Advaxis believes the patient died due to the progression of cervical cancer, but FDA is asking for additional information to confirm the company's experimental therapy, axalimogene filolisbac, played no role. Until the FDA's concerns are resolved, four clinical trials involving Advaxis' axalimogene filolisbac are on clinical hold.
Shares of Advaxis fell 25% to $10.31 in after-hours trading on news of the clinical trials halt. The bad news couldn't come at a worse time as investors are already in a sour mood over a prolonged and painful retrenchment in biotech stocks.
The safety report involved a single event in one patient with end-stage cervical cancer who last received axalimogene filolisbac in early 2013 in a company-sponsored trial. In late July 2015 the patient was hospitalized for symptoms related to her cancer. During her stay, routine blood cultures detected Listeria monocytogenes (Lm). Further analysis determined that it was the highly attenuated strain of Lm used in axalimogene filolisbac, which was incapable of causing infection and was very sensitive to antibiotics. The patient received intravenous antibiotics and was discharged. A few weeks later, the patient returned to the hospital with respiratory distress caused by her metastatic cancer and died later that day. The investigator determined that the cause of death was due to the progression of her cervical cancer.
and we still have an hour to go today, who will hold through the weekend, robo computer not.
Short Form. The presence of fatty liver was determined using ultrasonography.
Of the people studied, nearly 40,000 had NAFLD. Importantly, the researchers found that both prolonged sitting time and decreased physical activity level were independently associated with increasing prevalence of NAFLD. Remarkably, these associations were also observed in patients with a body mass index (BMI) of less than 23.
Most likely South Koreans.
Our Chairs Are Killing Us,' Say Researchers
Amsterdam, The Netherlands, September 15, 2015 -- Prolonged sitting time as well as reduced physical activity contribute to the prevalence of non-alcoholic fatty liver disease (NAFLD) in a study of middle-aged Koreans. These findings support the importance of both reducing time spent sitting and increasing physical activity, say researchers. Their results are published in the Journal of Hepatology.
Physical activity is known to reduce the incidence and mortality of various chronic diseases. However, more than one half of the average person's waking day involves sedentary activities associated with prolonged sitting such as watching TV and using the computer and other devices.
Recently, attention has focused on the damaging effects of sedentary behavior regardless of additional physical activity. A growing number of epidemiologic studies have suggested an association between sedentary behavior and chronic diseases including obesity, diabetes, insulin resistance, metabolic syndrome, cardiovascular disease, cancer, and even death that is distinct from those related to a lack of physical activity. This association was still observed among patients participating in high levels of moderate to vigorous physical activity, indicating that regular high levels of physical activity do not fully protect against the risks associated with prolonged periods of sedentary behaviors. However, the association between physical activity and NAFLD has been largely unexplored.
In the current study researchers examined the association of sitting time and physical activity level with NAFLD in Korean men and women to explore whether any observed associations were related to the amount of body fat. They studied records of nearly 140,000 Koreans who underwent a health examination between March 2011 and December 2013. Physical activity level and sitting time were assessed using the Korean version of the international Physical Activity Questionnaire
oday’s drug discovery around G protein-coupled receptors (GPCRs) is quite different from decades ago, when GPCRs weren’t even known to be the target of the newest drugs on the market. Are today’s knowledge-based drug discovery approaches better and faster though? Join your scientific colleagues for this day and a half meeting to debate these questions and more. Learn how the latest functional screening strategies and cutting-edge GPCR crystal structures are/can be applied to drug discovery and development. Also hear case studies around drug candidates developed against specific GPCRs and keep abreast of their progress in the clinic and pharmacological challenges.
8:40 KEYNOTE PRESENTATION:
Harnessing the Functional Selectivity of GPCRs for Drug Discovery
Michel Bouvier, Ph.D., Professor, Department of Biochemistry, University of Montreal
G protein-coupled receptors can engage multiple signaling cascades that may or may not involve G protein activation. This functional selectivity of GPCRs is controlled by the ligand that binds the receptor. Such ligand-biased signaling can be exploited for the development of new drugs with increased selectivity profiles and less undesirable effects. I present approaches we used involving both BRET-based biosensors and label-free methods that hold promise for large scale drug discovery applications.
9:40 GPCR Biased Ligands: Translating Theory to Improved Therapies
Jonathan Violin, Ph.D., Head of Biology, Trevena
Biased GPCR ligands selectively engage or elude distinct receptor signaling mechanisms, and may provide a strategy for designing safer and more efficacious GPCR-targeted drugs. Two examples illustrate how biased ligands can elicit novel pharmacological profiles: TRV027, a beta-arrestin biased ligand of angiotensin II type 1 receptor, and TRV002, a G protein-biased ligand of the mu opioid receptor. These compounds highlight the concept, mechanism of action, and utility of biased ligands.
