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Cyclacel’s CDK Inhibitor CYC065 Causes Anaphase Catastrophe, a Novel Cancer-Specific Mechanism of Action, in Research Published in JNCI

On March 7, 2017 Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) ("Cyclacel" or the "Company"), reported the publication of a peer-reviewed journal article featuring the company’s cyclin dependent kinase 2/9 (CDK2/9) inhibitors (Press release, Cyclacel, MAR 7, 2017, View Source [SID1234518016]). In an article published in the Journal of National Cancer Institute (JNCI), preclinical data demonstrated that both Cyclacel’s CYC065, a second-generation, clinical stage, CDK2/9 inhibitor, and CCT68127, a pre-clinical stage CDK2/9 inhibitor, demonstrated prominent antitumor activity against lung cancer through anaphase catastrophe, a novel, cancer specific mechanism of action.

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The Journal of National Cancer Institute article entitled, "Next-Generation CDK2/9 Inhibitors and Anaphase Catastrophe in Lung Cancer," demonstrates that CYC065 and CCT68127 cause multipolar anaphase and apoptosis in lung cancer cells with supernumerary centrosomes, known as anaphase catastrophe. This novel mechanism of action offers an innovative approach to combat aneuploid cancer cells which contain abnormal numbers of chromosomes. Aneuploidy is a hallmark for cancer development and occurs in virtually every cancer, but is particularly found in lung cancer. Approximately 90 percent of cancer cells in solid tumors and blood cancer are aneuploid.

The article further reported that inhibition of CDK2 was the key mechanism of action and, as a consequence, lung cancer cells underwent apoptosis or cell suicide by induction of a novel mechanism called anaphase catastrophe. Similarly to a previous report on seliciclib (Cyclacel’s first generation CDK inhibitor), lung cancer cells with mutant KRAS were particularly sensitive to CYC065 and CCT68127. Combination of CCT68127 with the MEK inhibitor, trametinib, was synergistic. An efficacy study in syngeneic cancer models of lung cancer with mutant KRAS demonstrated tumor growth inhibitory effect and a significant decrease of circulating tumor cells.

Citation:
Kawakami M, Lisa, Mustachio M, Rodriguez-Canales J, Mino B, Roszik J, Tong P, Wang J, J. Lee J, Myung JH, Heymach JV, Johnson FM, Hong S, Zheng L, Hu S, Villalobos PA, Behrens C, Wistuba I, Freemantle S, Liu X, Dmitrovsky E. Next-Generation CDK2/9 Inhibitors and Anaphase Catastrophe in Lung Cancer. J Natl Cancer Inst (2017) 109(6): djw297.

About CYC065

Cyclacel’s second generation CDK2/9 inhibitor, CYC065, is being evaluated in an ongoing, first-in-human, Phase 1 trial in patients with advanced solid tumors. In addition to determining safety and recommended dosing for Phase 2, the study aims to investigate CYC065’s effects on the Mcl-1 biomarker, which is implicated in the evolution of resistance in cancer. Evidence of target engagement with prolonged Mcl-1 suppression in peripheral blood cells was observed in patient samples from the study, as well as decreases in kinase substrate phosphorylation and increases in PARP cleavage, which were consistent with the Company’s preclinical data. CYC065 is mechanistically similar but has much higher dose potency, in vitro and in vivo, and improved metabolic stability than seliciclib, Cyclacel’s first generation CDK inhibitor. Similar to palbociclib, the first CDK inhibitor approved by FDA in 2015, CYC065 may be most useful as a therapy for patients with both liquid and solid tumors in combination with other anticancer agents, including Bcl-2 antagonists, such as venetoclax, or HER2 inhibitors, such as trastuzumab.

10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

Corcept Therapeutics has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Corcept Therapeutics, 2018, MAR 6, 2017, View Source [SID1234527932]).

10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

Akebia has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Akebia, 2017, MAR 6, 2017, View Source [SID1234521564]).

Virogin Biotech Ltd. Announces $5 Million in Series A+ Financing

On March 6, 2017 Virogin Biotech Ltd. ("Virogin") reported the completion of its Series A+ round of financing for a total of $5 million USD on February 28th, 2017 (Press release, Virogin Biotech, MAR 6, 2017, View Source [SID1234518865]). Virogin Biotech Ltd. specializes in cancertherapeutics research and discovery with a strong focus on innovative oncolyticvirotherapy.

The financing was led by Sangel Capital and co-funded by bothexisting investors – Purity Star Ltd., Dahua Investment Corp. and Top FortuneVentures Ltd., and new strategic investor, FuRong Capital. FuRong Capital isthe industrial investment and commercialization arm of Shanghai FudanUniversity. The continued financial support from existing investors, alongsidethe endorsement by FuRong Capital, reflect investor confidence in Virogin’songoing development and further success.

