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It would be interesting to hear about some new approaches to AD outside of the amyloid approach. I came across a paper suggesting targeting TLRs, such as TLR9, could be a beneficial approach in AD. Not clear to me if this was distinctly related to the amyloid hypothesis or not though. Need to find that again.
Take a look at PKC epsilon. Neurotrope
https://www.tcd.ie/academicunits/schools/medicine/physiology/assets/docs13_14/lynchma/PG4700%20PG4750%20SS%20Cell%20Physiology/PKC%20and%20aging.pdf
CTRV - anyone follow this one?
The trial failed previously. Is reducing the number of patients from getting phn from 12 to 20 percent a valid endpoint?
http://www.proactiveinvestors.com/companies/news/10884/inhibitex-hit-hard-after-drug-for-treatment-of-shingles-misses-primary-endpoint-10884.html
Inhibitex hit hard after drug for treatment of shingles misses primary endpoint
15th Dec 2010, 2:01 pm by Jason Chew Inhibitex hit hard after drug for treatment of shingles misses primary endpoint
Shares of Inhibitex sank yesterday after the release of top-line data of its lead drug, FV-100, for the treatment of shingles. While the results showed improvements in the reduction in the severity and duration of shingles-associated pain of 3 and 7 percent for the 200mg and 400mg patient cohorts, it was a far cry from the 25% reduction called for as the primary endpoint, and not statistically significant.
The FV-100 Phase II trial was a randomized, three-armed, controlled study comparing two doses of FV-100 to Valtrex, the current standard of care. The compound had never been tested in shingles patients, only healthy volunteers. The rationale for study design and endpoints were therefore somewhat arbitrary, based mainly on preclinical data and results of marketing studies.
In other words, they were going in blind.
Inhibitex had good reason to believe in their molecule; it was extremely potent and fast acting against the Herpes Zoster virus that causes outbreaks of shingles, much more so than current treatments. It had excellent PK and PD properties, allowing once-a-day dosing, compared to the three-times a day treatment with Valtrex.
But the company believed it needed more than a dosing advantage in a marketplace where all three top treatments- including Valtrex- are generic. Market research led it to select pain reduction of 25% over Valtrex as the primary endpoint partially due to the belief that such a large reduction would vault FV-100 into a position to become the standard of care.
It is therefore not surprising that FV-100 missed this artificial goal. The trial did show that Inhibitex has a compound that is at least as good as Valtrex in pain reduction with a similar side effect profile and lower pill burden. What many investors may not have noticed is the 400mg FV-100 cohort had only a 12.4% incidence of postherpetic neuralgia (PHN) compared to 20.2% for Valtrex, one of the secondary endpoints. PHN is the most common complication of shingles and occurs when the nerve pain associated with shingles persists beyond one month, even after the rash is gone.
This is a setback for sure, but FV-100 is in all likelihood an approvable drug. The difference now is a reassessment of its market potential and partnering ability. What management once considered a $1 billion opportunity may no longer exist. It is likely new endpoints will need to be selected for the Phase three to prove superiority, or a higher dose may be used. This is likely to create uncertainty in the trial outcome.
Management spoke of partnering possibilities, suggesting an Asian partner is likely to emerge before any other. Big US and European Pharmas certainly seem to have lost interest in primary care drugs; it’ll take gangbuster results to get their attention. In a sane world, Pharmas would partner it before the great results. Inhibitex believes it can take FV-100 into Phase III on its own.
Stealing the spotlight from FV-100 is INX-189, the company’s lead candidate for HCV treatment. The program seemed to come out of nowhere when they first presented data at the 22nd Annual International Conference on Antiviral Research. But as with FV-100, it was in-licensed from the lab of Prof Chris McGuigan of UK’s Cardiff University; in this case, in 2008.
INX-189 belongs to a class of RNA nucleotide polymerase inhibitors and appears to be promising. As with all compounds of its class, it has a high barrier to resistance: viruses reproduced for three months in lab tests before a mutant was found. Management claims that their compound is 5-10 times more potent than other compounds in its class.
Phase Ia studies in healthy volunteers have been complete. INX-189 has shown a clean safety profile and good PK sufficient for once daily dosing. A Phase Ib, 7-day trial in treatment naïve patients is now fully enrolled. This trial consists of 6 cohorts receiving various doses in monotherapy plus 2 cohorts treated with a combination of INX-189 and ribavirin. Results had been anticipated for the end of this year, but are now expected to roll in through the first quarter 2011 beginning in January. A 12-week Phase II combination study is being planned to follow soon after.
Inhibitex has a rare commodity on its hand with INX-189 and it knows it. There are only a handful of nucleotide polymerase inhibitors in development. The company is planning to develop the compound rapidly. A partner may be considered for Phase II if considered helpful.
After losing 24% in regular trading, the stock has lost nearly all its gains leading up to the FV-100 data release, leaving it with a market capitalization of $136 million. Any value in the company then, appears to be assigned to INX-189.
Buyers of the stock appear to get FV-100 for free.
bad news for BIOD and UNIS
Biod has to waste 9 months of overhead because of this delay
BIODEL INC.
GEM Registration Studies Delayed 9+ Months; Maintain BUY; Lower PT to $3.50
Please click here for full report.
3Q FY results. Biodel reported a 3Q FY15 net loss of $6.5 million, which was wider than the $5.4 million loss we estimated, primarily due to higher than anticipated R&D expenses. Biodel ended June 2015 with $44.4 million in cash, including $32.1 million in net proceeds from a public offering in April. At a burn rate of ~$5 to $7 million per quarter, we believe Biodel has sufficient cash to run into mid-2017.
FDA guidance on Glucagon Emergency Management (GEM) program development is now clear, but the registration studies will be delayed for 9+ months due to delay in delivery of registration batch device. At the end of a Phase 2 meeting with the FDA for the GEM program, Biodel indicated it reached agreement with the Agency on the design of the summative human factors study (HFS), the design and objectives of the pivotal bioequivalence (BE) study and the product stability and analytical similarity plan for the proposed 505(b)2 NDA application for GEM. Although the regulatory pathway is now clearly defined and confirmed by the FDA, Biodel surprisingly updated that registration batch devices for the GEM studies will be received no sooner than 3Q16, versus prior expectation of 4Q15. The registration batch devices are required for the pivotal BE study, the HFS and the stability study. The device is being manufactured by Unilife Corp. (UNIS, $1.40, Buy rated). Biodel did not provide the specific reasons for the delay; however, we think the device design is complete but UNIS has failed to meet its contractual obligation. The registration BE, HFS and stability studies will not start until 3Q16, at the earliest, pushing an NDA filing for GEM to mid-2017 at the earliest. We are surprised by the sudden delay and have adjusted our timeline projection for the potential GEM NDA filing and launch. Accordingly, we lower our price target to $3.50 from $4.00.
Phase 2b study for BIOD-531 is on hold due to the FDA's request for additional testing on the U-400 syringe used to deliver BIOD-531. Biodel also surprisingly indicated the BIOD-531 Phase 2b study currently is not recruiting patients, as FDA required additional testing of the dosing accuracy of the U-400 syringe used to deliver BIOD-531. Meanwhile, 7 patients had already been randomized into the BIOD-531 arm in the study, which are now converted into the active control arm. The U-400 syringe uses new calibrations printed on the syringe body, which has been used in other marketed products. The new calibrations on the syringe enables patients to directly read out the units of insulin injected (the previous syringe only shows injection volume and requires the patient to calculate the conversion from injection volume to insulin units, which is error-prone). Biodel has done accuracy testing spanning a number of dose gradients on the U-400 syringe according to ISO standards. However, Biodel now updated that FDA has requested additional data on the dosing accuracy of the U-400 syringe. Biodel has performed additional accuracy testing spanning more dose gradients on the U-400 syringe and will submit the data to FDA in the next few weeks. The FDA will then have 30 days to review the data and give feedback. We are disappointed by this surprise hold, but do not expect the syringe issue to cause a substantial delay.
We lower our price target to $3.50 from $4.00 due to the surprising GEM program delay and temporary hold of BIOD-531 Phase 2b study.
Risks
The primary risks of an investment in BIOD shares include (but are not limited to): Biodel may not be able to obtain FDA approval for pipeline products and/or approvals may be delayed substantially, both of which would reduce the company’s growth prospects. Biodel’s products may not demonstrate safety and efficacy in clinical trials, which could lead to pipeline projects being terminated. Biodel’s products may not be well received by patients and physicians, which could result in revenues falling below estimates. Biodel’s sales and marketing efforts or its partners’ sales and marketing efforts may not be effective in promoting its products, which could lead to revenues and earnings falling below estimates. Biodel may not be able to obtain favorable reimbursement of new products on formularies administered by managed care organizations, health insurers, and the government. Unfavorable reimbursement status could limit the market acceptance of products and limit Biodel’s revenue potential for those products. Biodel’s products could lose market share to existing branded products on the market and/or new branded products which launch in the future. If generic companies can prove non-infringement or invalidity of any patents protecting Biodel’s products, those products could face generic competition after any Hatch-Waxman exclusivities expire. Generic competition could result in a substantial decline in Biodel’s product sales. Financing transactions may be dilutive to existing shareholders. Manufacturing facilities may not pass preapproval inspections required by the FDA before pipeline products can be approved or may fall out of compliance with current Good Manufacturing Practice (cGMP) regulations, which could lead to supply disruptions and lower revenues to Biodel. Biodel or its contract manufacturers may not be able to produce enough product to meet market demand, leading to a loss of revenues. Biodel’s suppliers may not be able to supply enough active ingredient to meet manufacturing demand. Biodel’s SEC filings disclose additional risk factors.
Matt Kaplan
Managing Director
Biotechnology Equity Research
Ladenburg Thalmann & Co. Inc.
570 Lexington Avenue - 11th Floor
New York, NY 10022
Direct: 1.212.891.5247
mkaplan@ladenburg.com
Hedgefund short EXAS seeks CMS restrictions on Cologuard reimbursement:
I would say that CNS should hire hedge funds as consultants when determining prices for drugs and procedures because they totally unbiased and are just doing what is best for society.
I would say dwarfs are fine the way they are if Biomarin intends to charge 500k a year for them to grow.
Babylon Leaders Protect Great South Bay from Greatest Source of U.S. Water Pollution; Set Standard for Municipal Stormwater Treatment
08/15/2012
Green Infrastructure Solution Proves Critical, Affordable Last Line of Defense
BABYLON, N.Y., Aug. 15, 2012 /PRNewswire/ -- The Village of Babylon, located on the southern coast of Long Island and AbTech Holdings, Inc. (OTCQB: ABHD) ("AbTech"), a developer and manufacturer of patented innovative environmental technologies addressing issues of water pollution and contamination, announced today the results of a five-year study exploring the efficacy of AbTech's proprietary Smart Sponge® filtration technology in preventing stormwater contamination of The Great South Bay and the nearby Long Island Sound. The study, which analyzed the contents of AbTech's Smart Pak® cartridges from two outfall pipe installations located at Green and Alexander Avenues, found that Babylon's existing installations captured approximately 1,600 pounds of total contaminants from stormwater annually, including 1,400 pounds of toxic hydrocarbons.
