On December 14, 2015 Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) ("Cyclacel" or the "Company"), reported the presentation of preclinical data demonstrating the molecular basis for the development of CYC065 in triple negative breast cancer (TNBC), and in particular basal-like TNBC. CYC065 is a highly-selective, second-generation cyclin dependent kinase (CDK) inhibitor targeting CDK2/9 dependent tumors (Press release, Cyclacel, DEC 14, 2015, View Source [SID:1234508697]). The data were presented at the San Antonio Breast Cancer Symposium (SABCS), taking place December 8-12, 2015.

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"We have recently reported that CYC065 can target malignancies driven by CDK2/9 dependent oncogenic and leukemogenic pathways such as MLL-rearranged leukemias and tumors overexpressing MYC", said Spiro Rombotis, Cyclacel’s President and Chief Executive Officer. "The data presented at SABCS show CYC065 could be active in breast cancer patients with a poor prognosis and that its mechanism induces breast cancer cell death by apoptosis. In addition, we have identified approved and investigational anticancer agents, including our own sapacitabine, which combine effectively with CYC065. A first-in-human, Phase 1 clinical trial with CYC065 has commenced and we look forward to reporting data from this study."

Data presented at SABCS (Program Number: P5-03-10, View Source) demonstrated in particular the mechanistic rationale for clinical development of CYC065 in basal-like TNBC, a cancer with poor prognosis frequently associated with BRCA1 mutations. Molecular characteristics of TNBC include amplification or overexpression of Cyclin E, the partner protein of CDK2, and MYC. CYC065 directs a pro-apoptotic mechanism in breast cancer cell lines, which includes transcriptional down regulation of key pro-survival and oncogenic regulators, including MCL-1 and MYC.

CYC065 was shown to rapidly induce cell death in breast cancer cell lines, while transiently inducing G1 cell cycle arrest in non-malignant breast lines. CYC065’s potent anticancer activity has been confirmed in breast cancer xenograft animal models. CYC065 effectively combined with Cyclacel’s sapacitabine in breast cancer cell lines, as was the case with seliciclib, Cyclacel’s first generation CDK2/9 inhibitor, when combined with sapacitabine.

An oral regimen of seliciclib and sapacitabine is being evaluated in an on-going Phase 1 all-comer study of patients with various advanced cancers. In previously reported initial data from this study, durable partial responses have been observed in breast, ovarian and pancreatic cancer patients with germline mutations in Homologous Recombination (HR) repair genes, specifically BRCA1 or BRCA2.

CYC065 is in a first-in-human, Phase 1 clinical trial.

On December 14, 2015 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported that the Company will host a Key Opinion Leader breakfast focused on the treatment landscape for myelodysplastic syndromes (MDS), including the Company’s late-stage drug candidate, rigosertib, a small molecule Ras mimetic that inhibits cellular signaling (Press release, Onconova, DEC 14, 2015, View Source [SID:1234508570]). The event and live webcast will take place on Wednesday, December 16, from 8:00-9:30 AM Eastern Time in New York City.

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The meeting will feature presentations by Guillermo Garcia-Manero, M.D., Chief of the Section of Myelodysplastic Syndromes, Deputy Chair of Translational Research, Co-Director of the DNA Methylation Core, and Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, and Lewis R. Silverman, M.D., Associate Professor of Medicine in Hematology and Medical Oncology and Assistant Professor of Oncological Sciences at the Icahn School of Medicine at Mount Sinai. The Onconova management team will also provide an overview of the Phase 2 data from the combination trial of oral rigosertib and azacitidine in higher-risk MDS and AML that was recently presented at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, Florida, which took place December 5-8, 2015. A Q&A session with the featured experts and management will follow the presentations.

This event is intended for institutional investors and sell-side analysts. To reserve a place, please contact Mac MacDonald at 212-915-2567 or via e-mail at [email protected]. A live webcast and subsequent replay of the event will be available at View Source

Guillermo Garcia-Manero, MD, serves as Chief of the Section of Myelodysplastic Syndromes (MDS), Deputy Chair of Translational Research, Co-Director of the DNA Methylation Care, and Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center (MDACC). He is also on the faculty of The University of Texas Graduate School of Biomedical Sciences at Houston. He has previously served as Co-Chair of the MDS Clinical Research Consortium. The focus of his academic and clinical efforts has been to improve outcomes for patients with MDS.

