Gates-Backed Vicarious Surgical in Talks to Merge With D8 SPAC

 Vicarious Surgical, a developer of medical robot technology that’s backed by Microsoft Corp. co-founder Bill Gates, is in talks to go public through a merger with blank check-firm D8 Holdings Corp., according to a person with knowledge of the matter.

The companies are discussing a deal that values the combined entity at about $1.1 billion, said the person, who asked not to be identified because the talks are private. Terms aren’t final and it’s possible talks could fall apart.

Representatives for Vicarious and D8 didn’t immediately respond to requests for comment.

Charlestown, Massachusetts-based Vicarious Surgical, co-founded by Adam Sachs, Sammy Khalifa and Dr. Barry Greene in 2014, touts minimally invasive surgery using proprietary human-like surgical robots and virtual reality. Along with Gates, investors include E15 Capital, Khosla Ventures, Innovation Endeavors and AME Cloud Ventures.

Hong Kong-based D8, led by CEO David Chu and President Donald Tang, raised $345 million in a July initial public offering.

https://www.bloomberg.com/news/articles/2021-03-24/bill-gates-backed-vicarious-said-in-talks-to-merge-with-d8-spac

Flu shot associated with fewer, less severe COVID cases

 People who received a flu shot last flu season were significantly less likely to test positive for a COVID-19 infection when the pandemic hit, according to a new study. And those who did test positive for COVID-19 had fewer complications if they received their flu shot.

These new findings mean senior author Marion Hofmann Bowman, M.D., is continuing to recommend the flu shot to her patients even as the flu season may be winding down.

"It's particularly relevant for vaccine hesitance, and maybe taking the flu shot this year can ease some angst about the new COVID-19 vaccine," says Hofmann, an associate professor of internal medicine and a cardiologist at the Michigan Medicine Frankel Cardiovascular Center. Michigan Medicine is the academic medical center of the University of Michigan.

Researchers reviewed medical charts for more than 27,000 patients who were tested for a COVID-19 infection at Michigan Medicine between March and mid-July of 2020. Of the nearly 13,000 who got a flu shot in the previous year, 4% tested positive for COVID-19. Of the 14,000 who hadn't gotten a flu shot, nearly 5% tested positive for COVID-19. The association remained significant after controlling for other variables including ethnicity, race, gender, age, BMI, smoking status and many comorbid conditions, Hofmann says.

People who received their flu shot were also significantly less likely to require hospitalization, although the researchers didn't find a significant difference in mortality between the two groups. No one in the study tested positive for both infections at the same time.

The underlying mechanism behind the association isn't yet clear, Hofmann says.

"It is possible that patients who receive their flu vaccine are also people who are practicing more social distancing and following CDC guidelines. However, it is also plausible that there could be a direct biological effect of the flu vaccine on the immune system relevant for the fight against SARS-CoV-2 virus," she says.

Prospective longitudinal studies to examine the effect of the flu vaccine on respiratory illness are ongoing, including the Household Influenza Vaccine Evaluation (HIVE) study through the University of Michigan's School of Public Health.

"It's powerful to give providers another tool to encourage their patients to take advantage of available, effective, safe immunizations," says co-first author Carmel Ashur, M.D., M.S., an assistant professor of internal medicine and a hospitalist at Michigan Medicine.

Months ago, Hofmann was concerned about misinformation she kept seeing online that connected the flu vaccine with a COVID-19 infection. Prominent media outlets like Reuters debunked this theory, and she knew her team's data could also help address vaccine hesitancy.

"Instead of a concerning connection between COVID-19 and the flu shot, our publication provides more confidence that getting your flu shot is associated with staying out of the hospital for COVID-19," she says.

Before the pandemic hit, Hofmann and co-first author Anna Conlon, Ph.D., a U-M Medical School student, educated Frankel CVC patients about another encouraging association with the flu vaccine: cardiovascular protective effects.

"There's robust data that the flu shot prevents heart attack and hospitalizations for heart failure, which is an additional reason to get your vaccine every flu season," Conlon says.

https://www.eurekalert.org/pub_releases/2021-03/mm-u-fsa032321.php

Patients should receive COVID-19 vaccine before surgery to reduce risk of death

 Patients waiting for elective surgery should get COVID-19 vaccines ahead of the general population - potentially helping to avoid thousands of post-operative deaths linked to the virus, according to a new study funded by the NIHR.

