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By Dr Tomislav Meštrović, MD, PhD
Regardless of their origin and family, viruses have evolved elegant strategies to reach and enter specific target cells where they seize the cellular machinery to express viral genes and assemble progeny particles. In the same way, viral vectors represent the most effective means of gene transfer to modify specific cell type or tissue, and can be manipulated to express therapeutic genes.
Viral vectors are usually derived from parental wild type viruses whose viral genes (essential for replication and virulence) have been replaced with the heterologous genes intended for cell manipulation. They can be used as in vitro tools for biomolecular and gene functional studies, but also to accomplish more demanding tasks such as treat genetic disorders, fight cancer, drive tissue regeneration and monitor cell function.
In vitro and clinical use of viral vectors is based on RNA and DNA viruses that differ in their genomic structures and host range. Specific viruses have been picked as gene delivery vehicles according to their capacity to carry foreign genes, as well as their ability to conveniently deliver genes that are linked to efficient gene expression.
Each viral vector system is characterized by an inherent set of properties that affect its suitability for gene therapy or other specific applications. To generate a vector, coding genes and so-called cis-acting regulatory sequences must be separated into distinct nucleic acid molecules in order to prevent their reconstitution and formation of productive viral particles.
Like all replication-incompetent vectors and viruses, viral particles can only be constructed if missing functions are superseded. This can be in a form of a helper virus, but a single helper plasmid encoding for a full-length defective helper virus genome can also be utilized.
Selection of the best-suited vector is pivotal and requires focused in-depth knowledge of the delivery systems and their performances. There is no one-fits-all multipurpose viral vector appropriate for all demands; rather, each of the vectors has its own advantages, limitations and range of applications.
Five classes of viral vector can be categorized in two principal groups, according to whether their genomes integrate into host cellular chromatin (lentiviruses and oncoretroviruses) or persist in the cell nucleus predominantly as extrachromosomal episomes (adenoviruses, adeno-associated viruses and herpes viruses).
Aforementioned distinction is an important determinant of the suitability of each vector for particular applications. In short, non-integrating vectors can facilitate persistent transgene expression in cells that do not proliferate, whereas integrating vectors represent a right choice if there is a need for stable genetic alteration in dividing cells.
One of the first barriers that viral vectors have to bypass in the human organism is the immune response. Problems that may arise with gene transfer vectors include acute toxicity from the introduction of foreign materials, cellular and humoral immune responses directed against the transduced cells and products, as well as the potential for insertional mutagenesis by certain integrating vectors.
Furthermore, human trials have thus far used vectors that integrate into a relatively small percentage of cells within a target tissue. As more efficient vectors will target more cells, there is a possibility of inadvertent transmission into stem cells that capable of clonal growth and self-renewal, which subsequently raises important safety and ethical issues.
In conclusion, there is still a tremendous amount of work to be done in viral vector research. Continuous identification of potential hurdles and maintenance of a strong focus to improve vector systems will improve the promise gene therapy holds in treating a myriad of different diseases.
Last Updated: Oct 27, 2015
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subset: commoncrawl


text:
It sure wasn't in the field service regulations, and they sure as hell didn't teach it when I
was at Leavenworth [Command and General Staff College], and I didn't like it." This was
the second phase of the Fifth Chinese Offensive. The battle to hold Morae Kogae Pass
began on the night of 16 May 1951 and lasted all night (part of the larger battle of the
Soyang River, 16-21 May). The Marine slew 112 Chinese and captured 82 in the fight.
The enemy had been mowed down in droves.8 (See Map # 10)
General Thomas had disliked having one regiment out of mutual reinforcement
distance from the rest and took the opportunity of this attack to pull the 7th Marines back
to the No Name Line with the rest of the division. Then X Corps had the division shift
some of its units east to relieve the 9th Infantry, USA, part of the 2nd Infantry Division,
and south to strengthen the Marines' defensive posture. Thus the division had curved its
right flank towards the south above Hongchon. The division held here, and on 20 May, a
single battalion of the 5th Marines blistered a probe by CCF with its supporting arms,
resulting in 170 enemy dead. "The withdrawal and our rapid movement there had given
me confidence in what the division could do. It revealed the division, as I said a while
ago, as a real pro outfit. I doubt if there was a better outfit ever walked than the 1st
Marine Division on the 24th of April, 1951."9
IX Corps, to the left of X Corps on the line, received orders to mount a
counteroffensive while X Corps held steady, and the Marines were charged with
* Thomas said of the concept when asked his opinion of it in an interview: "Phony as a three dollar bill. It
is an invitation to disaster. The Army lost a lot of people in Korea because it got a lot of small units
scattered and isolated - failed to concentrate. A Marine infantry regiment could cut its way out of any
encirclement; a Marine battalion would be safe, even if encircled, provided other forces were ready to go
promptly to their relief." - Interview with Gerald C. Thomas by Col C. W. Harrison, no date, located in the
front of the Gerald C. Thomas Oral Memoir, page 2-3; Gerald C. Thomas Oral Memoir -- a leather bound
transcript of MajGen Tomas's "Career Interview," conducted by Benis M. Frank, 1966, (Washington Navy
Yard, U. S. Marine Corps Historical Center, Oral History Section): 742.
9 Ibid., 748.
Montandon, Joshua W. Battle for the Punchbowl: The U. S. 1st Marine Division 1951 Fall Offensive of the Korean War. Denton, Texas. UNT Digital Library. http://digital.library.unt.edu/ark:/67531/metadc3938/. Accessed January 23, 2017.


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text:
20 CFR 404.1295 - Commissioner's review—for wages paid prior to 1987.
Upon request by the State, the Commissioner will review the reconsidered determination (or the assessment, allowance or disallowance as initially issued if reconsideration is waived under § 404.1291). If necessary, the Commissioner may request the State to furnish additional evidence. Based upon the evidence considered in connection with the assessment, allowance or disallowance and any additional evidence submitted by the State or otherwise obtained by the Commissioner, the Commissioner affirms, modifies, or reverses the assessment, allowance or disallowance.
Title 20 published on 2015-04-01
The following are ALL rules, proposed rules, and notices (chronologically) published in the Federal Register relating to 20 CFR Part 404 after this date.


text:
"My fiancé bought me an Annello ring, but it was not a set. It has a square shape with a "lip" so we are having a hard time finding a band to fit. I dont want a band that has a cut out for the "lip", I'd prefer a diamond band. Would this band fit under the lip of the square on my engagement ring (17210853)? We tried rings on in a jewelry store today and I tried one that looks very similar to this and it fit perfect. It did not leave a space between the engagement ring and band, which is exactly what I want. I want them to be flush together with no specs....thanks"
Great ring just didn't fit with my current ring....
Annello by Kobelli 14k White Gold 1/4ct TDW Diamond Curved Wedding Band (G-H, I1-I2)by Annello
ITEM#: 14151651This prong-set round-cut diamond wedding band shimmers in 14-karat white gold in a highly polished finish.
White Diamonds
- Diamond cut: Round
- Diamonds: 11
- Weight: 1/4 carat
- Color: G-H
- Clarity: I1-I2
- Setting: Prong
- Metal: 14k white gold
- Finish: High polish
- Style: Contour
- Band: 2 mm wide
Diamond total weight: 1/4* carat TW
All weights and measurements are approximate and may vary slightly from the listed information. *T.W. (total weight) is approximate. 1/4 carat T.W. may be 0.22 to 0.28 carat. Treatment code N. See Click here for ring sizing guide for further information.
