Axon Neuroscience Eyes Promising Peptide Vaccine Against COVID-19

AXON Neuroscience (“Axon”), a clinical-stage biotech company and an industry leader in treating and preventing neurodegenerative diseases, is developing a promising vaccine candidate against COVID-19.

Axon has over 20 years’ experience in development of safe and immunogenic peptide vaccines. Its well-established scalable technology allowed the company to move quickly in recent weeks to create a novel peptide vaccine in support of the global fight against COVID-19.
Norbert Žilka, Chief Scientific Officer of Axon, said: “We have over sixty scientists with expertise in key disciplines – immunology, pharmacology, structural biology, proteomics, genomics – making Axon ideally placed to deliver a rapid solution for combatting the new coronavirus.”
Axon used its established peptide-based vaccine platform to produce a novel prophylactic COVID-19 vaccine, intended to treat infected patients and protect healthy individuals from infection. Axon’s vaccine contains only selected epitopes capable of inducing desirable T cell and B cell mediated immune responses to prevent interaction of the virus Spike (S) glycoprotein with its target human cells, thus preventing the virus from entering the cells and spreading. This approach is designed to prevent the unwanted serious side effects observed in previous studies of conventional vaccines against SARS-CoV.
The elderly patients most at risk for COVID-19 are prone to develop serious respiratory complications and pneumonia, which might result in permanent lung damage or even death. In general, elderly individuals typically do not respond as well to vaccination, resulting in ordinary vaccinations having a limited effect. Axon has developed innovative proprietary technologies to stimulate the immune systems of elderly people and people with immunodeficiencies in order to produce a high antibody response in these vulnerable populations.
“The human immune system slowly deteriorates with age. This immunosenescence, combined with other comorbidities, makes elderly people highly sensitive to SARS-CoV-2 infections and prone to severe respiratory complications. We believe we have a safe and effective vaccine concept to prevent future outbreaks of COVID-19 and at the same time protect the most vulnerable groups,” said Professor Eva Kontsekova, Immunologist and the Head of Immunotherapy at Axon.
The recent workshop co-chaired by both the European Medicines Agency (EMA) and Food and Drug Administration (FDA) confirmed that an expedited regulatory pathway could be available for well-tested vaccine platforms, such as Axon’s. Data from Axon’s previous Alzheimer’s Disease clinical trials could facilitate a quick move to first-in-human clinical trials with the new COVID-19 vaccine.
Peptide vaccines represent a promising alternative to conventional vaccine approaches, particularly given their speed of development and ease of production. Axon’s longstanding strategic collaboration with the European-based global leader in peptide vaccine manufacturing means that the transfer to GMP production is quick, inexpensive and highly scalable due to the established analytical and manufacturing methods used in Axon’s other development programs.
https://www.biospace.com/article/releases/axon-neuroscience-has-a-promising-peptide-vaccine-against-covid-19-in-development/

