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Friday, July 9, 2021

Sight Sciences pitches $150M IPO for its glaucoma, dry eye devices

 Ophthalmic device developer Sight Sciences hopes to see its way to nearly a $1 billion valuation through a $150 million Nasdaq IPO.

The company’s portfolio includes the Omni Surgical System, a hand-held, single-use device used to help drain fluids from the eye and reduce intraocular pressure in patients with glaucoma. The system can also help deliver a viscoelastic material through a microcatheter to enlarge the eye’s canals and relieve pressure through an alternative surgical method.

Meanwhile, its nonsurgical device, the TearCare system, is worn over the eyelid to apply localized heat as a treatment for dry eye as well as gland dysfunction. Between glaucoma and dry eye disease, Sight estimates the two markets total about $16 billion, with the former making up 94% of the company’s revenues over 2020.

And despite the COVID-19 pandemic, last year saw positive sales growth compared to the 2019 calendar year, with revenues of $27.6 million over $23.3 million, respectively.

By going public, the Menlo Park, California-based company hopes to fund ongoing and future clinical trials for both of its marketed systems as well as other R&D and commercial efforts, according to a prospectus filed with the Securities and Exchange Commission. The IPO includes 7 million shares under the ticker symbol "SGHT" at a price ranging from $20 to $23, according to Renaissance Capital. Sight had previously filed for a $100 million IPO in late June.


In March 2020, the company raised $30 million through a series E round led by D1 Capital Partners to help expand its commercial efforts. A year later, Sight counted more than 100 on its direct sales, marketing and support staff, according to the prospectus.

https://www.fiercebiotech.com/medtech/sight-sciences-pitches-150m-ipo-for-its-glaucoma-dry-eye-devices

Moving the vaccination needle: Behavioral tactics that work—and don’t

 One of the big questions today is how to get more people vaccinated. Should you offer free stuff? That works sometimes. Remind them that they’re good parents? That actually doesn’t work.

It turns out that not getting vaccinated is pretty irrational, thanks to human beings’ cognitive biases.

Marketers often try to overcome cognitive bias by using behavioral interventions to temper the personal subjective realities that behavioral scientists label with fancy handles like "confirmation bias" or "loss aversion."

But when it comes to vaccinations, which interventions work and which don't?

ZS researchers wanted to find out. So they put 19 different behavioral interventions for cognitive biases to the test. They surveyed three different groups of vaccine-hesitant people—those who were wary about COVID-19 vaccines, adult vaccines or pediatric vaccines, Jacob Braude who leads the applied behavioral science team at ZS said.


The result? Only 10 of the 19 tactics worked. Seven worked for COVID vaccine-hesitant people, four for those worried about adult vaccinations and five with pediatric concerns. While some tactics worked across one or two of the vaccine-hesitant groups, only one behavioral intervention worked across all three groups.

Confirmation bias, which has been getting a lot of media attention recently in the context of politics, was the only successfully mitigated behavior in ZS’ study of more than 6,300 vaccine-hesitant people across seven countries.

What is confirmation bias? In general, it’s the tendency by people to favor or overvalue information that supports what they already think and to ignore contradictory information. So if a person believes vaccines aren’t safe, they can and will find media, data and reports that support that belief.

Knowing that confirmation bias is likely rampant in the vaccine-hesitant group, ZS didn’t test for it, but they did try a mitigation tactic.

Researchers told people that they understood the person doesn’t want a vaccine but asked them to think about reasons why other people might want to get vaccinated. After the test subjects went through the mental exercise using their own thoughts and words, ZS researchers asked if they were interested in getting vaccinated. And some said yes.


Overall, 20% more people said they would get vaccinated when compared to the baseline group. Among men under age 50, the jump was even higher with 22% changing their minds.

“Often we see people trying to persuade by saying ‘OK, here are the facts. Here’s why you should get vaccinated,’ ” Braude said. “But this research says actually what you should say is ‘OK, why would someone want to get vaccinated?’ and have them go through the process in their own words. That works much better than the persuasion techniques we see people trying to use.”

Another behavioral tactic springing up around COVID vaccination drives is prospect theory. States giving out prize money, or as they are in West Virginia, chances to win trucks and shotguns, are using a winning tactic.

