Advaxis (NasdaqCM: ADXS) presented 2 posters providing updates on select cervical and orpharyngeal trials.
Poster #1: Phase I study evaluating high dose ADXS11-001 treatment in women with carcinoma of the cervix.
This poster provided an update on Advaxis’s Phase I/II open-label, dose-escalation trial to determine ADXS-HPV can be safety
administered at doses higher than 109 cfu. The primary endpoint is maximum tolerated dose as determined by the frequency and severity
of AEs. The first 3 patients have been enrolled and treated at 5 x 109 cfu, and this initial cohort has been expanded to include an additional
3 patients. According to the study investigator, dosing of the next cohort is expected to begin next week. Patients in this trial are receiving
pre-medication to minimize symptoms associated robust immune activation.
Advaxis and the Gynecologic Oncology Group (GOG) are planning a Phase III study, AIM2CERV, with ADXS-HPV in the adjuvant
setting. This trial will use 109 cfu, which is appropriate for this patient population. The ongoing dose-escalation trial will be especially
useful for further studies where ADXS-HPV will be used to treat patients with a large tumor burden outside of the adjuvant setting.
Poster #2: Window of Opportunity Trial of HPV E7 antigen-expressing Listeria-based therapeutic vaccination prior to robotic surgery for HPV-positive
This poster provided an update on an open-label Phase II trial with ADXS-HPV in patients with newly diagnosed, Stage II-IV
oropharyngeal cancer. Dr. Andrew Sikora at Mount Sinai is conducting the study. A maximum of 22 patients will be enrolled in the study
arm and 10 in an observation arm where no ADXS-HPV will be administered. The major goal of the study is to understand how ADXSHPV
impacts the tumor microenvironment through CD8+ T-cell targeting and suppressor T-cell balance. As of the poster presentation,
8 patients have been enrolled in the study arm and 2 in the observational arm.
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.
Advaxis and Incyte Announce FDA Clearance of Investigational New Drug Application for Phase 2 Study
to conduct a Phase 2 study of ADXS-HPV (ADXS11-001) alone or in combination with Incyte Corporation's (NASDAQ: INCY) investigational oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, epacadostat (INCB24360), for the treatment of Stage I-IIIb human papillomavirus (HPV)-associated cervical cancer.
Reuters) - The U.S. Environmental Protection Agency on Wednesday said greenhouse gases from aircraft endanger human health, taking the first step toward regulating emissions from the domestic aviation industry.
The EPA's endangerment finding kicks off a process to regulate greenhouse gas emissions from the aviation industry, the latest sector to be regulated under the Clean Air Act after cars, trucks and large stationary sources like power plants.
The finding allows the EPA to implement domestically a global carbon dioxide emissions standard being developed by the International Civil Aviation Organization (ICAO).
The U.N. agency is due to release its CO2 standard for comment in February 2016 and adopt it later that year.
The EPA had been under pressure from environmental groups who first petitioned it to regulate aircraft emissions under the Clean Air Act in 2007 and sued it in 2010. A federal court ruled in favor of those green groups in 2012.
Aviation accounted for 11 percent of energy-related carbon dioxide emissions from the transportation sector in 2010 in the United States, according to the International Council on Clean Transportation.
The airline industry has favored a global standard over individual national standards since airlines operate all over the world and want to avoid a patchwork of rules and measures, such as taxes, charges and emissions trading programs.
"If you're a big airline and you're flying to 100 countries a day, then complying with all those different regimes is an administrative nightmare," said Paul Steele, senior vice president at the International Air Transport Association, the main global airline industry group.
But some environmental groups are concerned that the standard being discussed at ICAO will do little to change the status quo since it would only apply to new and newly designed aircraft that will not be in operation for several years.
"The stringency being discussed at ICAO is such that existing aircraft are already meeting the standard they are weighing," said Sarah Burt, an attorney at Earthjustice, one of several groups that sued the EPA to regulate aircraft. (Reporting By Valerie Volcovici; additional reporting by Victoria Bryan in Miami; Editing by Susan Heavey and Doina Chiacu)
Fuel cell technology developer Ballard Power Systems (Vancouver, B.C.) announced that it has reached license and supply agreements with Nantong Zehe New Energy Technology Co., Ltd. and Guangdong Synergy Hydrogen Power Technology Co., Ltd. under which Ballard will provide fuel-cell power products and related technical services in support of the planned development of fuel cell-powered bus fleets in two Chinese cities.
