10-Q – Quarterly report [Sections 13 or 15(d)]

Gilead Sciences has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Gilead Sciences, NOV 7, 2016, View Source [SID1234516365]).

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10-Q – Quarterly report [Sections 13 or 15(d)]

Sarepta Therapeutics has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Sarepta Therapeutics, NOV 7, 2016, View Source [SID1234516356]).

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SignalRx Announces Publication of Research Results on SF1126 as a First-In-Class Dual PI3K/BRD4 Inhibitor for Treating HCC

On November 7, 2016 SignalRx Pharmaceuticals Inc., a clinical-stage company focused on developing more effective oncology drugs with designed multiple target-selected inhibition profiles, reported the publication of key research supporting the use of its clinical stage drug SF1126 alone and in combination with Sorafinib for the treatment of hepatocellular carcinoma (HCC) (Press release, SignalRx, NOV 7, 2016, http://www.ireachcontent.com/news-releases/signalrx-announces-publication-of-research-results-on-sf1126-as-a-first-in-class-dual-pi3kbrd4-inhibitor-for-treating-hcc-600328031.html [SID1234517420]). The research was published in the November issue of Molecular Cancer Therapeutics journal from the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Mol Cancer Ther November 1 2016 15 (11) 2553-2562; DOI:10.1158/1535-7163.MCT-15-0976).

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Researchers at the University of California, San Diego School of Medicine and Moores Cancer Center, led by Dr. Donald Durden, Professor and Associate Director of Pediatric Oncology and senior scientific advisor for SignalRx, report results supporting the use of SF1126 as a novel therapeutic agent for the treatment of hepatocellular carcinoma (HCC), the most common kind of liver cancer and second most common cause of cancer death worldwide.

SF1126 is an anticancer agent shown to have an excellent therapeutic window with excellent tolerability and safety in Phase I clinical trials (Clinicaltrials.gov: NCT00907205). While most anti-cancer drugs only interact with a single cancer target, SF1126 inhibits two key cancer signaling molecules in liver cancer cells, phosphatidylinositol 3-kinase (PI3K) and bromodomain-containing 4 (BRD4). SF1126 represents a "first in class" approach to treat liver cancer by hitting two central signaling nodes of the liver cancer cell with only one therapeutic agent. The published work shows that this novel strategy kills liver cancer cells and prevents the growth of liver cancer tumors in mice.

Targeting two pathways with one drug can provide a significant therapeutic advantage since this approach also reduces the risk of severe "off-target" side effects resulting from the combination of side effects associated to each of the multiple drugs used. The treatment of HCC remains a challenge with Sorafenib as the only FDA-approved drug for liver cancer since it prolongs life for an average of only 2-3 months and can have significant side effects. Work from the Durden laboratory shows that using SF1126 with Sorafenib provides a dramatically improved anticancer effect by killing liver cancer cells in synergy.

In HCC, the deregulation of the PI3K/AKT/mTOR, Ras/Raf/MAPK and c-Myc signaling pathways are of prognostic significance. While Sorafenib blocks the Ras/Raf/MAPK pathway, it does not inhibit the PI3K/AKT/mTOR pathway or c-Myc activation. SF1126 controls c-Myc by inhibiting BRD4, which results in blockage of c-Myc production, and by inhibiting PI3K, which leads to enhanced c-Myc degradation. Hence, a combination of SF1126 with Sorafenib offers a new mechanism-driven mode of action to inhibit/treat HCC.

In particular, the research results published in Molecular Cancer Therapeutics demonstrate that:

SF1126 (pan PI3K/BRD4 inhibitor), as a single agent or in combination with Sorafenib, inhibits cancer cell proliferation (Hep 3B, Hep G2, SK-Hep1 and Huh7 HCC cell lines) by effectively inhibiting the PI3K/AKT/mTOR and Ras/Raf/MAPK pathways.
SF1126’s active moiety LY294002 binds to and blocks BRD4 interaction with the acetylated histone-H4 chromatin mark protein and displaces the BRD4 co-activator protein from the transcriptional start site of MYC in Huh7 and SK-Hep-1 HCC cell lines.
SF1126 blocks expression of c-Myc in HCC cells.
SF1126, either alone or in combination with Sorafenib, shows significant antitumor activity in vivo.
These published results establish SF1126 as a dual PI3K/BRD4 inhibitor and the first epigenetic/kinase inhibitor in the clinic. SF1126 has completed a Phase I clinical trial in humans with good safety profile, has received Orphan Drug Designation by the FDA, and is currently in a pediatric Phase I clinical trial in children with neuroblastoma.

