Wired : A Creator of the Ebola Vaccine Has Hope for Slowing Covid-19

A Creator of the Ebola Vaccine Has Hope for Slowing Covid-19
Gary Kobinger says a vaccine targeting groups like the elderly could be ready in less than a year, and control measures are slowing the disease's spread.

WHEN THE LATE Bob Simon interviewed Gary Kobinger for 60 Minutes in 2015, Kobinger was working principally in a space suit in a special clean room behind bulletproof glass. At the time, he was a top virologist at Canada’s National Microbiology Lab, where he became a critical player in the development of the early Ebola vaccine ZMapp. Now he’s the director of the Infectious Disease Research Center at the Université Laval in Quebec City, his hometown. His lab helped with the early development of Inovio Pharmaceuticals’ Zika vaccine in 2017.

Today, Kobinger is among hundreds of scientists worldwide working on potential Covid-19 vaccines; he is working with Inovio and Medicago, another drug company. WIRED talked with Kobinger by phone last week. The conversation has been condensed and edited.

WIRED: You've been watching and helping with epidemics your entire career. How does Covid-19 compare to, say, the Ebola epidemic?

GARY KOBINGER: Well, it's on a global scale of course, so it’s more widespread than Ebola. But it’s also important to remember that this virus has a less than 5 percent fatality rate, versus 80 percent for Ebola before vaccines. [There were 28,652 Ebola cases during the 2014-2016 outbreak in West Africa and 11,310 deaths, according to the Centers for Disease Control and Prevention. There are more than 775,000 Covid-19 cases, according to Johns Hopkins University. It has killed more than 37,000 people.]

But pandemics are so similar in the way societies respond. I went to many different countries in Africa because of Ebola outbreaks. And often we were accused of being the ones bringing in the virus and infecting the population. We have the same thing today, where countries are saying it’s the Army or a secret Defense Department plan or whatever to export the virus.

We also see the same delays. There’s this natural optimism of societies, where you think the virus isn’t going to come here, and you end up facing exactly the same last-minute urgent needs for things like PPEs [personal protective equipment like masks and gowns]. China had problems with PPEs in mid-January. So you could argue that we should have planned for that. Instead we are scrambling as if we never saw it coming.

The difference this time is, because Covid-19 is affecting so many countries, you see a lot more sense of urgency to develop countermeasures—vaccines, treatments, better supportive care like ventilators. Compare that to being in the middle of the tropical forest in Africa, like we were with Ebola. We would have liked to have had all that fancy equipment. But people were not that interested in what we were doing. With Covid-19, I’ve had all levels of the Canadian government coming to me, saying, “Gary, if you need anything, please let us know. We are here to help.” I've never had that kind of support in my career.

There are dozens of labs worldwide working on a Covid-19 vaccine, including yours. Is that a good thing, or should we be coordinating and focusing that effort more to maybe get a vaccine faster?

It’s a good thing. It’s actually important to test a lot of vaccines. We don’t want to put all our eggs into one basket, only to have that one vaccine fall short in clinical trials. If we could have five vaccines that are safe and work and are potent, that would be much better. It also reduces the chances for manufacturing bottlenecks. With five vaccines, maybe we could manufacture enough for everybody on the planet. But with only one manufacturer, I don’t think it will be possible.

But it needs to be done the right way. If you develop a vaccine that’s not powerful enough to counter the virus, it can actually make the infection harder to treat. What you could see are people becoming more susceptible to acquiring the infection and maybe more susceptible to severe disease. That's something to really watch out for.

We also see the same delays. There’s this natural optimism of societies, where you think the virus isn’t going to come here, and you end up facing exactly the same last-minute urgent needs for things like PPEs [personal protective equipment like masks and gowns]. China had problems with PPEs in mid-January. So you could argue that we should have planned for that. Instead we are scrambling as if we never saw it coming.

The difference this time is, because Covid-19 is affecting so many countries, you see a lot more sense of urgency to develop countermeasures—vaccines, treatments, better supportive care like ventilators. Compare that to being in the middle of the tropical forest in Africa, like we were with Ebola. We would have liked to have had all that fancy equipment. But people were not that interested in what we were doing. With Covid-19, I’ve had all levels of the Canadian government coming to me, saying, “Gary, if you need anything, please let us know. We are here to help.” I've never had that kind of support in my career.

