On March 7, 2017 GlycoMimetics, Inc. (NASDAQ:GLYC) reported that the first of two patient cohorts in its Phase 2 acute myeloid leukemia (AML) trial of GMI-1271 has completed enrollment (Press release, GlycoMimetics, MAR 7, 2017, View Source [SID1234518028]). This cohort is comprised of 25 patients 60 years of age or older with newly diagnosed AML. The study is designed to evaluate the potential of GMI-1271, GlycoMimetics’ E-selectin antagonist drug candidate, in combination with chemotherapy, as a treatment for patients with both newly diagnosed and relapsed/refractory AML. Enrollment in the study’s second arm is expected to complete in the middle of this year. The two arms combined will enroll a total of about 90 patients.

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"At the ASH (Free ASH Whitepaper) meeting in December, we showed that GMI-1271 was well-tolerated and demonstrated a high remission rate among the patient volunteers who were enrolled early in the study," said Helen Thackray, M.D., Chief Medical Officer of GlycoMimetics. "We are enthusiastic about that data, and as such, we look forward to opportunities later in the year to report initial treatment outcomes for this study."

GMI-1271 data were presented in 2016 at meetings of the European Hematology Association (EHA) (Free EHA Whitepaper) and the American Society of Hematology (ASH) (Free ASH Whitepaper), showing high remission rates and lower than expected 30- and 60-day mortality rates in early evaluations of patients with relapsed/refractory AML.

In addition to the ongoing Phase 1/2 trial, clinical investigators are currently evaluating GMI-1271 in an ongoing Phase 1 clinical trial in multiple myeloma. Preclinical data supporting the multiple myeloma study is scheduled to be shared in an oral presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 in April. Specifically, the newly announced preclinical results show a strong effect on cancer cells in combination with chemotherapy and are supportive of the ongoing Phase 1 clinical studies of GMI-1271 in multiple myeloma.

About AML

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. AML is the most common type of acute leukemia in adults. Each year in the United States, about 19,900 people (usually older than 45 years of age) are diagnosed, and about 10,400 people die from all forms of the disease, according to the American Cancer Society. Unlike other cancers that start in an organ and spread to the bone marrow, AML is known for rapid growth of abnormal white blood cells that gather in the bone marrow, getting in the way of normal blood cell production. The lack of normal blood cells can cause some of the symptoms of AML, including anemia (shortage of red blood cells resulting in tiredness and weakness), neutropenia (shortage of white blood cells that may lead to increased infections), and thrombocytopenia (shortage of platelets in the blood that may lead to excessive bleeding). Current treatment options for AML consist of reducing and eliminating cancer cells mainly through chemotherapy, radiation therapy, and stem cell transplantation.

On March 7, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported fourth quarter and year-end 2016 financial results (Press release, Loxo Oncology, MAR 7, 2017, View Source [SID1234518023]). Loxo Oncology will not be conducting a conference call in conjunction with this earnings release.

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"2016 was a very productive year for the company. We received breakthrough therapy designation from the U.S. FDA, presented updated clinical data at the AACR (Free AACR Whitepaper) and ESMO (Free ESMO Whitepaper) Asia meetings, and developed clarity around the commercial opportunity for larotrectinib," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "In 2017, we are focused on preparing larotrectinib for global regulatory submissions, and expanding our clinical pipeline to include LOXO-292, our highly selective RET inhibitor, and LOXO-195, our next-generation TRK inhibitor intended to address acquired resistance."