Taken together, this published data strongly warrants additional clinical trials of SF1126 in advanced HCC as well as a combination Phase I trial with Sorafenib.

SignalRx is seeking partners for the clinical development of SF1126 as well as the acceleration of the company’s preclinical pipeline with novel and proprietary nM potent small molecules into first-in-man clinical trials.

SignalRx’s novel dual inhibitors have a unique competitive advantage over combining separate agents in cancers where lethality requires simultaneous target inhibition for maximal effect with minimal side-effects. Because it provides a single pharmacodynamics profile the dual inhibition in a single molecule approach provides the optimal way to effect simultaneous target inhibition with significantly less toxicity than combinations of inhibitors.

Verastem Reports Third Quarter 2016 Financial Results

On November 7, 2016 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer, reported financial results for the third quarter ended September 30, 2016, and also provided an overview of certain corporate developments (Press release, Verastem, NOV 7, 2016, View Source;p=RssLanding&cat=news&id=2220267 [SID1234516784]).

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"Last week, we announced the inlicensing of the late-stage oncology product candidate duvelisib from Infinity Pharmaceuticals. This transaction brings a complementary development program on attractive financial terms," said Robert Forrester, President and Chief Executive Officer of Verastem. "Duvelisib has a proven mechanism of action and has clinically demonstrated anti-cancer activity, along with a manageable safety profile, in several lymphoid malignancies. We believe duvelisib has the potential to help patients with lymphoma."

Mr. Forrester continued, "Since the beginning of 2016, we have made significant progress with our immuno-oncology focused clinical development program aimed at advancing our FAK inhibitors in combination with immunotherapies and other current and emerging standard of care treatments. We recently announced a new clinical collaboration with Cancer Research UK and MSD to evaluate defactinib in combination with MSD’s anti-PD-1 immunotherapy pembrolizumab (Keytruda) MSD’s PD-1 immunotherapy in patients with mesothelioma, non-small cell lung and pancreatic cancer. This is our third clinical collaboration to be announced this year and we are delighted to be working with such prestigious organizations to clinically elucidate the potential of defactinib in combination with immunotherapeutics across several different cancer types."

Third Quarter 2016 and Recent Highlights:
Duvelisib
Inlicensed Late-stage, Complementary Oncology Product Candidate Duvelisib – Last week, Verastem and Infinity Pharmaceuticals, Inc. (Infinity) announced the signing of an agreement under which Verastem licensed exclusive worldwide rights to develop and commercialize Infinity’s duvelisib, an investigational product candidate currently in development for hematologic malignancies. In consideration for duvelisib, Verastem will pay to Infinity no upfront payment, and up to $28 million in milestones. Positive data from DUO, a Phase 3, randomized monotherapy study of duvelisib in patients with relapsed or refractory CLL, triggers the first milestone payment. Verastem will also pay royalties on worldwide net sales. Duvelisib is well aligned with Verastem’s strategic focus of developing novel anti-cancer therapeutics that modulate the tumor microenvironment.

Phase 2 DYNAMO Data to be Reported at ASH (Free ASH Whitepaper) 2016 – Phase 2 clinical data for duvelisib will be presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, which is being held December 3-6, 2016 in San Diego. In an oral presentation, titled "A phase 2 study demonstrating the clinical activity of duvelisib in patients with relapsed refractory indolent non-Hodgkin lymphoma," (Publication ID: 1218) Ian Flinn, MD, PhD, Director, Hematologic Malignancies Program, Sarah Cannon Research Institute, will describe the results from DYNAMO, a Phase 2 study evaluating the efficacy and safety of duvelisib in relapsed/refractory iNHL. The oral presentation will take place on Monday, December 5, 2016, at 7:30 PM PT at the San Diego Convention Center, Ballroom 20BC.