"Untreated stormwater runoff is the single greatest source of water pollution in the United States, and The Great South Bay has been particularly affected with the intense development of Long Island," said Robert F. Kennedy, Jr. , President of the Waterkeeper Alliance. "Municipalities are at the heart of the fight to preserve water resources for future generations and Babylon has set the bar for cities nationwide in reducing the runoff of fertilizers, pesticides, pathogens, and petroleum products."
In 2008, Babylon announced its plans to retrofit 96 outfall pipes with AbTech's stormwater treatment systems, utilizing a matching grant of $310,000 provided by Suffolk County once testing was complete. The initiative marked one of the first efforts nationwide by a municipality to address stormwater pollution using a green infrastructure solution. It is expected that once all 96 installations are complete, collectively more than 8,000 pounds of contaminants, including 7,000 pounds of toxic hydrocarbons will be prevented from entering The Great South Bay annually.
"When we set our stormwater management plan in motion, we hoped it would serve as an attainable model for our neighbors throughout Suffolk County," said Village of Babylon Mayor Ralph Scordino . "But after seeing these results, we are confident that our model will be employed throughout the country."
AbTech's treatment systems cost Babylon between $5,000 and $6,000 per unit to install and are retrofitted into existing stormwater infrastructure, eliminating the need for costly new construction. The systems require no electricity and minimal maintenance, and are effective at removing over 85 percent of toxic hydrocarbons from stormwater, in addition to sediments, heavy metals and other harmful pollutants. Once absorbed, hydrocarbons are permanently bound to the Smart Sponge polymer and cannot be leached away. Spent Smart Sponge material can be landfilled or burned as a high BTU, low emissions fuel source.
"Babylon's stormwater initiative is a perfect example of the progressive thinking that has made Suffolk County one of the best places to live, work and play in the nation," said Suffolk County Executive Steven Bellone . "Our political leaders are constantly pushing the envelope to get the job done for taxpayers through innovative and cost-efficient ways."
Babylon will begin installation of additional stormwater treatment systems in November.
Media Relations Contact:
Megan Esteves
Senior Account Manager/Deputy Team Leader
Regan Communications Boston
(617) 488-2868
mesteves@regancomm.com
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or
In what Suffolk officials call Long Island's most extensive municipal effort to reduce storm water pollution, the Village of Babylon plans to install filters at every village outfall pipe that leads to the Great South Bay.
"We're doing 93 of them," Mayor Ralph Scordino said at a news conference yesterday next to a canal at Green Avenue, where the village installed a prototype two years ago.
The plan addresses one of Long Island's biggest water quality problems: contaminated runoff from heavy rains that washes oil, chemicals and animal waste off the land and into creeks and bays. Funneled via storm drains, the polluted runoff can temporarily close bathing beaches and make shellfish unsafe for human consumption.
Citing Babylon's history of fishing and clamming on the Great South Bay, Scordino said, "It's our duty to make sure that asset and that resource is here for our children, and our children's children."
Suffolk County provided $310,000 to help the village buy and install the filters in a matching grant approved by the legislature earlier this week. The village plans to start retrofitting the outfall pipes next spring.
The filter units will be placed in underground concrete vaults that intercept storm water from catch basins. Special sponges held in an aluminum frame soak up oil, grease and bacteria that would otherwise end up in local waterways. After flowing through the filters, the treated storm water goes out the other end and into the bay. The filters capture 80 to 90 percent of pollutants, according to their manufacturer, AbTech Industries of Scottsdale, Ariz.
"When we cleaned this system out, we had upwards of 80 pounds of hydrocarbons that were absorbed into those pillows," said village engineer Bruce Savik, holding up a sopping used sponge from the Green Avenue unit that had turned completely black.
Each filter unit runs between $5,000 to $6,000 to install. The sponges cost $125 and must be replaced about every year, depending on the volume of water that flows through the unit, Savik said.
The village had tested two prototypes to make sure they would hold up to high tides and heavy rains. Now, a study based on water samples before and after heavy rains will measure the filters' effectiveness. "If it works as anticipated, this can be a model for the rest of Long Island, the rest of the state and the rest of the nation," County Executive Steve Levy said.
Local governments across the country are updating their storm water management plans to meet with federal requirements intended to limit polluted runoff. Almost 90 percent of Long Island municipalities are in compliance, according to the state Department of Environmental Conservation.
Hundreds of similar and larger-scale storm water filters have already been installed on Long Island, according to AbTech and Fabco Industries, a Jericho-based manufacturer. Nassau County has said it plans to install 2,000 more filters next year.
Nassau lawmakers say they had no knowledge that Skelos' son worked for county contractor
Updated April 17, 2015 6:28 PM
By PAUL LAROCCO paul.larocco@newsday.com
191 Reprints + -
Adam Skelos stands outside his home in RockvilleAdam Skelos stands outside his home in Rockville Centre, Thursday, April 16, 2015. Adam and his father Dean Skelos are being federally investigated. Photo Credit: Steve Pfost
Why does it matter if Adam Skelos is a consultant if their technology is the best
Nassau County legislators who approved a large contract that federal prosecutors reportedly are scrutinizing as part of a corruption probe into State Senate Majority Leader Dean Skelos said Thursday that they did not know the winning bidder had employed Skelos' son.
Public works officials awarded AbTech Industries a $12 million storm-water treatment contract in 2013, saying the firm provided "the best value" even though its proposal cost more than the closest competitor's.
The county legislature's Rules Committee voted unanimously for the agreement in July 2013 with no public discussion, legislative records show.
STORYDA to probe Nassau contracting processSTORYTitle co. in Skelos probe has supported DemsSTORYSkelos: Investigation report 'irresponsible'
County Executive Edward Mangano's administration provided lawmakers with 98 pages of documents related to the AbTech deal. None of the documents, including a required disclosure of company principals that included nine people, mentioned Adam Skelos, the son of Dean Skelos (R-Rockville Centre). Adam Skelos was working then for the Arizona company and had introduced county public works employees to AbTech, said a county source.
"If that was disclosed to us, we would have taken a whole different direction in questioning," Minority Leader Kevan Abrahams (D-Freeport) said. "It's concerning."
Presiding Officer Norma Gonsalves (R-East Meadow) said through a spokesman that majority Republicans didn't know about Adam Skelos' connection to AbTech, but declined further comment.
The New York Times reported Wednesday Preet Bharara, the U.S. attorney for the Southern District of New York, is investigating whether Dean Skelos exerted any influence in matters involving AbTech. Dean Skelos has declined to comment other than to say he is cooperating with authorities. Adam Skelos, also of Rockville Centre, has declined to comment.
Neither has been accused of wrongdoing.
PoliticsDean Skelos through the years
AbTech's contract was approved by the four Republicans and three Democrats on the Rules Committee. Legislative leaders in both parties said Thursday that county public works officials mentioned nothing about Adam Skelos.
Contract documents show that AbTech was one of three companies to respond to a county request for proposals for storm-water treatment.
A three-person "evaluation committee" of public works department officials "scores" RFP respondents based on criteria including cost, the company's experience and the feasibility of their proposal. Deputy public works Commissioner Richard Millet and department aides Ken Arnold and Brian Schneider scored three firms: AbTech, Newport Engineering, of Oyster Bay, and Primer Construction Corp., of Brooklyn.
Public works officials did not respond to requests for comment Thursday. But a May 2013 memo from department Commissioner Shila Shah-Gavnoudias to Rob Walker, Mangano's chief deputy, describes AbTech, with a quoted project fee of $1.9 million, as a better choice than Newport, whose fee was $1.5 million. The fees were based on a total construction estimate of $10 million, which officials said they expected to be reimbursed by state storm-preparedness grants.
Shah-Gavnoudias cited Newport's failure to provide "adequate information" about its technology and its higher installation costs. AbTech received an overall score of 83.7, with Newport receiving 64 and Primer 61.7.
"In our professional judgment, the proposal submitted by AbTech Industries, having receiving the highest technical rating and proposing a reasonable cost for the services represents the best value to the county," Shah-Gavnoudias wrote.
Mangano, a Republican, held a news conference in July 2014 to tout AbTech's antimicrobial sponge technology that would be installed in an outfall pipe near the Bay Park Sewage Treatment Plant in East Rockaway. He called the project "a major step forward in protecting our environment."
Newport president Nicholas DeSantis said in an interview Thursday he was never made aware his firm had submitted the lowest-cost proposal. Primer Construction didn't return calls Thursday.
AbTech has been paid $144,548 to date, according to the office of Nassau County Comptroller George Maragos.
Brian Nevin, a Mangano spokesman, said the administration was cooperating with federal authorities. "The vast majority of what has been requested are documents that are publicly available and which had been reviewed and approved by the county attorney, unanimously by County Legislature, [county] comptroller" and the county's state fiscal control board, the Nassau Interim Finance Authority, Nevin said.
Suffolk County spokesman Justin Meyers said the county doesn't use AbTech's technology and has no contract with it.
Village officials in Babylon and Sag Harbor that do use the company's sponges said they were unaware of Skelos' involvement in the technology.
In 2006, Babylon Village installed the "Smart Sponge" technology from AbTech Atlantic in vaults to treat stormwater runoff before entering the Great South Bay.
Mayor Ralph Scordino, who was also mayor at the time, said the approximately $300,000 project has been "very effective" at treating runoff.
"Sen. Skelos or his son never approached anyone at the village, as far as my knowledge," Scordino said. "I'm sure someone like that would've raised a flag with someone here."
Scordino said the idea to use the Smart Sponge came from the firm that serves as the village engineer, Ronkonkoma-based Savik and Murray.
Dee Yardley, Sag Harbor superintendent of public works, said the village installed the sponges near Havens Beach in June 2013. "We had no problem with the vault or the sponges," he said. Since then, the bathing beach has passed county health tests "with flying colors."With Robert Brodsky,
Robert E. Kessler and
David M. Schwartz
Below is an article from before this recent Fiasco mentioning Dee Yardley and how well the smart sponge has performed in Sag Harbor. So you have a few people quoted above in the Newday article that could have just said no comment. They have said the product works well, and after giving it a few weeks to let things die down you should perhaps reach out to them, thanking them for supporting your product instead of hiding under a destk.
some how we should try to figure out a way to take the exposure you have received and turn it into a force for good instead of evil.
http://www.abtechindustries.com/news/news-98/AbTech-and-Smart-Sponge-in-Erosion-Control-Magazine-Feb-2015
AbTech and Smart Sponge in Erosion Control Magazine Feb 2015
02/10/2015
Erosion Control Magazine 2-4-15
Sag Harbor Village -
EPA estimates that between 1988 and 1994, there were over 12,000 instances where people could not swim safely in US coastal beaches because of high pollution and bacteria levels. Population increases and development along coastal areas will put additional pressures on water quality in these regions, forcing communities to develop more stringent water quality management plans.
Sag Harbor is an incorporated village on Long Island in Suffolk County, NY. The 2010 census put the population of the village at a little over 2,000. Sag Harbor has historical roots that date back to the American Revolution and the War of 1812. Even further back, it was declared an international port by 1789 and soon became a major whaling port. The whaling industry peaked around the 1840s but collapsed in 1847 with the discovery of kerosene and coal oils.