The proceeds from this round offinancing will be used towards three areas: completion of pre-clinical research and IND enabling studies for VG161 – Virogin’s firstoncolytic virus product to enter clinical stage, continued expansion andoptimization of the research team with emphasis on clinical development andregulatory approval, and further development of the company’s product andproject pipelines.

"We are very grateful for the level of supportand dedication demonstrated by our existing investors during this round of financing,and we delightedly welcome FuRong Capital to the Virogin family." said Mr. Chris Huang, co-founder and CEO of Virogin, "Combinationtherapy will be the future direction of cancer immunotherapy, and oncolyticvirotherapy is inherently advantageous in achieving combination therapy;therefore, we expect it to be at the center of attention in the near future. Asone of the pioneers in the field of oncolytic virotherapy, Virogin possessesthe necessary technical expertise, proprietary technology and innovativeproduct design concept to be at the leading edge of this field. With thecapital infusion from this round of financing, we will be able to ensureprogress of our clinical and product development plans."

Dr. William Jia, co-founder and CSO of Virogin, also expressed hisexcitement, "We really appreciate the confidence and encouragement from theinvestors. In the past 20 months, Virogin has been growing at an incrediblepace, and has established its unique product pipeline with proprietarytechnology and innovative product design. Our first product VG161 showedexcellent pre-clinical results and we are looking forward to initiating clinicaltrials soon. The successful completion of this round of financing will fuel ourfast running engine to achieve higher speed and reach new heights. "

Dr. NanxingHe, Managing Partner at Sangel Capital, added, "As one of the earliestinvestors of Virogin, we have witnessed the level of progress the companyachieved in less than 2 years, and we sincerely admire their dedication and entrepreneurship.Dr. Jia and his research team are both knowledgeable and trustworthy. As aprofessional investment institution in the field of biomedicine, we willcontinue to be a strong supporter of Virogin, and we look forward to a brightfuture for the company."

"Weare delighted to participate in Virogin’s Series A+ round of financing," statedDr. Pengjun Sun, General Manager of FuRong Capital, "Better yet, Virogin isco-founded by a distinguished scientist and a seasoned entrepreneur, both ofwhom are alumni of Shanghai Fudan University. They have demonstrated strongexpertise and experience in their respective fields, thus we are confident inVirogin’s market competitiveness and growth potential in the biotech andpharmaceutical industry. We look forward to further collaboration betweenVirogin and Shanghai Fudan University in the areas of research and discovery,human capital, and clinical development. Collectively, we will be able tofurther promote the growth and development of Virogin."

Deciphera Pharmaceuticals Initiates a Phase 1 Clinical Trial of DCC-3014

On March 6, 2017 Deciphera Pharmaceuticals, a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported that it has initiated a multi-center Phase 1 clinical trial of DCC-3014, a highly-selective small molecule CSF1R inhibitor, in patients with advanced malignancies (Press release, Deciphera Pharmaceuticals, MAR 6, 2017, View Source [SID1234518029]).

"We are excited to initiate this first-in-human Phase 1 clinical trial of DCC-3014, our small molecule switch control inhibitor of CSF1R," said Michael D. Taylor, Ph.D., Deciphera’s President and Chief Executive Officer. "Preclinical data from a number of cancer models have demonstrated that DCC-3014 has potent macrophage checkpoint inhibitory activity. We believe DCC-3014 has great potential as a novel immunomodulatory agent and an important new therapy for cancer patients."

The Phase 1 clinical trial is designed to evaluate the safety, pharmacokinetics and pharmacodynamics of multiple ascending doses of DCC-3014. Up to 55 patients with advanced malignancies will be enrolled across both dose-escalation and expansion phases of the study. For more information about the clinical trial design please visit www.clinicaltrials.gov.

"DCC-3014 inhibits tumor associated macrophages which are believed to play a key role in the tumor microenvironment," said Oliver Rosen, M.D., Chief Medical Officer at Deciphera. "By blocking macrophage immune checkpoints, DCC-3014 has demonstrated additive or synergistic immunomodulatory activity in combination with PD-1 inhibition in multiple preclinical models."

About DCC-3014
DCC-3014 was purposefully designed using the company’s proprietary Switch Control Inhibitor platform to be a highly-specific macrophage immunomodulatory agent. In preclinical models, DCC-3014 has demonstrated potent inhibition of the colony stimulating factor 1 receptor (CSF1R), an important target for the treatment of many cancer indications. Deciphera reported preclinical data demonstrating potent macrophage checkpoint inhibition with DCC-3014 in multiple cancer models both as a single agent and in combination with a PD1 inhibitor at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2016. DCC-3014 is currently in Phase 1 clinical development in patients with advanced malignancies.