There are dozens of labs worldwide working on a Covid-19 vaccine, including yours. Is that a good thing, or should we be coordinating and focusing that effort more to maybe get a vaccine faster?

It’s a good thing. It’s actually important to test a lot of vaccines. We don’t want to put all our eggs into one basket, only to have that one vaccine fall short in clinical trials. If we could have five vaccines that are safe and work and are potent, that would be much better. It also reduces the chances for manufacturing bottlenecks. With five vaccines, maybe we could manufacture enough for everybody on the planet. But with only one manufacturer, I don’t think it will be possible.

But it needs to be done the right way. If you develop a vaccine that’s not powerful enough to counter the virus, it can actually make the infection harder to treat. What you could see are people becoming more susceptible to acquiring the infection and maybe more susceptible to severe disease. That's something to really watch out for.

But the ultimate goal is to find a vaccine that keeps people from getting the virus at all. Sometimes patients who get it are left with lung damage that's not repairable. And even if the virus recedes, it could come back worse later. In 1918 the Spanish flu in the spring was a very mild wave, and then it came back with a vengeance in the fall.

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Are there other potential therapies?

Plasma transfer. I think they are doing this already, where you take blood from someone who has recovered, isolate their antibodies, and then you can transfuse others who are infected. This is old technology from the 1700s, and in clinics they are very good at managing the side effects. It didn’t work very well against Ebola, because we couldn’t concentrate it enough. It needed to be 20 times more concentrated than it was to have an effect. You needed 20 donors for one recipient. Usually you do two or three donors per recipient. If I had to put money on something that would help the most, it would be that. It's not to say other drugs we’re trying won't work. But I wouldn’t expect miracles, because we would know already if they worked really well.

How is the pandemic affecting your work day to day?

The schools are closed, and a lot of people who work at the lab have kids, so some need to stay home during the day. It’s interfering with the normal activities of the lab. We have to work in shifts, so those who don’t have childcare can work when their spouse or partner is home with the kids.

Are you worried?

No. My parents are at high risk now, so I worry about them. But from a high-level perspective, when you look at other infectious diseases, this one is not that alarming. It will get worse before it gets better, but a lot of the control measures are working. Those may not reduce the final number of infections, but they will delay them. And by delaying them, more people will survive, because more will have access to advanced care.

Yes, flattening the curve may be one of the hardest concepts to understand, especially for young people. Do you have a message for them?

It’s not right to have them acting like, “Well, I won’t get very sick anyway.” There is data out of Southeast Asia that suggests that young people have been driving 30 to 40 percent of cases, including cases among the elderly. So they need to take more responsibility, to make sure they aren’t vectors of transmission.

Reuters : Smoking diners to take it outside as Tokyo ban kicks in

Smoking diners to take it outside as Tokyo ban kicks in

TOKYO (Reuters) - Patrons of Tokyo restaurants and bars will be able to light up indoors for the last time on Tuesday as one of the world’s most cigarette-friendly cities starts enforcing anti-smoking laws from April 1.

Japan lags behind many countries in its efforts to reduce tobacco usage, and the ban - just in Tokyo - only applies to traditional cigarettes, not so-called “heat not burn” devices for which Japan is the world’s biggest market. E-cigarettes that use liquid nicotine are banned.

The ban was part of Tokyo’s preparations for the now-delayed 2020 Olympics, and covers establishments with hired employees, meaning many of the family-owned-and-operated bars and restaurants that the city is famous for are exempt.

It took two years for the ban to come into effect - parliament approved the law in 2018 along with other national anti-smoking legislation - highlighting the hurdles anti-smoking activists face in a country where the biggest tobacco maker, Japan Tobacco, is one-third owned by the government and its products provide substantial tax revenue.

“This year’s law is still not sufficient,” politician and anti-smoking campaigner Shigefumi Matsuzawa told Reuters. “We had to set many compromises in order for it to pass, so there are several loopholes.”