About 100 years later, in 1947, a giant drainage “ditch” was cut through Havens Beach in Sag Harbor. The ditch was 900 feet long and 25 feet wide, and 137 acres drained into it, explains Dee Yardley, superintendent of public works for Sag Harbor Village. “It had to have some way to go out. And back then, that’s just the way it was done.
“It was a trench that went all the way out to the beach,” he continues. “All the water just flowed to the lowest area. It was stormwater runoff and in some areas, the water just sat there.”
As the Suffolk County Department of Health monitored beach water quality in recent years, it found that the bacteria counts increased in the ditch. Stormwater runoff from the village was accumulating in the old ditch area, Yardley says. And while the situation had been under study for a number of years, in 2012 it got a welcome supporter. The mayor of Sag Harbor, Brian Gilbride, was very active in his support stormwater improvements at Havens Beach. Upon his re-election as mayor, he took on the project, commenting that he was looking forward to “tackling the stormwater runoff pollution at Havens Beach, as well as erosion at the West Water Street.”
Nancy Pierson, senior public health sanitarian with the Suffolk County Department of Health Services’ Office of Ecology, explains, “In an effort to protect public health, the Suffolk County Department of Health Services’ Office of Ecology conducts a comprehensive bathing beach water-quality-monitoring program from mid-May through mid-September at approximately 191 beaches. The frequency of sampling is determined using a tiered, risk-based approach, with more testing conducted at beaches that have historically demonstrated periods of poor water quality or are potentially at risk because of their proximity to pollution sources. Sampling at these beaches is typically performed at least twice per week.”
To evaluate beach water quality, levels of indicator organisms are used as an estimate of fecal contamination. Although the organisms are usually considered to be harmless, they may indicate that fecal contamination is present, along with other disease-causing organisms. Per recommendations from EPA under the BEACH (Beaches Environmental Assessment and Coastal Health) Act and the requirements of the New York State Sanitary Code for Bathing Beaches, Suffolk County uses Enterococci as the indicator organism for its marine beaches.
Pierson says that obtaining grant funding through the BEACH Act has allowed Suffolk County to expand its beach monitoring program significantly in recent years. Where it collected approximately 520 samples in 2002-03, it increased its collections to more than 4,000 in 2013. In 2003 only the beach was being sampled. But in 2008 resident complaints and concerns about possible bacterial contamination led Suffolk County to start sampling the end point of the long trench.
“Decisions regarding beach closures are based on sample results as well as various beach-specific factors, including knowledge of potential sources of contamination in the beach watershed, historic water quality data, past criteria exceedances, weather, and area flushing characteristics,” she notes. “Under certain conditions, such as during or in anticipation of unusually heavy rainfall, or other events or situations that can pose a risk to public health, advisories recommending against bathing are issued. Precautionary advisories are typically issued for a 24-hour period to allow for sufficient tidal exchange to dilute any contamination that may be present. And although beaches may close in response to these advisories, they are not an indication that unacceptable bacterial levels exist, but rather are a precaution against potential contamination.”
However, while the bacteria counts at the Havens Beach outfall continued to rise, potentially threatening beach water quality, officials searched for a source or sources and for alternatives to solve the problem. The Village of Sag Harbor, together with Inter-Science Research Associates Inc. as its environmental and planning consultant, approached the Suffolk County Department of Health Services’ Office of Ecology to get input, data, and expertise in this area. Richard Warren, AICP, president of Inter-Science Research Associates, and Mike Schiano, environmental planner with the company, became involved with Havens Beach as site designers, planners, and coordinators, together with S.L. Maresca Associates, a local consulting engineering firm.
“On Long Island, most septic systems are subsurface systems and could potentially be a problem,” explains Schiano. “All the testing came up inconclusive.” He says the Suffolk County Department of Health Services conducted dye testing of some nearby septic systems to see if any of them were contributing to the ditch’s bacteria levels, but they came back negative. But, because the bacteria levels were high, officials wanted a solution: “Fix the problem!”
“At marine and coastal beaches in Suffolk County, stormwater runoff is the predominant source of bacteria-laden water,” says Pierson. “The effects of the runoff on water quality are site specific, and are influenced by a number of factors, including the type of land use, area topography, and the degree of tidal flushing. Both Enterococci andEscherichia coli bacteria can be introduced to recreational waters from a variety of sources, including stormwater runoff, resident waterfowl populations, failing or poorly operating septic systems, sewage spills, boats and marinas, floatable debris, and from bathers themselves.”
“We knew we would need more than just one technique to ensure the highest removal efficiency,” says Schiano. “The ditch area needed to be dredged to remove the material that had been building up in it since it was created in 1947. Once the ditch was dredged, it was filled with clean sand to provide a stable bottom for planting material. We also included a settling basin that extended about 200 feet from the inlet pipe, a check dam at the end of the basin, and an area about 700 feet by 20 feet for a wetland with aquatic plants that helped to remove nitrogen and other typical stormwater pollutants.”
In planting the bioswale, Schiano explains, all of the plants were planted in clean sand with no soil amendments. The mix of native plants included duck potato (Sagitaria latifolia), pickerelweed (Pontederia cordata), soft rush(Juncus effusus), tussock sedge (Carex stricta) and narrow-leaved cattail (Typha angustifolia). All plant plugs were planted 1-foot on-center. Plant populations were installed, alternating dense and open, to allow water to flow and seep.
By the time the bioremediation portion of the Havens Beach project was designed, he says, planners had already decided on AbTech Industries to supply its Smart Sponge Plus for bacteria removal on the site. AbTech Industries is a stormwater management firm located in Scottsdale, AZ. Smart Sponge Plus can be used anywhere there is a need to remove excessive bacteria. These locations vary but are often near beaches, rivers, and lakes.
The Smart Sponge Plus structure is porous and elastic, giving it excellent hydraulic properties, along with its chemical properties that make it chemically selective towards hydrocarbons. Smart Sponge is hydrophobic, so it repels water, while being oleophilic to attract oil and grease. The oil and grease are permanently bound to the Smart Sponge and will not leach back into the environment. Saturated Smart Sponge has passed EPA Toxicity Characteristic Leaching Procedure (TCLP) testing as a “non-leaching” product, and therefore can be disposed of in any nonhazardous (Class D) landfill, waste-to-energy facility, or cement kiln.
The Smart Sponge Plus contains an antimicrobial agent that is chemically bound to the polymer surface. The permanent bond allows the agent to be active without leaching out downstream, thereby avoiding toxicity issues at other locations. The organosilane derivative that is used in the Smart Sponge Plus is used in a variety of products including medical and dental products, consumables, pool equipment, and other consumer goods. Using no electricity, chlorine, or heavy metals, the mechanism works to inactivate microorganisms at the cellular level. Using flow rates and bacteria concentration, AbTech engineers the Smart Sponge Plus to meet the desired performance requirements of each individual customer.
After determining a number of factors such as flow rate, bacteria levels, sediment loading, desired bacteria reduction, and various others, AbTech recommends using a specific size Smart Sponge Plus Smart Pak bed depth. This Smart Pak bed depth will reflect the proper empty bed retention time to meet the customer’s desired bacteria reduction through the biostatic charge of the media.
Smart Sponge Plus is typically used in a vault system. Once installed, the system requires minimal routine maintenance and replacement of the antimicrobial Smart Paks to keep it operating at peak efficiency. When the Smart Paks become saturated with sediment, oil, and grease, they need to be replaced. Typically, 10–15% of the antimicrobial Smart Paks will need to be replaced each year.
Superintendent Dee Yardley described the AbTech vault installation at Havens Beach. “All the material in the ditch was dredged. There was about 5,000 to 10,000 tons dredged from there. Then they put the new sand back in. That’s the biofiltration area before it gets to the Smart Sponge Plus vault.” He continues, “It was installed in 2013, and using a crane they literally dug a large hole to install the precast vault. It’s a giant concrete vault with stainless steel compartments for the antimicrobial Smart Sponge Plus ‘pillows,’ or Smart Paks. You can’t tell it’s even there.”
The 10-foot by 10-foot vault that houses the Smart Paks is inconspicuous to beachgoers, but there is a manhole cover on the cement top so that he, or AbTech service technicians, can go inside to service the filters.
The bacteria levels that had previously reached as high as 12,500 in October of 2009 have remained below 1,000, a greater than 92% reduction, since the Smart Sponge Plus installation in August 2013, as determined by a data chart supplied by Nancy Pierson. Also noted in the data, of 16 effluent samples taken since August 2013, 11 had bacteria levels below 300. The bioswale area is doing its part to filter the stormwater runoff as well. The data for samples taken before and after the bioswale show that 8 out of 12 samples were remarkable after passing through the bioswale. When using the data chart supplied by Pierson, even though numbers seem erratic, there is an overall downward trend since the Smart Sponge Plus was installed.
Yardley concludes that since the Smart Sponge Plus was installed in 2013, there has been no instance of bacteria exceeding the acceptable levels at Havens Beach.
archive
What do you think insurers will pay for the color blind therapy to be performed
I think people might have to pay out of pocket for that one
You put links to Ophthotech's phase 3 trials showing that they not excluding occult patients, the problem is that if you go to their phase 2 trial is doesn't show them excluding occult patients either. It is only mentioned in the sec docs
from phase 2
https://clinicaltrials.gov/ct2/show/NCT01089517?term=ophthotech&rank=8
A Safety and Efficacy Study of E10030 (Anti-PDGF Pegylated Aptamer) Plus Lucentis for Neovascular Age-Related Macular Degeneration
Eligibility
Ages Eligible for Study: 50 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:
Subfoveal choroidal neovascularization (CNV) due to AMD
Exclusion Criteria:
Any of the following underlying diseases including:
Diabetes mellitus
History or evidence of severe cardiac disease (e.g., NYHA Functional Class III or IV - see Appendix 19.6), history or clinical evidence of unstable angina, acute coronary syndrome, myocardial infarction or coronary artery revascularization within 6 months, or ventricular tachyarrhythmias requiring ongoing treatment.
Clinically significant impaired renal or hepatic function.
Stroke (within 12 months of trial entry).
Any major surgical procedure within one month of trial entry.
Known serious allergies to the fluorescein dye used in angiography (mild allergy amenable to treatment is allowable), to the components of the ranibizumab (Lucentis) formulation, or to the components of the E10030 formulation
Bottom line is they didn't accrue occult patients in phase 2. Why would anyone care if the imaging info wouldn't be available? Imaging wasn't thee primary endpoint visual acuity was.
David Guyer is great at making excuses. I asked him a simple question at a conference once. I asked him why he did not enroll diabetics into his trial? At least 20 percent of wet AMD patients have diabetes. That is a big piece of the market to ignore. David Guyer's answer was that it is very rare for a patient with wet AMD to also have diabetic retinopathy. That wasn't my question.
there is nothing to argue about. the data will be out by the end of the month. I am glad I brought the company to the attention of the board. It allows them to do the due diligence on the company should they choose to do so.
Feuerstein and you believe it is a scam. That is fine, we will know shortly. looking at the data from the first 60 patients I feel good about its chances. Cowen released a nice report on Ohr today. They are somewhat biased because they banked the raise a few weeks ago, but they have a good reputation and probably would not have done the raise if they thought the drug was worthless.
Jason Slakter, one of the top retina specialists in the country, and the company CMO put 200 k of his own money into the deal. If he did not think it would work why would he do that knowing the data would be coming out a month later, and he would not be able to trade out of it.