Lewis R. Silverman, MD, is Associate Professor of Medicine in Hematology and Medical Oncology and Assistant Professor of Oncological Sciences at the Icahn School of Medicine at Mount Sinai (ISMMS). He leads the Myelodysplastic Syndrome and Myeloproliferative Disease Program at ISMMS, where he served as the Principal Investigator for several national clinical trials exploring treatments for patients with MDS. He played an important role in the completion of the AZA-001 trial, which led to the approval of the first drug for the treatment of MDS, azacitidine (VIDAZA).

On December 14, 2015 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number:4875), reported that it has received a notice of allowance for a new patent from the Chinese Patent Office which covers MN-029 (denibulin) di-hydrochloride (Press release, Avigen, DEC 14, 2015, View Source;p=RssLanding&cat=news&id=2122476 [SID:1234508573]).

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Once issued, the patent maturing from this allowed patent application is expected to expire no earlier than July 2032. The allowed claims cover the compound, pharmaceutical compositions and a method of treating certain cell proliferative diseases, including cancer, using denibulin di-hydrochloride. MediciNova intends to use denibulin di-hydrochloride in future development.

"We are very pleased that the Chinese Patent Office will grant our compound patent for MN-029 especially considering that a compound patent is typically very highly valued in China. We will now consider developing a program for MN-029, perhaps through our Chinese joint venture," commented Yuichi Iwaki, MD, PhD, President and CEO of MediciNova, Inc.

About MN-029

MN-029 is a novel, small molecule vascular disrupting agent (VDA) being developed for the treatment of solid tumor cancers. MediciNova licensed MN-029 from Angiogene Pharmaceuticals, Ltd. Several preclinical pharmacology studies conducted by Angiogene Pharmaceuticals and MediciNova have assessed the mechanism of action and anti-tumor activity of MN-029 in vivo in rodent models of breast, adrenocarcinoma, colon carcinoma, lung carcinoma and KHT sarcoma. In these studies, MN-029 damaged poorly formed tumor blood vessels by weakening tumor blood vessel walls and causing leakage, clotting and eventual vascular shutdown within the tumor. These studies suggest that MN-029 acts quickly and is rapidly cleared from the body, which may reduce the potential for some adverse effects commonly associated with chemotherapy. Shutdown of tumor blood flow in tumor models was confirmed through the use of dynamic contrast-enhanced MRI. In two Phase 1 clinical studies conducted by MediciNova, MN-029 was well-tolerated at doses that reduced tumor blood flow.

On December 14, 2015 X4 Pharmaceuticals reported the launch of the company’s development strategy for its pipeline of C-X-C receptor type 4 (CXCR4 inhibitors), including two clinical studies initiating in 2016 in refractory cancers with its lead drug candidate, X4P-001 (Press release, X4 Pharmaceuticals, DEC 14, 2015, View Source [SID:1234508555]). The formation of X4 is based on drug compounds that originate from a portfolio of oral CXCR4 inhibitors exclusively licensed from Sanofi.

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Development of X4’s CXCR4 inhibitors will be funded initially through a $37.5 million Series A financing, which the Company recently closed. Maxim Merchant Capital, a wholly owned division of Maxim Group LLC, served as the sole placement agent for the financing, with Cormorant Asset Management serving as lead investor.

Henri Termeer, the former Chairman, president and CEO of Genzyme, and a founding advisor and investor in X4, stated, "X4 has assembled the expertise, drug assets and strategies to build extraordinary value for its constituents, including the potential to have a significant impact on the treatment of cancer."

X4 will launch multiple clinical studies with X4P-001 in 2016 in advanced cancers, including refractory clear cell renal cell carcinoma (ccRCC) and a second solid tumor indication. A second drug program, X4P-002, which is currently in pre-clinical development, is being optimized for the treatment of brain cancers, and is expected to enter the clinic in 2017. Inhibition of CXCR4, a receptor over-expressed in many cancers, is designed to block non-cancerous immuno-suppressive and pro-angiogenic cells from populating the tumor, thereby disrupting the cancer microenvironment and restoring normal immune surveillance functions. The novel mechanism of CXCR4 inhibition increases the ability of T-Cells to track and destroy cancer.

"CXCR4 inhibition is a novel approach to immunotherapy whose potential we are only beginning to explore for the treatment of cancer," said Keith Flaherty, MD, the director of the Henri and Belinda Termeer Center for Targeted Therapies at the Massachusetts General Hospital and co-founder of X4. "Immune system surveillance is the front line of keeping cancer in check and CXCR4 plays a key role in the trafficking of immunosuppressive cells. Inhibition of this receptor may be beneficial in addressing a broad range of cancers, offering the potential to improve both the magnitude and durability of treatment responses."