Less than a fifth of Japanese still smoke, down from about half the population half a century ago, but cigarettes are widely available and affordable: a pack of 20 costs around 500 yen ($4), a third of the price in fellow Group of Seven member Britain. Activists say second-hand smoke kills around 15,000 people a year in Japan, many of them women and children.

Kenji Ogura, a senior vice president at Japan Tobacco, expected the ban to have an impact on sales at a “certain level” but did not give any details. Japan Tobacco has been struggling to make its heated tobacco devices more popular than those by rival Philip Morris International Inc, and last year cut its profit outlook for this financial year.

Smokers like 30-year-old Daiki Watanabe said the law would do little to change habits. “Human will is a weak thing,” he said. “I don’t want to stop. If I am able to smoke, I will.”

But several restaurants, worried about losing customers, have built designated smoking areas. “For customers who don’t smoke, we have listened to their voices,” said Akihiro Funyuu, manager of a Tokyo izakaya, or bar. “But here, we’ve created a smoking room to listen to the smokers’ voices too.”

The law takes effect as Japan is battling a coronavirus outbreak that has so far infected more than 2,000 people and killed 59.

The WHO has said tobacco users are likely to be more vulnerable to being infected by the virus, but for smokers like Ryo Okumura, that’s not enough of an incentive to quit.

“If I get the virus, I get the virus,” he said. “I can’t just stop. It’s an indulgence.”

FT : Coronabonds are no easy fix

Lorenzo Bini Smaghi had a ringside at the eurozone’s last economic crisis. Now chair of Société Générale, Bini Smaghi was an executive board member of the European Central Bank from 2005 until 2011. In this piece he argues that there are similarities between then and today — namely that mutualised debt is back in fashion. Yet the barriers then remain in place now, and it is difficult to see them being surmounted.

Eurobonds are back in fashion. We have even had a term — Coronabonds — coined.

Eurobonds are a great idea in theory. European countries would have access to funds to boost spending and lower taxes without increasing their national debt.

In practice, however, it’s more complicated.

The adoption of Eurobonds entails a major political choice of transferring sovereignty to Europe on a whole range of issues. While this may be desirable, it is certainly not easy to achieve quickly.

Why is this? The attractiveness of any bond issued in the markets depends on its guarantors. Investors want assurance interest will be regularly paid and that the outstanding debt is sustainable. Public bonds are generally guaranteed by the states’ assets and its ability to collect tax. So in order to issue Eurobonds, the Union needs to be able to generate new fiscal revenue.

An oft-touted advantage of a Eurobond is that it would make it cheaper, in the aggregate, for countries to borrow. Yet that would mean the bonds would have to carry the highest credit rating. Would a triple-A be offered without a direct EU fiscal authority? I view it as very unlikely.

There is a way round this. Whole parts of national budgets could be pooled into a European budget, under the authority of European institutions. For instance, it could be decided health systems are not any more under the authority of the member states but become a European competence.

This is not an impossible scenario, maybe a desired one in the view of many. However, it would be an illusion to think that this would be easy and quick to achieve politically.

Could Eurobonds be purchased by the European Central Bank, directly at issuance, thereby circumventing the need for a guarantor? That would be no panacea. If the market value of the purchased bonds was lower than the face value, the central bank would incur a loss that would translate into lower seigniorage paid back to the national Treasuries. In any case, the Statutes of the ECB do not permit the purchase of government bonds on the primary market.

The guarantees would be less of an issue if Eurobonds were used to finance investments, such as European infrastructure, rather than current expenditure. The investments, and their proceeds, would represent the guarantees.

An alternative is to resort to the European Stability Mechanism, which has a Triple A rating, thanks to its capital basis. The ESM has already issued bonds to finance the adjustment programs of countries like Spain, Portugal, Greece and Ireland. The ESM can issue an additional €400bn, and even more if its capital was further increased. This mechanism does not avoid an increase in the national debt, but the borrowing cost would be lower.

Using the ESM raises another political issue. The ESM can grant loans only on the basis of an adjustment program agreed with the European institutions, which contains a series of conditions. Resorting to the ESM thus creates a stigma. It may signal a fragility to the markets and a relative loss of sovereignty with respect to the strings attached. Rather unfair during a crisis with its roots in exogenous health factors, rather than fiscal indiscipline.