All Eyes on Gilead’s Readout of Remdesivir for COVID-19

Gilead Sciences is expected to report data from a clinical trial of its antiviral drug remdesivir against COVID-19 soon. Although the data hasn’t been released yet, analysts are making predictions based on what little they do know.
With a likely vaccine a year out, optimistically, the drug, which was originally developed to treat Ebola, is considered the closest hope for a treatment. It is involved in at least five clinical trials in the U.S. and China.
On April 4, the company announced it had accelerated production of the drug based on overwhelming demand. It currently has 1.5 million individual doses available, enough to treat 140,000 patients. More than 1,700 patients have been treated on an individual compassionate use basis to date.
Reading the tea leaves, analysts with Barclays think there is only a 20% chance that two of the clinical trials being run in China, one in mild-to-moderate cases and another in severely ill, will succeed. Barclays is more focused on what will happen to the company’s stock, even though at this time Gilead indicates it does not plan to charge for the drug. Barclays cites the drug’s complex manufacturing process, which normally takes a year to make, but has been streamlined to about six months, and the difficulties of setting a price and selling a drug for and during a global pandemic.
Barclays also expressed concern that the people being treated by the drug after the disease was well advanced, instead of at a point where it would be more effective.
Other analysts are studying what few moves the company is making publicly to make their predictions. For example, according to clinicaltrials.gov, the remdesivir trial page was updated, changing the size of a study in severe patients from 400 to 2,400, and the moderate patient trial from 600 to 1,600.
RBC believes these numbers include the compassionate use programs and writes, “It is unclear whether all of these patients will be considered in the primary endpoint, but any additional patients should help improve the powering to detect a potential treatment effect (though also indicates they believe more patients would be needed to be able to show a benefit).”
They go on to write, “We believe the changes improve alignment to the latest understanding of COVID-19’s course and should maximize sensitivity to detect any potential treatment effect, though they also imply that—perhaps based on data the company may be observing from ongoing experience with the drug—the magnitude of benefit, if any, is likely to be modest. This aligns with our view that remdesivir, like other COVID-19 drugs in development, would be more likely to have incremental effects in specific populations vs. proving to be a panacea.”
RBC suggests that Gilead’s decision to modify the trial, moving patients on ventilators to a different arm and changing the endpoints, moving to an improvement on a 7-point ordinal clinical assessment scale, means they may be looking for ways to identify if the drug is making more modest positive effects because more obvious ones may not have been possible in the previous design. “Overall, however, these endpoint modifications also underscore our view that based on evolving data to date, both published and followed internally by the company, Gilead may not be expecting to see dramatic benefits.”
Umer Raffat, an analyst at Evercore ISI, however, is more optimistic, writing in a note to investors that “since the Gilead-run trials are open label, the changes made were likely informed by emerging data from these trials. These trials now have LOTS more patients and different endpoints … but allow me to focus on key conclusions…”
The first conclusion of Raffat’s is that the likelihood of success in the moderate-patient trial has increased with the new endpoints, suggesting patients might be recovering more quickly, although it may not have a major impact on how quickly patients are discharged from the hospital, which was a previous primary endpoint, “but remdesivir likely did improve patient status while in hospital.”
The scope of the patients with severe disease has been expanded to include a higher severity level. Raffat interprets this to mean if researchers weren’t seeing any signals in this patient population, they wouldn’t be expanding the criteria to an even higher level. The earlier trial did not include patients on mechanical ventilation, but a “Part B’ has been added to include those patients.
Analysts, of course, are largely focusing on financial up- or downsides for the company. Most of the rest of the world is more interested in whether the drug works. We should get the first sense of that soon.
https://www.biospace.com/article/all-eyes-on-gilead-s-readout-of-remdesivir-for-covid-19/

Glaukos expects Q1 revenues below estimates; withdraws FY20 guidance

Glaukos (NYSE:GKOS) now expects Q1 revenue in the range of $55.0M to $55.3M vs. a consensus of $59.9M.

Due to the continued uncertainties from the impact of COVID-19, Glaukos has withdrawn its previously announced Q1 and FY20 guidance.

GKOS expects the impact of COVID-19 will be significant in the near-term.

Previously: Glaukos melts down after soft guidance, rating cut (Feb. 28)

https://seekingalpha.com/news/3559698-glaukos-expects-q1-revenues-below-estimates-withdraws-fy20-guidance

Morgan Stanley CEO recovers from coronavirus

Morgan Stanley (MS +5.9%) CEO James Gorman says he has fully recovered from COVID-19, Reuters reports, citing a video sent to the bank’s employees today.

He tested positive for the virus and had been fully cleared by doctors more than a week ago, he said.

Gorman, who started to experience flu-like symptoms in mid-March, is currently working remotely from home.

A Morgan Stanley spokesman said Gorman’s illness wasn’t disclosed publicly because it wasn’t considered material since the illness didn’t incapacitate him.

The spokesman said that Gorman led every one of the bank’s daily operating committee calls since testing positive for COVID-19.
https://seekingalpha.com/news/3559716-morgan-stanley-ceo-recovers-from-coronavirus

Feds loosen virus rules to let essential workers return

In a first, small step toward reopening the country, the Trump administration issued new guidelines Wednesday to make it easier for essential workers who have been exposed to COVID-19 to get back to work if they do not have symptoms of the coronavirus.

Dr. Robert Redfield, director of the the Centers for Disease Control and Prevention, announced at the White House that essential employees, such as health care and food supply workers, who have been within 6 feet of a confirmed or suspected case of the virus can return to work under certain circumstances if they are not experiencing symptoms.

The new guidelines are being issued as the nation mourns more than 14,000 deaths from the virus and grapples with a devastated economy and medical crises from coast to coast. Health experts continue to caution Americans to practice social distancing and to avoid returning to their normal activities. At the same time, though, they are planning for a time when the most serious threat from COVID-19 will be in the country’s rear-view mirror.

President Donald Trump said that while he knows workers are “going stir crazy” at home, he can’t predict when the threat from the virus will wane.

“The numbers are changing and they’re changing rapidly and soon we’ll be over that curve. We’ll be over the top and we’ll be headed in the right direction. I feel strongly about that,” Trump said about the coronavirus, which he called “this evil beast.”