Ballard and Nantong Zehe are collaborating with electric bus manufacturer Jiangsu GreenWheel New Energy Electric Vehicle Co. Ltd. to deploy a fleet of fuel cell-powered buses in the city of Rugao in Jiangsu province. In a separate arrangement, Ballard and Guandong Synergy are working with electric bus manufacturer Foshan Feichi Automobile Manufacturing Co. Ltd. to deploy fuel cell-powered buses in the city of Yunfu in Guangdong province. Between the two projects, Ballard and its partners expect to place a total of 33 fuel cell-powered buses on the streets of these cities. The combined contracts have an estimated value of $10 million to Ballard.
Market Caps: BLDP 323.52M`` HYGS 106.95M
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.
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.
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.
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.
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.
Dr. Figlin will present ADAPT trial insights at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting at McCormick Place in Chicago during the Genitourinary (Nonprostate) Cancer poster session on Monday, June 1st from 1:15-4:45pm CT. The poster is titled, "Patient identification and eligibility insights in the synchronous metastatic RCC population: An update from the ongoing ADAPT phase 3 study experience" (abstract TPS4582).
23 Mar 2015
CHINA: A prototype tram powered by hydrogen fuel cells was unveiled at the CSR Sifang factory in Qingdao on March 19. According to CSR Qingdao Sifang Chief Engineer Liang Jianying, the tram is able to run for 100 km at speeds up to 70 km/h before the cells need to be refilled, which takes 3 min. Water is the only emission during operation.
The three-section 100% low-floor tram has six double doors and capacity for 380 passengers including 60 seated. It meets the EN 15227 crashworthiness standard and can withstand an impact of up to 100 MPa.
CSR Sifang says that the tram will be available in a modular design of two to five sections.
From: Clinical Trial Protocol: 1002-01 25 October 2013
Test Product, Dose, and Mode of Administration:
Ten of the 14 Safety Cohort subjects and those randomized to receive CAP-1002 in the
Randomized and Exploratory Cohorts will receive a single dose administration of 25 million
cells (CAP-1002) suspended in cryopreservation solution (CryoStor® CS10, BioLife
Solutions, Inc.) containing 10% dimethyl sulfoxide (DMSO), 1800 units heparin, and 450
mcg nitroglycerin delivered with a Trek over-the-wire balloon catheter in the infarct related
artery. Additionally, an intermediate wash solution containing saline, 1200 units heparin,
and 600 mcg nitroglycerin is used in divided doses between infusion cycles. CAP-1002 will
be supplied as a ½ dose (12.5 million cells) for the first 4 subjects treated in the Safety
RE: The Rome License. June 21, 2006.
Cardiosphere-derived cells are isolated from atrial or ventricular biopsy specimens of patients undergoing heart surgery. After tissue processing and culturing, a fibroblast-like cell layer forms. A number of cells begin to migrate onto this layer, and are further isolated and cultured to form cardiospheres. After expansion, the vast majority of CDCs were CD105+, with significant pluralities that were c-Kit+, CD90+, CD34+, and CD31+. These cells were also MDR1−, CD133−, and CD45−, as well as negative for a cocktail of blood lineage markers.
Isolation & Growth Conditions
Cut isolated myocardial tissue into 1- to 2-mm pieces, wash with PBS, and digest with trypsin (0.2%) and collagenase IV (0.1%). Discard the obtained cells and wash the remaining tissue fragments with complete explant medium (CEM) (Iscove’s Modified Dulbecco’s Medium [IMDM]) supplemented with fetal calf serum (10%), penicillin (100 U/mL), streptomycin (100 μg/mL), L-glutamine (2 mM), and 2-mercaptoethanol (0.1 mM). Culture as explants at 37°C and 5% CO2. After a period ranging from 1 (embryo) to 3 (adult) weeks, a layer of fibroblast-like cells is generated from adherent explants over which small, phase-bright cells migrate. These phase-bright cells can be collected by pooling two washes with PBS, at room temperature under visual control. Seed the obtained cells at ≈0.5-2×10^5 cells/mL in poly-D-lysine-coated multiwell plates in cardiosphere-growing medium (CGM: complete IMDM (35%), DMEM–Ham F-12 (65%), B27 (2%), 2-mercaptoethanol (0.1 mM), epidermal growth factor [EGF; 10 ng/ml], basic fibroblast growth factor [bFGF; 20 ng/ml], cardiotrophin-1 (40 nmol/L), thrombin (40 nmol/L), antibiotics, and L-Glu, as in CEM). Isolation of the cardiosphere-forming cells can be performed from the same explant at least 4 times, at 6-10-day intervals. Passage cardiospheres every 2-3 days by partial changing of the medium and mechanical trituration of the larger clusters.