Recent Highlights

Larotrectinib (LOXO-101) Regulatory Update and Completion of Clinical Trial Enrollment for NDA Primary Efficacy Analysis: Loxo Oncology provided a regulatory and enrollment update for the larotrectinib program. Based on written feedback from the U.S. Food and Drug Administration (FDA), which affirmed the target enrollment goal for the primary efficacy analysis data set to support a New Drug Application (NDA), Loxo Oncology has completed clinical trial enrollment. Loxo Oncology expects to be in a position to report top-line data for the NDA dataset in the second half of 2017 and expects to submit an NDA in late 2017 or early 2018 and a European Marketing Authorisation Application (MAA) in 2018. All larotrectinib clinical trials will remain open to provide a mechanism for drug access to newly identified patients during forthcoming regulatory interactions and review.
Larotrectinib Phase I Update at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Congress: Results from the larotrectinib adult Phase 1 study were reported in an oral presentation at ESMO (Free ESMO Whitepaper) Asia. As of a November 10, 2016 data cutoff, 59 patients with refractory solid tumors had been enrolled and treated with single agent larotrectinib, including eight patients with cancers harboring TRK fusions. Seven patients with TRK fusion cancers were on study sufficiently long for an efficacy assessment, while an eighth TRK fusion patient had been recently enrolled and was not yet evaluated for response. Six of the seven efficacy evaluable patients achieved a confirmed partial response, as defined by standard RECIST criteria. The seventh patient, as previously reported, demonstrated clear radiographic tumor regressions, including in the central nervous system, and remains on study, but had not met the threshold required for a RECIST response. All responders remained in response, with one patient in cycle 22, one patient in cycle 19, one patient in cycle 18, two patients in cycle 15 and one patient in cycle 11. Each cycle is 28 days, or approximately one month. See the full data here.
Pipeline Update: Loxo Oncology presented preclinical data on LOXO-292 and LOXO-195 at the 28th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium. Data presented illustrated the potency, specificity, and favorable in vivo properties of LOXO-292 and LOXO-195.
Equity Financing: Soon after the close of the fourth quarter, Loxo Oncology announced the closing of its previously announced underwritten public offering of 4,450,500 shares of common stock at a public offering price of $31.00 per share, which included the exercise in full by the underwriters of their option to purchase 580,500 additional shares of common stock. Gross proceeds to Loxo Oncology from this offering were approximately $138 million. Based on the current operating plan, Loxo Oncology believes existing capital resources, including proceeds from the January 2017 common stock offering, will be sufficient to fund anticipated operations to mid-2019.
Fourth Quarter and Year-End 2016 Financial Results

Cash, cash equivalents and investments totaled $141.8 million as of December 31, 2016, compared to $153.9 million as of December 31, 2015.

As adjusted for the $129.4 million in net proceeds resulting from the Company’s January 2017 common stock offering, the Company had, on a pro forma basis, $271.2 million in adjusted cash, cash equivalents and investments at December 31, 2016. Based on the current operating plan, the company believes existing capital resources will be sufficient to fund anticipated operations to mid-2019.

Research and development expenses were $23.4 million for the fourth quarter of 2016 compared to $9.8 million in the fourth quarter of 2015. This increase was primarily due to expanded clinical development activities for larotrectinib, recognition of a $6 million Array development milestone achieved during the fourth quarter of 2016, as well as additional expenses related to the preclinical pipeline. Loxo Oncology recognized research and development-related stock-based compensation expenses of $1.4 million during the fourth quarter of 2016, compared to $1.5 million for the fourth quarter of 2015.

Research and development expenses were $58.3 million for the year ended December 31, 2016, compared to $25.6 million for the year ended December 31, 2015. This increase was primarily due to expanded clinical development activities for larotrectinib, recognition of a $6 million Array development milestone achieved during the fourth quarter of 2016, as well as additional expenses related to the preclinical pipeline. Loxo Oncology also recognized research and development-related stock-based compensation expense of $3.5 million during the year ended December 31, 2016, compared to $3.3 million for the year ended December 31, 2015.

General and administrative expenses were $4.0 million for the fourth quarter of 2016 compared to $3.2 million in the fourth quarter of 2015. This increase was primarily due to employment costs and professional fees. Loxo Oncology also recognized general and administrative-related stock-based compensation expense of $1.2 million during the fourth quarter 2016, compared to $0.8 million for the fourth quarter 2015.

General and administrative expenses were $14.9 million for the year ended December 31, 2016, compared to $10.5 million for the year ended December 31, 2015. This increase was primarily due to increased professional fees. Loxo Oncology also recognized general and administrative-related stock-based compensation expense of $4.5 million during the year ended December 31, 2016, compared to $2.8 million for the year ended December 31, 2015.

Net loss attributable to common stockholders was $27.2 million for the fourth quarter of 2016, compared to $12.9 million for the fourth quarter of 2015. Net loss attributable to common stockholders was $72.4 million for the year ended December 31, 2016, compared to $35.9 million for the year ended December 31, 2015. This increase in net loss is primarily driven by the increases in operating expenses.

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.