Other behavioral intervention tactics that worked for COVID vaccine hesitators were effort justification (I put a lot of effort into something so it’s valuable, even if it’s not) and social facilitation (if people know others are watching them, they will behave more pro-socially).

What about other tactics being used? Celebrity endorsements, for instance, probably work—right? Nope, not according to ZS’ study.

Researchers asked people to name any celebrity or public figure who they believe to be a credible authority. The answers ranged widely—some people in the U.S. chose controversial Fox opinion show host Sean Hannity—but the result was always the same.


ZS tested the participants by repeating back the same credible authority they named along with a second choice of someone the participant said was not credible and said these people recommend getting vaccinated. The test subjects’ response? No thanks—even when the recommendation came from the exact credible authority they chose.

Interestingly, that doesn’t mean all recommendations don’t work. Among vaccine-hesitant parents in the pediatric study group, something called in-group bias did work. The bias is the tendency to go along with people you like and agree with and consider to be in your group more often than you would agree with people outside your perceived group. When told that people in their group are getting their kids vaccinated, they were more likely to also do it, Braude said.

The tricky part of individual bias is just that, they’re individual.

“The way biases work is that every person has a different set of mental shortcuts,” Braude said. “The goal is to layer these bias triggers in a way to try to drive vaccinations. If we look at all of the individual responses, we got anywhere from 20 to 44% of people who started the survey saying they wouldn’t get vaccinated to change their mind.”

Braude acknowledged it is a study but added while the results may be less in the real world “even half, I would take that. If we could get 20% of people to get vaccinated who previously wouldn’t, I would take that in a heartbeat.”

https://www.fiercepharma.com/marketing/moving-vaccination-needle-study-examines-behavioral-tactics-work-and-don-t

Canada, US are easing pandemic border-crossing restrictions

 Pandemic restrictions on travel between Canada and the U.S. began to loosen Monday for some Canadians, and Prime Minister Justin Trudeau said plans to totally reopen the border would be announced over the next few weeks.

Canadian citizens and permanent residents who have had a full dose of a coronavirus vaccine approved for use in Canada can skip a 14-day quarantine that has been a requirement since March 2020. Eligible air travelers also no longer have to spend their first three days in the country at a government-approved hotel.

Restrictions barring all non-essential trips between Canada and the United States, including tourism, will remain in place until at least July 21.

Trudeau said the easing of the rules marks a "big step″ toward re-opening the .

"We're very hopeful that we're going to see new steps on reopening announced in the coming weeks," he said at a news conference in Sault Ste. Marie, Ontario. "We're going to make sure that we're not seeing a resurgence of COVID-19 cases because nobody wants to go back to further restrictions, after having done so much and sacrificed so much to get to this point."

Julia Dunn, who landed at Toronto's Pearson International Airport from the United States while on her way to Halifax, said she was glad the restrictions had eased.

"It's very freeing being able to get home to family without having to spend those two weeks alone,″ she said.

Dunn, who is originally from Cape Breton but now lives in Houston, said she booked her trip to Canada after learning about the planned easing of quarantine rules a few weeks ago.

Trudeau said he understands how eager people are to see the border reopen but noted that the pandemic continues and "things aren't normal yet."

"Nobody wants us to move too fast and have to reimpose restrictions as case numbers rise like we're seeing elsewhere in the world,″ he said. ``We need to do this right."

https://medicalxpress.com/news/2021-07-canada-easing-pandemic-border-crossing-restrictions.html

Inhaled COVID-19 vaccine prevents disease and transmission in animals

 In a new study assessing the potential of a single-dose, intranasal COVID-19 vaccine, a team from the University of Iowa and the University of Georgia found that the vaccine fully protects mice against lethal COVID-19 infection. The vaccine also blocks animal-to-animal transmission of the virus. The findings were published July 2 in the journal Science Advances.

"The currently available vaccines against COVID-19 are very successful, but the majority of the world's population is still unvaccinated and there is a critical need for more vaccines that are easy to use and effective at stopping  and transmission," says Paul McCray, MD, professor of pediatrics-pulmonary medicine, and microbiology and immunology at the UI Carver College of Medicine, and co-leader of the study. "If this new COVID-19 vaccine proves effective in people, it may help block SARS-CoV-2 transmission and help control the COVID-19 pandemic."