Click here for ring sizing guide
See Treatment Guide for further information.
Available in an array of extended sizes for the perfect fit.
|Diamond Color
|G-H, White
|Total Diamond Weight
|Up to .5 Carats
|Ring Style
|Diamond Cut
|Gold Karat
|Band Width
|2-3 mm
|Diamond Properties
|Natural Diamond
|Jewelry Setting
|Metal Color
|10, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5
|3.2 mm - 2 mm wide.
|Limited Lifetime Manufacturer Warranty
|Model Number
|Country of Origin
|United States
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Customer Reviews
Most Helpful
Don't waste your money!!
I just received this wedding band, and will be returning tomorrow. This image isnt clear enough to show you that there are not diamonds on all the top half. You have five diamonds in center, then it skips a space on each side, then diamonds continue. I had to look really hard to notice that this was actually how the ring is made, and its not missing these two diamonds. Also, inside and out, the ring is very rough around the edges, making it uncomfortable moving up and down your finger. I do not recommend this ring. I have purchased beautiful jewelry from overstock before, but this ring does not meet my expectations.Read More
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Beautiful Ring
Great ring just didn't fit with my current ring.Read More
I love this ring! Price was perfect and it gives off the most amazing sparkleRead More
Perfect fit
We purchased my engagement ring which was an estate piece, so knowing that when the time came about to say 'I do", we searched and searched for the perfect fit to go along side my engagement ring. I saw this on Overstock and kept looking at my ring and trying to judge if the slight curve was what would fit along side....and it's as if it was made for my ring all the way down to the tiny details, I was so amazed, it's perfect, almost as if it was a set and divided until I found it. I love this band!!!! Thank you Overstock!!Read More
Of course my fiancee' loved the ring. Because it was not compatible or fit with the already given engagement ring. It is beautiful and sparkles well.Read More
Questions & Answers
Hello Bolstak12/31, In order for the wedding set to show the least amount of gap, we recommend item#11747196 for engagement ring item#17210853. Any straight band will show a significant gap between the wedding set.
Thank you for your help!
Shopping Tips & Inspiration
Diamond Band Buying Guide
Traditional as wedding rings and popular as fine fashion jewelry, the diamond band is a ring you need in your jewelry wardrobe.
Shopping for the Modern Bride - Wedding Bands
Shopping for the Modern Bride: Wedding Bands from Overstock.com. Our guides provide customers with information about shopping for modern wedding bands.
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If you're giving the ultimate Christmas gift by taking the next step with the one you love, then congratulations! Since it's a time when family and friends gather and celebrate, the holidays are a romantic time to propose. Before you pop the question, make sure you're ready with the perfect engagement ring to make the moment unforgettable. Keep reading to learn about the best engagement ring styles to help you pick the right one for your loved one this Christmas.
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text: Athens: India came from behind to record a remarkable 4-2 win against South Africa and keep their Olympic medal hopes alive in the men's hockey competition today. Trailing 0-2 at one stage, the eight-time gold medallists showed their class to emerge victorious in the thrilling contest, which they needed to win to remain on track for a semifinal berth from Pool B. India were greatly served by their three most senior players -- Dhanraj Pillay, Baljit Singh Dhillon and Dilip Tirkey, all of whom scored a goal apiece before Gagan Ajit Singh's last minute goal brought the emphatic win for the side. (PTI)


text:
Changes in the price and availability of wheat can have significant impacts on food security in the five Central Asian Republics and Afghanistan. Read more >>
Changes in the price and availability of wheat can have significant impacts on food security in the five Central Asian Republics and Afghanistan. Read more >>
USAID's Sustainable Water and Sanitation in Africa project expands and improves water services to residents.
Where one in six child deaths is related to waterborne diseases, USAID is helping communities build sustainable pipe networks.
USAID and partners are helping refugees from Syria meet their water needs. Read more >>
Overhaul of dilapidated infrastructure means a lasting source of water comes to hundreds of thousands of DRC's most vulnerable. Read more >>
Read the latest edition of USAID's FrontLines to learn how the Agency is working to provide safe water to the millions who live without this vital resource Read more >>
USAID's Middle East Regional Cooperation Program brings together Arab and Israeli scientists and students to create and share solutions to regional development challenges like water while promoting a peaceful exchange between neighbors. Read more >>
USAID has supported Egypt's water sector – including its water and wastewater utilities – for more than three decades. Read more >>
In the 1980s, USAID created the Famine Early Warning Systems Network to monitor and predict developments that affect food security in the Middle East and other areas. Read more >>
USAID is successfully demonstrating that with transparent planning, modest investment and strong community support, infrastructure improvements can be made to bring reliable water service to residents in small communities in Crimea. Read more >>


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Having routed the idolaters, Hudibras parades the captured Crowdero through town. He claps Crowdero in the stocks while displaying his trophies of victory, Crowdero's fiddle and case.
Purchased with money from the John Herron Fund for the John Herron Art Institute, now the Indianapolis Museum of Art, in 1911.


text:
Current Round
Min Deposit: 1.00 Max: 20 Skins
cheap csgo keys
The claims come from the Global Offensive community on Reddit, where estimates put the number of banned cheaters at around 1,600 - and that's a conservative guess. That's a lot of banhammers dropping through the Valve Anti-Cheat System.His response, minus the profanity, should be the headline of any betting site. You gamble at your own risk and if you're in a position and constantly blaming others for your loss, you have a gambling problem. There is a reason why gambling sites and casinos have an age restriction, there is supposed to be a level of responsibility and maturity which come with throwing money away, a restriction which CSGOLounge and Dota2Lounge do not have. That's an article for another day.Seven professional Counter-Strike: Global Offensive players have been banned from Valve-sponsored events, including the upcoming ESL One Katowice. The bans come as the result of an August 2014 match between iBUYPOWER and NetcodeGuides.com, which has now been confirmed as having been fixed. An Australian Counter-Strike Global Offensive player and streamer has had his prayers answered, after Valve dipped into their legendary bag of "one-time" gestures."We needed to keep these goals in mind while deciding which angles to focus on," Grimes noted. That's why the team realized early on that character skins wouldn't work, since it was a lot of work for customization that a player would rarely see -- it's a first-person game, after all.Cooler Master, on the other hand, has taken a classic approach with the Quick Fire XTi, opting for a heavy duty chassis with no logos or detailing. If not for LED backlighting, the Cooler Master could pass for an office keyboard.The tale of how one man from Canada became the kind of person who pays a monthly fee to cheat at video games is like many stories about good people who slide toward the more nefarious extremes of life.
"The Huntsman Case and Community Sticker Capsule have been revised to replace the copied and discontinued items."It really is a grey area," said Tomas "Morte" Kerbush, a professional gamer who plays Battlefield 4, another popular first person shooter. His team-mate Erik "2-Easy" Van Hoorn was more explicit: "Underage kids are betting and there is no way to control it." The system would work by randomly rewarding a few players with cases at the end of rounds played on official servers. The trick was that a case could only be opened with purchase of a $2.49 key. Upon being opened, these cases would provide the player with one of more than a dozen weapon skins at random, some common, while some ultra-rare.
