Virgin wants to fly to Japan. Virgin Australia is to conduct a sweeping review of its operations, layoff staff and streamline its various divisions to return to the airline to profitability after reporting an Underlying Loss Before Tax of A$71.2 million and a statutory loss after tax of A$315.4 million for the 12 months ended 30 June 2019.The Underlying Loss Before Tax of $71.2 million, compared to an Underlying Profit Before Tax of $64.4 million for the prior year, was a decline of $135.6 million.However, despite the loss, the Group continues to focus on strengthening its balance sheet, increasing its cash position to $1.7 billion at 30 June 2019, a $324.5 million improvement on the prior corresponding period.WATCH a stunning colour video of the Boeing 707 that started the jetset. The Virgin Group is made up of: Virgin Domestic, Virgin International, Tigerair and Velocity.The airline said that the result was driven by “subdued trading conditions in the second half of the financial year, combined with fuel and foreign exchange headwinds and increased operational costs.”The Group reported an increase in total revenue of 7.6 per cent to $5.8 billion for the full year, including a 2.1 per cent improvement in Revenue Per Available Seat Kilometre (RASK).However, market demand moderated in the second half of the financial year, impacted by the timing of the Easter holiday period and the Federal Election, which saw both the corporate and leisure travel sectors soften the airline said.The airline said that the challenging trading environment in H2 FY19 was “compounded by increasing costs including fuel and foreign exchange headwinds of $158.8 million and a $15.0 million investment in Trans-Tasman routes following the cessation of the Air New Zealand alliance.”Group Cost per Available Seat Kilometre (CASK), excluding fuel and foreign exchange, rose by 4.0 per cent for the 12 months to 30 June 2019.Virgin said that the statutory loss after tax of $315.4 million was impacted by $223.2 million in restructure costs. This result was impacted by major accounting adjustments following a review of the Group’s asset values in accordance with accounting standards.The Group is responding to these challenges with a series of immediate improvement initiatives to streamline operations and reduce costs. These include a simplified organizational structure, organizational rightsizing program, fleet and network capacity review and a Group-wide review of supplier contracts. These initiatives are being implemented whilst the Group’s ongoing strategic review is undertaken to improve business performance.Virgin Australia Group Chief Executive Officer and Managing Director, Paul Scurrah, said in a statement that “today’s results were disappointing and underscored the need for change.”“There is no doubt that we are operating in a tough economic climate with high fuel, a low Australian dollar, and subdued trading conditions. However, today’s results show that we must improve our financial performance. While we have continued to grow revenue and have a strong loyal customer base, we need to make changes to our costs to ensure we see financial benefit from the growth in our business,” he said.“Today, we have announced a number of changes to help drive business improvement. This includes a restructure of our leadership team to take in group-wide accountability across all brands, a reduction of 750 roles from our workforce, a review of all supplier contracts and agreements, and a fleet and network review which will see a tight focus on capacity management going forward.“It’s important to note that we have already addressed a number of other business priorities including the restructure of our Boeing 737 MAX order, which deferred a significant amount of capital expenditure.“Regarding the reduction of our workforce, I am acutely aware of the impact this has on our team members. However, if we are to position the business for the future, create new opportunities, improve competitiveness, and continue to deliver for our customers, we need to make tough but important decisions that are in the long-term interests of the Group.“These are just some of the strategic decisions that have been made to help in the short-term. However, there’s more work we need to do on the long-term focus and positioning of the business. We will be focused on being the best value airline for both the corporate and leisure traveller, offering the strong and unique Virgin experience and proposition that we know will appeal to all market segments.“As I’ve said previously, key to our success is ensuring we strike the right balance between the interests of our team members, customers and our shareholders. We’ll be focused on delivering for all three groups.”
By Kelly ServickFeb. 1, 2017 , 2:30 PM Mind-blowing dataModerna now has more money to throw at those molecules than most biotechs can dream of, though it’s far from the only group chasing mRNA drugs. The German biotech CureVac, for example, has brought mRNA-based vaccines for rabies and cancer to clinical trials, and Karikó now heads a research team at BioNTech in Mainz, Germany, that focuses on mRNA-based drugs.But few companies have delved into nucleoside engineering the way Moderna has, or pursued such a broad range of diseases from the start. Beyond its $100-millionper-year platform research, Moderna runs four wholly owned ventures focused on drugs for infectious diseases, rare diseases, immuno-oncology, and personalized cancer vaccines. It has about 430 full-time employees, spilling across three buildings around biotech-dense Kendall Square. Higher-ups are identified by black-and-white headshots hanging at their office doors.Lavish funding has allowed Moderna to set up production facilities that can manufacture more than 1000 new, made-to-order mRNA a month. (“Moderna has probably made more RNA by in vitro transcription than all of humankind ever,” quips Edward Miracco, a senior scientist on its process innovation team.) And it has allowed for many parallel animal experiments to characterize different mRNA and select the most promising. “If you need to run a 25-arm experiment, just do it,” Bancel recalls telling his team. “We have the money, we have the infrastructure. Just do the right science.” V. Altounian/Science Hacking the kingdom of lifeThe vision of an mRNA drug has