Unlike traditional vaccines that require an injection, this vaccine is administered through a nasal spray similar to those commonly used to vaccinate against influenza. The vaccine used in the study only requires a single dose and it may be stored at normal refrigerator temperatures for up to at least three months. Because it is given intranasally, the vaccine may also be easier to administer, especially for those who have a fear of needles.

"We have been developing this vaccine platform for more than 20 years, and we began working on new vaccine formulations to combat COVID-19 during the early days of the pandemic," says Biao He, Ph.D., a professor in the University of Georgia's Department of Infectious Diseases in the College of Veterinary Medicine and co-leader of the study. "Our preclinical data show that this vaccine not only protects against infection, but also significantly reduces the chances of transmission."

The experimental vaccine uses a harmless parainfluenza virus 5 (PIV5) to deliver the SARS-CoV-2 spike protein into cells where it prompts an  that protects against COVID-19 infection. PIV5 is related to common cold viruses and easily infects different mammals, including humans, without causing significant disease. The research team has previously shown that this vaccine platform can completely protect experimental animals from another dangerous coronavirus disease called Middle Eastern Respiratory Syndrome (MERS).

The inhaled PIV5 vaccine developed by the team targets mucosal cells that line the nasal passages and airways. These cells are the main entry point for most SARS-CoV-2 infections and the site of early virus replication. Virus produced in these cells can invade deeper into the lungs and other organs in the body, which can lead to more severe disease. In addition,  made in these cells can be easily shed through exhalation allowing transmission from one infected person to others.

The study showed that the vaccine produced a localized immune response, involving antibodies and cellular immunity, that completely protected mice from fatal doses of SARS-CoV-2. The  also prevented infection and disease in ferrets and, importantly, appeared to block  of COVID-19 from infected ferrets to their unprotected and uninfected cage-mates.


Explore further

Successful MERS vaccine in mice may hold promise for COVID-19 vaccine

More information: Dong An et al, Protection of K18-hACE2 mice and ferrets against SARS-CoV-2 challenge by a single-dose mucosal immunization with a parainfluenza virus 5–based COVID-19 vaccine, Science Advances (2021). DOI: 10.1126/sciadv.abi5246
https://medicalxpress.com/news/2021-07-inhaled-covid-vaccine-disease-transmission.html

How vaccine-induced immune thrombotic thrombocytopenia (VITT) happens

 A McMaster University team of researchers recently discovered how, exactly, the COVID-19 vaccines that use adenovirus vectors trigger a rare but sometimes fatal blood clotting reaction called vaccine-induced immune thrombotic thrombocytopenia or VITT.

The findings will put scientists on the path of finding a way to better diagnose and treat VITT, possibly prevent it and potentially make vaccines safer.

The researchers' article was fast-tracked for publication today by the journal Nature in its accelerated article preview because of the importance of the research.

"Our work also answers important questions about the connection between antibodies and clotting," said Ishac Nazy, principal investigator and corresponding author of the study. He added it will have both diagnostic and therapeutic implications.

Nazy is the scientific director of the McMaster Platelet Immunology Laboratory and an associate professor of medicine for the Michael G. DeGroote School of Medicine at McMaster.

The COVID-19 vaccines using adenoviral vectors, such as those from AstraZeneca and Johnson and Johnson, are associated with the VITT clotting disorder caused by unusual antibodies to blood platelets that are triggered by the vaccine.

The study shows, at a molecular level, how those unusual antibodies stick to components from blood platelets causing them to trigger clot formation.

"The antibodies stick to the platelet protein called platelet factor 4 (PF4) in a very unique and specific orientation, which allows them to align with other antibodies and platelets in the precise formation that leads to a self-perpetuating vicious cycle of clotting events," said Nazy.

"These disease-causing aggregates quickly activate platelets, creating a highly intense clotting environment in patients," he added.

The dangerous reaction to the adenovirus vector vaccines has been found to occur in one in 60,000 of people receiving the vaccine in Canada.