Between 0.6% and 1.6% of patients develop COVID-19 infection after elective surgery. Patients who develop COVID-19 infection are at between 4- and 8-fold increased risk of death in the 30 days following surgery. For example, whereas patients aged 70 years and over undergoing cancer surgery would usually have a 2.8% mortality rate, this increases to 18.6% if they develop COVID-19 infection.

Based on the high risks that surgical patients face, scientists calculate that vaccination of surgical patients is more likely to prevent COVID-19 related deaths than vaccines given to the population at large - particularly among the over-70s and those undergoing surgery for cancer. For example, whereas 1,840 people aged 70 years and over in the general population need to be vaccinated to save one life over one year, this figure is only 351 in patients aged 70 years and over having cancer surgery.

Overall, the scientists estimate that global prioritisation of pre-operative vaccination for elective patients could prevent an additional 58,687 COVID-19-related deaths in one year.

This could be particularly important for Low- and Middle-income Countries (LMICs) where mitigation measures such as nasal swab screening and COVID-free surgical pathways, which can reduce the risk of complications related to the virus, are unlikely to be universally implemented.

The COVIDSurg Collaborative international team of researchers, led by experts at the University of Birmingham, has published its findings today in BJS (incorporating the British Journal of Surgery and the European Journal of Surgery), after studying data for 141,582 patients from across 1,667 hospitals in 116 countries -including Australia, Brazil, China, India, UAE, UK and USA - creating the world's largest ever international study on surgery.

Co-lead author Mr Aneel Bhangu, from the University of Birmingham, commented: "Preoperative vaccination could support a safe re-start of elective surgery by significantly reducing the risk of COVID-19 complications in patients and preventing tens of thousands of COVID-19-related post-operative deaths.

"Many countries, particularly low- and middle-income countries, will not have widespread access to COVD for several years. While vaccine supplies are limited, governments are prioritising vaccination for groups at highest risk of COVID-19 mortality. Our work can help to inform these decisions."

Co-lead author Dr Dmitri Nepogodiev, from the University of Birmingham, commented: "Restarting elective surgery is a global priority. Over 15,000 surgeons and anaesthetists from across 116 countries came together to contribute to this study, making it the largest ever scientific collaboration. It's crucial that policy makers use the data we have collected to support a safe restart to elective surgery; COVID vaccination should be prioritised for elective surgery patients ahead of the general population."

During the first wave of the pandemic, up to 70% of elective surgeries were postponed, resulting in an estimated 28 million procedures being delayed or cancelled. Whilst surgery volumes have started to recover in many countries, ongoing disruption is likely to continue throughout 2021, particularly in the event of countries experiencing further waves of COVID-19. Vaccination is also likely to decrease post-operative pulmonary complications - reducing intensive care use and overall healthcare costs.

https://www.eurekalert.org/pub_releases/2021-03/uob-psr032221.php

Drugmakers flock to Vineti's fix for a cell, gene therapy problem

 

• A coalition of drugmakers has agreed to work with Vineti, a San Francisco-based technology company, to usher in new standards that could ease some of the safety and logistic concerns surrounding advanced medicines like cell and gene therapies.
• These medicines often pass through complex networks of manufacturers, transporters and healthcare providers before they're delivered to patients. As many of them are personalized and meant to treat very ill patients, it's critical to know exactly whom each therapy is for and where it is along the supply chain. And yet, modern cell and gene therapies still use the same patient identifiers as more "legacy" treatments like bone marrow transplants — standards that, according to Vineti, "do not always cover all the use cases presented by today's personalized therapeutics."
• Vineti wants to establish a new, flexible patient identifier akin to a digital ID badge that could work for all types of advanced medicines and improve traceability, control costs and better ensure patient safety. The company now has more support, too, from that coalition of drugmakers, which includes several biotechs as well as large pharmaceutical firms like Novartis and Takeda.
• The cell and gene therapy field hit major milestones over the last few years. In the summer of 2017, the Food and Drug Administration approved a first-of-its-kind cellular medicine from Novartis for a hard-to-treat form of leukemia. Less than two months later, another cell therapy developed by Kite Pharma was cleared for patients with a different blood cancer.