beguiled scientists for decades. “It’s a huge idea,” says Michael Heartlein, who heads mRNA research at a competing biotech called RaNA Therapeutics just a few blocks away. “Any protein target [where] you can think of a potential therapeutic, you can approach that with mRNA.” The single-stranded molecule sets up a temporary protein factory outside a cell’s nucleus and attaches to ribosomes. This cellular machinery translates its sequence of four kinds of nucleosides—adenosine, cytidine, uridine, and guanosine—into a protein. Then it degrades within a day.Assembling these chemical instructions could be a faster and more adaptable way to make drugs than manufacturing the individual proteins themselves in large bioreactors. And it would allow scientists to deliver proteins that act inside cells or span their membranes, which are a challenge to introduce from the outside. An mRNA drug would also be easier to control than traditional gene therapy. Like mRNA, gene therapy can induce cells to make therapeutic proteins, but it typically introduces DNA that can integrate unpredictably into the genome.If you can hack the rules of mRNA, “essentially the entire kingdom of life is available for you to play with,” says Hoge, a physician by training who left a position as a health care analyst to become Moderna’s president in 2012. Adjusting mRNA translation to fight disease “isn’t actually super high-risk biology,” he adds. “It’s what your genes would do if they were rational actors.”One key problem, however, is that our bodies would normally destroy incoming mRNA before it could get cranking. It’s a relatively large molecule that is prone to degradation, and as far as our cells are concerned, it’s supposed to come from the nucleus, where it’s transcribed from DNA. RNA invading from outside the cell is the hallmark of a virus, and our immune system has evolved ways to recognize and destroy it. CAMBRIDGE, MASSACHUSETTS—In a recent morning meeting of scientific leaders at Moderna Therapeutics, conversation swerved toward the philosophical. Biochemist Melissa Moore, recently hired to head RNA research at the Boston-area biotech, had something on her mind: hype.Specifically, she was thinking about Gartner’s hype cycle, a glib model cooked up by an IT research firm, in which every new technology ascends a “peak of inflated expectations,” sinks into a “trough of disillusionment,” then climbs the “slope of enlightenment” to reach a “plateau of productivity.” Where on this curve, she wondered to Moderna’s president, Stephen Hoge, was their technology?The question is apt. Moderna was founded on the idea that messenger RNA (mRNA), the molecule that relays genetic instructions from DNA to the cell’s proteinmaking machinery, could be re-engineered into a versatile set of drugs and vaccines. These strands of instructions could teach our cells to make whatever was needed to treat or prevent disease—virus-slaying antibodies, wastegobbling enzymes, heart-mending growth factors. The willingness of pharmaceutical giants and investors to bet on that premise to the tune of nearly $2 billion has unleashed waves of both hype and skepticism.Sign up for our daily newsletterGet more great content like this delivered right to you!Country *AfghanistanAland IslandsAlbaniaAlgeriaAndorraAngolaAnguillaAntarcticaAntigua and BarbudaArgentinaArmeniaArubaAustraliaAustriaAzerbaijanBahamasBahrainBangladeshBarbadosBelarusBelgiumBelizeBeninBermudaBhutanBolivia, Plurinational State ofBonaire, Sint Eustatius and SabaBosnia and HerzegovinaBotswanaBouvet IslandBrazilBritish Indian Ocean TerritoryBrunei DarussalamBulgariaBurkina FasoBurundiCambodiaCameroonCanadaCape VerdeCayman IslandsCentral African RepublicChadChileChinaChristmas IslandCocos (Keeling) IslandsColombiaComorosCongoCongo, The Democratic Republic of theCook IslandsCosta RicaCote D’IvoireCroatiaCubaCuraçaoCyprusCzech RepublicDenmarkDjiboutiDominicaDominican RepublicEcuadorEgyptEl SalvadorEquatorial GuineaEritreaEstoniaEthiopiaFalkland Islands (Malvinas)Faroe IslandsFijiFinlandFranceFrench GuianaFrench PolynesiaFrench Southern TerritoriesGabonGambiaGeorgiaGermanyGhanaGibraltarGreeceGreenlandGrenadaGuadeloupeGuatemalaGuernseyGuineaGuinea-BissauGuyanaHaitiHeard Island and Mcdonald IslandsHoly See (Vatican City State)HondurasHong KongHungaryIcelandIndiaIndonesiaIran, Islamic Republic ofIraqIrelandIsle of ManIsraelItalyJamaicaJapanJerseyJordanKazakhstanKenyaKiribatiKorea, Democratic People’s Republic ofKorea, Republic ofKuwaitKyrgyzstanLao People’s Democratic RepublicLatviaLebanonLesothoLiberiaLibyan Arab JamahiriyaLiechtensteinLithuaniaLuxembourgMacaoMacedonia, The Former Yugoslav Republic ofMadagascarMalawiMalaysiaMaldivesMaliMaltaMartiniqueMauritaniaMauritiusMayotteMexicoMoldova, Republic ofMonacoMongoliaMontenegroMontserratMoroccoMozambiqueMyanmarNamibiaNauruNepalNetherlandsNew CaledoniaNew ZealandNicaraguaNigerNigeriaNiueNorfolk IslandNorwayOmanPakistanPalestinianPanamaPapua New GuineaParaguayPeruPhilippinesPitcairnPolandPortugalQatarReunionRomaniaRussian FederationRWANDASaint Barthélemy Saint Helena, Ascension and Tristan da CunhaSaint Kitts and NevisSaint LuciaSaint Martin (French part)Saint Pierre and MiquelonSaint Vincent and the GrenadinesSamoaSan MarinoSao Tome and PrincipeSaudi ArabiaSenegalSerbiaSeychellesSierra LeoneSingaporeSint Maarten (Dutch part)SlovakiaSloveniaSolomon IslandsSomaliaSouth AfricaSouth Georgia and the South Sandwich IslandsSouth SudanSpainSri LankaSudanSurinameSvalbard and Jan MayenSwazilandSwedenSwitzerlandSyrian Arab RepublicTaiwanTajikistanTanzania, United Republic ofThailandTimor-LesteTogoTokelauTongaTrinidad and TobagoTunisiaTurkeyTurkmenistanTurks and Caicos IslandsTuvaluUgandaUkraineUnited Arab EmiratesUnited KingdomUnited StatesUruguayUzbekistanVanuatuVenezuela, Bolivarian Republic ofVietnamVirgin Islands, BritishWallis and FutunaWestern SaharaYemenZambiaZimbabweI also wish to receive emails from AAAS/Science and Science advertisers, including information on products, services and special offers which may include but are not limited to news, careers information & upcoming events.Required fields are included by an asterisk(*)Moderna has shared little detail in published papers about the technology it’s developing, though there are clues in its abundant patent filings. Until recently, even the targets of drugs already in