Defactinib (VS-6063)
New Clinical Collaboration with Cancer Research UK and MSD to Evaluate Defactinib in Combination with Immunotherapy in Mesothelioma, Non-small Cell Lung and Pancreatic Cancer – In September 2016, the companies announced a new clinical trial collaboration agreement to evaluate the combination of Verastem’s defactinib and MSD’s PD-1 immunotherapy pembrolizumab (Keytruda). This clinical collaboration is based on discoveries by scientists at the Edinburgh Cancer Research UK Centre at the University of Edinburgh who showed that inhibiting FAK increases the effectiveness of anti-PD-1 agents. The trial is expected to enroll up to 60 patients and will commence in early 2017.

Published Preclinical Research in Nature Medicine – In July 2016, Verastem announced the publication of preclinical research conducted by its scientific collaborator, David G. DeNardo, PhD, Assistant Professor of Medicine, Division of Oncology, Department of Immunology, Washington University School of Medicine in St. Louis. In the published study, Dr. DeNardo demonstrates that FAK inhibition decreases fibrosis and immunosuppressive cell populations in pancreatic ductal adenocarcinoma, rendering previously unresponsive tumors sensitive to chemo- and immunotherapy. These findings provide important support and rationale for the ongoing Phase 1 dose-escalation clinical studies evaluating Verastem’s FAK inhibitors in combination with pembrolizumab and gemcitabine, and, gemcitabine and Abraxane in patients with pancreatic cancer.

Third Quarter 2016 Financial Results
Net loss for the third quarter ended September 30, 2016 (2016 Quarter) was $7.9 million, or $0.21 per share, as compared to a net loss of $15.4 million, or $0.42 per share, for the third quarter ended September 30, 2015 (2015 Quarter). Net loss includes non-cash stock-based compensation expense of $1.3 million and $2.1 million for the 2016 Quarter and 2015 Quarter, respectively.
Research and development expense for the 2016 Quarter was $4.2 million compared to $11.3 million for the 2015 Quarter. The $7.1 million decrease from the 2015 Quarter to the 2016 Quarter was primarily related to a decrease of $5.3 million in contract research organization expense for outsourced biology, chemistry, development and clinical services, which includes our clinical trial costs, a decrease in personnel related costs of approximately $653,000 due to lower headcount as a result of our reduction in force in Q4 2015, a decrease of approximately $491,000 in consulting fees, a decrease in lab supplies of approximately $228,000, and a decrease in stock-based compensation and other expenses of approximately $376,000.

General and administrative expense for the 2016 Quarter was $3.8 million compared to $4.2 million for the 2015 Quarter. The decrease of approximately $387,000 from the 2015 Quarter to the 2016 Quarter primarily resulted from decreases in stock-based compensation expense of approximately $665,000 and personnel costs of approximately $108,000. These decreases were partially offset by increases in professional fees of approximately $235,000 and consulting and other costs of approximately $151,000.
As of September 30, 2016, Verastem had cash, cash equivalents and investments of $86.9 million compared to $110.3 million as of December 31, 2015. Verastem used $6.0 million for operating activities during 2016 Quarter.

The number of outstanding common shares as of September 30, 2016, was 36,992,418.

Financial Guidance
Based on current operating plans, we expect to have sufficient cash, cash equivalents and short-term investments to fund our research and development programs and operations into 2018.

About the Tumor Microenvironment
The tumor microenvironment encompasses various cellular populations and extracellular matrices within the tumor or cancer niche that support cancer cell survival. This includes immunosuppressive cell populations such as regulatory T cells, myeloid-derived suppressor cells, M2 tumor-associated macrophages, as well as tumor-associated fibroblasts and extracellular matrix proteins which can hamper the entry and therapeutic benefit of cytotoxic immune cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s compounds duvelisib, defactinib, VS-4718 and VS-5584 also target the tumor microenvironment as a mechanism of action to potentially improve a patients response to therapy.

About Duvelisib
Duvelisib is an investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes that are known to help support the growth and survival of malignant B cells and T cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib is currently being evaluated in late- and mid-stage clinical trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed/refractory chronic lymphocytic leukemia (CLL)4, and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL) that achieved its primary endpoint of overall response rate upon topline analysis of efficacy data5. Duvelisib is also being evaluated for the treatment of hematologic malignancies through investigator-sponsored studies, including T cell lymphoma. Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.6