You are a bright guy but you aren't right of all the time.
As per my previous post if no one cares about whether a patient has a classic or occult lesion why is ophthotech excluding occult patients from their trials?
When Ohr released their interim data I bought a lot of stock on the open market even though they were a former client. I still own all of those shares.
I do currently do some consulting for them but I am posting as a shareholder.
The proportion of patients with 3 lines of vision is the more important endpoint.
I know of Ophthotech having some vision improvement in a randomized trial vs lucentis. Are the other drugs you mention in placebo controlled trials or open label?
The definitions in my post are right from Ophthotech
It says that they are not including occult patients in their trials.
If they expect the drug to work why wouldn't they include those patients. Occult patients are 40 percent of wet amd market.
Squalamine didn't reduce the number of lucentis injections, but it increased visual accuity.
People do not realize that Ophthotech excludes occult patients from their trials. Opht only includes classic patients in their trials.
When you look at classic only patients squalamine outperformed fovista. We shall see if that is still the case later this month when the rest of the squalamine data is released
from page 82 of Ophthotech s1
The term “pure classic” applies if 100% of the patient’s abnormal new blood vessels are well defined or located above the RPE. The terms “predominantly classic” and “minimally classic” are sometimes used to indicate some classic component of the disease, such as when only a portion of the patient’s abnormal new blood vessels are well defined or located above the RPE. The term “pure occult” applies if none of the patient’s abnormal new blood vessels are well defined or located above the RPE. Based on enrollment of untreated wet AMD patients in third-party clinical trials, the pure occult subtype accounts for approximately 40% of the cases of subfoveal wet AMD in the wet AMD patient population. Some occult choroidal neovascularization is present in predominantly classic and minimally classic choroidal neovascularization. For example, in minimally classic choroidal neovascularization up to 99% of the blood vessels may be characterized as occult, thus only 1% different from 100% or pure occult.
Ohr's data includes occult and diabetic patients
from page 88 of the Ophthotech s1
We made no meaningful changes to the inclusion and exclusion criteria in our Phase 2b clinical trial from those we used in our Phase 1 clinical trial. As in our Phase 1 clinical trial, We believed that data regard we did not enroll patients with pure occult choroidal neovascularization because it would be difficult to adequately observe and measure the changes in the choroidal neovascular morphology using routine imaging techniques in patients without any classic component to their choroidal neovascularization.ing neovascular regression would be useful in assessing the effects of Fovista in combination with Lucentis and in supporting the proposed mechanism of action for Fovista.
GS Conference Call (in 30 mins): Takeaways from Annual Macula Society Meeting
The analyst was asking about protocol T and then the Novartis drug rth258
Towards the end the Dr. Nguyen mentioned that the Squalamine data was very interesting. I have sent you the coordinates of the call. If you would like to discuss Squalamine with Ohr Pharmaceutical or myself, please do not hesitate to call.
The balance of the phase 2 data will be out by the end of March.
: Lau, Irene [mailto:Irene.Z.Lau@gs.com] On Behalf Of Flynn, Terence
Sent: Friday, February 27, 2015 12:02 PM
Subject: GS Conference Call (in 30 mins): Takeaways from Annual Macula Society Meeting - TODAY 12:30pm ET
Goldman Sachs Global Investment Research
Goldman Sachs Conference Call
Takeaways from Annual Macula Society Meeting
Quan Dong Nguyen, MD, Msc, Professor and Chair of Ophthalmology at University of Nebraska
Hosted by:
Terence Flynn
GS Biotechnology Analyst
Friday, February 27, 2015
12:30PM ET
Dial-in information:
US (Toll-Free): 1-877-208-2954
International: 1-973-528-0056
Conference Entry Code: 704999
Replay information:
US (Toll-Free): 1-800-332-6854
International: 1- 973-528-0005
Code: 704999
**Replay will be available for two weeks**
Discussion will include Protocol-T Phase 3 data evaluating Eylea vs. Lucentis vs. Avastin in DME, and NVS’ RTH-258 Ph2 wet AMD data
Potential names to be discussed include REGN, NVS, ROG.VX.
Cowen, Ohr Pharmaceutical Equity Research Initiating Coverage
LINK TO FULL REPORT & DISCLOSURES
https://cowen.bluematrix.com/sellside/EmailDocViewer?encrypt=95f9f06d-c9a7-4b4f-9868-e2399d7e86e2&mime=pdf&co=cowen&id=world-cowen-morningnotesdistribution@cowen.com&source=mail
Pharmaceuticals/Specialty
Ohr Pharmaceutical
Equity Research
Initiating Coverage
March 2, 2015
Price: $7.69 (02/27/2015)
Price Target: $25.00
OUTPERFORM (1)
Initiation: OHR-102 Success In Wet AMD Likely To Create Tremendous Value
Tyler Van Buren, M.Sc.
646.562.1338
tyler.vanburen@cowen.com
Ken Cacciatore
646.562.1305
ken.cacciatore@cowen.com
Sal Rais, M.D.
646.562.1420
sal.rais@cowen.com
The Cowen Insight
We are initiating on Ohr with an Outperform and $25 PT. Our rating is predicated on the potential for OHR-102 to be successfully developed in wet AMD. If it has a competitive efficacy profile and is ultimately approved, our consultants suggest that the vast majority of treated wet AMD patients will be on OHR-102 therapy as it has a superior product profile relative to other development candidates.
OHR-102 Could Become The First Eye Drop For The Treatment Of Wet AMD
The Company’s lead program is OHR-102, which is a first-in-class anti-angiogenic compound that inhibits growth factors VEGF, PDGF, and bFGF, and is being developed as a combination therapy with anti-VEGFs for wet AMD. OHR-102 is currently in a Phase II clinical development program, which has already reported positive interim visual acuity data, and final data is expected to readout by mid-to-late March. If the final data are positive – which we and our consultants believe has a good probability of occurring – Ohr plans to move OHR-102 into Phase III clinical trials in Q2:2015. Ultimately, our consultants suggest that the vast majority of treated AMD patients will want better visual acuity and therefore go on PDGF treatment.
Consultants Believe Early Visual Acuity Data Are “Surprising†And “Intriguingâ€
The ongoing Phase II IMPACT study has enrolled 142 patients and is designed to measure the impact of twice-daily OHR-102 on visual acuity in combination with PRN Lucentis injections versus placebo drops plus PRN Lucentis. At interim (n=62), the mean change in visual acuity at the end of 9 months for OHR-102 eye drops plus Lucentis PRN was +10.4 letters versus +6.3 letters for placebo plus Lucentis PRN – a mean +4.1 letter improvement in visual acuity (p=0.18). Additionally, 48.3% of OHR-102-treated patients showed BCVA gains of >3 lines (Phase III primary endpoint confirmed with the FDA) compared with 21.2% in the placebo arm, which was statistically significant (p=0.025). This result simply needs to be repeated to be successful. Overall, our consultants suggest that the visual acuity results “look very much like Ophthotech's†and “the curves and outcomes look remarkably similar.â€
A Risk/Reward Play Skewed Towards The Upside
We assume a potential US OHR-102 approval and launch in early 2019 with a peak penetration of treated wet AMD patients eligible for anti-PDGF treatment just above 35% by year 7, which assumes other PDGF competition. This results in a peak US sales potential of $1B+. Ex-US, we assume an early 2020 launch and an ultimate peak penetration of 25% by year 6-7 factoring in other PDGF competition. This results in a peak Ex-US sales potential of $750MM+. Providing a necessary high discount rate given the still early stage of development to these estimates yields an equity value of $800MM+ or $25 per fully-diluted share, which is the basis of our price target. If the final Phase II data are successful, our discount rate would correspondingly decrease resulting in a higher equity value. Worth noting, our valuation does not give any credit to OHR-102’s follow-on indications of RVO, PVR, and DME, or the Alcon-partnered sustained-release programs.
www.cowen.com
Please see addendum of this report for important disclosures.
Topical AMD Therapy: Will it Make a Splash?..
The new squalamine looks to improve outcomes—and could potentially expand the OD's role.
http://www.reviewofoptometry.com/content/c/52937/
By Robert Murphy, Contributing Writer
2/15/2015
The vision loss that may accompany wet age-related macular degeneration is vexing not only owing to the toll it exacts on the patient’s quality of life but also because the disease often resists an eye doctor’s best efforts to prevent such an outcome. This is tremendously frustrating to any clinician who manages these patients. While the concern of eye doctors is to act in their patients’ best interests, outcomes may not always match intentions. Clinicians are then left to accept a rather dismal course of events, with patients undergoing chronic therapy and not necessarily showing notable improvement.
With the introduction of the injectable anti-vascular endothelial growth factor (VEGF) agent Avastin (bevacizumab, Genentech) in 2004 as an ingenious off-label use and then the FDA approval of Lucentis (ranibizumab, Genentech) in 2006, doctors finally had treatments with which to arrest the advance of macular degeneration in some patients, and to improve vision to by potentially as much as three lines of Snellen acuity. The introduction of Eylea (aflibercept, Regeneron) in 2011 brought to the scene a third medication of this kind. Its duration of activity is said to be longer than that of its counterparts, thus perhaps allowing for greater intervals between injections, although clinical response can vary. “It seems to do a much better job of ‘drying’ the area, with less frequent injections,” says Paul M. Karpecki, OD.
“Currently, the best available treatment for wet AMD is intravitreal anti-VEGF, which has been a tremendous boon for a disease where there was previously little hope of vision stabilization, let alone any sort of recovery,” says Elyse L. Chaglasian, OD, an associate professor at the Illinois College of Optometry in Chicago.
In some patients with wet AMD, however, intravitreal anti-VEGF injections have resulted in little more than marginal visual improvement. Their limited clinical efficacy is not the only problem. The injections themselves may not be painful—retina specialists of course use topical lidocaine to numb the site—but no one looks forward to having a needle stuck in their eye. Returning for monthly or otherwise periodic injections is inconvenient not only for the patient but also in many cases for the caregiver who must drive the patient to the clinic. The cost to insurers, and by extension to society—the on-label drugs cost about $2,000 per injection—cannot be gainsaid. Fortunately, most patients can participate in copay assistance programs, often making the cost less than that of off-label options, says Dr. Karpecki.
All of which leaves eye doctors in something of a quandary. “The current system of inject, inject, inject is really not sustainable,” says Steven Ferrucci, OD, of the US Department of Veteran Affairs in North Hills, Calif., and a professor at the Southern California College of Optometry at Marshall B. Ketchum University in Los Angeles. “So, we have to find other ways—whether it’s longer-acting injections, or drops, or an oral agent that works as an adjunct to allow for fewer injections. I don’t know what the answer is, but we do need to do something.”
Anti-VEGF injections, while demonstrably beneficial, suffer from some fundamental drawbacks. A care protocol revolutionized a decade ago is already in need of another leap forward.
AMD Drug Delivery Developments
The unpleasantness and inconvenience of intravitreal injections in treating wet AMD, plus their high cost, put a premium on innovative ways to lengthen an anti-angiogenic medication’s activity through sustained release once it is injected. Alternatively, researchers are looking for effective ways to deliver a compound through topical means to complement, or perhaps one day supplant, intravitreal injections in these patients.