clinical trials weren’t publicized. We’ve had failures. We’ve gone down blind alleys. But because we’ve been quiet about it, nobody’s seen that. Moderna’s President Stephen Hoge (left), RNA research director Melissa Moore, and CEO Stéphane Bancel aim to transform messenger RNA into drugs and vaccines. Melissa Moore, Moderna Therapeutics But as more trials get underway, Moderna is gingerly opening up. The company agreed to Science’s request for access to some of its researchers and labs over the past few months. And last month, at the annual J.P. Morgan Healthcare Conference in San Francisco, California, CEO Stéphane Bancel unveiled Moderna’s first round of drug candidates, which include vaccines for Zika and flu, and a therapy for heart failure.Expectations are high. Being a startup valued at more than a billion dollars—an anomaly that venture capitalists dub a unicorn—comes with scrutiny, and many wonder whether Moderna’s pipeline, consisting mostly of vaccines for now, will expand to match the company’s original vision of mRNA as a broad treatment platform. “There were a lot of really big promises made,” says Jason Schrum, a biotechnology consultant in San Francisco and a former Moderna employee. “That’s what people latched onto; they want the promises to be true, and they want to see the investment really turn it into something meaningful.”In other words, the trough of disillusionment, if it’s still ahead, threatens to be deep. Biochemist Katalin Karikó heard this argument over and over as she tinkered with mRNA in her University of Pennsylvania (UPenn) biochemistry lab in the early 2000s. But she and her UPenn colleague Drew Weissman found a way to tame cells’ typical inflammatory response by modifying one of mRNA’s four building blocks, uridine. Assembling mRNA using pseudouridine, a nucleoside variant that occurs naturally in the body, greatly reduced the tendency of immune sentinels called dendritic cells to shoot out inflammatory molecules in response, they reported in 2005.In mouse studies, this mRNA proved stable enough to stick around in the body and make proteins. Karikó and Weissman founded a company hoping to develop drugs from the discovery, and won nearly a million dollars in small business grants from the U.S. government for animal studies. But shortly after the money came through, Karikó says, the university sold the intellectual property license, and the effort never reached clinical trials. “I could not find any ear,” she recalls, “someone that would say, ‘Oh, let’s try it.’”But when stem cell biologist Derrick Rossi’s team at Boston Children’s Hospital used pseudouridine-containing mRNA to encode proteins that transformed mature cells into stem cells, he found quite a few ears. Serial entrepreneur Robert Langer of the Massachusetts Institute of Technology (MIT) and Noubar Afeyan, CEO of the venture capital firm Flagship Pioneering, both in Cambridge, saw the makings of a whole new class of drugs—and the idea of Moderna was born.The company, which launched operations in 2011 with Flagship funding, quickly set its sights on new (and patentable) nucleoside modifications that would provoke an even smaller immune response than pseudouridine. “This stuff was working a little bit,” says Hoge, “so why not make it work a lot?”Initially operating in “stealth mode”—without announcement of its existence—Moderna’s team screened mRNA assembled from various modified nucleosides and hit on one called 1-methylpseudouridine. It bore a chemical “bump” that the team suspected kept it from locking into key receptors on the surface of immune cells.As the data flowed in during 2011 and 2012, Bancel, who had come to Moderna from the French diagnostics company bioMérieux, began to work up a pitch. He was catching potential investors at an inauspicious time: Many were smarting from disappointing trials of RNA interference therapies, which use short, double-stranded RNA to disrupt the production of disease-causing proteins. “No one had cracked how to make RNA stable enough to be a therapeutic,” says Mene Pangalos, who heads the Innovative Medicines and Early Development Biotech Unit at AstraZeneca in Cambridge, U.K.Bancel showed Pangalos and his team two studies in which an injection of modified mRNA containing pseudouridine prompted nonhuman primates to express two human proteins. Among dozens of mouse studies, he presented work led by Moderna Co-Founder Kenneth Chien, then at Harvard Medical School in Boston, showing that mice recovering from induced heart attacks survived longer and had stronger hearts when injected with mRNA encoding a protein that drives blood vessel formation—vascular endothelial growth factor (VEGF).”That got us excited,” says Pangalos, who was eager to build up AstraZeneca’s pipeline of cardiovascular drugs. “It was incredibly high risk. It was untried and untested.” But if it could work for one disease, it would likely work for many. Changing the disease target didn’t require developing or identifying a whole new drug, just altering the mRNA sequence. And although many of the initial animal studies used mRNAs with pseudouridine, Moderna’s new chemistry was already starting to outperform that first generation in rodent studies. “I don’t think it was such a stretch to imagine the technology would continue to improve, given what they were doing,” Pangalos says. In March 2013, a few months after Moderna announced itself to the world, AstraZeneca put an up-front $240 million into a partnership to pursue up to 40 drug candidates using Moderna’s technology.Schrum, who led early chemistry research at Moderna and made some of the discoveries behind its initial patents, had left the company by the time the AstraZeneca deal was sealed. To him, the sum was astonishing, given the preliminary findings he had seen. “There was a lot of excitement that this [technology] can be applied to anything, and that this is a panacea,” he says. Before meetings with potential investors and partners, he remembers the Moderna team being “frantic to get some sort of data, just general data, without a whole lot of specifics attached.” Winning those early investments, by his estimate, “comes down to salesmanship.”Moderna’s bold premise inspired headlines comparing it to a young Genentech, the most famously successful of all biotechs. Bancel, meanwhile, insists that he never hyped the company. “We never said, ‘Oh look at mRNA; we’re going to cure 2 million diseases.’ No, we said, ‘What if? What if this could work?’” But as more cash poured in—$100 million from Alexion Pharmaceuticals to pursue rare diseases, $100 million from Merck for a set of antiviral drugs—the image of Bancel as a brash newcomer with a crisp suit and an audacious pitch became part of the company’s mystique.Afeyan at Flagship, who recruited Bancel, calls such a portrayal irrelevant “social science” that gives Moderna’s technology short shrift. “There is real science here,” he says. “There’s real data, there’s real molecules.” Engineering the messenger Moderna aims to design messenger RNA (mRNA) that directs cells to make a protein that works as a drug or vaccine. To succeed, the mRNA has to enter the cell, avoid degradation, and be translated efficiently. This mysterious $2 billion biotech is revealing the secrets behind its new drugs and vaccines The biotech Moderna delivers messenger RNA (blue) into cells to be translated into proteins by ribosomes. © Ken Richardson J. You/ Science It has taken a lot of science to make mRNA act like a drug. Some of Moderna’s most promising early candidates, although they could tiptoe past the immune system, produced underwhelming amounts of protein in animal studies. The same nucleoside modifications that made mRNA more stealthy also made it less recognizable to the ribosome. “If you’re trying to sneak in there and make a thing, you have to look pretty darn natural,” Hoge says. Moderna needed to figure out what features of naturally occurring mRNA were most important for translation, and how to restore them.By the summer of 2013, word of the company’s ambitions was wafting through academic labs, including Melissa Moore’s at the University of Massachusetts Medical School in Worcester. Moore had spent her career studying the intricacies of how nascent mRNA gets spliced in the nucleus and loaded with proteins to become a complex known as a messenger ribonucleoprotein (mRNP). Over those years, she had also grown frustrated by how many more male than female scientists held consulting roles at biotech companies. When a colleague told her about Moderna, she decided to go out on a limb.”Although we have many common connections, I don’t believe you and I have ever met,” she wrote in an email to Tony de Fougerolles, who was then Moderna’s chief scientific officer. “I am arguably the world’s expert on how the synthetic history and protein complements of mRNPs contribute to gene expression.” Maybe, Moore suggested, her knowledge could improve Moderna’s product. “I remember going home and being emotionally depleted, because I had completely just put myself out there,” she says. “I had never done anything like that before, but I knew I had to do it.”De Fougerolles invited Moore to give a seminar, which led to a sponsored research agreement, and, eventually, a position on the scientific advisory board. Last year, Moore left her tenured position to become chief scientific officer of Moderna’s research platform. “I could have spent the next 15 years turning the crank, putting out more papers, training more students,” she says, “but when I’m 80 or 90 and I look back at my life, I would regret that decision.”Moore’s academic work has advanced a counterintuitive theory about mRNA. It might seem that secondary structure—the folds and loops caused by bonding between nucleosides in the strand—should hinder protein production. Too much structure could force the ribosome to do extra work untangling the strand or even stall translation altogether. But findings in Moore’s lab supported the view that mRNA strands with more of the nucleosides that tend to form tight bonds are, in fact, easier for ribosomes to translate.The bioinformatics team at Moderna was making parallel discoveries. Even between mRNAs with the same sequence, they were finding that different modified nucleosides produced different amounts of protein. And nucleosides with a tendency to form tighter structures were more productive. The team knew that the frequency and placement of the modified nucleosides in the strand changed how it folded, and hence how it interacted with the ribosome. And because trillions upon trillions of different nucleoside sequences can code for the same protein, there were plenty of ways to engineer more efficient ones—providing they could be predicted.Doing so took the Moderna team deep into the structure of mRNA. To model how single-atom changes affected bonding between nucleosides, they enlisted a quantum chemistry expert, Michelle Hall. “When I started looking for industry jobs, people were like, ‘Oh that’s adorable. Nobody does that in industry,’” Hall remembers. “Turns out, not true.”Her calculations informed an algorithm that predicts, for a given protein, what mRNA sequence would produce the structure most appealing to a ribosome. Across many drug candidates, the team saw a several-fold increase in protein production using the new designs. Bancel recalls the meeting when they described this breakthrough: “They blew my brain on the walls.” Avoiding the hype curveOutside researchers can’t yet weigh in on how mind-blowing Moderna’s fundamental research might be. “It would be stupendous to see the data out of Moderna,” says Paul Agris, an analytical biochemist at the State University of New York in Albany’s RNA Institute who has spent decades studying the consequences of modifying RNA nucleosides.But for now, the company’s only published paper is the one from Chien’s group on producing VEGF in mice. It hasn’t revealed which modified nucleoside is in its newest generation of drug candidates. And it launched its first two phase I trials without announcing what diseases they targeted—a decision Bancel attributes to fears that financial markets would prematurely pigeonhole the company into a particular field. (Investigators are not required to register phase I trials with ClinicalTrials.gov.)Moderna’s leaders argue that they’ve disclosed research the way most private companies do—by detailing it in patent filings. “It wasn’t a deliberate effort to be secretive,” Hoge says. “The act of publication was not, in and of itself, a focus for us. In fact, it wasn’t even clear that it was anywhere on our priority list.”For many researchers who have worked with companies, that