About Defactinib
Defactinib (VS-6063) is an investigational inhibitor of Focal Adhesion Kinase (FAK), a non-receptor tyrosine kinase encoded by the PTK-2 gene that mediates oncogenic signaling in response to cellular adhesion and growth factors.7 Based on the multi-faceted roles of FAK, defactinib is used to treat cancer through modulation of the tumor microenvironment, enhancement of anti-tumor immunity, and reduction of cancer stem cells.8,9 Defactinib is currently being evaluated in three separate clinical collaborations in combination with immunotherapeutic agents for the treatment of several different cancer types including pancreatic, ovarian, non-small cell lung cancer, and mesothelioma. These studies are combination clinical trials with pembrolizumab and avelumab from Merck & Co. and Pfizer/Merck KGaA, respectively.10,11,12 Information about these and additional clinical trials evaluating the safety and efficacy of defactinib can be found on www.clinicaltrials.gov.

Threshold Pharmaceuticals Reports Third Quarter Financial Results

On November 7, 2016 Threshold Pharmaceuticals, Inc. (Nasdaq:THLD), a clinical-stage biopharmaceutical company developing novel therapies for cancer, reported financial results for the third quarter ended September 30, 2016 and provided an update on the Company’s corporate and clinical development activities (Filing, Q3, Threshold Pharmaceuticals, 2016, NOV 7, 2016, View Source [SID1234516782]).

"We plan to initiate a clinical trial evaluating evofosfamide in combination with checkpoint inhibitors with our collaborators at MD Anderson Cancer Center while at the same time continue to pursue registration of evofosfamide in Japan for the treatment of pancreatic cancer. In addition, we continue to pursue potential collaborations to expand our development pipeline while we complete IND-enabling toxicology studies with TH-3424 with the goal of reaching the clinic with a new compound in 2017", said Barry Selick, Ph.D., Chief Executive Officer of Threshold.

Recent Highlights

Evofosfamide – The Company’s lead product candidate is an investigational hypoxia-activated prodrug that is designed to be activated under tumor hypoxic conditions, a hallmark of many cancers.

· First meeting scheduled with the Japanese PMDA (Pharmaceutical and Medical Devices Agency) to present the improvement in overall survival that was observed in the Japanese sub-population of the MAESTRO Phase 3 trial;

· The Company announced a partnership with Caris Life Sciences to develop a customized assay for pancreatic cancer patients to predict likelihood of response to evofosfamide;

· Clinical development collaborations investigating evofosfamide in patients with pancreatic neuroendocrine tumors (pNET), recurrent glioblastoma (GBM) and hepatocellular carcinoma (HCC) remain ongoing;

· A recent presentation by one of the Company’s collaborators from the MD Anderson Cancer Center highlighted the promise of evofosfamide in combination with a class of checkpoint inhibitor antibodies to improve the efficacy of this class of potent anti-cancer therapies; and

· The Company plans to initiate a clinical trial in various solid tumors evaluating evofosfamide in combination with one or more checkpoint inhibitor antibodies in development.

Tarloxotinib – The Company had been prosecuting Phase 2 proof of concept studies with tarloxotinib, a hypoxia-activated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which was designed to selectively release an irreversible EGFR-TKI in hypoxic tumors.

· During the quarter, the Company announced interim results from two proof-of-concept, Phase 2 clinical trials in patients with advanced non-small cell lung cancer (NSCLC) and patients with metastatic squamous cell carcinoma of the head and neck and skin. While results in patients with squamous cell carcinoma of the skin were minimally sufficient for continuation, the response rate in the NSCLC trial and the head and neck arms of the squamous cell cancer trial did not meet the minimum response rate hurdles for study continuation. Accordingly, enrollment in both Phase 2 clinical trials and further development of tarloxotinib has been discontinued.

TH-3424 – TH-3424 is the Company’s small-molecule drug candidate being evaluated for the treatment of hepatocellular (liver) cancer (HCC), castrate resistant prostate cancer (CRPC), T-cell acute lymphoblastic leukemias (T-ALL), and other cancers expressing high levels of aldo-keto reductase family 1 member C3 (AKR1C3). Tumors overexpressing AKR1C3 can be resistant to radiation therapy, chemotherapy and anti-androgen therapy. TH-3424 is a prodrug that selectively releases a potent DNA cross-linking agent in the presence of AKR1C3.

· TH-3424 has been selected as a lead candidate and Investigational New Drug (IND)-enabling studies have been initiated in collaboration with Ascenta Pharmaceuticals, Ltd.

