenia (low platelet counts) was observed at doses above 40 mg/m2. Generally, DLT-related symptoms resolved rapidly and spontaneously without concomitant treatment.

Based on these data, DelMar initiated a Phase II expansion cohort utilizing the 40mg/m2 dosing regimen in June 2015 at five clinical centers in the United States: Mayo Clinic (Rochester, MN); UCSF (San Francisco, CA) and three centers associated with the Sarah Cannon Cancer Research Institute (Nashville, TN, Sarasota, FL and Denver, CO). DelMar announced the completion of enrollment in a Phase II expansion cohort in September, 2015.

Further details can be found at View Source

The production of coagulation factor VII by adipocytes is enhanced by tumor necrosis factor-α or isoproterenol.

A relationship has been reported between blood concentrations of coagulation factor VII (FVII) and obesity. In addition to its role in coagulation, FVII has been shown to inhibit insulin signals in adipocytes. However, the production of FVII by adipocytes remains unclear.
We herein investigated the production and secretion of FVII by adipocytes, especially in relation to obesity-related conditions including adipose inflammation and sympathetic nerve activation.
C57Bl/6J mice were fed a low- or high-fat diet and the expression of FVII messenger RNA (mRNA) was then examined in adipose tissue. 3T3-L1 cells were used as an adipocyte model for in vitro experiments in which these cells were treated with tumor necrosis factor-α (TNF-α) or isoproterenol. The expression and secretion of FVII were assessed by quantitative real-time PCR, Western blotting and enzyme-linked immunosorbent assays.
The expression of FVII mRNA in the adipose tissue of mice fed with high-fat diet was significantly higher than that in mice fed with low-fat diet. Expression of the FVII gene and protein was induced during adipogenesis and maintained in mature adipocytes. The expression and secretion of FVII mRNA were increased in the culture medium of 3T3-L1 adipocytes treated with TNF-α, and these effects were blocked when these cells were exposed to inhibitors of mitogen-activated kinases or NF-κB activation. The β-adrenoceptor agonist isoproterenol stimulated the secretion of FVII from mature adipocytes via the cyclic AMP/protein kinase A pathway. Blockade of secreted FVII with the anti-FVII antibody did not affect the phosphorylation of Akt in the isoproterenol-stimulated adipocytes.
Obese adipose tissue produced FVII. The production and secretion of FVII by adipocytes was enhanced by TNF-α or isoproterenol via different mechanisms. These results indicate that FVII is an adipokine that plays an important role in the pathogenesis of obesity.