isn’t surprising. “It’s a highly competitive field, and they’ve made the decision that they don’t want to publish a bunch of papers. That makes sense,” says Daniel Anderson, a molecular geneticist who develops drug delivery systems at MIT. “Publishing papers can generate excitement. … But if you have a whole lot of people and a whole lot of money, it may be smart just to stay quiet and develop your technology and patent the heck out of it.” Votes of confidence Venture capitalists, pharmaceutical companies, and others have invested heavily in Moderna’s vision of mRNA-based drugs. V. Altounian/Science Holding its data close doesn’t seem to have hurt Moderna’s ability to raise money and advance its drugs. But now that treatments are being injected into people, “there’s a certain obligation to patients to start to tell that story,” Hoge says. The company has submitted several manuscripts to journals, and last month described the collection of drugs in its pipeline.Human safety trials have already begun for vaccines against two flu strains and the Zika virus, and for a fourth undisclosed viral vaccine developed in collaboration with Merck. In each case, the mRNA encodes viral proteins that infected cells would normally present to activate the immune system and beat back an infection. Last month, Moderna also began trials of its VEGF drug, developed with AstraZeneca. Intended to treat cardiovascular diseases as well as slow wound healing in diabetes, the growth factor-encoding mRNA is first being injected under the skin of trial participants to evaluate safety.Moderna is also doing animal safety tests of a personalized cancer vaccine that would code for immune-activating proteins unique to a person’s cancer cells, based on genetic sequencing of their tumor. Another possible cancer drug, awaiting regulatory approval for a clinical trial, consists of mRNA for a surface protein called OX40L that would, when injected into a tumor, prompt T cells to proliferate and attack.Last month’s presentation also got attention for what it didn’t describe—trials of drugs that replace missing or deficient proteins to treat chronic diseases. Most of Moderna’s advanced candidates are vaccines, which require just a low dose of mRNA that makes enough protein to kick the immune system into gear. And all of them are administered locally, under the skin or into a muscle or tumor. To tackle lifelong diseases where patients are missing a key protein, such as an enzyme that removes toxic compounds from the body, mRNA drugs will likely have to be delivered intravenously for decades. That makes even mild toxicity or subtle immune reactions a potential deal-breaker.Much of the risk comes down to formulation—the molecular packaging that ferries mRNA into cells and protects it from being hacked apart by enzymes along the way. “That’s where the breakthroughs are really needed,” says RaNA’s Heartlein. Many RNA drugs to date have encapsulated the nucleic acid in nanoparticles made of lipids. But because mRNA is so large—roughly 100 times the length of the RNA used for interference therapies—it’s harder to stabilize and to encapsulate. And many lipid nanoparticles are not easily degraded in the body, so they can cause toxic buildup in the liver. “We’re going to find applications [for mRNA drugs],” Heartlein says, but “it may not be as broadly applicable at the end of the day as people are thinking.”Hoge acknowledges that some conditions may be off limits to mRNA drugs simply because they require higher levels of protein than the mRNA can make at a safe dose. Muscular dystrophies or skin disorders where patients lack a key structural protein, for example, are a long shot. “A lot of people think that gene therapy might be the only solution for some of these diseases. And certainly for some of them, it might be,” he says.Moderna is developing delivery systems that may limit toxicity. Among its proprietary nanoparticles is a family of engineered lipids that its scientists have found to be more biodegradable—and thus more tolerable at higher doses—than existing formulations. A separate “delivery innovation” team is developing nonlipid formulations, such as polymers that form solid, porous structures interspersed with mRNA.AstraZeneca’s Pangalos says his group has its sights set firmly on mRNA drugs for chronic use, and expects a drug intended for repeated dosing to enter trials in the next 18 months. But Moderna has had to retreat from optimistic predictions about a partnership with Alexion to treat a rare disease called Crigler-Najjar syndrome. The mRNA treatment would code for an enzyme that breaks down bilirubin, a toxic substance that builds up in patients’ blood. Before it can enter human testing, the companies must be sure the dose needed to impact the disease is many-fold lower than the dose that causes toxicity.In 2015, Moderna and Alexion predicted that the drug would advance to clinical trials in 2016, but late last year they informed investors that the trials would be delayed, so that the formulation could be optimized. “Lavishly funded Moderna hits safety problems,” announced an article published by STAT after Bancel left the drug out of last month’s presentation.A missed milestone, particularly in preclinical studies, hardly signals a catastrophe, says Eric Schmidt, a biotech analyst at Cowen Group in New York City. “I’m just surprised at the drama around the situation,” he says. “Why, just because this company has been successful at raising money, is it being treated differently in the popular press?” That may be the price of Moderna’s unicorn status: The higher the hopes are for a new treatment approach, the more consequential its warts and blunders become.But wealth and secrecy may also be protective. Maybe, as Moore and Hoge concluded from their morning meeting, you don’t have to ride up and down Gartner’s hype curve if you can work through the biggest setbacks before the public ever sees them.Most small biotechs have to publicize every step of their early research in a scramble to raise money, Moore notes. “Then people get to see all the failures. We’ve had failures. We’ve gone down blind alleys. But because we’ve been quiet about it, nobody’s seen that,” she says. “That’s why I think we’re going to end up on the slope of enlightenment without passing the trough of disillusionment.”