“I can’t tell you in terms of the date,” Trump said, adding cases could go down and then once again “start going up if we’re not careful. ”

At some point, he said at his daily briefing, social distancing guidelines will disappear and people will be able to sit together at sports events. “At some point we expect to be back, like it was before,” he said.

Dr. Anthony Fauci, the nation’s top infectious disease expert, said if the existing guidelines asking people to practice social distancing through the end of April are successful in halting the spread of the virus, more relaxed recommendations could be in order.

He said the White House task force was trying to dovetail public health concerns with practical steps that need to be in place when the 30-day guidelines end at the end of the month so the nation can “safely and carefully march toward some sort of normality.”

If, by fall, things start to return to normal, Americans will still need to wash their hands frequently, sick schoolchildren should be kept home and people with fevers need to refrain from going to work, Fauci said during an online interview Wednesday with the editor of the Journal of the American Medical Association.

People also should never shake hands again, Fauci said, only half-jokingly.

“I mean it sounds crazy, but that’s the way it’s really got to be,” he said. “Until we get to a point where we know the population is protected” with a vaccine.

Under the new guidelines for essential workers, the CDC recommends that exposed employees take their temperatures before their shifts, wear face masks and practice social distancing at work. They also are advised to stay home if they are ill, not share headsets or other objects used near the face and refrain from congregating in crowded break rooms.

Employers are asked to take exposed workers’ temperatures and assess symptoms before allowing them to return to work, aggressively clean work surfaces, send workers home if they get sick and increase air exchange in workplaces.

Fauci said he hoped the pandemic would prompt the U.S. to look at long-term investments in public health, specifically at the state and local level. Preparedness that was not in place in January needs to be in place if or when COVID-19 or another virus threatens the country.

“We have a habit of whenever we get over a challenge, we say, ‘OK, let’s move on to the current problem,’” he said. “We should never, ever be in a position of getting hit like this and have to scramble to respond again. This is historic.”

Even the new guidelines will not be a foolproof guard against spreading infection.

Recent studies have suggested that somewhere around 10% of new infections might be sparked by contact with individuals who are infected but do not yet exhibit symptoms. Scientists say it’s also possible that some people who develop symptoms and then recover from the virus remain contagious, or that some who are infected and contagious may never develop symptoms.

As of Wednesday, the U.S. had more than 400,000 confirmed cases of infection.

https://apnews.com/fab319a90ead9aae057f7fab059c2ccb

Some doctors moving away from ventilators for virus patients

As health officials around the world push to get more ventilators to treat coronavirus patients, some doctors are moving away from using the breathing machines when they can.

The reason: Some hospitals have reported unusually high death rates for coronavirus patients on ventilators, and some doctors worry that the machines could be harming certain patients.

The evolving treatments highlight the fact that doctors are still learning the best way to manage a virus that emerged only months ago. They are relying on anecdotal, real-time data amid a crush of patients and shortages of basic supplies.

Mechanical ventilators push oxygen into patients whose lungs are failing. Using the machines involves sedating a patient and sticking a tube into the throat. Deaths in such sick patients are common, no matter the reason they need the breathing help.

Generally speaking, 40% to 50% of patients with severe respiratory distress die while on ventilators, experts say. But 80% or more of coronavirus patients placed on the machines in New York City have died, state and city officials say.

Higher-than-normal death rates also have been reported elsewhere in the U.S., said Dr. Albert Rizzo, the American Lung Association’s chief medical officer.

Similar reports have emerged from China and the United Kingdom. One U.K. report put the figure at 66%. A very small study in Wuhan, the Chinese city where the disease first emerged, said 86% died.

The reason is not clear. It may have to do with what kind of shape the patients were in before they were infected. Or it could be related to how sick they had become by the time they were put on the machines, some experts said.

But some health professionals have wondered whether the breathing machines might actually make matters worse in certain patients, perhaps by igniting or worsening a harmful immune system reaction.

That’s speculation. But experts do say ventilators can be damaging to a patient over time, as high-pressure oxygen is forced into the tiny air sacs in a patient’s lungs.

“We know that mechanical ventilation is not benign,” said Dr. Eddy Fan, an expert on respiratory treatment at Toronto General Hospital. “One of the most important findings in the last few decades is that medical ventilation can worsen lung injury — so we have to be careful how we use it.”

The dangers can be eased by limiting the amount of pressure and the size of breaths delivered by the machine, Fan said.

But some doctors say they’re trying to keep patients off ventilators as long as possible, and turning to other techniques instead.