Before the end of that year, Spark Therapeutics received the first-ever FDA nod for a gene therapy targeting an inherited disorder. And since then, a small crop of advanced medicines developed by Kite, Juno Therapeutics and AveXis have come to market.

These successes have, in turn, enticed more companies to invest in cell and gene therapy research. Gilead, best known for its work fighting viruses, dropped $12 billion to buy Kite right before its first treatment got approved. Novartis then agreed to buy AveXis for almost $9 billion in 2018, and was soon followed by Roche, which announced in early 2019 it would acquire Spark for $5 billion.

Experts don't foresee the field calming down anytime soon, either. The FDA has said it expects to be reviewing and approving between 10 and 20 cell and gene therapies each year by 2025.

Yet, an influx of advanced medicines could exacerbate some of the existing challenges in making and delivering them. Cell therapy developers like Novartis, for example, have already run into problems commercializing their products, which has caused certain investors to take a more tepid view of the field.

Vineti is hoping its new identifier can iron out some of these problems. As it stands, Vineti's proposal is to have a seven-part ID that would work for all advanced medicine types, including personalized cancer vaccines, cancer immunotherapies, and autologous cell and gene therapies.

The ID would have a "core ID" piece, which shows the company making the product and the specific patient meant to receive it. Then there would be a "treatment ID" piece to identify the product and the order. Lastly, there would be a "specimen ID" piece to detail what procedure is taking place, the run of this procedure, and the number of items produced from it.

So, according to one example posed by Vineti, if a patient is receiving an advanced medicine called ABC from the hypothetical company Acme Pharma, and the first step in that process is to collect one bag of raw material through one session of apheresis, the resulting code would be ACM123456-ABC01-AP0101. In that code, ACM represents the company, 123456 is the patient number, ABC is the therapy, the first 01 is the order number, AP signals apheresis and the last pair of 01s indicate that this is session 1 and should create one bag of material.

Vineti is currently accepting industry-wide feedback on its proposal.

https://www.biopharmadive.com/news/vineti-cell-gene-therapies-identification-coalition/597254/

Nanoparticle flu vaccine blocks seasonal and pandemic strains

 Researchers have developed experimental flu shots that protect animals from a wide variety of seasonal and pandemic influenza strains. The vaccine product is currently being advanced toward clinical testing. If proven safe and effective, these next-generation influenza vaccines may replace current seasonal options by providing protection against many more strains that current vaccines do not adequately cover.

A study detailing how the new flu vaccines were designed and how they protect mice, ferrets, and nonhuman primates appears in the March 24 edition of the journal Nature. This work was led by researchers at the University of Washington School of Medicine and the Vaccine Research Center part of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Influenza virus causes an estimated 290,000-650,000 deaths per year. Available flu vaccines, which need to be taken seasonally, often fail to protect against many circulating flu strains that cause illness, and the threat of another influenza pandemic looms.

"Most flu shots available today are quadrivalent, meaning they are made from four different flu strains. Each year, the World Health Organization makes a bet on which four strains will be most prevalent, but those predictions can be more or less accurate. This is why we often end up with 'mismatched' flu shots that are still helpful but only partially effective," said lead author Daniel Ellis, a research scientist in the laboratory of Neil King. King is an assistant professor of biochemistry at the UW School of Medicine and a researcher at the Institute for Protein Design at UW Medicine.

Neil King of the Department of Biochemistry at the University of Washington School of Medicine and a research at the UW Medicine Institute for Protein Design describes the development of an experimental nanoparticle vaccine against a variety of seasonal and pandemic influenza strains. Credit: Randy Carnell/UW Medicine

To create improved influenza vaccines, the team attached hemagglutinin proteins from four different influenza viruses to custom-made protein nanoparticles. This approach enabled an unprecedented level of control over the molecular configuration of the resulting vaccine and yielded an improved immune response compared to conventional flu shots. The new nanoparticle vaccines, which contain the same four hemagglutinin proteins of commercially available quadrivalent influenza vaccines, elicited neutralizing antibody responses to vaccine-matched strains that were equivalent or superior to the commercial vaccines in mice, ferrets, and nonhuman primates. The nanoparticle vaccines—but not the commercial vaccines —also induced protective antibody responses to viruses not contained in the vaccine formulation. These include avian influenza viruses H5N1 and H7N9, which are considered pandemic threats.