Panda Security researcher Bart Blaze unearthed the scam via TeamFortress.tv."You cannot do that right now, when the beta comes back up loot boxes are only rewarded based off of game and player level," he replied. "But we've had this system in for about two months internally, and it's something that a lot of us really want is the ability to purchase additional loot boxes. So we're definitely exploring if that's a system we can pursue, and there's a lot of interest around it. It's definitely something we'd like to do."Envanterinizdeki kullanmad???n?z skin'lerden bir ?ekilde faydalanmak ve daha ?nce sahip olamad?klar?n?z? almak istiyorsan?z, Kinguin'den size harika bir haber var!The Operation Wildfire event, which runs through to June 17, gives everyone access to seven new community maps, including Tulip, Cruise, Coast and Empire, in addition to the spruced-up Nuke. However, if you're willing to pay the $6 entry fee, the Operation Wildfire Access Pass comes will a host of new features.Two new campaigns are available: the Wildfire Campaign, made up of Casual, Deathmatch and Arms Race missions, and the co-op Gemini Campaign which packs three all-new Co-op Strike missions and 23 Guardian missions. Both campaigns reward mission XP with each success, and by completing Challenge Missions you can upgrade your flashy Wildfire Coin, shown off alongside your avatar.The issues are legion with the most serious centring around Ubisoft's servers. At launch these had a tick rate of 30, which is how many times per second it updates the position of each player. This is not nearly high enough for a competitive shooter (CS:GO pro matches are on 128-tick servers), and sure enough one of the first switches was to 60-tick servers. Latency was a major issue at launch too, but despite patches that claimed to fix it you can still be shot by someone that you just didn't see. Even worse, the killcams often show how unfair everything was, with your killer shooting a full second after you got into cover, yet the boomerang headshot still landing.The CS:GO skins are the creation of Chris Le, who recently directed and wrote the screenplay for Juarez 2045. That's a sci-fi action-adventure which stars Danny Trejo, along with Brad Schmidt and Alex Heartman. Heartman's one of the main stars in the Power Rangers Super Samurai series, in case you were wondering.You also can't simply leave a match to avoid subjecting yourself to a hacker. Abandoning a match for any reason penalizes you, preventing you from playing competitive mode for a period—for days at a time, for frequent offenders. It's a method of circumventing the matchmaking system (often as a way to play with friends who aren't near the same rank), one not unfamiliar to League of Legends players and other free-to-play games. When I'm up against such a player, there's no tool within the reporting system for me to flag their account—and why should there be? As far as Valve's concerned, that player is another legitimate customer. Solutions like IP banning would be over-aggressive: what if that account is legitimately a friend or sibling?
It's a stark message for those tempted to claim ownership for another's work. The new Contraband rarity and Valve-designed paint-job has, of course, meant a spike in the skin's desirability. Since the item was updated, StatTrak Minimal Wear versions have been sold for around $400. Rails, Resort, Zoo, Log, and re-released versions of Agency and Season are included in the Bloodhound Access Pass, which also opens up two new "campaigns," a continuation of the web of challenges players can complete to earn weapon skins or unlockable crates.More dramatic is what happened afterwards. Wolski recorded a call between himself and MYM manager Sebastian "Falli" Rotterdam. During the call—published by The Daily Dot's Richard Lewis—Rotterdam pleads with Wolski. Later in the call, Rotterdam threatens Wolski's mother—saying that, because she signed Wolski's contract, he would ensure that she lost her house.There was a time not so long ago when Counter-Strike appeared to be a dying game. As competitive esports, both the original game and its successor, Counter-Strike: Source, were waning in popularity. Source had been hit particularly hard by the 2008 demise of the Championship Gaming League, the largest competitive league for the game, and original CS (generally referred to as "1.6" by players), was being eclipsed in the public eye by the RTS and MOBA esports du jour.The ESL One Cologne tournament will take place at the 20,000-seat Lanxess Arena in Cologne on August 22-23. Tickets to the event will go on sale on February 23. Every Monday in Shooterology , Evan writes about FPSes.The ESEA has also issued bans against the seven players in question, saying that while the bans are currently set for one year, it reserves the right to extend them indefinitely. It noted that it has since implemented its own policy explicitly forbidding players, managers, and sponsors from betting on their own matches, adding, "We strongly encourage all organizations, regardless of their affiliation with Valve, to mirror and enforce these bans so that a clear message is sent—there is no place for match fixing in professional gaming."It's also a huge sum for a 21-year-old still living under his parents' roof, but the young entrepreneur isn't too caught up on numbers. "We want to give back to the community but it's also an excellent way to advertise our product."
To be honest, I think the FPS genre is just so saturated, and CS:GO has really just made it difficult for FPS games to compete in this market. CS:GO has done a great job of making the experience so polished. It's got everything you'd really want from an FPS game. The whole presentation and everything is so... it's just really difficult for us to really draw a crowd away from these guys.Truth be told, I think our game would have done better if it wasn't free-to-play. That's my opinion - I don't represent the opinions of the people that I work with. If I was in charge, I wouldn't have gone that route. Free-to-play works for certain games that really allow you to have a lot of items and a lot of cosmetic visual upgrades.Het speciale Bowie mes is dus alleen beschikbaar voor de mensen die betaald hebben voor de coin. Of je ook extra voordelen hebt met het mes, of dat deze er alleen erg tof uitziet weten we nog niet, dat moeten we eerst zelf uitproberen.Dawid Rozek, cofundador y director de marketing, dijo que este desarrollo es resultado de las recientes celebraciones de aniversario, donde los invitados expresaron un decidido interés en contar con una biblioteca selecta de skins para sus juegos. A?adió: "Tuvimos que crear un producto que respondiera a los intereses de los gamers de corazón que aman la variedad". G2A Winter Wonderland Party - Celebrating the Birthday of the G2A.com MarketplaceIn order to do that, we had to rewrite a lot of the game design. A lot of things had to be changed in order to accommodate free-to-play. We had to make sure that it wasn't going to be unbalanced, but at the same time, we had to come up with things we could sell, because if you can't monetize your game, there's no point putting it out there.there was a huge challenge in making a realistic shooter free-to-play friendly. There's only so many items you can introduce before the game becomes too unrealistic. You sort of see that with CS:GO, with the whole skins for guns etc. It's not realistic, and kind of takes away... there's no consistent art style, the guns are just sort of wacky and crazy. That's the route you have to go down to monetize your game - you have to be really creative.However, continuing technical issues with its online-focused racing title DriveClub have alarmed many players and pundits. "There's no two ways about it – DriveClub is a disaster from an online perspective," says Leadbetter. "The fact that it is Sony's key exclusive title for the holiday period is a real problem for them. There's the perception that Xbox Live is more reliable and it certainly seems to have fewer "maintenance periods", but it's important to point out that an equally important game – Halo: The Master Chief Collection – has also experienced issues, though not to anything like the same extent."Both Xbox One and PS4 allow you to play Blu-ray and DVD discs, while the Wii U does not natively support either. All three machines also offer access to a wide range of video-on-demand apps and services.Shortly afterwards the Electronic Sports League, one of the main tournament organizers, said it would create a formal drug policy with help from Germany's anti-doping agency. It conducted its first doping tests at a tournament in Cologne in August, and said in a statement the random screening "returned negative results for all tested players." A spokeswoman declined to disclose how many tests were conducted, and for which substances.Though eSports organizers are beginning to grapple with drug use, gambling presents a new set of challenges. Betting on competitions is growing rapidly on mainstream sites; U.K. bookmaker William Hill has taken 14,000 bets on games so far this year, spokesman Joe Crilly said, of about £250,000 ($395,000) in total. Four times that much will likely be bet over the next year, he said.