11:10 Discovery and Characterization of a Novel Chemical Class of GABA-BR Allosteric Potentiators
Geraldine Parenty, Ph.D., Senior Scientist, in vitro Pharmacology, Addex Pharma
The allosteric modulation of GABA-BRs is offering an attractive and novel approach to identify new drug candidates for the treatment of disorders such as anxiety, depression, schizophrenia, pain or GERD, that are devoid of side effects associated with GABAB receptor agonists (e.g. baclofen), and represent a major advance in the drug discovery process. Addex has recently demonstrated in vivo efficacy of such novel PAMs in pre-clinical models of anxiety, inflammatory pain and osteoarthritis pain models.
At June 30, 2015, we had cash and cash equivalents of $214.7 million, a majority of which is invested in money market funds at several highly rated financial institutions.
Common Stock March 31, 2015 29.3 million.
Cash per Share is $7.33.
Austin, TX's microRNA replacement specialist Mirna Therapeutics last week announced its up to $81 million Nasdaq IPO plans on the same day that the Nasdaq Biotechnology Index plummeted 23%, though it ended the day down 4%.
The company is developing a tumor suppressor or known as MRX34 that inhibits multiple oncogene pathways to fight cancer while (hopefully) limiting the development of drug resistance. The candidate is in currently in a Phase I dose escalation study to determine its maximum tolerated dose against a variety of cancers, including primary liver cancer, lymphoma and melanoma.
The microRNA is delivered using the Smarticles platform and formulation, licensed from Marina Biotech, which describes its tech as "amphoteric liposomes composed of unique combinations of lipids having anionic and cationic groups that work together to enable cell uptake, to provide serum stability, and to provide pH-triggered endosomal escape."
We license the technology related to SMARTICLES from Marina. Our license with Marina imposes various development, regulatory, commercial diligence, financial and other obligations. If we fail to comply with our obligations under the agreement with Marina, or otherwise materially breach the agreement with Marina, and fail to remedy such failure or cure such breach, Marina may have the right to terminate the license. The loss of the license from Marina would affect a portion of the patent portfolio for MRX34, which would adversely affect our ability to proceed with any development or potential commercialization of MRX34, and could subject us to claims of patent infringement by Marina if MRX34 is covered by the affected patents.
We determined that the SMARTICLES formulation technology, owned by Marina Biotech, Inc., or Marina, had a favorable combination of efficient systemic delivery of miR-34 mimics to solid tumors in mice, a high therapeutic activity of formulated miR-34 in mouse models of cancer, low or no toxicity, and low or no cytokine stimulation in both animal models and an ex vivo human whole blood assay.
Efficient Systemic Delivery
The SMARTICLES formulation demonstrated key benefits in preclinical studies, including the ability to deliver very high numbers of microRNA mimics to tumors.
We have paid Marina approximately $2.1 million in the aggregate to date in up-front and milestone payments (including the milestone prepayment under the May 2015 amendment) and as consideration for the inclusion within the license of the three additional compounds. As we progress development and commercialization of products covered by the license, we will be required to make payments to Marina based upon the achievement of certain development and regulatory milestones, totaling up to $6 million in the aggregate for each licensed product. We are also required to pay up to an additional $4 million per licensed product upon the achievement of certain regulatory milestones for a specified number of additional indications, leading to a maximum cap on all milestone payments of $10 million per product. The exception to this is for our lead therapeutic product, MRX34, where the aggregate of all remaining development and regulatory milestone payments due to Marina, including for all additional indications, is $3.7 million. In addition to milestone payments, we will be required to pay low single digit royalties on net sales of licensed products other than MRX34, subject to customary reductions and offsets. As a result of our 2013 amendment to our agreement with Marina, we are no longer required to pay a royalty to Marina with respect to sales of our lead therapeutic product, MRX34.
M Fool says, re Vivent " If the buyout goes through the downside will be less than SunEdison's plunge, but SunEdison's stock drop lowers Vivint Solar's buyout price. "
The Fed’s rate hike plans are on a collision course with the economic cycle. In fact, the Fed is signaling a rate hike this year – if not by September, then by December – clearly expecting a pickup in growth. ECRI’s leading indexes suggest the opposite.
Indeed, a service sector slowdown has already joined the manufacturing slowdown that started last fall, and so the slowdown in overall growth is likely to intensify in the coming months. As such, hopes for a “second-half rebound” are likely to be dashed.
ECRI’s indicators show that the U.S. economy is in a GRC downturn that is poised to persist. The key question is whether there is a significant risk of recession in the context of possible shocks, including those from China, the Fed, or any other source. The answer from our indicators is that, for the time being, the U.S. economic expansion is in a cyclically resilient phase where it is resistant to shocks that could tip the economy into recession.
Prosensa's drug failed to beat a placebo in significantly improving boys' ability to complete a 6-minute walk test--the classic measure of success in this field. But left to its own devices the biotech completed fresh analysis of new extension study data that backed a theory that providing the drug earlier while extending treatment could delay disease progression. The biotech held what it called "positive" reviews with the FDA and began a rolling submission of the application just weeks ago. Evidently BioMarin has high hopes of success where GlaxoSmithKline saw nothing but failure. November 24, 2014.