Exploring the topical route, researchers wish to develop means to penetrate the eye’s anatomical barriers so that an agent can arrive at the target tissue in adequately potent therapeutic concentrations. Using animal models, researchers at University College of London were able to create formulations of tiny nanoparticles loaded with Avastin to deliver significant topical concentrations of the drug to the macula. This is especially notable in that Avastin and Lucentis were thought to consist of molecules too large to penetrate the cornea as an eye drop.
Lucentis-maker Genentech has reported progress in using a device known as a port delivery system aimed at reducing the number of injections in wet AMD patients. The tiny capsule is implanted in the eye above the iris. In subsequent visits, the doctor can then refill the capsule with an anti-VEGF agent such as Lucentis. Early research showed that the delivery system can provide four months of therapy before the next refill.
Another new sustained-release drug-delivery device is under development at pSivida, whose Durasert technology is designed to deliver Avastin through an injection of a powdery, bioerodable and porous silicon capsule. The drug is released as the silicon erodes. The Durasert is also designed to treat diabetic macular edema, posterior uveitis and glaucoma.
Meantime, Ophthotech has completed a Phase II study of Fovista, an anti-platelet-derived growth factor (PDGF) agent designed for use with anti-VEGF drugs. The study found that patients treated with a combination of Fovista and Lucentis gained an average of 10.6 letters vs. 6.5 letters for those receiving Lucentis monotherapy. Phase III studies are underway.
Fovista prevents PDGF from binding to receptors on pericytes, the external cells of new blood vessels, thereby stripping off these cells. This leaves the endothelial cells unprotected and thus more readily vulnerable to the effects of anti-VEGF agents. This combined activity would enhance the treatment’s efficacy and thereby reduce the number of injections needed to bring about a desirable therapeutic effect.
This is why ongoing development of the topical anti-angiogenic agent squalamine lactate 0.2% (Ohr Pharmaceutical) is exciting to the eye doctors who follow its progress. The prospect of an eye drop that patients may instill daily to inhibit neovascular growth in wet AMD and forestall the consequent vision loss is one eye doctors look to as a promising potential means to counteract the frustration that occurs with present treatment options.
Swimming With Sharks
Squalamine is a small-molecule anti-angiogenic aminosterol agent that inhibits multiple growth factors and pathways responsible for angiogenesis. These include not only VEGF, but also platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF). It binds to and “chaperones” the messenger protein calmodulin to prevent growth factor signaling.
Discovered in the tissues of the dogfish shark (Squalus acanthias), squalamine was found early on to have potent broad-spectrum antimicrobial activity, which may explain the predator’s hardy resistance to infection. Besides its use in wet AMD, squalamine is currently being investigated for the treatment of diabetic retinopathy.
Its numerous avenues of anti-angiogenic activity give reason to suspect that squalamine may yield clinically salutary effects in a synergistic mechanism with anti-VEGF injectable medications. “The drug addresses multiple endogenous protein growth factors of angiogenesis,” says Joseph J. Pizzimenti, OD, an attending optometric physician at the Nova Southeastern University College of Optometry in Ft. Lauderdale. “Attacking choroidal neovascularization from several pathways represents the best chance of minimizing vision loss.”
Which sounds good in theory, but how much of the topical drop actually reaches the target tissue in the posterior segment? There’s no way to know other than what might be inferred from clinical outcomes. But the molecule’s mechanism of drug delivery suggests it may achieve therapeutic levels.
Dr. Chaglasian charts the drop’s itinerary on its journey to the macula. Squalamine first enters the conjunctiva and anterior sclera, and begins penetrating the corneal epithelium. “A mucoadhesive agent increases corneal residence time so that the drug diffuses slowly to the posterior sclera, resulting in delivery of sustained concentrations of squalamine via retardation of loss of the drug through nasolacrimal duct drainage.” Viscosity-enhancing properties soothe the ocular surface, a penetration-enhancing agent allows for greater diffusion into the corneal epithelium and a stabilizing agent acts as an antioxidant and can thwart the chemical degradation of the formulation, she explains. “Buffering agents allow for the drug to be at a near-neutral pH, compatible with ocular administration,” Dr. Chaglasian says. “The tonicity modifier in the formulation produces the appropriate osmolality of the ophthalmic formulation.”
Trials and Ministrations
Even the most glorious drug delivery mechanism is worth little if the drug being delivered arrives at its target with little to say for itself. The results from the recently completed Phase II FDA trials show visual improvement at nine months in wet AMD patients receiving a combination of Lucentis injections plus squalamine vs. monotherapy with just Lucentis.1
At left is an untreated endothelial cell. At right is a cell treated with squalamine—the drug binds to the messenger protein calmodulin to prevent growth factor signaling. Photo: Ohr Pharmaceutical
Ohr’s interim data show that 48.3% of those receiving the combination therapy had gains of three lines or more of best-corrected visual acuity on the ETDRS chart, vs. 21.2% treated solely with Lucentis. Not only that, those getting squalamine plus Lucentis were twice as likely to gain five or more lines of vision compared with the study’s monotherapy arm. Overall, patients treated with the combined topical/injectable regimen went home with a mean visual acuity gain of 10.4 letters compared with 6.3 for those treated only with Lucentis.1
The visual gains sometimes come swiftly. “One of the interesting things is that a lot of these patients recovered vision in the short term,” says Sherrol A. Reynolds, OD, associate professor at Nova Southeastern University College of Optometry. “The study was nine months, but some of them had improvement of their vision in four to eight weeks.”
While visual acuity is where the rubber hits the road, there was also improvement in physiological parameters. The combination treatment resulted in an average decrease of 139µm in central subfield thickness vs. 117µm in the monotherapy group. A series of cases reported last year were characterized by resolution of subretinal hyperreflective material as well as intraretinal and subretinal edema.2
This may look promising, but there’s a catch. Ohr’s primary endpoint in the study looked at the potential for reducing the number of injections needed to manage these patients optimally, and this didn’t happen. “The really disappointing fact is that it did not result in a decrease in the number of injections,” says Mark T. Dunbar, OD, director of optometry at the Bascom Palmer Eye Institute in Miami. “So, this is not a medication that can stand alone as monotherapy, or at least it would seem that way.”
Patients still receive the same amount of injections, albeit with some improvements in visual acuity because of the additional agent added to the regimen. “I’m not sure that it’s really significantly better,” Dr. Dunbar says, “but it is a little bit better in the eyes that received the combination.”
Phase III studies are set to begin sometime in the first half of this year. Here again the visual endpoints will be the same as those of Phase II, yet with a larger patient population.
Subretinal hyperreflective material is a marker for choroidal neovascular activity (images on right). Combination therapy with squalamine and ranibizumab resulted in the resolution of subretinal hyperreflective material as well as intraretinal and subretinal edema (images on left). The top images show a patient on combination therapy who had improvement of 21 letters of vision. A similar patient on the bottom improved by 26 letters. Photo: Ohr Pharmaceutical
“The FDA has agreed to a nine-month primary efficacy endpoint based on the proportion of patients achieving a greater than or equal to three-line gain in visual acuity,” Dr. Chaglasian says. “Considering that the nine-month data of the Phase II study showed twice the number of patients who received squalamine twice daily with ranibizumab as needed achieved this goal compared to those receiving ranibizumab monotherapy, this would appear to be a very achievable endpoint.”
Dr. Chaglasian describes the upcoming study’s design and timeline. During the first year of the study, she says, patients will be randomized to receive monthly ranibizumab injections with squalamine drops twice daily or monthly ranibizumab injections with placebo eye drops. During the second year, they will receive ranibizumab injections as needed plus squalamine or placebo drops. “Though it will be a two-year study, the FDA will look at the data at nine months,” she says. “Considering this drug was fast-tracked in 2012, there is a possibility it will be approved prior to 2017.”
Purview of Optometry?
The most fundamental benefit of a potentially efficacious topical treatment for wet AMD, which is also readily amenable to patient satisfaction and compliance, is of course improved visual outcomes. Meanwhile, what might the prospective FDA approval of topical squalamine mean for the role of optometrists in managing these patients?
Dr. Chaglasian is optimistic. “The approval of a topical eye drop for AMD would be groundbreaking,” she says. “Up until now, once an optometrist detected wet AMD, that patient was most likely lost to our practice. We will no longer need to refer every patient for painful, costly, frequent injections to a retinal specialist. Having the capability to prescribe a safe, effective drop for this disease is equivalent to what we already do for our glaucoma patients. This would be an absolute win-win for our patients and our profession.”
Maybe so, but we still must await the Phase III results and further clinical experience with topical squalamine in treating wet AMD to gain a fuller sense of its ultimate implications for the OD’s role in managing these patients. Time will tell.
“I think as it stands now, this is going to remain a disease in the hands of the retinal specialists,” Dr. Dunbar says. Patients will still be followed closely by the treating ophthalmologist, as they’ll continue to need intravitreal injections on a regular basis. “If you’ve got a good relationship with a retinal specialist and you’re following a treat-and-extend protocol, an ophthalmologist or treating retinal specialist may be comfortable having an optometrist follow that patient until they develop fluid, and then at that point you refer them back,” he says. “But I don’t see a situation where an optometrist is going to be following these patients alone only on a topical eye drop, unless they get to a point where they’re stable.” He says the data have not yet borne out that possibility. Should that eventually happen, perhaps the patient may remain under the abiding purview of the optometrist’s care.
That is, the optometrist’s role in managing patients with wet AMD extends beyond treatment to the kinds of things they already do, namely diagnosis, monitoring and patient education.
For instance, we know that the AREDS study found that the long-term use of the antioxidant carotenoids lutein and zeaxanthin may forestall to some degree the progression of macular degeneration in some patients. Optometrists may wish to encourage patients to take these as supplements as well as to embrace a diet rich in antioxidants, including certain fruits and vegetables, especially dark, leafy ones.
Initial diagnosis and ongoing monitoring of wet AMD patients will remain key roles for optometrists. The use of spectral-domain ocular coherence tomography (SD-OCT) is a critical tool in doing so.
“You still need to closely monitor and educate patients, so they understand when there are changes in their vision,” Dr. Reynolds says. Instruct patients to regularly use the Amsler grid at home, for example.
‘It’s Getting Better All the Time’
Paul McCartney had reason for optimism when he wrote that lyric in 1967, and it’s not a stretch to say that optometrists have reason for, let’s say, measured optimism when contemplating potential advances in the management of wet AMD patients.
Topical squalamine may not represent the Holy Grail. Yet, its multi-pronged mechanism of anti-angiogenic activity coupled with its convenient and noninvasive delivery method suggest a potentially useful addition to the treatment of these patients, not to mention significant prospective cost savings in a global sense.
The potential impact on optometry may readily be inferred. “I would like to think that we could start prescribing the drop, and that would allow us to be more engaged with retinal specialists, and to follow these patients and comanage them with retinal specialists more,” Dr. Ferrucci says.
If topical squalamine is shown to improve visual outcomes in treating AMD in a safe, effective and patient-friendly manner, patients may stand to benefit in a significant way. Optometrists likewise figure to expand their role in managing these patients. And not just to expand this role, but to enjoy the satisfaction of seeing their patients experience better outcomes. Talk about a win-win scenario.
Robert Murphy is a freelance medical writer in Watertown, NY.