Competitive Counter-Strike continues to draw a healthy amount of spectators as Valve's FPS has grown significantly since the end of 2013. Following Katowice earlier this year, the ESL Championship begins 3 AM Eastern on Thursday, the first matches of ESL One Cologne 2014 will kick off in Germany, culminating in a final match on Sunday.As crazy as 0.64% might sound, which equates to one out of every 200 cases, obtaining a knife is brutally rare, sitting at 0.16%. That means you aren't likely to see a knife unless you open roughly 625 cases! And if you're hoping for a StatTrak variant of an item, then good luck. You're only going to see StatTrak on an item once in a blue moon, estimated to be somewhere around 10% of the time for a given item.ʏһҳúbuy cs go case key
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The first is to be known as Fiat SpA, and will encompass the automotive brands, including Alfa Romeo, Lancia, Maserati and, of course, Fiat. The second, Fiat Industrial SpA, will presumably include the likes of Iveco, Case New Holland and French motorcoach division Irisbus. (Ferrari's future hangs in the balance as reports alternately confirm and deny plans to sell off parts of the Maranello-based automaker and racing team.)
The de-merger was made in accordance with a shareholder vote on September 16. As a result, both new corporate groups have received new logos to help differentiate one from another, as both will be listed separately on the Milan Stock Exchange. While the move likely won't have any immediate, direct impact on the Chrysler Group, if an official merger is to take place between the Turin and Auburn Hills auto groups, it's likely to encompass the Fiat auto group and leave the industrial group alone. Official announcement in the press release after the jump.
[Source: Fiat (both of 'em)]
FIAT SpA AND FIAT INDUSTRIAL SpA: TWO NEW GROUPS, TWO NEW IDENTITIES
On 1 January 2011, as a result of the demerger approved by shareholders on 16 September, there will be two new Fiat groups (both quoted on the Milan Stock Exchange) with two distinct logos: Fiat SpA and Fiat Industrial SpA.
Fiat SpA, with a clear focus in the automobile sector, will be identified by a logo displaying the word Fiat in condensed blue lettering. The new logo has been created in response to the need to differentiate the automobile group from the product-related brand, reinforcing the parent company's role in the management of a multi-brand group. The graphic design is intended, in particular, to create a visual identity which portrays the strong link between past and future. This has led to the reinterpretation of an iconic logo from the past, which is also strongly evocative of the modern and innovative.
Fiat Industrial SpA, which includes trucks, commercial vehicles, agricultural and construction equipment, and related powertrain activities, has maintained the visual identity created for Fiat Group, thereby preserving the concept of solidity representative of a large industrial group. In contrast to the Fiat Group logo, the background colour is the company's traditional blue and the name Fiat Industrial appears in burnt gold lettering.
The new logos, designed by Robilant Associati, replace the Fiat Group logo adopted in October 2005.


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Thai and European breakfast
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Rated 4.6 out of 5 by 9 reviewers.
Rated 5 out of 5 by Yogini Plump & Succulent Excellent product. Delicious both as a snack and in cooking. 21 December 2015
Rated 5 out of 5 by Whyhaveallmychoicesbeen Cranberries Love these. Mix them with my Wheetabix, muesli or other breakfast cereals. They have a really nice sharp tangy taste 11 August 2015
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4 posts tagged with civilwar by kliuless.
Displaying 1 through 4 of 4.
predicting civil unrest
Professors' global model forecasts civil unrest against governments - With protests spreading in the Middle East (now Yemen - not on the list) I thought this article and blog on a forecast model predicting "which countries will likely experience an escalation in domestic political violence [within the next five years]" was rather interesting. [more inside]
All you need is love
Mass wedding for former Tamil fighters Fifty-three couples of former Tamil Tiger rebels were married Sunday ... at a rehabilitation camp near the northern town of Vavuniya. [more inside]
Civil War: Political Violence and Robust Settlements
Civil War: Political Violence and Robust Settlements -- an article from the Santa Fe Institute Bulletin about game theoretical approaches combined with on the ground field studies to analyze war and conflict. The article centers around work (Forging Democracy From Below: Insurgent Transitions in South Africa and El Salvador | Insurgent Collective Action and Civil War in El Salvador) done by Elisabeth Jean Wood, an NYU professor of political science with a background in physics. "The reason to study violence and suffering," says Wood, "is to understand its origins, processes, andâ?"ideallyâ?"to contribute to its cessation."
Before you get that cell phone
Before you get that cell phone check to see where the tantalum inside it comes from. You could be funding a civil war in the Congo.
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Parliament Resort - Gay Men's Resort features a nightclub and puts you within a 15-minute drive of Augusta National Golf Club. After splashing around at the outdoor pool, you can grab a bite to eat at the restaurant or unwind with a drink at one of the 2 bars/lounges. A spa tub, a steam room, and a terrace are other highlights.


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8 x 10 inches (20.3 x 25.4 cm)
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Publication date: 6/20/2011
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Chicago is famous for its role in fostering modern architecture. Now Jeanne Gang, founder of Studio Gang Architects, is giving the epithet "Chicago School" a new meaning. Her recently completed 82-story Aqua residential tower is already an icon of the Chicago skyline and has been universally hailed as a masterwork for the young firm.
presents an in-depth look at the firm's unique work and working process through drawings, diagrams, sketches, and photographs that illuminate the evolution of each of the book's eight featured projects, both public and private, and ranging in size from exhibition to high-rise.
Jeanne Gang leads Studio Gang Architects, a practice generating innovative and award-winning works of architecture. Gang earned her B.S. in architecture at the University of Illinois and her M.Arch with Distinction from the Graduate School of Design at Harvard University. A Rotary Fellow in 1989, she has also studied at the ETH Swiss Federal University of Technical Studies in Zurch. Prior to forming her own firm, she worked for OMA/Rem Koolhaas in Rotterdam.
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Antares Pharma (NASDAQ:ATRS)
Q1 2014 Earnings Call
May 09, 2014 8:30 am ET
John J. Howarth - Vice President of Corporate Affairs
Paul K. Wotton - Chief Executive Officer, President and Director
Leroux Jooste - Senior Vice President of Pharmaceutical Sales and Marketing
Robert F. Apple - Chief Financial Officer, Chief Accounting Officer, President of the Parenteral Products Division, Executive Vice President and Secretary
Louise Alesandra Chen - Guggenheim Securities, LLC, Research Division
Matthew L. Kaplan - Ladenburg Thalmann & Co. Inc., Research Division
Akiva Y. Felt - Oppenheimer & Co. Inc., Research Division
Ladies and gentlemen, welcome to the Antares Pharma First Quarter 2014 Operating and Financial Results Conference Call. [Operator Instructions] I would now like to hand the conference over to Jack Howarth, Antares Vice President of Corporate Affairs. Please go ahead, sir.
John J. Howarth
Thank you, Damien, and good morning, everyone. Thank you for joining us on today's call. We announced first quarter 2014 operating results and recent achievements earlier this morning, and the press release can be found on the Antares website at www.antarespharma.com under the Investor Relations tab.