"The responses that our vaccine gives against strain-matched viruses are really strong, and the additional coverage we saw against mismatched strains could lower the risk of a bad flu season," said Ellis.

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Universal flu vaccine with nanoparticles that protects against six different influenza viruses in mice

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More information: Quadrivalent influenza nanoparticle vaccines induce broad protection, Nature (2021). DOI: 10.1038/s41586-021-03365-x

https://medicalxpress.com/news/2021-03-nanoparticle-flu-vaccine-blocks-seasonal.html

First-ever vaccine for malignant brain tumors reported safe, effective in early trial

 Tumor vaccines can help the body fight cancer. Mutations in the tumor genome often lead to protein changes that are typical of cancer. A vaccine can alert the patient's immune system to these mutated proteins. For the first time, physicians and cancer researchers from Heidelberg and Mannheim have now carried out a clinical trial to test a mutation-specific vaccine against malignant brain tumors. The vaccine proved to be safe and triggered the desired immune response in the tumor tissue, as the team now reports in the journal Nature.

Diffuse gliomas are usually incurable brain tumors that spread throughout the brain and are difficult to remove completely by surgery. Chemotherapy and radiotherapy often have only a limited effect. In many cases, diffuse gliomas share a common feature: In more than 70% of patients, the tumor cells have the same gene mutation. An identical error in the DNA causes a single, specific protein building block to be exchanged in the IDH1 (Isocitrate dehydrogenase 1) enzyme. This creates a novel protein structure, known as a neo-epitope, which can be recognized as foreign by the patient's immune system.

"Our idea was to support patients' immune systems and to use a vaccine as a targeted way of alerting it to the tumor-specific neo-epitope," explained study director Michael Platten, Medical Director of the Department of Neurology of University Medicine Mannheim and Head of Division at the German Cancer Research Center (DKFZ). The IDH1 mutation is a particularly suitable candidate here, as it is highly specific to the gliomas and does not occur in healthy tissue. Moreover, the IDH1 mutation is responsible for the development of these gliomas: "That means that a vaccine against the mutated protein allows us to tackle the problem at the root," Platten added.

Promising preclinical results

Platten's team generated an artificial version of the segment of the IDH1 protein with the characteristic mutation several years ago. This mutation-specific peptide vaccine was able to halt the growth of IDH1-mutated cancer cells in mice. In 2019, Platten was awarded the German Cancer Prize for this discovery.

Encouraged by these results, Platten and a team of physicians decided to test the mutation-specific vaccine for the first time in a phase I study in patients newly diagnosed with a IDH1-mutated glioma (WHO grades III and IV astrocytomas). A total of 33 patients at several different centers in Germany were enrolled in the study. In addition to the standard treatment, they received the peptide vaccine produced by Michael Schmitt, head of cellular immunotherapy, Department of Hematology, Oncology and Rheumatology at Heidelberg University Hospital, and Stefan Stevanovic, professor of molecular immunology at the Department of Immunology, University of Tübingen. The immune response was evaluated in 30 patients.

The physicians did not observe any serious side effects in any of the patients who were vaccinated. In 93% of the patients, the immune system showed a specific response to the vaccine peptide and did so regardless of the patient's genetic background, which determines the immune system's important presentation molecules, the HLA proteins.

In a large proportion of the vaccinated patients, the physicians observed pseudoprogression, swelling of the tumor caused by a host of invading immune cells. These patients had a particularly large number of T helper cells in their blood with immune receptors that responded specifically to the vaccine peptide, as single cell sequencing revealed. "We were also able to demonstrate that the activated mutation-specific immune cells had invaded the brain tumor tissue," reported Theresa Bunse from DKFZ, who coordinated the immunological analyses for these studies.

The three-year survival rate after treatment was 84% in the fully vaccinated patients, and in 63% of patients tumor growth had not progressed within this period. Among the patients whose immune system showed a specific response to the vaccines, a total of 82% had no tumor progression within the three-year period.

Vaccine concept being pursued

"We cannot draw any further conclusions about the vaccine efficacy from this early study without a control group," remarked Michael Platten. "The safety and immunogenicity of the vaccine were so convincing that we continued to pursue the vaccine concept in a further phase I study."