According to Navigant Research, worldwide revenue from energy storage enabling technologies (ESETs) is expected to total nearly $75 billion from 2015 to 2024. In its recent report Navigant analyzes the global market for ESETs across four market segments: utility-scale storage, community storage, residential storage, and commercial storage. Broadly speaking, the three main components of the ESET value chain are hardware, software, and services, which together ensure the intelligence, durability, and profitability of energy storage systems (ESSs). Now that battery prices have responded to cost pressures, the rest of the balance of plant—or the ESET portion of system cost—is under more pressure to deliver more consistent pricing, which is expected to bring more transparency in overall ESS pricing, allowing the industry to scale further.
While the European Medicines Agency said it "does not question that the benefits of HPV vaccines outweigh their risks," on Monday it announced a safety review of the shots that have thus far failed to live up to expectations partly due to safety concerns and a sex-related stigma. The safety watchdog said it'll analyze available data with a focus on rare reports of complex regional pain syndrome--a chronic pain condition affecting the limbs--and postural orthostatic tachycardia syndrome, in which the heart rate increases abnormally after sitting or standing up.
Our DNAi platform technology is based on the breakthrough discovery at Wayne State University and Karmanos Cancer Institute that single-stranded DNA oligonucleotides can interact with genomic DNA in order to interfere with gene transcription. We acquired this technology and subsequently developed an algorithm that we employ for rationally designing our DNAi product candidates using bioinformatics and our understanding of gene regulatory domains. In March 2007, we entered into an exclusive license agreement with Novosom AG (Novosom) to use certain patented lipid nanoparticle (LNP) delivery technology used in PNT2258. In July 2010, the original Novosom license agreement was acquired by Marina Biotech, Inc. (Marina), but Novosom retained the right to receive all future payments related to PNT2258. In March 2012, we and Marina entered into another exclusive license agreement for the use of certain of Marina’s patented delivery technology, including LNP technology, for any of our current or future DNAi product candidates other than PNT2258. In exchange for this exclusive right, we paid Marina an upfront payment of $0.3 million and will also be required to pay Marina milestone payments of up to an aggregate of $14.5 million for each DNAi product candidate other than PNT2258 as well as low single-digit royalties on net sales for DNAi product candidates other than PNT2258. In April 2014, we entered into a license payment agreement with Novosom, pursuant to which we made a one-time payment to Novosom of $11.0 million in April 2014 and terminated the other payment obligations owed to Novosom for PNT2258 except for one remaining $3.0 million payment due upon regulatory approval of PNT2258 and a low single-digit royalty on net sales of PNT2258.
ProNAi Therapeutics, which is developing cancer therapies based on DNA interference, raised the proposed deal size for its upcoming IPO on Wednesday.
The Vancouver, Canada-based company now plans to raise $138 million by offering 8.1 million shares at a price of $17. The company had previously filed to offer 6.7 million shares at a range of $14 to $16. At the revised price, ProNAi Therapeutics will raise 37% greater proceeds than previously anticipated.
ProNAi Therapeutics, which was founded in 2003, plans to list on the NASDAQ under the symbol DNAI. Jefferies and BofA Merrill Lynch are the joint bookrunners on the deal. It is expected to price this week.
The new microneedle patch is made of dissolvable material, eliminating needle-related risks. It is also easy to use without the need for trained medical personnel, making it ideal for use in developing countries, where healthcare resources are limited.
“Our novel transcutaneous vaccination using a dissolving microneedle patch is the only application vaccination system that is readily adaptable for widespread practical use,” said Prof. Shinsaku Nakagawa, one of the authors of the study and Professor of Biotechnology and Therapeutics at the Graduate School of Pharmaceutical Sciences at Osaka University. “Because the new patch is so easy to use, we believe it will be particularly effective in supporting vaccination in developing countries.”
The new microneedle patch – MicroHyala – is dissolvable in water. The tiny needles are made of hyaluronic acid, a naturally occurring substance that cushions the joints. When the patch is applied like a plaster, the needles pierce the top layer of skin without causing pain and dissolve into the body, taking the vaccine with them.
The researchers compared the new system to traditional needle delivery by vaccinating two groups of people against three strains of influenza: A/H1N1, A/H3N2 and B. None of the subjects had a bad reaction to the vaccine, showing that it is safe to use in humans. The patch was also effective: people given the vaccine using the microneedles had an immune reaction that was equal to or stronger than those given the vaccine by injection.
“We were excited to see that our new microneedle patch is just as effective as the needle-delivered flu vaccines, and in some cases even more effective,” said Dr. Nakagawa. “We have shown that the patch is safe and that it works well. Since it is also painless and very easy for non-trained people to use, we think it could bring about a major change in the way we administer vaccines globally.”