Before we begin, please be advised that during the course of this call, we may make forward-looking statements concerning the company that are not historical facts. These forward-looking statements may include, but are not limited to, statements concerning the timing of product sales, market estimates, market potential and growth prospects, technology platforms and working capital needs. Forward-looking statements provide Antares' current expectation or forecast of future events. Actual results could differ materially from those reflected in these forward-looking statements due to decisions of regulatory authorities and Antares' ability to execute on its development plans, capital needs and general financial, economic, regulatory and political conditions affecting the pharmaceutical industry generally.
Additional information concerning these risks and uncertainties are contained in the Risk Factors section of the Antares' annual report on Form 10-K and in Antares' periodic filings and other filings made with the Securities and Exchange Commission.
Antares is providing this information as of the date of this release, and does not undertake any obligation to update any forward-looking statements made in this earnings call as a result of new information, future events or circumstances after the date hereof, except as required by law or otherwise. The company cautions investors not to place undue reliance on these forward-looking statements.
Joining me on the call today are Dr. Paul Wotton, President and Chief Executive Officer; Robert Apple, Chief Financial Officer and President of the Parenteral Products Group; and Leroux Jooste, Senior Vice President and General Manager, Pharmaceuticals. After the presentation, we will open the lines for question-and-answer.
I'll now turn the call over to Paul Wotton. Paul?
Paul K. Wotton
Thanks, Jack, and good morning, everyone. We've made significant progress on a number of fronts during the first quarter, and I'd like to review some of our accomplishments before I then turn the call over to Leroux to talk about the progress we made in the early stages of the OTREXUP launch. After witch, Bob will discuss the financials.
On a personal note regarding the launch, I've made a number of visits to rheumatologists in the New Jersey and Washington, D.C. areas due to this initial launch phase, and I'm delighted with the positive feedback that I've heard about OTREXUP. Today, our total prescriptions grew by 22% compared to the prior week, and we are starting to see repeat prescriptions coming in with significant numbers. We had our training for a 40-person commercial team in late January of this year, and our reps started detailing rheumatologists in February. We've had success gaining access to our physician offices, and our OTREXUP message is resonating with physicians. They understand the value of OTREXUP and seeing it being a considerable part of their RA treatment regimen in the future.
As an additional part of the initial launch phase of OTREXUP, our sales and marketing partner, LEO, started marketing OTREXUP in March to dermatologist for the psoriasis indication. We also announced the receipt of a second $5 million milestone payment from LEO in conjunction with reaching a certain percentage of lives covered by commercial insurance plans. The OTREXUP psoriasis indication has strong possibilities for us. There are approximately 7 million psoriasis patients in the U.S., and up to 10% of these may have severe recalcitrant, or debilitating, psoriasis, which is our current label.
LEO Pharma has a large data base, some 50,000 psoriasis patients, and as we've previously disclosed, we'll be using 85 sales reps to target approximately 7,000 dermatologists. We ultimately chose to partner with LEO, because of their competence and expertise in psoriasis, and their expert, established relationships with dermatologists and patients.
I anticipate that the launch of OTREXUP to dermatologists by LEO will soon begin to drive additional revenues for our company.
I will now hand it over to Leroux for more detailed overview of the OTREXUP launch. Leroux?
Leroux Jooste
Thank you, Paul, and good morning, everybody. Now before I comment on the launch of OTREXUP, I'd like to talk about the unique nature of this product, and why we believe it fits perfectly into the treatment regimen for rheumatoid arthritis and psoriasis. The value proposition and the positioning of OTREXUP is to extend the use of methotrexate beyond oral therapy, providing both patients and doctors another treatment option before adding or switching patients to more expensive options like biologics. The goal of OTREXUP is to create a new category of treatment between oral methotrexate and biologics. As this disease progresses, so should the treatment. And a tailored individualized approach is necessary to control this disease, and this can take several weeks as rheumatologists and dermatologists determine the specific treatment plan for each patient.
The OTREXUP bioavailability data presented at last year's American College of Rheumatology meeting showed for the first time that absorption of methotrexate following oral dosing had a plateau effect at doses of 15 milligrams or greater. The greater bioavailability of OTREXUP could extend the benefit of methotrexate in patients who have had inadequate response to oral methotrexate due to efficacy or tolerability. As this important finding has now been published in the prestigious Annals of Rheumatic Disease. So while still early in the launch, rheumatologists have viewed the OTREXUP value position and proposition favorably, and we've had a good start with strong momentum gained in the first 3 months. We estimate that in February, 85 patients started treatment, and that by the end of March, 369 patients were treated with OTREXUP. We estimate that almost 1,000 patients have been treated through the end of April with OTREXUP.
The market research soon after the launch and the data from Symphony Health Solutions has confirmed that rheumatologists have a high level of awareness and an intent to prescribe OTREXUP. This favorable perception is also reflected by the sales force experience and feedback in the first 12 weeks after launch. Through the first 3 months of the launch, we have made more than 8,500 calls on rheumatologists and it reached 76% of our targeted customers and this excludes LEO. More importantly, we have reached 93% of the high methotrexate prescribing rheumatologists with the greatest potential for driving OTREXUP utilization, and we'd had orders for more than 6,000 samples. The weekly prescriptions continue to grow and has regained momentum over the past 2 weeks following the short holiday week a few weeks ago.
Prescription drug coverage for OTREXUP, as reported by MMIT, a formulary coverage service provider for more than 4,000 plans, commercial plans, shows that 90% of commercial lives have some form of coverage and 48% either have referred, preferred or good access, just requiring a prior authorization to oral methotrexate.
Our 40-person commercial team has been very successful in generating launch momentum with actual prescriptions written in the first 2 months, which has more than doubled the number of the actual dispensed prescriptions. And there's absolutely no doubt that we can increase the number of dispensed prescriptions by making sure that the prior authorization requirements for some plans are met and that the patient out-of-pocket expense is acceptable when our copay assistant program is used. Our sales force continues to increase the emphasis and focus on educating rheumatologists, on identifying the right patients medically and financially, and the sales force is also making it a high priority for rheumatology nurses and office managers to use our free insurance verification and benefits investigation service to confirm that patients will be able to initiate treatment with OTREXUP without any prior authorization or copay surprises. We continue to work with major health insurance plans where we seek to obtain a favorable formulary status for OTREXUP, and have made good progress in discussing the cost offset to the expensive biologics. And last, but not least, we've engaged 22 key opinion leaders in a nationwide speaker bureau program to educate rheumatologists, physician assistants, nurses and pharmacists on the value of OTREXUP. All these speakers have had expressed in using OTREXUP and will be sharing this with their colleagues. Lastly, LEO launched OTREXUP, as Paul mentioned, to dermatologists in March, and early feedback indicates that OTREXUP is also recognized as an option for many patients to consider before a biologic is prescribed. We look forward to continued progress with LEO and our partner in the dermatology segment.
And I'll now turn it back to Paul.