The ICC Cricket World Cup is the international championship of One Day International (ODI) cricket.The event is organised by the sport’s governing body, the International Cricket Council (ICC), every four years. Here are 10 lesser known facts about the Cricket World Cup:1. The first World Cup was organised in England in June 1975. However, the first ODI cricket match was played only four years prior to this.2. England is the only country that has hosted highest numbers of World Cup tournaments (4 times). From the 1987 tournament onwards, hosting has been shared between countries under an unofficial rotation system, with fourteen ICC members having hosted at least one match in the tournament. India celebrating the ICC Cricket World Cup 2011 victory 3. Out of the ten editions of the ICC Cricket World Cup tournaments played and concluded till now, Australia has won four times, followed by the West Indies and India (twice each) and then Pakistan and Sri Lanka (once each). 4. Indian player Chetan Sharma is also known as World Cup hat-trick man for his record in the ICC World Cup.In the World Cup 1987, Sharma took the first hat-trick in the history of tournament when he clean bowled Ken Rutherford, Ian Smith and Ewen Chatfield of New Zealand off consecutive balls.5. South Africa’s Gary Kirsten has the highest score in a World Cup match, making 188 not-out against UAE in 1996.6. Clive Lloyd of West Indies and Ricky Ponting of Australia are the only captains to win the ICC Cricket World Cup trophy twice.Lloyd won the cup in 1975 and 1979 while the Australian batsman won in 2003 and 2007.advertisement7. The highest score of World Cup matches is 433-5 in India verses Bermuda match in 2007 and the lowest is 36 between Canada and Sri Lanka in 2003.8. Kepler Wessels is the only player to represent two countries in the history of ODI.He played for Australia from 1982 to 1985 and then represented South Africa in 1991.9. In 1996, Nolan Clarke of the Netherlands became the oldest player (47 years, 257 days) to play in a World Cup.10. For the ICC Cricket World Cup 2015, two opening ceremonies were held (first time in the history of ODIs) separately in Christchurch, New Zealand and Melbourne, Australia, on February 12, 2015, two days before the first two matches.Also, the ICC has declared a total prize money pool of 10 million dollars for the tournament, which is 20 percent more than the 2011 edition. The prize money will be distributed according to the performance of the winning team members.
READING, MA — Reading Cooperative Bank (RCB) has donated $1,000 to the Ipswich River Watershed Association to help support its clean water initiatives. The Ipswich River Watershed Association works to protect nature and make sure that there is enough clean water for people, fish, wildlife and the children of tomorrow.The Ipswich River Watershed Association is the voice of the Ipswich River. They work to protect nature and make sure that there is enough clean water for people, fish and wildlife, today and for our children and theirs. The Ipswich River and streams, ponds and coastal waters of our region are healthy and beautiful. Clean water flows year-round, and native fish and wildlife thrive. Natural areas help keep the river clean and provide places for families to enjoy nature. The Ipswich River Watershed Association works in partnership with communities, businesses, schools, and other organizations and residents to protect the river.“Protecting the environment means protecting our communities,” said Bryan Greenbaum, Senior Vice President and Chief Operating Officer. “It’s important to support efforts which seek to ensure that our drinking water is clean and safe.”To learn more about or donate to the Ipswich River Watershed Association, please visit their website: https://www.ipswichriver.org/About Reading Cooperative BankReading Cooperative Bank is a depositor owned co-operative founded in 1886. This community-centric North Shore financial service provider has branches in Reading, Wilmington, North Reading, Andover, and Burlington. They also operate teaching branches at Northeast Metro Tech in Wakefield (open to the public) and at Reading Memorial High School (students and staff only), as well as an online branch at http://www.readingcoop.com.(NOTE: The above press release is from the Reading Cooperative Bank.)Like Wilmington Apple on Facebook. Follow Wilmington Apple on Twitter. Follow Wilmington Apple on Instagram. Subscribe to Wilmington Apple’s daily email newsletter HERE. Got a comment, question, photo, press release, or news tip? Email firstname.lastname@example.org.Share this:TwitterFacebookLike this:Like Loading… RelatedReading Cooperative Bank Donates $2,500 To Ipswich River Watershed AssociationIn “Business”Ipswich River Watershed Association Announces Paddle-A-Thon 2018, Registration Now OpenIn “Community”Recommended Winter Hikes From Ipswich River Watershed AssociationIn “Community”
For years I thought Apple was forging its own path in the smart home, that there was a purpose behind its slow-boil approach to working with smart-home partners and integrating Siri voice control features — that at some point the company’s strategy would make sense. Sure, to some extent it does make sense. If you’re an Apple loyalist, the pathway is clear: You probably already have Apple Music, you’re likely going to buy a HomePod smart speaker and you’ll look for lights, locks, thermostats and other smart home gadgets that work with Apple HomeKit. You’ll overlook Apple’s other limitations because the platform works well enough. And who knows what potential innovations await with the hiring of Google alum John Giannandrea, now Apple’s chief of machine learning and AI strategy.But there are some serious, lingering limitations with HomeKit, Siri and Apple’s overall approach to smart home hardware that should have been addressed by now. Alexa and Google Assistant continue to move forward while Apple’s platform lags far behind. Let’s take a look at the current state of the Apple smart home and discuss what we’d like to see from it next year. Comments Aug 31 • Best smart light bulbs for 2019 (plus switches, light strips, accessories and more) Apple Music Spotify Siri Apple Apple HomeKit Apple Music now works on Amazon Alexa smart speakers Great sound, but it’s trapped in Apple’s world Siri vs. Alexa vs. Google Assistant Smart Home Wireless & Bluetooth Speakers CNET’s Holiday Gift Guide for 2018: The gifts they’ll loveStocking stuffers: The best gifts under $25 Aug 30 • Battling bot vacs: iRobot Roomba S9+ vs Neato Botvac D7 Connected Aug 31 • The best coffee grinders you can buy right now 1:08 Share your voice See All Tags Smart lightbulb tips and tricks Now playing: Watch this: CNET Smart Home 35 34 Photos Aug 31 • Alexa can tell you if someone breaks into your house • At $349 each, the HomePod smart speaker is pricey. Where’s the more affordable HomePod? Rumors of a “HomePod Mini” have been discussed for months, but we have yet to see it. There’s no Siri-enabled HomeKit smart display, either. New HomePod features and improvements to Siri Both