Third Quarter 2016 Financial Results

· Cash, cash equivalents and marketable securities totaled $28.1 million at September 30, 2016 compared to $33.6 million at June 30, 2016; the net decrease of $5.5 million was a result of operating cash requirements for the quarter ended September 30, 2016. With the previously announced decision to cease joint development of evofosfamide under the Company’s former collaboration with Merck KGaA, the decision in September to discontinue further development of tarloxotinib, and the workforce reduction, the Company continues to expect its operating cash requirements to be lower for the fourth quarter of fiscal year 2016 and fiscal year 2017.

· No revenue was recognized in the third quarter ended September 30, 2016 compared to $3.7 million for the same period of 2015. Revenue for the quarter ended September 30, 2015 related to the amortization of the aggregate of $110 million in upfront and milestone payments received from the Company’s former collaboration with Merck KGaA, Darmstadt, Germany. The revenue from the upfront payment and milestone payments received under the agreement were previously being amortized over the relevant performance period, rather than being immediately recognized when the upfront payment and milestones were earned or received. As a result of Merck KGaA, Darmstadt, Germany’s and the Company’s decision to cease further joint development of evofosfamide in December 2015, the Company immediately recognized all of the remaining deferred revenue into revenue during the quarter ending December 31, 2015. Also as a result of the termination of the agreement, the Company is no longer eligible to receive any further milestone payments from Merck KGaA, Darmstadt, Germany.

· Research and development expenses were $3.5 million for the third quarter ended September 30, 2016, compared to $8.1 million for the same period in 2015. The decrease in research and development expenses, net of reimbursement for Merck KGaA, Darmstadt, Germany’s 70 percent share of total eligible collaboration expenses for evofosfamide, was due primarily to a $2.8 million decrease in employee related expenses, including a $0.4 million decrease in non-cash stock-based compensation expense and a $1.8 million decrease in clinical development expenses and consulting expenses. The Company expects research and development expenses to continue to decline in 2016 as a result of the decision to cease further joint development of evofosfamide under the Company’s former collaboration with Merck KGaA and the workforce reduction.

· General and administrative expenses were $1.7 million for the third quarter ended September 30, 2016 compared to $2.4 million for the same period in 2015. The decrease in general and administrative expenses was due primarily to a $0.5 million decrease in employee related expenses and a $0.2 million decrease in consulting expenses.

· Non-cash stock-based compensation expense included in total operating expenses was $0.8 million for the third quarter of 2016 compared to $1.5 million for the same period in 2015. The decrease in stock-based compensation expense was due to the amortization of a smaller number of options with lower fair values.

· Net loss for the third quarter of 2016 was $5.7 million compared to $6.4 million for the same period in 2015. Included in the net loss for the third quarter of 2016 was an operating loss of $5.2 million and non-cash expense of $0.5 million compared to an operating loss of $6.8 million and non-cash income of $0.3 million for the third quarter of 2015. The non-cash income or expense is related to changes in the fair value of the Company’s outstanding and exercised warrants that was classified as other income (expense).

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About Evofosfamide
Evofosfamide (previously known as TH-302) is an investigational hypoxia-activated prodrug of a bis-alkylating agent that is preferentially activated under severe hypoxic tumor conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic.

About Tarloxotinib Bromide
Tarloxotinib bromide (previously known as TH-4000), or "tarloxotinib", is a prodrug designed to selectively release a covalent (irreversible) EGFR tyrosine kinase inhibitor under severe hypoxia, a feature of many solid tumors. In September 2016, the Company announced the discontinuation of any further development of tarloxotinib.

About TH-3424
TH-3424 is small-molecule drug candidate being evaluated for the potential treatment of hepatocellular (liver) cancer (HCC), castrate resistant prostate cancer (CRPC), T-cell acute lymphoblastic leukemias (T-ALL), and other cancers expressing high levels of aldo-keto reductase family 1 member C3 (AKR1C3). Tumors overexpressing AKR1C3 can be resistant to radiation therapy and chemotherapy. TH-3424 is a prodrug that selectively releases a potent DNA cross-linking agent in the presence of AKR1C3. Preliminary nonclinical toxicology studies suggested an adequate therapeutic index that the Company believes warrants conducting Investigational New Drug (IND)-enabling toxicology studies, which are being done in collaboration with Ascenta Pharmaceuticals, Ltd.