Paul K. Wotton
Okay. Thanks, Leroux. So on the development area, this past February, we announced positive results from a multi-center phase IIb clinical study, which evaluated the clinical pharmacokinetic profile of testosterone administered once weekly by subcutaneous injection at doses of 50 milligrams and 100 milligrams using the VIBEX QuickShot auto-injector. 29 adult males with low testosterone and testosterone blood levels less than 300 nanograms per deciliter were randomized into 2 groups. The first group received 50 milligrams of testosterone administered subcutaneously with QuickShot device, and the second group received 100 milligrams. Both groups received once weekly injections for 6 weeks, and the study patients were then followed for another 4 weeks after last dose. Results of this study showed rapid restoration and consistent maintenance of normal testosterone levels and dose proportionality of both dosage strengths. We are very optimistic about potential for self-administered at-home once-weekly subcutaneous dose of testosterone based on the outcome of this study. It's clear to us that the administration of testosterone using our proprietary QuickShot device showed that normal testosterone levels can be rapidly restored, and reliably maintain with reduced peak to trough ratios relative to those associated with intramuscular injections, which are also studied as part of this trial.
We believe that the injectable testosterone market will continue to grow due to the current underpenetration, a growing awareness of the benefits for treating testosterone deficiency, and the FDA's willingness to continue to look for and approve new therapies of treatment, such as the most recent product, Aveed. It's worth reminding everyone here that the injectable space has grown over the past 5 years so the compound annual prescription growth rate of around 40%, outstripping Joe prescription growth of 14% in the same period.
Injectable testosterone currently accounts for more than 1/3 of total testosterone prescriptions written annually. Given the current force of injectable testosterone, we believe that a once weekly, convenient, precise quick-to-administer subcutaneous dose of testosterone will become the choice route of administration.
Earlier this week, we announced that the meeting was held to the FDA to discuss the proposed Phase III registration study that will include approximately 150 testosterone deficient males, and we plan to begin recruitment in the third quarter this year. This study is designed to show that once-weekly self-administration of testosterone with the QuickShot auto-injector can safely achieve normal blood levels of testosterone and hypogonadal in men with an injection that's only going to take about 5 minutes -- 5 seconds to administer.
In April, we announced the issuance of new patents, RE44846 and RE44847. The significance of these reissued patents traces back to Antares' inventions made in the late 1990s, and these patents capture innovations in the field of auto-injectors, but originally established Antares Pharma position as a leader and innovator in medical injection device technology. More importantly, these patents add protection to OTREXUP, as well as our other pipeline products.
Antares is already taking steps to supplement the current Orange Book listings related to OTREXUP. We continue to believe that our overall patent portfolio coverage exemplifies the company's intellectual property strategy of obtaining patents that are directed towards devices, combination products including drugs, and methods for delivering injectable drugs, which the company has earned on its filed invention. We are very confident about the intellectual property portfolio covering the OTREXUP asset, and is extremely comprehensive. We intend to assert it in defense of our products to the fullest extent possible.
Finally, we announced at the Annals of Rheumatic Diseases, the published results from an open label head-to-head randomized crossover study comparing the relative bioavailability, safety and tolerability of OTREXUP to oral methotrexate and adult patients with rheumatoid arthritis. This peer reviewed publication reported results from previously conducted multi-center three-way crossover study in patients greater than or equal to 18 years old, with adults already undergoing treatment with MTX for 3 months or more. 47 patients completed the study, and the results show that the systemic availability of methotrexate following oral dosing plateaus at 15 milligrams and greater.
Following administration of OTREXUP, the systemic availability increased proportionately at every dose, which extended the range of exposure compared to patients receiving oral medication. No unexpected adverse events were noted for either formulation in the short-term study, and high systemic methotrexate exposure was not associated with any increase in adverse events.
I'd like to turn the call over now to Bob to talk about the financial results. Bob?
Paul K. Wotton
Thanks, Paul. Our first quarter financial and operating results were as follows: Total revenues were $5.2 million and $4.5 million for the 3 months ended March 31, 2014 and 2013, an increase of 15%. Product sales were $1.8 million and $2.5 million for the 3 months ended March 31, 2014 and 2013. In the first quarters of 2014 and 2013, sales of our reusable needle-free injectable devices and disposable components were $1.2 million and $1.1 million, and were generated primarily from sales to Ferring and Teva.
Products sales in the first quarter of 2014 also included $300,000 in sales of pre-commercial pen injector devices to Teva. Additionally, in the 3 months ended March 31, 2014, the company shipped $2.7 million of OTREXUP to wholesalers and recognized net product sales of $200,000 from sales of OTREXUP based on prescriptions dispensed.
The OTREXUP revenue recognized is net of estimated wholesaler discounts, prompt pay discounts, and patient discount programs. We are 12 weeks into the launch of OTREXUP and the prescription data for our new product such as OTREXUP is not always consistent with respect to the length of each prescription written in the refill data.
Data suggest that some rheumatologists are writing a prescription for 1 month with no refills, and then asking the patient about their experience before writing the next perception. The next prescription could either be for the same dose with a refill or the rheumatologists may choose to titrate off to the next dose with no refills. Either way, this would count as a new prescription and not as a refill. So based on what we've seen to date with new patient starts, it's still too early to project refills based on current prescribing trends. What I can tell you is that the average length of new prescriptions has progressed beyond 28 days, suggesting rheumatologists are writing multiple month prescriptions. We now have the first 8 weeks of data, and we are analyzing not only high prescribers, but prescribing trends as well. Another point to note is that not all OTREXUP sales will be captured by a prescription. OTREXUP has been dispensed by specialty pharmacies, NVA, which do not typically show up as a script. Currently, basing on our OTREXUP product revenue and prescription is likely underreporting our revenue until we start to book revenues based on sales to distributors. This will likely happen when the shipments to distributors is more aligned with the level of prescription sales value, which I estimate will be towards the end of 2014.
Product sales in the first quarter of 2013 include a $600,000 of initial sales of Teva over VIBEX auto-injector for Teva's generic epinephrine auto-injector product, and included $500,000 of sales to our top -- for our topical oxybutynin gel 3% product to Actavis in connection with their marketing of Gelnique 3%.
Development revenues were $1.4 million and $800,000 for the 3 months ended March 31, 2014 and 2013. The development revenue in the first quarter each year was primarily related to auto injector and pen injector development work for Teva.
As you can see based on the increase in development revenue year-over-year, the Teva programs continue to progress. We are now in the commercial stools -- commercial tooling stage for all 3 development programs. We have successfully made pre-commercial devices for the epi program, and are now gearing up for the pre-commercial phase of the 2 undisclosed pen programs.
On a different front, our partner, Pfizer, has informed us that the first of 2 Phase III studies on the undisclosed OCC product has completed enrollment and should finish in Q3. And the second Phase III study is expected to be done by late Q4 2014 or early Q1 2015.
Licensing revenue was $900,000 and $100,000 for the 3 months ended March 31, 2014 and 2013. The licensing revenue in the first quarter of 2014 were primarily due to revenue recognized in connection with our license and promotion agreement with LEO pharma executed in November 2013.
Revenue from royalties was $1 million and $1.2 million for the 3 months ended March 31, 2014 and 2013. We received royalties from Teva and Ferring related to our needle-free injected device sales and/or hGH sales, from Meda Pharma on sales of Elestrin and from Actavis on sales of Gelnique 3%.
Total gross profit increased in the first quarter of 2014 to $4 million from $2.5 million in 2013, an increase of 61%. The increase in the quarter was primarily related to license revenue recognized under the license and promotion agreement with LEO pharma and development revenue from Teva.
Total operating expenses were $12.8 million and $5.9 million for the first quarters of 2014 and 2013. The increases was primarily due to the increased investment in sales and marketing activities of $5.5 million in connection with the launch of OTREXUP, along with an increase in expenses related to the completed Phase II study of our VIBEX QS T for testosterone replacement therapy of approximately $1.3 million.