stereo pairing and multiroom audio were added to the HomePod in May, a few months after the smart speaker’s initial product launch. A few other HomePod updates have trickled in, including calling, searching for a song by its lyrics and setting multiple timers. The additions have helped keep Siri and the HomePod somewhat competitive, but Apple’s voice assistant still struggles to keep up with Alexa and Google Assistant. Amazon and Google have made significant progress with natural language, making Alexa and Google Assistant conversational. Use the Google Assistant on the Google Home Hub to cook a meal and it will walk you through the steps, tutorial-style. Amazon smart speakers now offer a “whisper mode” — it sounds kind of creepy, but it means you can use your Alexa speaker during your kid’s nap time. These nuances make Alexa and Google Assistant more appealing and more natural to use in a variety of scenarios. Apple just isn’t there yet. Enlarge ImageAsk Siri to adjust HomeKit-enabled lights, locks, thermostats and other smart home devices. Tyler Lizenby/CNET Support for third-party devices Apple has make some strides as far as opening up its platform. Manufacturers no longer need to stick an MFi hardware chip in every HomeKit-enabled device like they used to. Apple has also announced a software developer kit making it easier for developers to partner with Apple on HomeKit projects. At the same time, Apple lags way behind Amazon and Google Assistant when it comes to third-party smart-home partners. It has more than it used to, but it’s nowhere near catching up with Amazon, which reached 50,000 Alexa skills back in September according to Voicebot.AI. An open platform I know, I know. Apple and “open platform” don’t necessarily go together, but there are just two things I want to see from Apple that would make a big difference in the smart home: Make an Android version of the Home app Add support for Spotify and other third-party music streaming services to HomePod Apple’s Home app is where you go on your iOS phone or tablet to add and make adjustments to your HomeKit, Siri-enabled smart devices. It’s a decent enough app and Apple added it to MacOS Mojave in 2018, so you can view, manage and control your smart home products straight from your Mac. The HomePod currently only works natively with Apple Music. You can use Airplay 2 to play audio from third parties on the HomePod, but they don’t work seamlessly via Siri. Apple should make the HomePod compatible with Spotify at the very least. Amazon now works with Apple Music, as well as Spotify, Pandora, Amazon Prime Music, Amazon Music Unlimited, iHeartRadio, TuneIn and SiriusXM. Enlarge ImageA look inside the Apple Home app for iOS and how to automate the lights turning on. Screenshots by Ry Crist/CNET The outlook Given the success of Alexa and Google Assistant, why isn’t Apple doing more with Siri, HomeKit and the HomePod? There are so many different things they could address to stay more competitive. Where’s the HomePod that’s actually affordable? Why isn’t there an Apple smart display? When will Siri be able to answer more questions (and better)? The list goes on and on. We’ll continue to keep an eye on things here, as always, and hope that Giannandrea ushers in a new age for the Apple smart home. Prove us wrong, Apple.Apple declined CNET’s request for comment. reading • Hey Siri, are you there? Siri runs the smart home with these Apple HomeKit gadgets CNET Smart Home Related links More Apple hardware The HomePod is Apple’s only piece of smart home hardware to date, introduced in early 2018. (You can make a case for the Apple TV counting as well since it works with Airplay 2, but it’s more smart-home-adjacent than smart-home-exclusive.) Fortunately, the HomePod is a great speaker, delivering excellent sound quality in a relatively compact package. Pair two HomePods together for stereo sound in the same room — or put them in different rooms to enable multiroom audio (these come via Airplay 2). It’s a solid device. But Amazon and Google have many more smart speaker options. There’s even a limited selection of third-party devices that work with Alexa and Google Assistant. The Facebook Portal and Portal Plus work with Alexa and so does the Sonos One. Google Assistant is built into the JBL Link View and the Lenovo Smart Display, among others.
The badge of a Ford carReutersAmerican multinational automaker Ford is likely to cut about 10 percent of its salaried workforce worldwide. The decision comes at a time when the brand aims to boost its profits and stock price.While the company is yet to make any announcement on the rumoured job cut, Ford did say it intended to concentrate on cost optimisation and higher efficiency.”We remain focused on the three strategic priorities that will create value and drive profitable growth, which include fortifying the profit pillars in our core business, transforming traditionally underperforming areas of our core business and investing aggressively, but prudently, in emerging opportunities,” Reuters quoted the Dearborn company as saying.”Reducing costs and becoming as lean and efficient as possible also remain part of that work. We have not announced any new people efficiency actions, nor do we comment on speculation.”The move comes at a time when there have been doubts surrounding CEO Mark Fields and his strategy. While the company has made profits in the past and remains a key player in the automobile industry, Ford stock has seen a decline of 17 percent since January to $10.94 per share.Experts also believe Ford is considering job cuts to offset declining sales figures.”Belt tightening comes as no surprise with sales softening and profits squeezed,” Detroit Free Press quoted Michelle Krebs as saying. “Ford has been under particular pressure to take action to boost its stock price. The board meeting last week likely added pressure to get specific about cost cuts.” ReutersFord held the annual meeting last week and stakeholders are said to have expressed their displeasure over the falling stock of the company during the meet. Ford executive chairman Bill Ford told Detroit Free Press: “Look, we’re as frustrated as you are by the stock price. And a couple of people have said, ‘Well, does the Ford family care about the stock price?’ The short answer is yes, a lot. Much of our — most of our net worth is tied up in the company. And the stock price matters a lot to us.”Ford, along with other auto giants, has been criticised by US President Donald Trump for using Mexican plants to produce cars for the US. Post the criticism, Ford had decided to create about 700 jobs in Michigan, instead of building a $1.6 billion car factory in Mexico.It looks like the IT companies are not the only ones cutting jobs. Last week, IT giants such as Infosys, Wipro, Capgemini, Cognizant and TCS among others made news for laying off employees. While the companies said the sackings were part of the ongoing appraisal process, many firms have been accused of sacking employees in India and hiring workers in the US to appease the Donald Trump administration.