1. Abraham P. Interim Phase 2 Results of Squalamine Lactate Ophthalmic Solution 0.2% (OHR -102) In Neovascular Age-Related Macular Degeneration. Paper presented at American Academy of Ophthalmology 2014 Retina Subspecialty Day, October 18; Chicago.
2. Ohrpharmaceutical.com. Press release: Ohr Pharmaceutical Announces Additional Squalamine Eye Drop (OHR-102) Phase II Clinical Data in Wet-AMD; The IMPACT Study. August 13, 2014.
If are excited about liquid biopsy take a look at Trovagene, you get a larger sample in urine
The company you are looking at says they can detect.mutations in a couple of teaspoons. That sounds good but it is actually a negative. If you are monitoring a cancer patient looking for cancer mutations attempting to see 1 cancer mutation in a sample of 145,000 you wouldn't get a large enough sample to pick that one mutation in a sample of 2 teaspoons.
did you ever watch this analyst day webcast
Ohr Pharmaceutical, Inc. (NasdaqCM: OHRP), an ophthalmology research and development company, is hosting a Key Opinion Leader breakfast today, Friday, October 31, 2014, from 8:00 am-9:30 am Eastern Time in New York City. A live webcast and subsequent replay of the event will be available at http://lifesci.rampard.com/20141031 and will also be accessible through the Investors section of the Company’s website at www.ohrpharmaceutical.com.
Ohr hosted an analyst day last week. The data they presented is excellent. I know there are a lot of skeptics out there but this should be looked at with an open mind. The comparable in the market to look at is Ophthotech. This data is excellent compared to their's. If you listen to K. Bailey Freund one of the top retina docs in the country, the opht treatment may not be commercially viable.
The meeting will feature discussions by two retinal disease experts, K. Bailey Freund, MD, and Ohr’s Chief Medical Officer, Jason S. Slakter, MD.
Dr. Freund specializes in all retinal disorders and has been a principal investigator in several pivotal trials of novel treatments for retinal diseases, including macular degeneration, diabetic retinopathy, and retinal vascular and inflammatory diseases. He is a Clinical Associate Professor of Ophthalmology at the NYU School of Medicine and practices at New York Presbyterian Hospital, Manhattan Eye Ear & Throat Institute, and Vitreous-Retina-Macula Consultants of NY, the largest retina practice in the New York Metropolitan area.
Dr. Slakter, who currently serves as the Chief Medical Officer at Ohr, is an internationally recognized retinal and macular disease specialist and has played a major role in developing treatments for age-related macular degeneration, retinal vascular disease, diabetic retinopathy, and central serous chorioretinopathy. He is a Clinical Professor of Ophthalmology at NYU School of Medicine and practices at Vitreous-Retina-Macula Consultants of NY.
Ohr Pharmaceutical, Inc. (NasdaqCM: OHRP), an ophthalmology research and development company, is hosting a Key Opinion Leader breakfast today, Friday, October 31, 2014, from 8:00 am-9:30 am Eastern Time in New York City. A live webcast and subsequent replay of the event will be available at http://lifesci.rampard.com/20141031 and will also be accessible through the Investors section of the Company’s website at www.ohrpharmaceutical.com.
Ohr hosted an analyst day last week. The data they presented is excellent. I know there are a lot of skeptics out there but this should be looked at with an open mind. The comparable in the market to look at is Ophthotech. This data is excellent compared to their's. If you listen to K. Bailey Freund one of the top retina docs in the country, the opht treatment may not be commercially viable.
The meeting will feature discussions by two retinal disease experts, K. Bailey Freund, MD, and Ohr’s Chief Medical Officer, Jason S. Slakter, MD.
Dr. Freund specializes in all retinal disorders and has been a principal investigator in several pivotal trials of novel treatments for retinal diseases, including macular degeneration, diabetic retinopathy, and retinal vascular and inflammatory diseases. He is a Clinical Associate Professor of Ophthalmology at the NYU School of Medicine and practices at New York Presbyterian Hospital, Manhattan Eye Ear & Throat Institute, and Vitreous-Retina-Macula Consultants of NY, the largest retina practice in the New York Metropolitan area.
Dr. Slakter, who currently serves as the Chief Medical Officer at Ohr, is an internationally recognized retinal and macular disease specialist and has played a major role in developing treatments for age-related macular degeneration, retinal vascular disease, diabetic retinopathy, and central serous chorioretinopathy. He is a Clinical Professor of Ophthalmology at NYU School of Medicine and practices at Vitreous-Retina-Macula Consultants of NY.
I do not know about you but the idea of a muscle cramping drug gets my heart pumping
Christoph Westphal launches another biotech, with the help of some wealthy friends
By John Carroll Comment | Forward | Twitter | Facebook | LinkedIn
Christoph Westphal
Proving once again that Christoph Westphal has some of the best connections in the biotech industry, the controversial entrepreneur has pieced together a $40 million financing round for his new startup Flex Pharma. And he did it by tapping a long lineup of investors, including some high profile individuals in the Boston area.
Westphal assembled his brain trust for Boston-based Flex earlier in the year, which is pursuing new treatments for muscle cramps with the help of Harvard's Bruce Bean. Nobel Laureate Rod MacKinnon, a scientific co-founder, has helped supervise a study in healthy volunteers for its lead drug, which is aimed at stopping severe cramping caused by hyperactive nerves. Efficacy studies are now slated to get underway next year, with the financial support of former Apple CEO John Sculley, Alnylam CEO John Maraganore and a big cast of supporters.
Westphal's own Longwood Fund joined in with Bessemer Venture Partners, EcoR1 and Alexandria Equities, which developers facilities for biopharma companies, on the round. And the VIP list also included Bain Capital Managing Director (and Celtics co-owner) Stephen Pagliuca and Harvard professor Robert Kaplan.
Westphal had been CEO of Verastem ($VSTM) up until about a year ago, when he handed the reins over to president Robert Forrester. He is perhaps best known for launching Sirtris, which GlaxoSmithKline ($GSK) bought out for a whopping $720 million. The pharma giant then shut down the unit in 2013 after making little headway in the clinic, after generating a raucous controversy over the science involved. GSK then absorbed the R&D work into a larger research unit in Pennsylvania.
Westphal went on to run GSK's SR One venture group for a short stint and started up the Longwood Fund.
"Our early stage clinical studies have shown initial human efficacy related to muscle cramping in healthy volunteers," commented MacKinnon in a statement. "We are hopeful that we may be able to help individuals suffering from muscle cramps and other neuromuscular disorders."
- here's the release
Related Articles:
Biotech vet Westphal to exit CEO post of cancer drug developer Verastem
Banking on its R&D rep, Calithera looks to raise $80M in IPO
Westphal pulls off a rare stunt with $55M Verastem IPO
AbTech is a full-service environmental technologies and engineering firm dedicated to providing innovative solutions to communities, industry and governments addressing issues of water pollution and contamination. As the developer and manufacturer of Smart Sponge® and Smart Sponge Plus® technology, AbTech provides an effective, low cost solution that solidifies, separates and removes contaminants, including hydrocarbons, sediment and other foreign elements, found in stormwater, produced water and industrial waste water. Last year the company signed a 12 million dollar contract with Nassau County which should be over 80 percent complete this year. Abtech recently signed a contract to work with Corvias on a billion dollar project in Maryland. There are other projects in the pipeline.
Abtech can be viewed similarly to a biotech company with a drug for a large indication that has been going through clinical trials but has recently been approved and started the commercialization process. These projects will lead to other ones. Below are some videos and press releases discussing the product, science and opportunities.
Press conference held by Nassau County executive Edward Mangano discussing the contract to be installed by Abtech before the first frost.
http://www.ustream.tv/recorded/49788969
The Weather Channel reported a segment focused on the high rains on Long Island, NY and highlighted AbTech and its Smart Sponge(R). Please note the link below Smart Sponge to the Rescue
http://www.weather.com/video/smart-sponge-to-the-rescue-52368?cm_ven=Email&cm_cat=vide o_share
Robert Kennedy Jr. discussing the Abtech technology
Bloomberg
There was a Washington Post article about how the US govt is worried about terrorist groups like Boka Haram weaponizing Ebola.
I hope every terrorist tries to weaponize Ebola. They would all die in the process and leave the rest of us alone
The activity likely came mainly from CD20. Rituxan based combo showed Germinal center B cell-like (GCB) subtype of DLBCL has a significantly better clinical outcome than those with non-germinal center B cell-like (non-GCB) subtype.
of course the people in this trial had failed rituxan
Thanks. Where did you get this info?
The internet is a wonderful thing, you can get this information while sitting in your basement, in your underwear.
I was actually upstairs.
it doesn't matter what the prevalence is.
once it is on the market it would be used elsewhere. Especially if they price the combo for about the same price as the other orals cost by themselves.
It doesn't appear that ibruvica is active against the GCB subtype.
this could be a way to get an accelerated approval of breakthrought therapy for our little combination.
•Patients with the ABC subtype showed a preferential response to ibrutinib monotherapy compared to those with the GCB subtype (ORR = 41% vs 5%, respectively, p=0.007, Fisher's exact test).
•Median overall survival (OS) was 9.7 months for the ABC subtype, compared to 3.35 months for the GCB subtype.
•Safety data from 70 patients identified no new safety signals. Grade 3 or higher AEs were seen in greater than 3% of patients and included fatigue (9%), hyponatremia (9%), pneumonia (7%), dehydration (4%), and pleural effusion (4%).
Dr. Younes: One can consider the same agents [outlined above, as they are] also showing some activity in diffuse large B-cell lymphomas. Ibrutinib preferentially has activity in the non-GCB—[or] non–germinal center type—mainly the ABC subtype or the activated B-cell lymphoma subtype of diffuse large B-cell lymphoma.12
The PI3 kinase inhibitors as a class have not shown much activity in diffuse large B-cell lymphoma.3 Somehow, if you treat with mTOR inhibitors, which is [targeting] downstream of the PI3 kinase, there seem to be higher response rates compared with PI3 kinase inhibitors. So, for example, with everolimus or temsirolimus, one can achieve a 30% response rate range,13-16 compared with a less than 10% response rate for the PI3 kinase inhibitors. But this is a pathway of interest that is frequently activated in diffuse large B-cell lymphoma, and I think we'll see more trials targeting this pathway in the future.
In diffuse large B-cell lymphoma, there are data to suggest that lenalidomide has preferential activity also in the ABC subtype.17-20 And based on these data, there are two trials combining lenalidomide with R-CHOP concurrently or giving lenalidomide in maintenance or adjuvant setting after R-CHOP chemotherapy. Those trials are ongoing, and hopefully we'll get some information, again, in the next few years from now.
Narrator: Currently available data from the trials integrating lenalidomide in the R-CHOP regimen have shown an acceptable toxicity profile. The two-year overall survival was greater than 90%, and the two-year progression-free survival rate was 75% to 80%.19 A retrospective analysis also indicated that most of the benefit from adding lenalidomide to R-CHOP was limited to the patients with a non-GCB phenotype.20
have you looked at trov
Trovagene, Inc. (TROV - $3.41)
Buy
Target Price: $10.00
Ur'ine for improved oncology testing
Summary:
We are initiating coverage of Trovagene, Inc., an emerging molecular diagnostics company developing urine-based tests used for the detection and monitoring of diseases, with a Buy recommendation and a 12-month target price of $10.