Only a few weeks ago in New York City, coronavirus patients who came in quite sick were routinely placed on ventilators to keep them breathing, said Dr. Joseph Habboushe, an emergency medicine doctor who works in Manhattan hospitals.

But increasingly, physicians are trying other measures first. One is having patients lie in different positions — including on their stomachs — to allow different parts of the lung to aerate better. Another is giving patients more oxygen through nose tubes or other devices. Some doctors are experimenting with adding nitric oxide to the mix, to help improve blood flow and oxygen to the least damaged parts of the lungs.

“If we’re able to make them better without intubating them, they are more likely to have a better outcome — we think,” said Habboushe.

He said those decisions are separate from worries that there are not enough ventilators available. But that is a concern as well, Habboushe added.

There are widespread reports that coronavirus patients tend to be on ventilators much longer than other kinds of patients, said Dr. William Schaffner, an infectious diseases expert at Vanderbilt University.

Experts say that patients with bacterial pneumonia, for example, may be on a ventilator for no more than a day or two. But it’s been common for coronavirus patients to have been on a ventilator “seven days, 10 days, 15 days, and they’re passing away,” said New York Gov. Andrew Cuomo, when asked about ventilator death rates during a news briefing on Wednesday.

That’s one reason for worries that ventilators could grow in short supply. Experts worry that as the cases mount, doctors will be forced to make terrible decisions about who lives and who dies because they won’t have enough machines for every patient who needs one.

New York State Health Commissioner Dr. Howard Zucker said Wednesday that officials are looking into other possible therapies that can be given earlier, but added “that’s all experimental.”

The new virus is a member of the coronavirus family that can cause colds or more serious illnesses. Health officials say it spreads mainly from droplets when an infected person coughs or sneezes. There is no proven drug treatment or vaccine against it.

Experts think most people who are infected suffer nothing worse than unpleasant but mild illnesses that may include fever and coughing.

But roughly 20% — many of them older adults or people weakened by chronic conditions — can grow much sicker. They can have trouble breathing and suffer chest pain. Their lungs can become inflamed, causing a dangerous condition called acute respiratory distress syndrome. An estimated 3% to 4% may need ventilators.

“The ventilator is not therapeutic. It’s a supportive measure while we wait for the patient’s body to recover,” said Dr. Roger Alvarez, a lung specialist with the University of Miami Health System in Florida.

Zachary Shemtob said he was “absolutely terrified” when he was told his 44-year-old husband, David, needed to be put on a ventilator at NYU Langone last month after becoming infected with the virus.

“Needing to be ventilated might mean never getting off the ventilator,” he said.

Shemtob said the hospital did not give any percentages on survival, but he got the impression it was essentially a coin flip. He looked up the rates only after his husband was breathing on his own six days later.

“A coin flip was generous it seems,” he said.

But Shemtob noted cases vary. His husband is relatively young.

“David is living proof that they can really save lives, and how incredibly important they are,” Shemtob said.

https://www.modernhealthcare.com/safety-quality/some-doctors-moving-away-ventilators-virus-patients

Cancer Patients Face Therapy Delays, Uncertainty As Covid-19 Hits Hospitals

The federal government has encouraged health centers to delay nonessential surgeries while weighing the severity of patients’ conditions and the availability of personal protective equipment, beds and staffing at hospitals.
People with cancer are among those at high risk of complications if infected with the new coronavirus. It’s estimated 1.8 million people will be diagnosed with cancer in the U.S. this year. More than 600,000 people are receiving chemotherapy.
That means millions of Americans may be navigating unforeseen challenges to getting care.
Christine Rayburn in Olympia, Washington, was diagnosed with breast cancer in mid-February. The new coronavirus was in the news, but the 48-year-old did not imagine the outbreak would affect her. Her doctor said Rayburn needed to start treatment immediately. The cancer had already spread to her lymph nodes.
“The cancer tumor seemed to have attached itself to a nerve,” said Rayburn, who was a schoolteacher for many years. “I feel pain from it on a regular basis.”
After getting her diagnosis and the treatment plan from her medical team, Rayburn was focused on getting surgery as fast as possible.
Meanwhile, the coronavirus outbreak was getting worse, and Seattle, just an hour north of where Rayburn lives, had become a national focal point.
Rayburn’s husband, David Forsberg, began to get a little nervous about whether his wife’s procedure would go forward as planned.
“It did cross my mind,” he said. “But I did not want to bother with that possibility on top of everything else.”
Two days before Rayburn’s lumpectomy to remove the tumor, Forsberg said, the surgeon phoned, “pretty livid” with bad news. “She said, ‘Look, they’ve canceled it indefinitely,’” Forsberg remembered.
The procedure had been scheduled at Providence St. Peter Hospital in Olympia, a facility run by Providence Health & Services. Across Washington, hospitals were calling off elective surgeries, in order to conserve the limited supply of personal protective equipment, or PPE, and to prevent patients and staffers from unnecessary exposure to the new coronavirus.
“It just felt like one of those really bad movies, and I was being sacrificed,” Rayburn said.