Nusli WadiaTwitterChairman of the Wadia group of companies Nusli Wadia has urged capital market regulator Securities and Exchange Board of India (SEBI) to take action against three independent directors from three Tata group companies.Wadia alleged that these directors had made wrong declarations in the company annual reports, Business Standard (BS) reported.In his letter, Wadia named Tata Steel independent directors Andrew Robb and Mallika Srinivasan, and Nasser Munjee, an independent director on the boards of Tata Chemicals and Tata Motors.In the eight-page letter to SEBI Chairman Ajay Tyagi, Wadia requested Tyagi to conduct a “full and impartial investigation” under listing regulations on the reports submitted by the audit committees of the respective companies, BS reported.Citing annual reports, the audit committees have filed their responses with SEBI. The audit committee had also examined the charges made by Wadia.But Wadia said that Munjee, the chairman of the audit committee of both Tata Motors and Tata Chemicals, is not independent and the committee, therefore, was “wrongfully and illegally constituted”.”The audit committee of these companies, whose chairman though not independent, de facto and de jure, reported to Sebi that there has been compliance with all legal requirements and corporate governance standards,” Wadia wrote in his letter to SEBI.The chairman of Wadia family-owned conglomerate pointed out that committees were constituted in violation of the Companies Act.”The agenda is how to ensure independent spirit of the independent directors. There is a lot of criticism on whether the independent directors are really independent. This is a problem worldwide. All matters related to the role of independent directors are being discussed very thoroughly,” BS quoted Sebi’s whole-time member S Raman.This is the second letter Wadia has written to the regulator, alleging the independent director had a direct conflict of interest. He wrote the first letter on January 6 when he was holding position of as chairman of the nomination and remuneration committees of these companies.As an independent director, Nusli Wadia served on the boards of Tata Steel, Tata Motors and Tata Chemicals for over 25 years. Earlier, in October last year, when Cyrus Mistry was ousted as Tata Sons chairman, Wadia supported him. In January, Mistry and Wadia were removed from the boards of all Tata companies.Last year, Wadia had sent a defamation notice to the Tata Sons board asking it to withdraw “false” and “defamatory” allegations made against him or face a lawsuit. The industrialist had said that the company’s plans to remove him as an independent director had harmed his reputation and public image.
Vice President of Xiaomi Global, Hugo Barra gestures during the launch of Xiaomi’s Mi4i smart phone in New Delhi on April 23, 2015.MONEY SHARMA/AFP/Getty ImagesChinese smartphone maker Xiaomi is considering an initial public offering (IPO) as soon as next month with banks suggesting Hong Kong as the most likely destination, according to a Bloomberg report.The company, which was once the most valuable start-up in the world, has picked China’s Citic Securities to handle its issuance of Chinese depositary receipts (CDRs), the report said citing people familiar with the matter.Depositary receipts are not technically shares, but allow investors to hold shares listed elsewhere.The Beijing-based company may file for a public listing as soon as next month and is targeting a valuation of about $100 billion, said one of the people, according to the report. Xiaomi could be the biggest IPO since Alibaba Group Holding’s $25 billion debut in 2014.Xiaomi declined to comment on its listing plans.Chinese government has allowed launching depository receipts that would allow citizens to invest in the country’s top tech firms listed outside mainland China like Alibaba Group Holding, Baidu Inc, JD.com, and Tencent Holdings.With CDRs, companies that already trade on overseas exchanges, including Alibaba and Tencent Holdings, would issue securities that could be purchased in mainland China.Xiaomi has gained momentum in recent months after stumbling against local rivals such as Huawei Technologies and Oppo. The company, led by Lei Jun, has invested aggressively in retail stores and in India.Xiaomi has announced that it will invest Rs 60 – Rs 70 billion ($1-1.1 billion) in around 100 Indian tech startups over the next five years to strengthen its hardware and software ecosystem.The company plans to invest in tech startups which are concentrating on the mobile software business. The investment will help Xiaomi source software and hardware assistance, thereby helping it create apps for its smartphones and upcoming products.
Jatiya Samajtantrik Dal president ASM Abdur Rob speaks at the programme of Jatiya Oikya Front on Friday. Photo: Prothom AloJatiya Oikya Front will form a human chain in the city on 30 March next to push for its various demands, including the annulment of gas-tariff hike proposal, reports UNB.Leaders and activists of the alliance will form the human chain in front of the Jatiya Press Club at 11:00am.Besides, Oikya Front will hold rallies and public herrings in different divisions and districts in April demanding reelection, cancellation of 11th parliamentary polls.Nagorik Oikya convener Mahmudur Rahman Manna announced the programmes at a press conference after a joint meeting of steering committee of the alliance at its Old Paltan office.Manna said they will form the human chain also to register their protest against the government’s failure to ensure road safety, mismanagement in upazila polls, snatching students’ votes in DUCSU polls, destroying election system and limitless financial inequality and plundering by the government.“We’ll also hold rallies or public hearings in all divisions and different districts in April to spread our movement across the country,” he said.The Oikya Front leader said people did not go to cast their votes in the recent upazila polls as they lost their confidence in the election system after ‘vote robbery’ on 29 December in the national election.Under the circumstances, he said their alliance has decided to continue its movement to realise their demand for a fresh national election. “We’ll wage a movement based on that demand, and will continue it until we get the victory.”Manna said their meeting also chalked out a two-day programme to mark the Independence Day.As part of the programmes, he said leaders and activists of Oikya Front will place wreaths at the National Mausoleum in Savar at 9:00am on 26 March. The alliance will also will hold a discussion on 31 March at the Institution of Engineers, Bangladesh.Jatiya Samajtantrik Dal president ASM Abdur Rob, BNP standing committee member Abdul Moyeen Khan, Gono Forum executive president Subrata Chowdhury and general secretary Mostafa Mohsin Montu were, among others, present.