Net loss was approximately $8.8 million and $3.4 million for the first quarters of 2014 and 2013, respectively, and net loss per share was $0.07 and $0.03 in the first quarters of '14 and '13.
At March 31, 2014, Antares had approximately $63.1 million in cash and investments compared to approximately $69.1 million at December 31, 2013.
And then finally, as I mentioned in our year-end earnings call, until we can establish prescription trends and correlate shipments from distribution centers to pharmacies, and how they much up with prescription data, we will be booking quarterly revenues based on prescription data that we receive on a monthly basis. And as you can see from today's press release, the $200,000 we recorded in sales based on prescriptions dispensed is much less than the $2.7 million of OTREXUP we shipped to wholesalers. As we said in the past, we hope that the June, July time frame will start to give us a meaningful prescription trend so that we will be able to give you some guidance on what the 2014 revenue potential for OTREXUP might be on our second quarter results call in August.
And with that, I'll turn the call back to Paul.
Paul K. Wotton
Thanks, Bob. Well, we believe here that the OTREXUP launch has gotten off to a good start and have not changed our views on peak sales potential for the product. As Leroux said, it is very early in the launch, and we are following the metrics closely. In addition, formulary coverage is getting better all the time, and is actually very good given the limited period we have had of active marketing of OTREXUP. Our dermatology partner, LEO, has had some good reception in the physicians' office and has started to make progress on all of their core plans. Overall, we are very pleased with the progress of the launch thus far. And as I mentioned earlier, my visit to rheumatologists' office during April have confirmed that doctors and patients like the product.
On the pipeline front, we've already completed the market research on 7 product candidates, and we'll be adding 3 to the pipeline before the year is out. The revised pipeline will be heavily weighted to the CNS area, and I expect that this therapeutic area will become a key strategic focus as we continue to evolve as a specialty pharmaceutical company.
Before we go into Q&A, I'd like to make one quick comment on the Medac litigation. We have been advised by an outside counsel not to comment on, or speculate on the outcome or timing of this litigation. I can, however, tell you that we believe that our strategy is sound and we have every intention of protecting all of our pipeline assets based on our IP on behalf of shareholders.
So with that, I'd like to thank everyone for listening. And operator, could you now open the lines for the Q&A session please?
Question-and-Answer Session
[Operator Instructions] Our first question is from the line of Louise Chen with Guggenheim Securities.
Louise Alesandra Chen - Guggenheim Securities, LLC, Research Division
I had a few. So first on OTREXUP, I was curious how we should think about the launch trajectory and the Rx progression given some of the factors that you mentioned? So do you expect the sort of an acceleration in the second half of the year? And to be somewhat slower now, as the doctors kind of titrate patients up? And then I'm also curious, in terms of the IMS data, will the LEO scripts be captured under Antares or under LEO? And then on VIBEX QS T, I was wondering, so you're starting the Phase III trials in 3Q, and when you expect data and for those to be completed? And maybe more details on the trial design. And then, lastly, just on formulary coverage for OTREXUP, where do you stand currently, and where is upside from there as we progress throughout the year?
Paul K. Wotton
Okay. Thanks Louise. This is Paul here. Yes, the -- I can ask Leroux to comment on more details, but with respect to the launch of OTREXUP projections and progression which you asked, yes, we are titrating patients into the product right now. We do expect an acceleration of sales in the second half of the year. Patients typically see their physicians on a quarterly basis, and we think we have to go through 2 cycles of that. Bearing in mind, we launched in February. We're looking at the July/August timeframe when we expect to see the acceleration. With respect to LEO and the IMS prescriptions, Antares will be recording all of the revenues from sales of OTREXUP, whether it's in psoriasis or in rheumatology. And so all of the revenues for the product will be ours. We will be able to identify by specialty later on in the year under our arrangement with LEO in order to make sure we provide LEO with the correct compensation for the work that they're doing. I'll ask Leroux to comment on the formulary first, and then I'll come back on the QS T in a moment.
Leroux Jooste
Could you just repeat the specifics of the formulary question? I want to be sure I answer your question correctly.
Louise Alesandra Chen - Guggenheim Securities, LLC, Research Division
Yes, so basically, what is your coverage today for OTREXUP? And where do you think it'll be by the end of the year?
Leroux Jooste
So as I've mentioned, we get access to the MMIT database to inform us on formulary status. And the commercial plans that they monitor and track includes over 4,000 commercial plans. And on their latest report, we show that of the covered lives, commercially covered lives, 7% have a preferred status, about 41% have what they call a restricted status with usually a Tier 3 category. These are branded products, so then have a prior authorization or a step added, all those in place. And then there's about 42% of plans that are either covered or not yet listed, but it is available, they are still in the process of reviewing and determining the status. But as of the end of April, only 10% of commercially covered lives do not have access, and this is, as you know, mostly due to plans, some plans, rather big plans that have an exclude at launch policy. And so these plans usually take 6 to 8 months before they determine whether or not they will review the products and included in the form. Did that answer your question?
Louise Alesandra Chen - Guggenheim Securities, LLC, Research Division
Paul K. Wotton
Okay. So going back to QS T, Louise, we had a really good meeting with the agency about 10 days ago. We have received guidance on the program going forward including the Phase III trial, which, as I mentioned earlier, is going to involve 150 patients with low T. It's a clinical pharmacokinetic study. I anticipate that the top line data from this study will be available in Q1 of next year. A lot of the timing on this, of course, depends on our ability to enroll patients. And we're being prudent of this, but typically testosterone trials do enroll quite quickly. And so we're anticipating completing that program and finding the NDA with a view to being on the market source the very back in 2016, early part of 2017. And that's I think a really exciting program. I have to say that the discussions we have with the agency were extremely positive indeed. The opportunity that we provide here is for patients to self-inject with testosterone at home once a week. It gives you a better blood level profile than you would receive with an every 2, every 4 weeks injection of testosterone, which usually has to be given under medical supervision. This has been intramuscular injections, so you avoid this high peaks and low troughs. What we have is a blood level profile which gives you similar blood level profiles to the gels. But, of course, we don't have the transference issues with the gels, which are quite significant. So I think what we have here is the right product in the right place at the right time. And I was also delighted to see that the agency -- they were very clear that we have a good program here. And I have to say I think that they've been very helpful to us in designing our pathway going forward.
Our next question is from the line of Matt Kaplan with Ladenburg Thalmann.
Matthew L. Kaplan - Ladenburg Thalmann & Co. Inc., Research Division
I have several questions. I want to start out first with QS T and then move on to the OTREXUP. Based on your conversations, your discussions with the FDA, are there any specific cardiovascular safety requirements to your Phase III program that you have to execute before filing your NDA? This is obviously around the question that is based around the current cardiovascular questions that are out there.
Paul K. Wotton
Yes, Matt, that's a good point. And the answer to your question is no.
Matthew L. Kaplan - Ladenburg Thalmann & Co. Inc., Research Division
Great. That was easy. In terms of -- and then moving on to OTREXUP. Several questions there. What's the net sales price right now after the discounts and things like that? And then in terms of where you need to get to be -- sales levels you need to get to, to break even on the product? And then talk about some of the gross margin metrics as well. And then, do you see it being necessary to increase your sales expenses to reach your goals later this year? And I guess in particular, talk about where you are now, and where you hope to be by year end in terms of growth of scrips? And then, talk a little bit about -- also the breakdown of scrips where you are now in terms of derm versus rheumatologists? And where you hope to be at year end as well. Several questions there. I hope I didn't confuse you. I can repeat them if you like as we have the discussion.