Details:
We estimate that TROV penetrates 4% of the U.S. metastatic cancer market in 2018. There are an estimated 15.6M people in the U.S. with cancer, 1.7M new cases each year, and almost 600K annual deaths, a proxy for metastatic cancer. TROV has already introduced two LDTs (KRAS and BRAF V600), and it anticipates introducing eight more over the next two years. These assays target five different cancers that represent 50% of the metastatic cancer opportunity. Assuming that TROV successfully launches all of these multiplexed oncogene mutation assays, we estimate that the company could generate volume of 94,218 tests, or 4% of the total U.S. metastatic cancer market opportunity. Further upside could be provided by the penetration of the 15.6M people living with cancer in the U.S. (recurrence monitoring), as well as penetration of the global market (32.5M people living with cancer, 14.1M new cases each year, and 8.2M annual deaths).
Urine-based technology differentiates TROV's approach to molecular diagnostics. Urine can be collected at home (or in a hospital, physician's office, or clinic) in large volumes and at relatively low costs. These benefits enable more frequent, non-invasive monitoring of oncogene mutation status, disease progression, and disease recurrence. Other monitoring modalities (imaging, tissue biopsy, or blood-based tests) require medical professional collection, lack sensitivity, require invasive procedures, and/or involve expensive analyses.
Strong collaborations. In addition to introducing new assays, TROV is focused on building its body of clinical evidence in the near term in order to drive long-term clinical uptake and reimbursement. To do that, the company has been signing collaboration agreements with leading cancer centers, including MD Anderson Cancer Center, USC Norris Cancer Center, and Memorial Sloan-Kettering, as well as pharmaceutical collaborations. These partnerships should provide TROV with numerous publications and posters over the next couple of years. Moreover, we anticipate that TROV will announce additional collaborations as more organizations become aware of the benefits of the company's urine-based testing technology.
Recent pullback is a buying opportunity. Shares are trading near a 52-week low, down ~70% from a high of $10.27. In addition to trading down along with other high-growth healthcare stocks, shares are down due to a more conservative revenue outlook as assay launches and commercialization plans have been delayed, largely due to the company's platform transition to next generation sequencing (NGS), from droplet digital PCR. We expect the company's BRAF V600 assay to shift over to NGS and for future assay introductions to also be developed on NGS. We are confident in our outlook and believe that now is an attractive entry point, ahead of near- and medium-term catalysts.
Compelling valuation. Shares of TROV currently trade at 2017 and 2018 EV/revenue multiples of 1.1x and 0.6x, compared to peer average 2014 and 2015 EV/revenue multiples of 26x and 6.1x. Our 12-month target price of $10 is based on TROV trading at an EV/revenue multiple of 5.0x our 2018 revenue outlook and discounted back to 2015, which we believe is warranted given the global market opportunity and potential penetration rate of urine-based diagnostic tests.
Please click here for full report.
Bryan Brokmeier, CFA
Life Sciences Tools & Diagnostics
O: (212) 895-3845
E: bbrokmeier@maximgrp.com
https://maxim.bluematrix.com/sellside/EmailDocViewer?encrypt=5e3b70b7-ced8-4f0e-9d35-4b585b14a616&mime=pdf&co=maxim&id=tklein@maximgrp.com&source=mail
TGTX it should also be synergistic with their pi3k inhibitor
but it shouldn't have caused the upward move the stock had in the morning.
It clearly has some momentum behind it.
Squalamine's data is pretty good.
Patients receiving squalamine were also more than twice as likely to gain =4 and =5 lines of vision compared with placebo patients (=4 lines p=0.022, =5 lines p=0.059). It is important to note
that VA gains with placebo plus Lucentis PRN were consistent with those previously observed in other Lucentis monotherapy trials. Squalamine was well tolerated, with a comparable safety profile to placebo. We believe that squalamine's ability to improve VA in back of the eye disease may be due to its inhibition of
multiple angiogenic growth factors.
at least as good at opthotech's data
The VA results achieved with squalamine would at first glance appear comparable to the Phase 2b results with Fovista, but are actually better, in our view. In a Phase 2b trial with Fovista, patients receiving Fovista plus Lucentis gained 10.6
letters at week 24, versus 6.5 letters for patients taking placebo plus Lucentis (p=0.019), representing a 62% additional benefit. However, we note that the Lucentis control arm in the squalamine Phase 2 trial performed as expected, whereas the control arm in the Fovista Phase 2 trial underperformed historical
Lucentis monotherapy. By contrast to the Phase 2b Fovista trial, we note that the Ohr trial needed less than monthly Lucentis injections (2/3 fewer shots than Fovista/Lucentis dual therapy) to achieve the VA gains seen with Fovista combination therapy. The Fovista trial also enrolled only patients with classic lesions, whereas the squalamine trial enrolled a broader, more representative range of patients. With Fovista, a patient must receive an anti-VEGF injection, go back to the waiting room for at least 30 minutes, and then can receive Fovista, due to the intraocular pressure risk of injecting too much fluid from 2 injections into the eye over a shorter time period
Regeneron Pharmaceuticals, Inc. (NASDAQ:REGN; USD 280.22)
Why good Phase II squalamine data does not have to be bad for Eylea
FIRST GLANCE | COMMENT
June 23, 2014
RBC Capital Markets, LLC
Adnan Butt (Analyst) (415) 633-8588
John Chung (Associate)
Rating: Outperform
Phase II data for squalamine eye drops in wet AMD expected on 6/23 @ at 8:30 AM on OHRP call.
Interim Phase II data from OHRP’s squalamine in wet AMD are expected on June 23rd. While favorable results could be a significant positive for OHRP, as they could show a reduction in anti-VEGF injection frequency, they are not necessarily a negative for Eylea. Retina specialists agree that the ideal regimen would deliver anti-VEGF monthly or at least more frequently than the real world currently allows. In our view, if successful, chances of squalamine being used as an adjunct are higher than it replacing intravitreal injections altogether in wet AMD, RVO and/ or DME. OHRP is holding a call on June 23rd at 8:30 AM eastern to discuss interim results from its Phase II study.
Squalamine is a small-molecule eye drop that blocks VEGF, PDGF, and bFGF in Phase II for wet AMD. The Phase II trial enrolled 120 newly diagnosed wet AMD patients who received Lucentis on day 1 and were then randomized to placebo or squalamine drops twice per day. The primary efficacy endpoint is mean number of Lucentis injections while secondary endpoints are mean time to Lucentis retreatment and VA gains. Final data are expected by YE:14.
We envision four outcomes, three of which would not impact intravitreal anti-VEGF usage; however, some of them could still be beneficial for OHRP.
Reduction in injection frequency and improvement in vision – Eylea possibly impacted. This is the only scenario under which intravitreal anti-VEGF use could be impacted as it could show that squalamine has the potential to work by itself.
Reduction in injection frequency; no change in vision – Eylea not impacted or minimally impacted. There is a big difference between ‘on label’ and ‘real world’ injection frequency. Therefore, even if squalamine succeeds in increasing injection intervals it may not impact actual anti-VEGF injection usage unless it extends the period by more than 3- 4+ months.
No reduction in injection frequency but an improvement in vision – Eylea not impacted. Under this scenario anti-VEGF usage would not be impacted though squalamine could likely progress to Phase IIIs to evaluate adjunct use if final Phase II data are positive.
No reduction in injection frequency and no improvement in vision – Eylea not impacted. Since there are interim data final results could still matter for OHRP.
OHRP conference call on 6/23 at 8:30 AM eastern to discuss interim results. US: 1-877-407-0789; International: 201-689-8562.
theranos cover story at fortune magazine
she could star in the next Stepford wives movie
http://fortune.com/video/2014/06/19/take-the-blood-leave-the-pain/
the article..
http://fortune.com/2014/06/12/theranos-blood-holmes/
Trovagene looks like it could be a big winner over then next 2 or 3 years if the oncogenes mutation tests can be vaiidated in urine. They have the IP locked up.
http://seekingalpha.com/article/1956331-trovagene-is-developing-a-new-standard-of-care-to-manage-cancer-says-ceo
Trovagene Is Developing A New Standard Of Care To Manage Cancer, Says CEO
Jan. 21, 2014 7:04 AM ET | 13 comments | About: TrovaGene, Inc. (TROV)
The existence of cell free DNA and RNA in the human circulatory system has been known since the 1950s; however, intensive research in this area has been conducted for the last ten years. One of the companies that have been making progress in this area is Trovagene (TROV), a small-cap diagnostic company that has a unique technology platform, which is capable of analyzing systemic cell-free DNA and RNA isolated from urine. The company's proprietary technology has the potential to provide truly non-invasive diagnostic capabilities across various disease areas and health conditions, including cancer, infectious diseases, transplant medicine and prenatal diagnostics. However, Trovagene is primarily focused on developing a platform of diagnostic tests to monitor key mutations that drive cancer. The company's technology platform requires further validation, but based on early available data, there could be a significant market opportunity for Trovagene's technology longer-term.
This week, I have the pleasure of having Trovagene's CEO Dr. Antonius Schuh speak on his company and his expectations for the future. Dr. Schuh was named President and CEO of Trovagene in October 2011 and was simultaneously appointed to the firm's Board of Directors. Prior to joining Trovagene, Dr. Schuh served as Chairman of the Board and CEO of Sorrento Therapeutics (SRNE), a biopharmaceutical company based on a proprietary fully human antibody discovery platform. From April 2006 to September 2008, Dr. Schuh served as CEO of AviaraDx, a molecular diagnostic testing company focused on clinical applications in oncology. In 2008 He led the sale of the company to bioMerieux. From May 2000 to April 2006, Dr. Schuh served as CEO of Arcturus Bioscience and President and Chief Executive Officer of Sequenom (SQNM). Dr. Schuh is a certified pharmacist and earned his PhD in pharmaceutical chemistry from the University of Bonn, Germany.
Ben Yoffe: Dr. Schuh, how unique and potentially productive is Trovagene's cell-free molecular technology?
Dr. Schuh: Our uniqueness lies in our ability to utilize cell-free DNA in urine for diagnostic purposes in general and for cancer monitoring in particular; we are the only company using urine as a platform to develop multiple molecular diagnostic tests that can monitor cancer and the impact of treatment. We have pioneered the idea and refined the ability to detect rare genetic mutations in urine, which has only recently become commercially feasible due to the advances in molecular genetic technology (Digital PCR and Next Generation Sequencing).
In addition, our diagnostic tests are designed to monitor oncogene mutation levels in the urine of cancer patients to provide information useful for the selection of the most appropriate drugs and to determine the effectiveness of treatment. As a result, cancer therapy can be modified, if needed, to better treat the disease and improve an individual's treatment outcome. Additionally, if a treatment is not producing an effect, there is no need for the patient to be subjected to the therapy and its side effects. Using our technology, a clinician may find, in near real-time, that switching to a different treatment may be warranted, and importantly, the healthcare system only pays for those treatments that are benefiting the patient. In fact, new research is emerging that cancer patients should be treated based on the "actionable" mutation driving the cancer, rather than simply treating the cancer based on anatomical site (ex. breast, lung, colon cancers), which supports the use of our tests. Our diagnostics can eventually also enable cancer survivors to take a simple urine test once or twice annually to determine if their cancer has returned. Early detection of a recurring cancer can give patients a much greater chance of beating that cancer again, and living longer. This is true personalized medicine and we are focused on developing a new standard of care to manage cancer.