“It was like we just got cut off from the experts we were relying on,” her husband said.
The hospital said it would review the decision in a few weeks. But Rayburn’s surgeon said that was too long to wait, and they needed to move to Plan B, which was to begin chemotherapy.
Originally, chemotherapy was supposed to happen after Rayburn’s tumor surgery. And rearranging the treatment plan wasn’t ideal because chemotherapy isn’t shown to significantly shrink tumors in Rayburn’s type of breast cancer.
Still, chemotherapy could help stop the cancer from spreading further. But as the couple figured out the new treatment plan, they ran into more obstacles.
“She needed an echocardiogram, except they had canceled all echocardiograms,” said Forsberg.
They spent days on the phone trying to get all the pieces in place so she could start chemotherapy. Rayburn also started writing to her local lawmakers about her predicament.
Hospitals Prioritize Urgent Cases
In mid-March, Washington Gov. Jay Inslee banned most elective procedures, but he did carve out exceptions for certain urgent, life-threatening situations.
“It actually said that it [the ban] excluded removing cancerous tumors,” Rayburn said.
Providence hospitals use algorithms and a team of physicians to figure out which surgeries can be delayed, said Elaine Couture, chief executive of Providence Health in the Washington-Montana region.
“There are no perfect decisions at all in any of this,” said Couture. “None.”
Couture would not talk about specific patients but said she assumes other cases were more urgent than Rayburn’s.
“Were there other patients that even had more aggressive types of cancer that were [surgically] completed?” Couture said. “As sick as you are, there can be other people that are needing something even sooner than you do.”
Couture said hospitals are burning through supplies of masks, gowns and gloves and need to make tough calls about elective procedures.
“I don’t like that, either, and it’s not the way that we want our health care system to work,” Couture said.
Across the Providence hospital system, personal protective equipment is being used much faster than it can be replenished, she said.
No Single Standard
At the American Cancer Society, Deputy Chief Medical Officer Dr. Len Lichtenfeld is hearing from patients across the country who are having their chemotherapy delayed or surgery canceled.
“There was someone who had a brain tumor who was told they would not be able to have surgery, which was, basically, and appears to be a death sentence for that patient,” said Lichtenfeld.
This is uncharted territory for cancer care, he said. Hospitals are making these “decisions on the fly” in response to how the pandemic looks in a particular community. “There is no single national standard that can be applied. I am afraid this is going to become much more common in the coming weeks.”
The cancer society recommends that people postpone their routine cancer screenings — for now.
The American College of Surgeons has published guidance on how to triage surgical care for cancer patients. But Lichtenfeld said every decision ultimately depends on the availability of resources at the hospital and the pressures of COVID-19. In Washington state, which has been hit hard, hospitals are shifting surgical space and beds away from other kinds of treatment.
“We need to forecast two to three weeks down the line when there are more patients that are ill,” said Dr. Steven Pergam, medical director of infection prevention at the Seattle Cancer Care Alliance. “We need to make sure there’s adequate bed capacity.”
Pergam said the care alliance is adjusting treatment plans and, at times, avoiding procedures that would keep cancer patients in the hospital for a prolonged period.
“It really depends on the cancer and the aggressive nature of it,” he said. “We have looked at giving chemotherapy in the outpatient department and changing the particular regimens people get to make them less toxic.”
But Pergam said they expect to keep doing urgent surgeries for cancer patients, even as the pandemic grows worse.
Christine Rayburn in Olympia was steeling herself for the months of chemotherapy to come: staying inside her home and even avoiding contact with her adult daughters, to avoid any possible exposure to the coronavirus.
Then, two weeks ago, the surgeon called again. She had persuaded the hospital to allow the surgery after all, 10 days later than initially planned.
Rayburn and her husband wonder what would have happened if they hadn’t spoken up or pushed to get her lumpectomy back on the hospital’s surgical schedule. Forsberg said it’s possible they could have ended up without the care Rayburn needed.
“If we didn’t say anything, in my mind that may be where we would be at,” he said. “But in our minds, that was not an option.”
https://khn-org.cdn.ampproject.org/c/s/khn.org/news/cancer-patients-face-treatment-delays-and-uncertainty-as-coronavirus-cripples-hospitals/amp/