In this follow-on study, the researchers are combining the IDH1 vaccine with checkpoint inhibitor immunotherapy. "Checkpoint inhibitors act as an immune boost. We believe there is a good chance that they can activate the immune cells against the gliomas to an even greater extent." The study is being implemented in cooperation with other centers in Germany and with support from the German Cancer Consortium (DKTK).

The researchers are also preparing a phase II study to examine for the first time whether the IDH1 vaccine leads to better treatment results than the standard treatment alone. "Gliomas are diagnosed in around 5,000 people in Germany every year, of which about 1,200 are diffuse gliomas with an IDH1 mutation. Up to now, we have usually had only limited success in halting tumor progression in these patients. We believe that the IDH1 vaccine offers the potential for developing a treatment that can suppress these tumors more effectively and on a long-term basis," commented study co-director Wolfgang Wick, Medical Director of the Neurological Clinic of Heidelberg University Hospital and Head of Division at DKFZ.

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First positive results toward a therapeutic vaccine against brain cancer

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More information: A vaccine targeting mutant IDH1 in newly diagnosed glioma, Nature (2021). DOI: 10.1038/s41586-021-03363-z

https://medicalxpress.com/news/2021-03-first-ever-vaccine-malignant-brain-tumors.html

Leaky blood-brain barrier linked to brain tissue damage in brain aging disease

 As people age, changes in the tiniest blood vessels in the brain, a condition called cerebral small vessel disease, can lead to thinking and memory problems and stroke. These changes can also affect the blood-brain barrier, a layer of cells that protect the brain from toxins circulating in the blood. Now a new study has found that people with cerebral small vessel disease who have blood-brain barrier leakage had more brain tissue damage over two years than people with less blood-brain barrier leakage. The study is published in the March 24, 2021, online issue of Neurology.

"Previous research has shown that disruption of the blood-brain barrier is increased in people with cerebral small vessel disease," said study author Danielle Kerkhofs, M.D., of Maastricht University Medical Center in Maastricht, Netherlands. "People with cerebral small vessel disease also may have brain lesions called white matter hyperintensities. Such lesions are visible by MRI and believed to be signs of brain damage and a marker of the severity of disease. For our study, we wanted to see if a leaky blood-brain barrier was linked to degeneration of brain tissue even before these brain lesions appear. We looked at normal brain tissue, surrounding and close to the brain lesions, because we consider this 'tissue at risk.'"

The study involved 43 people with cerebral small vessel disease with an average age of 68. Researchers used MRI at the start of the study to measure the leakiness of the blood-brain barrier for each participant. They then used another brain imaging technique to measure the integrity of the tissue's microstructure surrounding brain lesions. This imaging technique was repeated two years later to see whether the brain tissue integrity has decreased.

Researchers measured the relationship between blood-brain barrier leakage and changes in brain tissue. They found the higher the tissue volume with blood-brain barrier leakage at the start of the study, the greater the loss of brain tissue integrity was around brain lesions two years later. For every 10% increase in leakage volume at the start of the study, after two years the diffusivity of the brain tissue increased by 1.4 %, representing a decrease in brain tissue integrity. They also found a similar relationship involving the leakage rate of the blood-brain barrier—a higher leakage rate at the start of the study resulted in more loss of tissue microstructure around the brain lesions.

"Our results support the theory that a compromised blood-brain barrier may play an early role in loss of brain tissue integrity as part of the cerebral small vessel disease process, even before brain lesions are visible on MRI," said Kerkhofs. "The change in integrity of brain tissue at risk, close to the brain lesions, could be a promising biomarker in future cerebral small vessel disease studies examining possible prevention strategies and treatment options."

A limitation of the study was that the short follow-up period may have underestimated the associations. Kerkhofs said future studies should measure such changes in larger groups of people over longer periods of time.

The study was funded by the European Union's Horizon 2020 Research and Innovation Program, SVDs@target—a research program for small vessel disease, the Netherlands Organization for Scientific Research, the Weijerhorst Foundation, and the Brain Foundation in The Hague, Netherlands.

https://medicalxpress.com/news/2021-03-leaky-blood-brain-barrier-linked-brain.html