Paul K. Wotton
Well, you might have to. As I get older, I forgot more and more.
Matthew L. Kaplan - Ladenburg Thalmann & Co. Inc., Research Division
I've forgotten them already. Don't worry.
Paul K. Wotton
Obviously, I'll need to be taking testosterone. The question around the metrics on the net sales price, I'm going to hand over to Bob. And then we'll follow up with Leroux on the projections going forward. Specifically, I think, we have to all be clear about one thing, which is we're very early in this launch phase. And to date, we don't have a breakdown of the scrips between rheumatologists and dermatologists. So I really can't answer that phase of the questions that you asked, but I'll hand over to Bob now with respect to the financial details on OTREXUP.
Robert F. Apple
Sure. On OTREXUP, our wholesale acquisition cost that we basically charge to the distributors is $548. We haven't given any discounts to anybody other than your traditional Medicare/Medicaid, VA type of pricing, that's negotiated. We do pay distributors for the distribution services for the majors, and that's part of that. That does reduce our net sales by about 7% or so. And then after that, we haven't entered into any contracts specifically, with any third party payers yet. And so the net price is typically the $548 less the 2% you give for QuickPay and then the distribution fees. So I think it's very traditional at this point. I do foresee that we will enter into some contracts with third party payers for the ones that don't allow access. The Kaizers of the world, the Blue Crosses of Massachusetts, and so forth because they're very tight programs or third party payers that really don't allow access unless you contract with them. And then we'll see where the balance of the plans are as far as any contracting, and so forth with their coverage. That's pretty much where we are with the pricing. One thing I will say about the terms and the RA scrips, because we did just get the March data and there is a delineation between the 2, and it is very heavily skewed right now towards RA. I mean, a very small percent with derm, because they just started detailing it in mid-March, I think there was like 15 scrips for derm. So we're going to expect to see that change over time. But again, we believe that for us, both areas are very potentially valuable for Antares both in the derm space and the RA space.
Matthew L. Kaplan - Ladenburg Thalmann & Co. Inc., Research Division
And then just to follow through on that on a question in terms of where you think it could be in terms of the balance at year end as your several more months into the launch, and LEO has some time to get some traction as well?
Robert F. Apple
That's a tough question to answer is only because the derm doctors, they use methotrexate, but it is not as prevalent as the RA doctors. I mean, for RA, methotrexate is a gold standards, kind of cornerstone. They use it all the time. But it's a difficult question, but I think we're going to probably be at the 30% to 70%. 70% being RA.
Matthew L. Kaplan - Ladenburg Thalmann & Co. Inc., Research Division
Okay, great. And then, just going back to I guess, the other metric in terms of where you think you need to be in terms of breaking even on the product? And if your gross margins right now, it sounds like they are basically close to 90%?
Robert F. Apple
Yes, that's correct. We have your traditional pharmaceutical margins on the branded product. And last quarter, we spent $5.5 million in sales and marketing. It's going to be about average at this point as to what we spend on a quarterly basis going forward based on our current plans. So you can figure it out, we would probably need to be in the $23 million to $25 million range to have a breakeven for OTREXUP, which again in the launch here, I think is amazingly good. And we are obviously hoping that the trends continue, and we see those results at the end of the year.
Matthew L. Kaplan - Ladenburg Thalmann & Co. Inc., Research Division
And then in terms of inventory levels at your distributors right now, do you see those -- are those growing? What do you see?
Robert F. Apple
No, I mean, I think that the inventory levels have been pretty consistent. We're seeing buying since -- you've seen buying from the distributors in April and May. And is basically replacing the inventory that they've been selling, and so we're very happy with the allocation that we have based on where -- throughout the country and where the products are being moved. So we don't see an inventory build. We actually see it being replenished on a regular basis.
Matthew L. Kaplan - Ladenburg Thalmann & Co. Inc., Research Division
And then one final question on OTREXUP. Any new initiatives or changes you're planning to make in terms of your marketing efforts? Any co-pay assistant programs or anything like that, that you're contemplating at this point?
Paul K. Wotton
Actually, Matt, we already have a co-pay assistance program in place. We have a good plan and we're sticking with that plan. And as you can see from the data, we had a growth in prescriptions again last week. This plan is working, so we continue to learn as we go through the process, and I'm very happy with the progress we've made to date and I expect it will continue.
Matthew L. Kaplan - Ladenburg Thalmann & Co. Inc., Research Division
In terms of the litigation with Medac, can you comment where you are in terms of that process? I'm not asking timing questions, seems like you can't answer those. But where you are, and will things -- frequently things move to settlement or is this something that goes to trial?
Paul K. Wotton
Matt, I was deposed last week and I really can't comment legally, but I will say that I believe personally that our intellectual property is very, very good indeed. My name is on one of the patents. And we intend to use the full intellectual property estate that we have around OTREXUP to make sure that we defend it to the fullest extent possible, as I said in my comments. For me to go beyond the comment like that will just be foolish. And I'm under advice not to say anything else as well, but suffice to say that we believe we have a very strong position here.
Matthew L. Kaplan - Ladenburg Thalmann & Co. Inc., Research Division
Okay, fair enough. Great. And then in terms of pipeline update, in terms of partner programs, Pfizer and Teva, can you give us any more color and detail on where those are, and what's happening with the products that you have partnered?
Paul K. Wotton
Well, the Teva programs continues to make good progress. You'll see from the numbers that we're getting a lot of development revenue from Teva right now. And the Pfizer program, Bob actually talked about in his commentary that wrapped up one of the Phase III trials on the product. Another one's coming to closure fairly soon. So that one looks like it's on track to hit the market in 2016 assuming a 12-month review cycle by the agency.
[Operator Instructions] Our next question is from the line of Akiva Felt with Oppenheimer.
Akiva Y. Felt - Oppenheimer & Co. Inc., Research Division
Just a quick follow-up to one of Louise's questions earlier. The trial design for the QuickShot testosterone, how close to the final design with the -- what you proposed to the FDA?
Paul K. Wotton
Yes, that's a good question. It was very close to what we proposed to the FDA. It is a pharmacokinetic trial. The only change I would say, that we were notified about was that we've gone to the agency with a proposal to run the study in 250 patients, and the number of patients we're actually going to be asked to look at is in fact 150 patients. So with that guidance from the agency, obviously, we're very happy. Helps us get through the trial a bit quicker than we would normally have been able to do. And like I said earlier, Akiva, I think that the agency were really helpful to us during those discussions. They're very cordial discussion and we've laid out our plan pretty much from now until the NDA filing, including over CMC worth, which is essential for our product like this to get approved.
Mr. Howard, I show there are no further questions at this time. Please continue with any closing remarks.
John J. Howarth
Thanks, Damien, and thanks again for joining us on today's conference call. If you have any follow-up questions you can reach me at (609) 359-3016. That completes today's call.
Ladies and gentlemen, if you like to listen to a replay on today's conference call, you may dial 1 (800) 406-7325 or (303) 590-3030 and enter the access code 4681721 followed by the pound key -- sign. This concludes the Antares Pharma First Quarter 2014 Operating and Financial Results Conference Call. Thank you for your participation. You may now disconnect.
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