On April 23, 2015 Commenting on the results, Joseph Jimenez, CEO of Novartis, reported: "Our focus on execution has resulted in a strong operational performance (Press release, Sandoz, APR 23, 2015, View Source [SID:1234506744]). We have completed the GSK and Lilly transactions and innovation continues to be strong. We had three approvals in Oncology, FDA priority review for LCZ696, Zarxio became the first biosimilar approved under the new pathway in the US and we launched Cosentyx globally. We are on track to deliver our full-year guidance."

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Continuing operations1 saw sales, core2 operating income and core EPS grow (cc2) in Q1
Net sales were USD 11.9 billion (-7%, +3% cc)2
Operating income was USD 2.8 billion (-1%, +15% cc)
Core operating income (-4%, +9% cc) grew faster than sales (cc), resulting in core margin of 30.6%
Core EPS was USD 1.33 (-1%, +11% cc))
Further strengthening of USD impacted sales by -10% and core operating income by -13%
Free cash flow2 increased 27% to USD 1.5 billion

For total Group, Q1 divestments resulted in exceptional operating income gains totaling USD 12.8 billion and net income gains of USD 10.8 billion

Strong progress on innovation continued in Q1
Three approvals in Oncology: Jakavi in polycythemia vera (EU), Farydak in multiple myeloma (US) and Jadenu for chronic iron overload (US)

LCZ696 granted FDA priority review and CHMP accelerated assessment in heart failure
Positive trials on Cosentyx in psoriasis showing superiority to Stelara, sustained two-year efficacy
Sandoz received FDA approval for first biosimilar Zarxio and in April for first substitutable generic version of Copaxone 20mg one-time-daily injection, Glatopa

Growth Products3 and Emerging Growth Markets3 continued to drive performance in Q4
Growth Products grew 14% (USD) to USD 4.7 billion, or 32% of Group net sales
Strong performance in Emerging Growth Markets (+12% cc)

Portfolio rejuvenation continued in Q1, reinforcing growth prospects for continuing operations
Growth Products3 grew 15% (USD) to USD 3.7 billion, or 31% of net sales
Strong performance in Emerging Growth Markets3 (+12% cc)

Continued progress in transforming portfolio and increasing productivity
Transactions with GSK and Lilly closed on March 2 and January 1, respectively; divestment of influenza Vaccines business to CSL expected to be completed in H2 2015
For continuing operations, core margin improved (+1.7 percentage points cc) mainly due to ongoing productivity initiatives

Outlook 2015 for continuing operations confirmed
Net sales expected to grow mid-single digit (cc); core operating income expected to grow ahead of sales at a high-single digit rate (cc) (cc)

On April 21, 2015 SignalRx Pharmaceuticals Inc., focused on developing more effective oncology drugs though molecular design imparting selected multiple target inhibition, reported the presentation of scientific data on the Company’s proprietary dual inhibitor program in oncology (Press release, SignalRx, APR 21, 2015, http://www.ireachcontent.com/news-releases/signalrx-presents-at-10th-annual-drug-discovery-chemistry-conference-on-its-dual-kinase-epigenetic-inhibitors-for-treating-cancer-500857951.html [SID1234527330]). The presentation by Dr. Donald L. Durden, MD, PhD, co-founder and science advisor to SignalRx was made at the Tenth Annual Drug Discovery Chemistry meeting at the Hilton San Diego Resort & Spa in San Diego, California.

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The oral presentation entitled "Discovery of Dual PI3K/BRD4 (kinase/epigenetic) Inhibitors" was given during the Second Annual Epigenetic Inhibitor Discovery track of the meeting at the "Advances in BET Bromodomain Inhibitor Development" session. The presentation highlighted a novel thienopyranone molecular scaffold that selectively inhibits both PI3 kinase (PI3K) and the bromodomain protein BRD4. The presentation described how molecular modeling studies were used to identify and design SignalRx’s single small molecules that can bind and inhibit simultaneously PI3K and BRD4. While the small molecule SF2523 inhibits PI3K via ATP competitive binding at the catalytic site, BRD4 inhibition appears to take place by binding in the acetyl-lysine recognition moiety of BRD4 thus blocking BRD4’s ability to alter chromatin structure and induce transcription. Blocking the binding of BRD4 to acetylated histones within chromatin can then block the transcription of various genes that are promoting cancer cell survival and growth. Recent reports suggest that BRD4 inhibition may block cancer cell resistance arising from widespread epigenetic kinome adaptation following exposure to targeted kinase inhibitor drugs which in turn may lead to more durable anticancer effects.