So what is the solution?

I think it would be two-handed. First, a special ESM facility could be created with conditionality limited to an ex-post monitoring of the resources used to address the systemic crisis, as proposed by, for instance, Olivier Blanchard. Second, several countries could apply simultaneously to reduce stigma. This would require a sign of solidarity, notably by countries that have a relatively good rating and would not directly benefit from accessing the ESM.

One final issue. Some suggested that the ECB should purchase the bonds issued by the ESM, under its various mammoth bond-buying programmes.

This would be a mistake. The bonds issued by the ESM are considered among the safest and are in high demand all over the world. Their issuance in the market would enhance the international role of the euro. It would thus make no sense for the ECB to create liquidity by purchasing an asset which is itself very liquid. This would not be the best way to counter market instability and to accommodate the appetite for liquidity.

The ECB should rather continue to purchase assets issued by the member states or by private institutions. This reduces significantly liquidity risk and aids the sustainability of countries’ debt burdens.

To conclude, two important political choices must be made on the following questions. The first is, should we promote a broad transfer of economic and social competences from the national to the European level? The second: should ESM aid come with fewer strings and less stigma?

These choices must be made explicitly and explained to the public. Otherwise it is useless, and illusory, to talk about Eurobonds.

FT : Big drugmakers under pressure to share patents against coronavirus

Big drugmakers under pressure to share patents against coronavirus
WHO backs making pharmaceuticals open up intellectual property as it did to fight HIV/Aids

Drugmakers are facing mounting calls to give up their patent rights for potentially life-saving treatments and vaccines for coronavirus as authorities worldwide race to curb the pandemic’s death toll.

The heads of the World Health Organization and Unitaid, a UN-backed group funding global health innovation, have welcomed a proposal devised by Costa Rica for companies voluntarily to pool their intellectual property for all medical interventions — including treatment, vaccines and diagnostics.

Doing so would enable governments or generic drugmakers to manufacture and sell the products at much lower prices than are currently available in the world market.

Marisol Touraine, Unitaid’s chair and a former French health minister, told the Financial Times that “extraordinary circumstances” warranted “extraordinary solutions”.

Pharmaceutical companies have joined intellectual property pools in the past that have enabled treatments for HIV/Aids, tuberculosis and Hepatitis C to be extended to low-income countries at affordable prices. The proposed coronavirus pool, however, would be available to countries worldwide.

Daniel Salas, Costa Rica’s health minister, told the Financial Times he was hopeful the WHO would soon go ahead with the plan.

In a statement, the WHO said it was committed to equitable access, including for interventions related to Covid-19, the disease caused by the novel coronavirus. “We are exploring all avenues to ensure people who need it have access to effective and safe products for Covid-19,” it said.

On Monday, a vast mobilisation of global healthcare groups to fight the virus accelerated with Johnson & Johnson announcing a potential vaccine that could be available early next year. Abbott Laboratories has also launched a rapid test kit.

Drugmakers are usually jealous guardians of their most lucrative patents, which expire years after they are first filed.

Gilead Sciences performed a U-turn last week, renouncing a so-called orphan drug designation in the US that granted special status to its potential coronavirus treatment remdesivir, and did so only 48 hours after first disclosing it.

Gilead said it was aware of the Costa Rican proposal and that it would evaluate any programme once it was defined by the WHO.

AbbVie, which makes a potential treatment known as Kaletra, gave up its global intellectual property rights for the drug after Israel issued a “compulsory licence” that enables the country to use it against coronavirus without the patent holder’s consent.

Germany, Canada, Australia and Chile have all taken steps or are weighing up moves to issue compulsory licences more easily.

Switzerland’s Roche, which makes testing kits for the virus, agreed to share the recipe for its testing liquid with the Dutch government after lawmakers there accused it of rationing supply and significantly decreasing national testing capabilities.

The company declined to comment on the shortage but noted there was no intellectual property protection surrounding the liquid.

Supporters of the Costa Rican proposal include the former patent chiefs of Switzerland’s Novartis and US biotech Gilead.

Members of the European Parliament and several groups, including Médecins Sans Frontières, have separately said monopolies should not be granted in the fight against the novel coronavirus.