"The intention of our study was to better understand how the severe clots which characterize VITT develop," said Donald Arnold, study co-investigator and co-medical director of the McMaster Platelet Immunology Laboratory.

"A basic principle of medical care is to understand how the disorder happens and, in doing so, develop better treatments."

John Kelton, co-investigator of the study and co-medical director of the McMaster Platelet Immunology Laboratory, added: "We believe that this study is important because it clarifies how the clotting ensues, and because we have been able to identify the molecules involved.

"The next step is to develop a rapid diagnostic and accurate test to diagnose VITT. Our major interest is now to move upstream from how the clots happen to preventing them from occurring."

Current rapid tests yield false-negative results, and testing relies on more time-consuming tests to confirm VITT. This study now explains why the rapid tests frequently fail and allows for new strategies to improve diagnostic testing.

The investigators altered the molecular composition of the PF4 protein and, using this technology, were able to identify the binding region on the protein.

The research team included Angela Huynh, a research scientist in the McMaster Platelet Immunology Laboratory, and Mercy Daka, a graduate student of McMaster's Department of Biochemistry and Biomedical Sciences.

The researchers thanked the agencies supporting the research, including the Public Health Agency of Canada, the Canadian Institutes of Health Research (CIHR), and the Ontario Ministry of Health.

Story Source:

Materials provided by McMaster UniversityNote: Content may be edited for style and length.


Journal Reference:

  1. Angela Huynh, John G Kelton, Donald M Arnold, Mercy Daka, Ishac Nazy. Antibody epitopes in vaccine-induced immune thrombotic thrombocytopeniaNature, 2021; DOI: 10.1038/s41586-021-03744-4

Tuning the immune system may enhance vaccines and ease disease

 Immunologists at St. Jude Children's Research Hospital have identified a biological pathway that selectively controls how key immune cells, called T follicular helper cells, mature into functional components of the immune system.

The finding offers the promise of developing drugs to activate the metabolic pathway to enhance the effectiveness of vaccines, including those that protect against COVID-19. Such medications could stimulate the immune system to respond more vigorously following immunization to produce more antibodies against a virus or bacterium.

The work also lays the foundation for drugs that dial down the pathway to alleviate autoimmune diseases such as lupus. In such disorders, an overactive immune system produces antibodies that attack the body's own tissues.

Led by Hongbo Chi, Ph.D. of the Department of Immunology, the researchers published their findings today in Nature.

Regulating the adaptive immune response

Chi and colleagues identified a metabolic control pathway that selectively regulates the development of specialized immune cells in the adaptive immune system. These cells are called T follicular helper cells.

The adaptive immune system is so named because when the body is infected by viruses or bacteria, it learns to target and attack them. T follicular helper cells activate the component of the adaptive immune system called humoral immunity. While humoral immunity attacks invaders circulating outside cells largely via the generation of antibodies, the other adaptive immune system component, cellular immunity, targets invaders inside infected cells.

In their experiments, the researchers sought to discover whether a metabolic control pathway existed that modified the T follicular helper cells to activate them. When such cells are activated, they help antibody-producing cells, called B cells, to mature and to generate infection-fighting antibodies.

Discovering a key pathway

To discover a possible control pathway, Chi and his colleagues used genetic techniques to delete in the T cells multiple enzymes known to be elements of such metabolic control pathways. Then, the scientists introduced the deletion-engineered T cells into mice followed by infection with a virus and tested whether the T cells lacking the enzyme were functional.

Their experiments revealed that one metabolic control pathway, called the CDP-ethanolamine pathway, selectively regulated the T follicular helper cells.

"This finding was a big surprise," Chi said. "First of all, this pathway was considered to have a housekeeping function leading to the production of building blocks for the cell membrane. But we discovered that it has a major signaling function. And secondly, we were surprised that this pathway -- and not other parallel pathways of this type -- was the only one involved in regulating T follicular helper cells."

As a complementary method to determine if the pathway selectively regulated the T follicular helper cells, the researchers deleted each of the key enzymes they identified in the CDP-ethanolamine pathway. They found that deletion of these enzymes, but not those of other parallel regulatory pathways, selectively impaired development of the T follicular helper cells, but not overall immune function.