Yoffe: Could you tell us a little about the intellectual property portfolio that the company has built around its proprietary?
Dr. Schuh: Cell-free DNA (or cfDNA) in urine is comprised of very short genetic sequences. This demands specific extraction, purification and detection approaches. TROV is the technology leader in the detection of short cfDNA in urine and has controlling method IPs. Further, the company is building a portfolio of composition-of-matter IP around the specific assays that the company designs.
Yoffe: Trovagene has recently launched its cell-free BRAF oncogene diagnostic which is the first commercially-available urine-based cancer mutation monitoring test. Could you describe the commercial opportunity that exists around the launch?
Dr. Schuh: The value proposition at Trovagene is about a platform of urine-based molecular diagnostic tests to detect and monitor actionable mutations that drive the many types of cancer. As such, Trovagene's value proposition is not about one test and its sales ramp right out of the gate. Having said that, the launch of our BRAF mutation test is significant because now clinicians can begin to use this test to monitor the progress of treatment for BRAF-associated cancers like melanoma, demonstrating the value of our technology. Importantly, many new cancer therapies that target specific mutations are emerging, making our platform that much more valuable for the monitoring of such treatments and their effectiveness in the real world. Our solution fits with companies like Foundation Medical (FMI), which is tailoring treatment to individual cancer patients by utilizing clinical tests to evaluate mutational status at the biopsy stage and to determine appropriate cancer therapy. Our technology builds upon this approach with an ability to monitor qualitative and quantitative changes in mutations as therapy proceeds. The clinical and commercial opportunity is large, as demonstrated by the value the market is placing on shares of FMI. Meaningful revenues from our platform are expected to really begin next year as more of our urine-based oncogene tests are launched, physician awareness of our tests becomes more widespread, and appropriate reimbursement levels for our tests are in place. Our goals in 2014 are based around these three initiatives as well as entering into partnerships and collaborations to further validate the utility of our platform. In the near-term, we believe that value creation for Trovagene should be based on the launch of our tests, the adoption of our tests by major cancer centers under clinical collaborations, and additional strategic partnerships with pharmaceutical companies and larger life science or diagnostic companies that are expressing interest in the utility of our platform.
Yoffe: Are there other tests expected to be launched in the upcoming months?
Dr. Schuh: With the integration of next generation sequencing as a detection platform into our analytical process, we will expand coverage to a set of KRAS mutations in the near-future. Subsequent coverage extensions will include EGFR and PIK3CA mutations. An estimated 2.3 million Americans are actual cancer patients or cancer survivors who could benefit from monitoring their BRAF, KRAS, or PIK3CA-mutationstatus regularly. For the treatment of cancers associated with EGFR mutations, such as lung cancer, understanding the specific mutation status of EGFR, including mutations like T790, can significantly influence treatment choices. Given that lung cancer is the most common cancer in the world, detecting and monitoring for EGFR mutational status also can be a large opportunity.
Yoffe: Can you provide insight into your commercialization strategy?
Dr. Schuh: We continue to enter into collaborations with major cancer institutions and treatment centers to develop data on the clinical utility of our cell-free molecular diagnostic tests. We recently issued a press release on our collaboration with US Oncology, a subsidiary of McKesson (MCK). As additional data is presented at medical meetings, and doctors using our tests in clinical trials become familiar with the benefits of near real-time monitoring of cancer mutations, the broader medical community is expected to begin adopting our technology for use in practice. We are supporting these efforts by ensuring that physicians and patients are not denied access to our tests due to early reimbursement bottlenecks, which goes hand-in-hand with building the body of clinical evidence demonstrating the value of using our urine-based cancer monitoring tests to improve patient outcomes.
Yoffe: What are your plans with respect to reimbursement?
Dr. Schuh: Reimbursement for our novel tests is a top priority, as physician and patient access to our technology is key to widespread adoption of our products. To gain initial reimbursement, our qualitative tests will be billed and reimbursed under established Tier I codes for their respective mutation (i.e. BRAF, KRAS, EGFR, etc.). These are CPT codes from the American Medical Association (MoPath system), which should enable us to bill and obtain reimbursement for our tests without much issue. As we develop our tests and demonstrate novel clinical utility in cancer monitoring, supported by our high analytical sensitivity, quantitative performance over a large dynamic range, and clinical experience, then Trovagene will pursue a "Not Otherwise Classified" (NOC) code for billing and reimbursement. Under these conditions, premium pricing is expected. Over time, Trovagene will pursue a permanent CPT code for its cancer monitoring diagnostics once sufficient value is being assigned under the NOC code system. We will engage with 3rd party payors including integrated healthcare networks and Medicare for reimbursement of our tests, with the goals of obtaining strong adoption of our tests, positive coverage decisions, and appropriate valuation of our tests on a widespread basis over time. We believe the proper groundwork has to be laid in order to maximize the value of our test platform, and 2014 is about developing clinical evidence and interacting with payors for our initial diagnostics such that in 2015, we can gain real market traction.
Yoffe: How is the company funded, and for how long could the current funding carry it?
Dr. Schuh: Trovagene ended 3Q 2013 with $27.8 million in cash. We stated on our 3Q 2013 earnings call that "We are comfortable with our financial position, and our ability to create shareholder value". We have also stated that "We believe our current cash position will enable us to meet our operating needs through 2014". In the first three quarters of 2013, the company's cash burn averaged about $1.8 million per quarter, so based on that math, the company has an ample cash runway to execute on its business plan. As Trovagene develops additional tests and commercializes them, the use of cash is expected to rise. However, we also have potential to raise non-dilutive capital should we enter into partnerships with other diagnostic and pharmaceutical companies seeking to leverage our technology.
Yoffe: In closing, could you please summarize the key events that could maximize shareholder value in the next 12 months?
Dr. Schuh: We expect the following key events and milestones to occur over the next 12 months, which should maximize shareholder value in both the near-term and long-term:
•Additional partnerships with larger molecular diagnostic (or life science) companies and pharmaceutical companies
•Additional clinical collaborations with major academic centers and institutions
•Additional diagnostic test launches including those targeting KRAS, EGFR, and PIK3CA mutations
•Announcements of clinical data supporting the utility of our cancer monitoring tests
•Presentations and/or peer-reviewed publications of such clinical data at key medical conferences and/or medical journals, respectively.
•Monetizing value from non-core applications of our platform in other diseases or conditions via out-licensing opportunities (HPV, prenatal genetics, transplant monitoring).
Conclusion:
TROV is targeting launch of the transrenal cell-free (CF) KRAS mutation assay in its CLIA lab and signing on additional clinical study partnerships with leading oncology centers and pharmaceutical and biotech companies by year-end. Based on early available data, there could be a significant market opportunity for Trovagene's technology longer-term, which could represent significant upside for shareholders.
Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.
TGTX from Roth Capital
TG announced updated monotherapy data at ASCO this weekend for both TG-1101 and TGR-1202 in advanced hematological malignancies. Discussing both data sets with KOLs, an underlying theme is not only the strong efficacy results, but also the level of safety shown to date, which should make combination therapy an easy next move. TG-1101 data in 30 patients showed both strong response rates and safety in multiple lymphoma types. Recall that patients in this study saw 2 or more prior Rituxan regimens and were relapsed/refractory (43% of patients were refractory to Rituxan). Across the different lymphoma types there was 30% PR and 13% CRs. The CLL patient group showed greater efficacy, showing 67% PR rate. In the TGR-1202 study, once per day dosing as well as favorable safety profile bolstered strong efficacy data as well. Marked efficacy was seen in relapsed/refractory CLL patients showing a 78% nodal response at doses 800 mg or higher (median time on study 6+ months).
Impact
We are impressed with the data and we received the same question from investors; "Did you expect the data to be this good?". The KOLs running the studies are strongly behind these clinical data, especially the safety profiles, which make the therapies amenable to combination therapy. We believe TG has delivered solid proof of concept data for both drugs. We now look to two key upcoming catalysts. Of particular note, we look forward to seeing the data from the potential "match made in heaven" combination studies; 1) '1101 + Imbruvica in advanced B-cell tumors and 2) '1101 + '1202 in advanced B-cell tumor shortly. Second, one or both of these drugs is expected to enter pivotal studies by the end of 2014.
ARQL
I agree with your comments. We do not know what we do not know but based on previous data the drug appears to work
I was at the credit suisse conference. They had an oncologist expert speaking about lung cancer drugs in general. The analyst never asked about Tivantinib so it didn't come up.
When he left I stopped him in the lobby and asked him about it and what he thought based on the metmab failure.
He said they took metmab through phase 3 based on a phase 2 trial with a lot of holes in it but he thought tivantinib should be further explored and has value
That is more comforting to me than the market or the ihub board.
caravan
The phase 2 trial that Roche ran with met mab had some really strange data. It had a very small N and it is hard to believe that they conducted a large phase 3 trial based on the data from phase 2
TGTX ($4.84, -10%) still selling off. Comments?
IF you listened to the Infinity webcast at the DB conference the analyst was focused on combo studies and the fact that infi doesn't own a second drug to go along with their PI3K inhibitor.
the reason I find that interesting is because the only company working in the space that owns a combo is TGTX.
pcyc, gilead, roche and abbott, do not have a combo.
Momenta Pharmaceuticals (MNTA) entered a $75M common stock ATM sales agreement with Stifel Nicolaus.
Cytokinetics Announces Top-Line Results From BENEFIT-ALS
This stock was on a tear recently
Company Summarizes Initial Data From Phase IIb Clinical Trial of Tirasemtiv; No Effect on Primary Efficacy Endpoint; Mixed Effects on Secondary Endpoints
South San Francisco, CA - April 25, 2014
Cytokinetics, Incorporated (Nasdaq: CYTK) announced today the top-line results of BENEFIT-ALS (Blinded Evaluation of Neuromuscular Effects and Functional Improvement with Tirasemtiv in ALS). Detailed results will be presented during the 66th Annual Meeting of the American Academy of Neurology (AAN) on Tuesday, April 29th at the Pennsylvania Convention Center in Philadelphia, PA.
BENEFIT-ALS did not achieve its primary efficacy endpoint, the mean change from baseline in the ALS Functional Rating Scale in its revised form (ALSFRS-R) on tirasemtiv versus placebo (-2.98 points in the tirasemtiv group versus -2.40 points in the placebo group, p = 0.11). Secondary efficacy analyses of the effect of tirasemtiv on respiratory function and other measures of skeletal muscle function produced mixed results.
"Patients with ALS desperately need new therapeutic alternatives to slow the course of their disease and loss of function. We stand with the ALS community in our disappointment that BENEFIT-ALS did not achieve its primary efficacy endpoint," stated Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. "The results from BENEFIT-ALS are just now becoming available to our team at Cytokinetics and will be shared in more detail with the broader scientific and medical community focused to research in ALS in the next few days. Understanding these results will require significant further review. Once we have fully evaluated the data from BENEFIT-ALS, we expect to determine whether there is a potential development path forward for tirasemtiv for the potential treatment of ALS and what may be the appropriate next steps."