The development of X4’s clinical candidates will be led by the company’s seasoned management team and founders, who bring unique experience in the study the CXCR4 pathway. The team is led by Chief Executive Officer Paula Ragan, PhD, who brings more than 15 years of experience in senior leadership roles at biotechnology companies, including Genzyme. Other members of the team include:

Robert Arbeit, MD, Senior Vice President of Clinical Development and Translational Research, who served in leadership roles at Idera Pharmaceuticals, Paratek Pharmaceuticals and Cubist Pharmaceuticals;
Alison Lawton, consulting Chief Operating Officer, who has 30 years of global biopharmaceutical experience, including 21 years at Genzyme where she led the regulatory team for the approval of plerixafor, a CXCR4 inhibitor, in 2008.
Alan Walts, PhD, co-founder of X4 and Interim Chairman, spent over 25 years with Genzyme, where his roles included President of Genzyme Pharmaceuticals, Senior Vice President of Corporate Development, and Managing Director of Genzyme Ventures

"With a strong financial foundation and leadership team in place, X4 is well positioned to bring forward CXCR4 inhibitors as an innovative new immunotherapy treatment approach for a broad spectrum of cancers," said Dr. Ragan. "We look forward to executing on our plans for advancing our CXCR4 pipeline programs, and to seeing the early promise of this approach translate in the clinic."

X4’s scientific founder is Renato Skerlj, PhD, whose work in immune-mediated drug discovery led him to become an inventor of both plerixafor, a stem cell mobilizer approved in 2008, and ertapenem, an anti-bacterial approved in 2001. Dr. Skerlj has over 20 years of pharmaceutical experience in the discovery and development of novel therapies. Most recently, he was the Head of Small Molecule Discovery at Genzyme and prior to joining Genzyme, was part of the executive team at AnorMED, a publicly-traded company acquired by Genzyme for $580 million in 2006.

About X4 Pharmaceuticals
X4 Pharmaceuticals is developing novel therapeutics designed to improve immune cell trafficking and increase the ability for T-Cells to track and destroy cancer cells. The company’s oral small molecule drug candidates inhibit the CXCR4 receptor, a pathway which plays a central role in promoting the immunosuppressive and pro-angiogenic microenvironment of many cancers. X4P-001, the company’s lead program, is expected to enter Phase 1/2 testing in refractory clear cell renal cell carcinoma (ccRCC) and other solid tumor indications, and its second program, X4P-002, is in pre-clinical development for oncology applications. X4 was founded and is led by a team with deep product development and commercialization expertise, including several former members of the Genzyme leadership team, and is located in Cambridge, MA.

On December 15, 2015 Takeda Pharmaceutical Company Limited ("Takeda") reported that "Leuplin PRO for Injection Kit 22.5 mg" (hereafter 24-week depot formulation), the 24-week depot formulation of "Leuplin" (generic name: leuprorelin acetate; hereafter "Leuplin"), is now available in Japan for the treatment of prostate cancer and premenopausal breast cancer (Press release, Takeda, DEC 14, 2015, View Source [SID:1234508575]).

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Leuplin is an LH-RH agonist that consistently stimulates the pituitary gland, resulting in suppressed production of male/female hormone. Leuplin is used as a treatment for hormone-dependent diseases such as prostate cancer and premenopausal breast cancer, and it is currently available in the United States, Europe, and Asia. The 24-week depot formulation becomes available for the first time in the world for the treatment of premenopausal breast cancer.

The 24-week depot formulation can maintain stable blood concentration by sustained release using Takeda’s unique microcapsule formulation technology through 24 weeks with a single injection. The new formulation providing sustained efficacy over a 24-week period will be a valuable addition to the available dosing options and provides the added benefit of less frequent dosing thus helping reduce the burden of treatment for patients with prostate cancer and premenopausal breast cancer.

"Given the high unmet needs that remain among patients with prostate cancer and premenopausal breast cancer, we have continued the Research and Development with our drug delivery for Leuplin even after its launch in Japan in 1992," said Masato Iwasaki, Ph.D., Director and President, Japan Pharma Business Unit of Takeda. "We are confident that the new 24-week depot formulation will help ease the various burden of treatment for patients with prostate cancer and premenopausal breast cancer".