The presentation also included a specific rationale for the dual PI3K/BRD4 inhibition approach in cancers driven by the key cancer promoting transcription factor MYC. MYC (both cMYC and MYCN) acts downstream of many cell receptor complexes and signal transduction pathways to activate genes that drive cancer cell growth and proliferation. To date, small molecule inhibitors of MYC have been elusive. Inhibition of PI3K enhances the degradation of the cancer promoting transcription factor MYC. Inhibition of BRD4 blocks the production of MYC; thus, a dual PI3K/BRD4 inhibitor can lead to maximal MYC extinction by inhibiting these two different mechanisms. Our approach enables us to go after cancers expected to be susceptible to maximal MYC extinction as a beneficial treatment, such as CLL, medulloblastoma, multiple myeloma, and certain ovarian cancers exhibiting elevated MYCN expression. In vivo data also showed that SF2523 (50 mg/kg 3X per week) exhibited potent antitumor efficacy and anti-metastatic effects without toxicity in renal cell carcinoma xenograft models, neuroblastoma mouse models, orthotopic pancreatic cancer model and Lewis lung cancer models. Lastly, pre-clinical in vivo proof-of-concept with SF2523 was presented showing the pharmacodynamic knockdown of both the PI3K pathway and MYC in mouse neuroblastoma tumor samples four hours after administration, confirming the dual PI3K/BRD4 inhibitory profile of lead compound SF2523. Further preclinical studies of several PI3K/BRD4 dual inhibitor thienopyranones are underway to identify and select a clinical candidate.

On April 21, 2015 OPKO Health, Inc. (NYSE:OPK) reported the online publication of a study entitled "Predicting High-Grade Cancer at Ten-Core Prostate Biopsy Using Four Kallikrein Markers Measured in Blood in the ProtecT Study" in the Journal of the National Cancer Institute (Press release, Opko Health, APR 21, 2015, View Source [SID:1234506587]). The study shows that the four kallikrein panel of biomarkers utilized in the OPKO 4Kscore Test (Total PSA, Free PSA, Intact PSA and hK2) accurately identifies risk for aggressive prostate cancer prior to prostate biopsy.

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The Prostate Testing for Cancer and Treatment (ProtecT) study is a prospective randomized controlled trial conducted in the United Kingdom for the purpose of evaluating the cost effectiveness of conventional treatments in PSA-detected, clinically localized prostate cancer. Of the 82,428 men recruited for the trial, a total of 6129 men with elevated PSA (≥3.0 ng/mL) who underwent prostate biopsy and provided an adequate blood sample were tested for the four kallikreins and their 4Kscore result was determined. The study showed that the four kallikrein panel enhanced aggressive prostate cancer detection compared with PSA and age alone. The area under the curve (AUC) for the 4K model was 0.820 (95% CI = 0.802 to 0.838) while the PSA model was 0.738 (95% CI = 0.716 to 0.761) for high-grade cancer.

"The ProtecT study is the latest in a series of peer-reviewed publications demonstrating the superior clinical value that testing with four kallikrein markers adds to risk prediction for aggressive prostate cancer compared to PSA alone," said Dr. Peter Scardino, Chair, Department of Surgery, Memorial Sloan Kettering Cancer Center. "The high level of discrimination for differentially detecting high-grade disease supports use of the four kallikrein panel as a reflex test prior to having a prostate biopsy for men with an elevated PSA."