... and burn the BS too !
LA is sooo clean.
That's because they put all their garbage on TV.
Halofuginone is a coccidiostat used in veterinary medicine. It is a synthetic halogenated derivative of febrifugine, a natural quinazolinone alkaloid which can be found in the Chinese herb Dichroa febrifuga (Chang Shan). Collgard Biopharmaceuticals is developing halofuginone for the treatment of scleroderma and it has received orphan drug designation from the U.S. Food and Drug Administration.
Halofuginone inhibits the development of T helper 17 cells, immune cells that play an important role in autoimmune disease, but it does not affect other kinds of T cells which are involved in normal immune function. Halofuginone therefore has potential for the treatment of autoimmune disorders.
Halofuginone is also an inhibitor of collagen type I gene expression and as a consequence it may inhibit tumor cell growth. Halofuginone exerts its effects by acting as a high affinity inhibitor of the enzyme Glutamyl-Prolyl tRNA synthetase. Inhibition of prolyl tRNA charging leads to the accumulation of uncharged prolyl tRNAs, which serve as a signal to initiate the amino acid starvation response, which in turn exerts anti-inflammatory and anti-fibrotic effects.
Akashi Therapeutics' Duchenne MD candidate shows encouraging results in early stage study
Jun 18 2015, 10:48 ET | By: Douglas W. House, SA News
Interim data from a Phase 1b/2a clinical trial assessing privately-held Akashi Therapeutics' product candidate for Duchenne muscular dystrophy (DMD), HT-100, showed that patients with at least six months of continuous dosing achieved average total muscle strength 22.3% greater that levels predicted by comparable steroid-treated external control. The results were determined by quantitative muscle testing (QMT) of upper and lower extremity muscle groups.
· The average increase in muscle strength compared to baseline over 18-22 months in the 10 patients in the trial was 11.7%. All study participants are on a stable regimen of corticosteroids.
· Orphan Drug- and Fast Track-designated HT-100 (delayed-release halofuginone) is an orally available small molecule designed to reduce fibrosis (scarring) and inflammation and promote healthy muscle fiber regeneration in patients with DMD.
· The trial completion date is January 2016. An open label extension study will run until February 2017.
With the NBA draft still 18 months away, Willie Cauley-Stein told reporters in late 2013 that he cut short his play in a recent college basketball game because of severe chest pain and shortness of breath due to a genetic disorder called sickle-cell trait.
That condition made Cauley-Stein, a 21-year-old, 7-foot-1, 240-pound forward/center and Southeastern Conference Defensive Player of the Year, a potential liability for any team that drafted him. But it didn’t stop the Sacramento Kings, which chose him Thursday as the sixth pick in this year’s draft.
Cauley-Stein and team vice president Vlade Divac said Saturday the condition should not affect his play.
“No big deal,” Divac said he concluded after talking to a team doctor about the condition.
“I don’t see that it had an effect on him” at Kentucky,” Divac told The Sacramento Bee after Cauley-Stein’s introductory news conference at the team’s J Street office adjacent to the arena construction site.
Cauley-Stein said it’s manageable with hydration and nutrition.
“There is no issue. You have to be cautious of it. You have to stay hydrated. You have to eat well. I eat really organic,” Cauley-Stein said.
In 2013, he described his condition to the Lexington Herald-Leader after having to leave the court after 25 minutes while playing in a game for Kentucky.
“My chest starts to hurt,” he said after the game against Boise State. “Some days, just randomly, I’ve had real bad chest pain. I can’t, like, breathe, and my heart rate won’t come down. I have to stop and wait for it to come down.”
Two days later, John Calipari, Kentucky’s head coach, said Cauley-Stein knew how to manage the illness.
“If he gets winded or he feels it, he’ll take himself out,” Calipari said, “He’s pretty good about it.”
So what is sickle-cell trait?
It disproportionately affects African Americans, and sufferers inherit one sickle-cell gene and one normal gene. People who inherit two sickle-cell genes, one from each parent, can develop