Ms Touraine, Unitaid chair, said: “Solidarity is not only a question of humanitarian approach and perspective, it’s also a very rational approach. To fight a global pandemic we need a global response and we need to provide equitable access to treatment.”

Jamie Love, of Knowledge Ecology International, an intellectual property advocacy group, said: “This is a moment, a crisis, that calls for people to co-operate and take care of each other. The effort to pool the rights in technologies and data globally is designed to make things happen faster and to have more equal outcomes, globally.”

Sanofi and Eli Lilly, which are investigating vaccines and potential treatment candidates, did not respond to requests for comment.

IFPMA, a European lobby group for drugmakers, said the effects of the pooling proposal on the current pandemic would likely be very limited. IFPMA however said the industry had a “strong sense of responsibility” to act alongside governments and health systems worldwide.

Bruno Bulic, a pharma analyst at Baader Helvea, said the industry had come under intense scrutiny in recent years over claims of profiteering. “The time has come to prove industry opponents wrong, and that's best done by lifting the toll booth,” he said.

>>> US Gapping down

Gapping down
In reaction to disappointing earnings/guidance:

  • RH -11.5%, VFF -11.3%, CRON -5.4%, BNTX -2.4%

Other news:

  • AMRN -70.7% (reports of an unfavorable patent ruling for Vascepa)
  • SVRA -7.7% (terminates enrollment in Phase 3 AVAIL and Phase 2a ENCORE studies due to COVID-19)
  • BBX -6.3% (drew down $60.0 mln under its $125.0 million revolving credit facility on March 19)
  • DPZ -5.7% (says Q1 comps were +1.6% at US stores, US sales were impacted by many factors)
  • HIBB -5.5% (names Robert Volke as CFO)
  • RETA -4.9% (provides COVID-19 update in connection with clinical programs; to stop Phase 3 CATALYST study)
  • ADC -4.6% (commences public offering of 2.5 mln shares)
  • CODX -4.5% (discloses it does not anticipate using its emergency COVID-19 tests in the near future )
  • LC -3.5% (provides update on effects of the coronavirus)
  • CCL -3.5% (Carnival and Carnival plc (CUK) commenced an underwritten public offering of $1.25 billion of shares of common stock of the Corporation)
  • PDM -1.5% (still evaluating impact on the co's earnings projection)

Analyst comments:

  • TWLO -2.2% (downgraded to Neutral from Overweight at Piper Sandler)
  • COUP -1.2% (downgraded to Neutral from Overweight at Piper Sandler)

>>> US Gapping up

Gapping up
In reaction to strong earnings/guidance:

  • SQNS +10.3%, CAG +4.3%

Other news:

  • AKRO +34.5% (reports all AKR-001 dose groups met week 12 efficacy endpoints in NASH Phase 2a BALANCED study)
  • MRSN +15.5% (reports updated data from Phase 1 dose escalation study of XMT-1536)
  • CVLT +8.6% (Starboard (Jeffrey Smith) discloses 9.3% active stake)
  • FANG +6.8% (reduces Q4 exit rate production guidance)
  • CTMX +5.2% (achieves clinical milestone CX-2029 program, triggering a $40 mln payment from AbbVie)
  • MT +4.9% (ArcelorMittal provides an update on the impact of COVID-19)
  • RDS.A +4.2% (provides production guidance)
  • CTSO +3.7% (cytokine adsorber has been approved to be marketed and sold in Mexico by the country's health authority)
  • CSPR +2.7% (extends closure of North America retail stores)
  • BA +2.4% (awarded $1.6 bln Navy contract modification)
  • GWPH +2.1% (GW Pharma and Greenwich Biosciences announce FDA acceptance of sNDA filing with priority review for Epidiolex)
  • PRQR +1.9% (reports positive findings from an interim analysis in the Phase 1/2 trial of QR-421a)
  • NICE +1.3% (reports significant uptake in agents adapting their contact center schedules in response to the recent outbreak of COVID-19)

Analyst comments:

  • APA +6.1% (upgraded to Neutral from Sell at UBS)
  • ACAD +4.6% (upgraded to Buy from Neutral at Goldman )
  • CRUS +3.6% (upgraded to Buy from Underperform at BofA/Merrill)
  • CAKE +1.8% (upgraded to Buy from Hold at Gordon Haskett)
  • HPE +1.5% (upgraded to Overweight from Equal Weight at Wells Fargo)

>>> US Early premarket gappers

Early premarket gappers

  • Gapping up:
    • CTMX +13.4%, CVLT +7.3%, AKRO +4.8%, MT +4.6%, RDS.A +4.6%, BA +3.8%, NCLH +3.4%, CSPR +2.7%, SGMS +0.8%, CRON +0.8%, PLNT +0.6%
  • Gapping down:
    • AMRN -65.9%, RH -9.6%, SVRA -7.7%, RETA -4.9%, DPZ -4.8%, ADC -4.6%, LC -3.5%, CODX -2.6%, PDM -1.5%, PZZA -1.2%, HIBB -1.2%, MRSN -0.9%

This crushing double blow for the oil sector could force a wave of consolidation

This crushing double blow for the oil sector could force a wave of consolidation, say analysts

Twin blows from price wars and a demand-crushing deadly virus could usher a new era of consolidation in the oil industry, some 20 years after the last big wave of mergers, say some observers.

“I would be gobsmacked if 18 months from now we didn’t have fewer names in the space as a whole. I don’t think that’s really a surprise,” James Gutman, Dolfin’s head of investment portfolios, told MarketWatch.

“Oil-related equities have fallen twice as far as the rest the market since the beginning of the year. It’s been a horror show for the market, but it’s been even worse for the oil patch,” Gutman said.

U.S. CLK20, 5.326% and Brent crude BRNK20, -0.43% were hovering at or under $20 on Monday, with prices down just over 50% so far this year. The Russia-Saudi Arabia oil-price war kicked off the pain for oil prices in early March, followed by a demand shock as global economies shut down from the coronavirus.

“We’re probably looking at a surplus of 10 to 12 million barrels [of oil] a day which is larger than anything we’ve seen in memory,” Gutman said, adding that the industry is still struggling to figure out how bad it will get.

In short, all of the above presents a major headache for oil companies trying to maintain dividends, or in some cases just keep going.

Read:World running out of tanks to store oil due to coronavirus and price war

Royal Dutch Shell RDS.A, +5.68%, whose shares have dropped 45% so far this year, is among those that have announced cost trimming, though big oil companies aren’t talking dividend cuts yet. There is a long list of highly leveraged energy companies, notably in the U.S. shale patch, that are in for a struggle if the dual crisis drags on.

Danilo Onorino, portfolio manager at Dogma Capital for the Dogma Energy and Materials Fund, told MarketWatch that he sees similarities between the current crisis and 1998 to 1999, when oil prices fell under $10, and some called for $5 a barrel.

“That was the bottom, but the effect of the price drop toward $10 a barrel was the starting point for megamergers across the sector,” he told MarketWatch. Among those, TotalFina and Elf Aquitaine formed Total FP, +6.33% TOT, +4.48%, BP Arco and Amoco created BP BP, +7.02% BP, +5.92% and Exxon and Mobil joined up XOM, +1.48%, noted Onorino.

“The logic is that you put together the assets and pick and choose what is good for you and you sell the others. Plus, because you are now one company you can easily save on your operating costs,” he said.

“The most obvious mergers in Europe are BP with Shell, Total with Eni ENI, +4.57% and Repsol REP, REP, +2.34% with Galp GALP, +2.42% in Portugal,” Onorino said, adding that a Shell/BP merger, which has actually been on the table for years, would bring lots of cost synergies.

While consolidation among the majors is possible, Dolfin’s Gutman said they are better placed to weather storms, and more likely would be hunting for opportunities among smaller companies, such as the shale patch, where “the distress signal are urgent right now.”

Greig Aitken, director of M&A research at Wood Mackenzie, said deal-making in the short term is less likely because“companies are “focused on survival” for now, and many are using cuts in capital expenditure and investment to stay afloat.

But if oil prices persist at these levels, “people will rightly start talking about them because ultimately, the industry would have to consolidate to survive,” he said.