"The 4Kscore biomarker algorithm has now been tested and published on over 20,000 men in 11 peer-reviewed publications covering multiple US and European cohorts," said David Okrongly, President of OPKO Diagnostics. "The results all demonstrated the high discrimination and favorable decision curve benefit of the 4Kscore algorithm for predicting the results of prostate biopsy pathology, as well as 20 year outcomes for risk of metastatic prostate cancer."

About Prostate Cancer

According to the World Health Organization, prostate cancer is the second most common cancer in men worldwide, with over 1.1 million men diagnosed with prostate cancer in 2012 and over 300,000 men dying from the disease. In countries like the U.S. where screening for prostate cancer with the PSA test began 20 years ago there has been a sharp increase in the number of prostate cancers detected. However, most of the prostate cancers detected are an indolent, non-life threatening form of the disease. The net result has been a decrease in prostate cancer mortality during the PSA era, but at a cost of over detection and over treatment of indolent prostate cancers.

About the 4Kscore Test

The 4Kscore is the only blood test that accurately identifies risk for aggressive prostate cancer. The 4Kscore measures the blood plasma levels of four different prostate-derived kallikrein proteins: Total PSA, Free PSA, Intact PSA and Human Kallikrein-2 (hK2). These biomarkers are combined with a patient’s age, Digital Rectal Exam (DRE) status (nodule / no nodule), and prior negative biopsy status (yes / no) using a proprietary algorithm to calculate the risk (probability) of finding a Gleason Score 7 or higher prostate cancer. The four kallikrein panel of biomarkers utilized in the 4Kscore Test is based on over a decade of research conducted by scientists at Memorial Sloan-Kettering Cancer Center and leading European institutions. The 4Kscore Test provides individualized risk for the presence of aggressive prostate cancer and adds new information to the shared decision making discussion between a Urologist and patient.

On April 21, 2015 Generex Biotechnology Corporation (www.generex.com) (OTCQB: GNBT) reported presentation of data from the on-going Phase II clinical trial of the AE37 breast cancer vaccine correlating local immune response to a reduction in relapse (Press release, Generex, APR 21, 2015, View Source [SID:1234506588]). AE37 is being developed by Antigen Express, Inc. (www.antigenexpress.com), a wholly-owned subsidiary of Generex. The presentation was made at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting held in Philadelphia, PA from April 18 to 22.

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The abstract entitled ‘Correlation of robust local reactions prompting GM-CSF dose reduction to clinical response in a Phase II trial of the AE37+GM-CSF HER2 peptide vaccine’ by Julia Greene, et al was presented at the Clinical Trials in Progress session of the AACR (Free AACR Whitepaper) on April 20. The goal of the study was to establish the importance of the local reaction to immunization with AE37. The controlled, randomized and single-blinded trial is comparing the ability of AE37 plus the adjuvant GM-CSF versus the GM-CSF adjuvant alone to reduce recurrence of breast cancer in early stage patients. The study found that those patients receiving AE37 who had the largest responses (requiring reductions in the amount of GM-CSF) had a relapse rate of 5.9% versus a rate of 14.2% in those who did not require dose reduction. This indicates that a robust stimulation of the immune system by AE37, as evidenced by the need for dose reduction, results in positive anti-cancer activity.

The AE37 vaccine is designed to activate critical components of the immune system to combat cancer cells. Prior analyses have shown a trend toward reduction of relapse in patients receiving the vaccine, particularly those who are not eligible for the cancer drug Herceptin as well as those with triple negative breast cancer. The current study correlates the extent of immune response with reduction in relapse. A priority in all forms of cancer immunotherapy today is in establishing means of identifying which patients are more likely to respond to treatment.

The current results add to prior studies both from the ongoing Phase II trial as well as a completed Phase I study of AE37 in patients with prostate cancer showing robust yet specific immunological responses together with almost negligible toxicity. The distinguishing feature of AE37 is its ability to specifically activate CD4+ T helper cells, which govern both the quality and magnitude of an immune response to a novel target. The correlation of a robust immune response with reduced relapse confirms the importance of this type of immunological activity in combating cancer.