Importantly, said Chi, those key enzymes could be targets for drugs that either enhance or inhibit the pathway, and thus the activity of the T cells.

"We are now exploring whether we can enhance the effectiveness of vaccines by using drugs that activate the pathway, to help these T cells mobilize the immune system to generate antibodies in response to a vaccine," he said.

"On the other hand, to treat autoimmune disease, we're interested in developing new ways to inhibit this pathway," he said. "This approach is promising because we know that such activation or inhibition is highly selective for T follicular helper cells and would not affect other immune functions."

The researchers are also delving into the structural mechanisms by which the enzymes work -- insights that could offer such drug targets, Chi said.

Story Source:

Materials provided by St. Jude Children's Research HospitalNote: Content may be edited for style and length.


Journal Reference:

  1. Guotong Fu, Clifford S. Guy, Nicole M. Chapman, Gustavo Palacios, Jun Wei, Peipei Zhou, Lingyun Long, Yong-Dong Wang, Chenxi Qian, Yogesh Dhungana, Hongling Huang, Anil KC, Hao Shi, Sherri Rankin, Scott A. Brown, Amanda Johnson, Randall Wakefield, Camenzind G. Robinson, Xueyan Liu, Anthony Sheyn, Jiyang Yu, Suzanne Jackowski, Hongbo Chi. Metabolic control of TFH cells and humoral immunity by phosphatidylethanolamineNature, 2021; DOI: 10.1038/s41586-021-03692-z



Stem cells can use same method as plants and insects to protect against viruses

 Researchers at the Francis Crick Institute have found a vital mechanism, previously thought to have disappeared as mammals evolved, that helps protect mammalian stem cells from RNA viruses such as SARS-CoV-2 and Zika virus. The scientists suggest this could one day be exploited in the development of new antiviral treatments.

On infecting a host, a virus enters cells in order to replicate. For most cells in mammals the first line of protection are proteins, called interferons. Stem cells, however, lack the ability to trigger an interferon response and there has been uncertainty about how they protect themselves.

In their study, published in Science today (8 July) the scientists analysed genetic material from mouse stem cells and found it contains instructions to build a protein, named antiviral Dicer (aviD), which cuts up viral RNA and so prevents RNA viruses from replicating. This form of protection is called RNA interference, which is the method also used by cells in plants and invertebrates.

Caetano Reis e Sousa, author and group leader of the Immunobiology Laboratory at the Crick says, "It's fascinating to learn how stem cells protect themselves against RNA viruses. The fact this protection is also what plants and invertebrates use suggests it might be something that goes far back in mammalian history, right up to when the evolutionary tree spilt. For some reason, while all mammalian cells possess the innate ability to trigger this process, it seems to only be relied upon by stem cells.

"By learning more about this process, and uncovering the secrets of our immune system we are hoping to open up new possibilities for drug development as we strive to harness our body's natural ability to fight infection."

In laboratory experiments which exposed engineered human cells to SARS-CoV-2, the virus infected three times fewer stem cells when aviD was present in the cells compared to when the researchers removed this protein.

The scientists also grew mini brain organoids from mouse embryonic stem cells and found that, when infected with Zika virus, the organoids with aviD grew more quickly and less viral material was produced than in organoids without this protein. Similarly, when organoids were infected with SARS-CoV-2, there were fewer infected stem cells in the organoids with aviD.

Enzo Poirier, author and postdoc in the Immunobiology Laboratory at the Crick says, "Why stem cells use this different mechanism of defence remains a mystery. It might be that the interferon process would cause too much harm to stem cells, so mammals, including humans, have evolved to shield these precious cells from this damage. There is still a lot of uncertainty about how these cells are protected from viruses, which we're excited to explore further."

The researchers will continue this work, creating a mouse model which allows them to further study the effects and importance of aviD in mammalian stem cells.


Story Source:

Materials provided by The Francis Crick InstituteNote: Content may be edited for style and length.


Journal Reference:

  1. Poirier, E.Z. et al. An isoform of Dicer protects mammalian stem cells against multiple RNA virusesScience, 2021 DOI: 10.1126/science.abg2264