Encouraging results from both the breast and prostate cancer trials of AE37 warrant further clinical development of AE37, both as mono- and/or combination therapy. The current study provides important biomarker information relevant to identifying those patients who may be expected to benefit most from AE37. Similarly, the information may help guide possible combination studies; i.e., using agents that may enable all patients to respond robustly to AE37 (e.g., checkpoint inhibitors).

On April 21, 2015 Blend Therapeutics, Inc., a biopharmaceutical company discovering and developing two distinct classes of targeted anti-cancer medicines to advance the treatment of patients with solid tumor cancers, presented preclinical data today on BTP-114, a novel personalized cisplatin prodrug, with demonstration of improved and sustained tumor growth inhibition in preclinical models as compared to the conventional platinum cytotoxic cancer drug, cisplatin (Press release, Tarveda Therapeutics, APR 21, 2015, View Source [SID:1234508888]). Results from preclinical studies were presented in a poster entitled "BTP-114: An albumin binding cisplatin prodrug with improved and sustained tumor growth inhibition" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Philadelphia, Penn.

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BTP-114 is Blend’s lead product candidate for which the company plans to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration in Q2 2015. Once administered, BTP-114 rapidly conjugates to serum albumin in blood with a high degree of specificity, and is preferentially taken up by cancer cells with certain molecular profiles, resulting in enhanced DNA damage and cell death.

"We are excited by the novel mechanism of action of BTP-114 that leverages our growing understanding of disregulated cancer metabolism and the molecular underpinning of cancers, enabling the development of the first personalized platinum marking a major advance in the field of platinum anti-cancer agents," said Richard Wooster, PhD, President of Research and Development of Blend. "Designed to overcome limitations of conventional platinum therapies which are the largest class of oncology drugs today, BTP-114 has the potential to increase the proportion of patients who respond and their duration of response to platinum-based therapies."

The data presentation at AACR (Free AACR Whitepaper) describes BTP-114’s novel mechanism as a platinum prodrug of cisplatin that covalently attaches to serum albumin in the blood giving a 15-fold increase in exposure and a predicted human plasma half-life of 10 days. The therapeutic dose of platinum was increased by up to 2-fold, resulting in a 15-fold increase in platinum accumulation in multiple xenograft models. BTP-114 was shown to improve efficacy in models of lung and ovarian cancer compared to cisplatin, while reducing key dose limiting toxicities of cisplatin.

BTP-114 was developed by researchers at Blend Therapeutics and builds on the breakthroughs in platinum chemistry pioneered by the company’s scientific co-founder, Professor Stephen J. Lippard of Massachusetts Institute of Technology (MIT).

About Blend Therapeutics

Blend Therapeutics, Inc., is a biopharmaceutical company discovering and developing two distinct classes of targeted anti-cancer medicines to advance the treatment of patients with solid tumor cancers. Blend’s pipeline includes its lead drug candidate, BTP-114, a novel, personalized cisplatin prodrug derived from the company’s R&D heritage in platinum drugs, as well as BTP-277 and other novel drug conjugates from the company’s proprietary Pentarin platform. Blend’s first Pentarin drug candidate, BTP-277, represents the proprietary components of Blend’s miniaturized biologic drug conjugate (mBDC) technology – a novel targeting ligand conjugated to a potent cell-killing agent with a chemical linker – incorporated into nanoparticles to enable the penetration of the conjugates deep in to the tumor tissue where they selectively bind to tumor cells. Blend’s strategy includes developing its own proprietary Pentarins as well as applying the Pentarin platform to enhance the therapeutic capabilities of the targeting protein scaffolds or payloads of pharmaceutical collaborators.

The company was founded by three leaders in the fields of chemistry and nanomedicine from the Brigham and Women’s Hospital (BWH)–Harvard Medical School (HMS), and Massachusetts Institute of Technology (MIT): Dr. Omid Farokhzad of BWH–HMS, and Dr. Robert Langer and Dr. Stephen J. Lippard of MIT. Blend has attracted top-tier investors including Eminent Venture Capital, Flagship Ventures, NanoDimension, and New Enterprise Associates.